Corporate FAQ

Corporate FAQ2021-11-16T16:14:47+01:00

WELCOME TO CORPORATE FAQ

Here Is The Most Frequently Asked Questions.

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Bibliography2019-12-30T11:58:43+01:00

Hirano T. Cellular pharmacodynamics of immunosuppressive drugs for individualized medicine. International Immunopharmacol 2007, 7: 3-22

Kurata Y, M Kato, T Kuzuya, Y Miwa, K Iwasaki, M Haneda. Pretransplant Pharmacodynamic Analysis of Immunosuppressive agents using CFSE based T cell proliferation assay. Clinical Pharmacology & Therapeutics 2009; 86 (3): 285-289

Gulimire Muhetaer, Hironori Takeuchi, Sakae Unezaki, Shigeyuki Kawachi, Hitoshi Iwamoto, Yuki Nakamura et al. Clinical Significance of Peripheral Blood Lymphocyte Sensitivity to Glucocorticoids for the Differentiation of High-risk Patients With Decreased Allograft Function After Glucocorticoid Withdrawal in Renal Transplantation. Clinical Therapeutic 2014;36 (8): 1264-1272

Francis DM, Dumble LJ, Bowes L, Clunie GJ, Macdonald IM. Adverse influence of recipient lymphoid resistance to in vitro immunosuppression on the outcome of kidney transplants. Transplantation. 1988 Dec;46(6):853-7.

Aurelie Premaud, Matthieu Filloux,  Philippe Gatault , Antoine Thierry , Matthias Büchler, Eliza Munteanu  et al.  An adjustable predictive score of graft survival in kidney transplant patients and the levels of risk linked to de novo donor-specific anti-HLA antibodies.  PLoS ONE 2017. 12(7): e0180236. https://doi. org/10.1371/journal.pone.0180236

Madhav C. Menon, Barbara Murphy, and Peter S. Heeger. Moving Biomarkers toward Clinical Implementation in Kidney Transplantation. J Am Soc Nephrol 2017 28: 735–747

Which impact has the IMMUNOBIOGRAM® in the outcomes and follow-up costs in patients in RT?2020-01-14T16:58:36+01:00

Graft failure in Kidney Transplant is associated with high direct costs and a decrease in patients quality of life due to the turn back to dialysis or retransplant. New interventions are needed to improve immunosuppressive drugs adjustment in an individualized way to prevent graft failure, reduce related adverse events and decrease the associated costs.

A pharmacoeconomic model has been developed to estimate the potential impact of the IMMUNOBIOGRAM® in clinical outcomes and cost savings in the follow-up of patients with RT. Cost savings are expected to emerge in patients with high immunological risk that show low-sensitivity patterns to the IMSs they are taking in the IMMUNOBIOGRAM®, and could benefit from a change in IMSs regimen to decrease the graft rejection risk. On the other hand, patients with low immunological risk and a high sensitivity pattern to IMSs can profit from dose adjustments that can decrease the risk of IMSs severe adverse reactions like opportunistic infections or malignancies.

The objective of this evaluation was to estimate the economic impact of Immunobiogram use for the Spanish National-Health-System (NHS). Immunobiogram can help physicians to select the most appropriate IS and doses based on the in vitro pharmacodynamic profile of immune response to IS of each patient that it offers.

A hypothetical cohort (1,000 patients 1 year after renal transplantation) was modeled using a probabilistic second-order Monte Carlo simulation for a time horizon of 5 years under Spanish NHS perspective. Only direct costs were considered.

The results of this evaluation showed that in patients with high risk of graft rejection, the use of the IMBG would entail a potential risk reduction, with a saving of costs per patient in 5 years of € 20,279 and a 100% saving probability. For stable, low risk patients, the use of the IMBG would entail an expected reduction in the adverse events rate with savings of € 3,328 per patient in 5 years, and a 99.5% saving probability.

In conclusion, the routinely use of the Immunobiogram in patients one year after their kidney transplant may have considerable savings for the Spanish NHS.

The pharmacoeconomic model for the IMMUNOBIOGRAM® communicated in the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Congress 2019.

This model is flexible in the sense that can be later easily adapted to different countries (as the model depends upon the different variables and outcomes of the renal transplant specific situation of each country and its associated costs)

When will the IMMUNOBIOGRAM® be commercially available?2019-12-30T11:51:29+01:00

The IMMUNOBIOGRAM® will be available in 2Q 2020.

Does the IMMUNOBIOGRAM® have CE mark for kidney transplantation?2019-12-30T11:50:56+01:00

Biohope expects to achieve CE mark on 2Q 2020, as the company will accomplish all the needed legal requirements . Our consultants for regulatory issues in Europe (Qarad https://www.qarad.com/) have confirmed that TRANSBIO study results are more than enough to get the CE mark by that date. Biohope has already achieved the ISO 13485 certification.

Which is the publication plan for the ongoing clinical studies?2019-12-30T11:48:46+01:00

Final results of the TRANSBIO STUDY in RENAL TRANSPLANTATION will be presented in the American Transplant Congress (ATC 20020).

It is planned to publish a paper with the results of the BH-PILOT STUDY 2015 and TRANSBIO INTERNATIONAL Study.

Which are the next steps in the IMMUNOBIOGRAM® Clinical Development?2019-12-30T11:47:54+01:00

THE IMMUNOBIOGRAM® will be studied in liver transplant and other autoimmune diseases like  Rheumatoid Arthritis, lupus or psoriasis.

Is there any publication of study results?2019-12-30T12:03:27+01:00

You can see them here

Could you share any registration of TRANSBIO clinical study?2019-12-30T11:44:55+01:00

Find attached the link to clinicaltrials.gov, where the main milestones of the study are described

https://clinicaltrials.gov/ct2/show/NCT03562845

For regulatory purposes a comparative study of the IMMUNOBIOGRAM® with a previously launched product or “gold standard” to prove its sensitivity and specificity should be performed?2019-12-30T11:43:13+01:00

There is no “gold standard” to compare with the IMMUNOBIOGRAM®. Because of that, typical sensitivity / specificity evaluation against another test will not be delivered.

A clinical program has been designed to cover the essential aspects of the technology that offers the data needed for the IMMUNOBIOGRAM® to be used in a reliable way. It is very important to consider that the IMMUNOBIOGRAM® will NOT directly guide physician prescription. This means that the tool does not ambition to tell the doctor what medicine should be used; we offer efficacy/potency information to be added to TDM and clinical characteristics, which altogether combined, will drive the decision. Thus, level 1 evidence is not mandatory from regulatory purposes.

In patients with a RT, the hard outcomes (in terms of graft failure or biopsy proven signs of immune rejection) are going to depend not only on the clinical decisions about the IMS regimen to be used,  but also on a pool of epidemiological (ie donors age, type-death or living donor-, recipient characteristics), clinical,  and immunological variables (ie level of HLA mismatch,  dnDSA appearance). Clinical decisions in clinical practice have always been made taking into account these important variables; the pharmacodynamic (IMMUNOBIOGRAM®) and pharmacokinetic (TMD) data will complement them, helping physicians to make more precise therapeutic decisions.

Which were the main results of the TRANSBIO INTERNATIONAL STUDY in renal transplantation?2019-12-30T13:36:09+01:00

TRANSBIO STUDY is an international, multicenter clinical study performed to confirm the BH-Pilot 2015 results and to achieve  the IMMUNOBIOGRAM® technical validation.  It was performed in nine major University Hospitals in Europe and USA:

  • Hospital del Mar, Parc de Salut Mar. Barcelona (Spain).
  • Hospital Vall d´Hebron, Barcelona (Spain).
  • Hospital La Paz, Madrid (Spain).
  • Hospital Universitario Puerta de Hierro (Madrid, Spain).
  • Hospital 12 de Octubre, Madrid (Spain)
  • Universitätsklinikum Essen (Germany)
  • Rigshospitalet, Copenhagen (Denmark).
  • Wroclaw Medical University (Poland)
  • Massachusetts General Hospital, Harvard Medical School, Boston (USA).

The study objectives were to evaluate the IMMUNOBIOGRAM® robustness, the association with clinical prognoses and its consistency in Kidney Transplantation (KT) ( 218 patients were recruited and 164 patients were evaluable).

TRANSBIO study had 2 parts: 

In part 1, the IMMUNOBIOGRAM® of patients with Bad-Clinical-Evolution (BCE) (with renal function deterioration and immunological markers/signs of graft rejection in previous 12-18 months) and with Good-Clinical-Evolution (GCE) were compared.

The IMMUNOBIOGRAM® (IMBG) allowed to quantify in vitro the sensitivity/resistance profile of patients´ immune cells to IMS. Each patient was classified as sensitive, resistant, partial-sensitive or normal responder per IMS tested.

Additionally, two scores allowed to summarize the IMBG patient profile for all IMS tested (with the Global IMBG Score) or only for the IMS taken (with the Prescribed IMBG Score) in a 7 levels scale, from more sensitive (Se++) to more resistant (Re++).

Significant differences were found in both IMBG Scores between patients with Bad Clinical Evolution and Good Clinical Evolution. The Prescribed IMBG Score showed that each step forward in the scale towards resistance increase the probability of a bad prognosis for the patient in a significant way.

PROGNOSIS

In part 2, the consistency of  the IMBG (for two key curve parameters of IMBG dose-response curves, the AUC and ID50) was evaluated. The preplanned intra-subject and inter-time consistency in terms of similarity were reached for AUC, and very close to the target for ID50.

CONCLUSIONS

  1. The IMMUNOBIOGRAM® allows to quantify in vitro patients´ PBMC sensitivity/resistance profile to a panel of seven immunosuppressive drugs in Kidney Transplantation recipients.
  2. Significant differences were found in terms of the IMMUNOBIOGRAM® patterns of resistance/sensitivity to immunosuppressive medication between patients with a Good Clinical Evolution and Bad Clinical Evolution.
  3. The IMMUNOBIOGRAM® showed intra-subject and inter-time consistency.
Which were the main results of BH-PILOT STUDY 2015 in renal transplantation?2019-12-30T11:34:53+01:00

BH-Pilot is a clinical study performed in 2015-2016 in “La Paz” and “Puerta de Hierro” University Hospitals (Madrid). The study included 70 renal transplanted patients at least 1 year after the transplant (immunosuppression maintenance period). They were classified into three categories depending on an immunological risk evaluation:

  • High-risk patients (with a history of rejection, positive HLA antibodies or impaired renal function, or combinations of the previous criteria)
  • Controlled patients (with conventional maintenance immunosuppression)
  • Low-risk patients (without risk criteria and with low levels of IMS for years).

Data of patients’ clinical and immunological history were collected; an extensive battery of biomarkers (proteomics, metabolomics and cell phenotyping) was performed to complement the risk information, and 10 ml of blood were taken to be tested with the IMMUNOBIOGRAM®.

The study outcomes indicated a positive proof of concept for the IMMUNOBIOGRAM® that can be summarized in the following points:

1) The IMMUNOBIOGRAM® provides an individualized patient response pattern to immunosuppressive medication.

2)  Sensitivity ranges can be determined in each patient for each of the drugs and doses tested.

3) Significantly associated low-sensitivity patterns to IMSs in the IMMUNOBIOGRAM®  have been observed in patients with high risk-profile who present worse clinical evolution.

4) Patients with a low-risk profile show better sensitivity scores to IMSs in the IMMUNOBIOGRAM® than standard patients and high-risk patients.

The classification of the immunoassay profiles can be reproduced accurately by a neural network and thus completely automatized.

The outcomes of the study indicate that the IMMUNOBIOGRAM® enables to measure the sensitivity/resistance profile of patients to immunosuppressant medication (IMS), and it can detect patients with bad prognosis due to IMS low sensitivity.

 

Which clinical studies have taken place with Immunobiogram in renal transplantation?2019-12-30T11:34:03+01:00

We have conducted two studies :

  • BH Pilot 2015: it was demonstrated that in the IMMUNOBIOGRAM® there is a direct correlation between high risk patients (patients with active rejection mechanisms) and drug resistance, and low risk patients and drug sensitivity patterns.
  • TRANSBIO International study: it is a study that has allowed to test the correlation between drug resistance in the IMMUNOBIOGRAM® and bad clinical evolution (progressive deterioration in renal function with a significant increase of creatinine and/or proteinuria plus rejection in biopsy, or an increase in strength of DSA expressed as Luminex MFI and with a titter of more than 3000UI). Also, it has allowed to test the correlation between drug sensitivity in the IMMUNOBIOGRAM® and good clinical evolution (patients without rejection episodes, negative DSA, stable renal function, and no changes in treatment). The IMMUNOBIOGRAM® consistency was also tested.

The IMMUNOBIOGRAM® has not been tested in a randomized clinical trial (RCT), but evaluated in an observational study which has included patients with proven bad clinical evolution due to active rejection mechanisms, and good clinical evolution in spite of very low immunosuppressant schemes.

An RCT in renal transplantation maintenance period (after >1 year post Tx) would have implied a large study with a long follow-up, while this kind of evidence is not needed for regulatory purposes to obtain marketing authorization.

BH-PILOT STUDY 2015 and TRANSBIO STUDY ensure that IMMUNOBIOGRAM® is ready for implementation in a clinical laboratory and reproducible.

Why the IMMUNOBIOGRAM® currently doesn´t test products such as IL-2 inhibitors?2019-12-30T11:33:03+01:00

The IMMUNOBIOGRAM® has been clinically tested in renal transplantation maintenance period (after >1 year post RT). The reason is that currently the major challenge for clinicians is to improve the graft survival after one year, reducing the risk of chronic allograft injury due to rejection, and avoiding at the same time the immunosuppressive adverse effects like infections and malignancies. Graft survival during first year has reached very good results (reaching 93% for deceased, and 97% for living-donor kidney transplant recipients in 2014, USA register report).

That´s why the IMs tested in the IMMUNOBIOGRAM® are Tacrolimus, Cyclosporin, Mycophenolate, Sirolimus, Everolimus, Azathioprine and Methylprednisolone, which are the ones used for renal maintenance therapy in clinical practice.

It is planned to test the IMMUNOBIOGRAM® for its use in patients just before transplantation in the near future. The inclusion of IL-2 inhibitor products will be approached in this phase of the IMMUNOBIOGRAM® development.

Would viral infections interfere with the performance of the test?2019-12-30T11:32:22+01:00

Regarding patients with systemic viral infections (VIH, VHC, VHB), they have been excluded in the clinical studies to ensure the protection of lab workers from risks related to exposure of biological agents at work. On the other hand, the impact of viral infections, typical in KT recipients, on the IMMUNOBIOGRAM® remains to be checked in clinical studies.

Would induction therapy with depleting agents influence the performance of the test?2019-12-30T11:31:50+01:00

It may affect lymphocyte activation in vitro, the distribution of leukocyte subpopulations, and the cell extraction performance.  Immunologists have advised us not to performed the IMMUNOBIOGRAM® during the first months of immunosuppressive therapy (during the induction therapy), as the treatment can reduce in a significant way the number and activity of T lymphocytes and the results could be seriously disrupted.  The advice is to perform it before kidney transplantation and wait at least 6 months after the transplantation to perform it again. Our studies, however, have focused until now in the maintenance phase of immunosuppressive treatment and all patients tested had been transplanted more than one year before.

Is the performance of the test influenced by the WBC count?2019-12-30T11:30:51+01:00

The white blood cell count can affect the extraction performance, not the test itself. The test needs approximately three million of T lymphocytes after the extraction and the freezing process to be viable.

Is the test influenced by the drug concentration? That is, does the process of PBMC separation changes the drug concentration in the blood of the patient?2019-12-30T11:30:14+01:00

The PBMC extraction process removes the presence of any medication in the patient´s blood  sample. Cell culture would also decreases – by the dilution effect- the concentration of any remaining drug in the sample. The cell activation that we perform in the culture process also buffers the residual effects of the drug.

Do you know if the test would work using PBMC from patients on dialysis?2019-12-30T11:29:32+01:00

This is a possibility that we have not researched yet at an experimental level. Theoretically, there is the possibility that the dialysis process affects the lymphocyte activation in the subjects. However, in order to carry out the IMMUNOBIOGRAM®, it is necessary to activate the subject’s sample in the laboratory. This in vitro activation possibly minimizes the basal activation differences.

In the specific case of Renal Transplantation what are the IMSs tested by the IMMUNOBIOGRAM®?2019-12-30T11:59:34+01:00

The immunosuppressive drugs tested by the IMMUNOBIOGRAM® in renal transplantation are the following:

  • tacrolimus
  • ciclosporin
  • mycophenolate mofetil
  • sirolimus
  • everolimus
  • azathioprine
  • Metilprednisolone
What qualifications are required for the lab technicians?2019-12-27T14:18:56+01:00

The qualification for the Laboratory technician is basic/mid-level knowledge or experience with laboratory practices and cell culture management. Under our supervision, only one month is needed to fully train a conventional lab technician to run the test.

How long does it take to process the IMMUNOBIOGRAM®?2019-12-26T17:38:17+01:00

The IMMUNOBIOGRAM® procedure takes 3-4 days, plus the time needed for the cells activation (time needed for the physiological stimulation of LT cells, which depends only on the immunological state of each patient, and is a time frame of 3-7 days (usually 4-5 days)).

Does the IMMUNOBIOGRAM® replace the therapeutic drug monitoring (TDM), or it will be used altogether with TDM?2019-12-26T17:37:25+01:00

The IMMUNOBIOGRAM® is not meant to replace the therapeutic drug monitoring (TDM), as TDM measure pharmacokinetics of the drugs but gives no information about the pharmacodynamic effect in the immune system. A concomitant evaluation of pharmacodynamics and pharmacokinetics of the drugs can be an advisable tool to perform successful patient-tailored immunosuppressive therapy.
The IMMUNOBIOGRAM® can support clinicians in the selection of the optimal combination/posology of immunosuppressant drugs and it will be a complementary tool to therapeutic drug monitoring (TDM).

How are the IMMUNOBIOGRAM® results reported to the physicians in clinical practice?2019-12-26T17:36:21+01:00

A report will be provided with the patient´s sensitivity/ resistance profile to each of the IMSs tested distributed in one of these categories: very resistant, resistant, undefined, sensitive or very sensitive.

Results are obtained by clusterization (very resistant, resistant, undefined, sensitive or very sensitive) and the categories correlate with clinical outcomes. These categories clusterize patients very well under a semi-quantitative method, including the result of the bioassay and some common clinical data. The IMMUNOBIOGRAM® is NOT, for example, like measuring glucose, it is more of a combination of several variables to cluster patients in the way that best correlates with clinical outcomes.

In the IMMUNOBIOGRAM® immunosuppressants are individually tested, but a patient may be given more than one and they will affect each other; how to deal with the effect among several types of immunosuppressants?2019-12-26T17:35:16+01:00

The logic behind the IMMUNOBIOGRAM® is the one of an antibiogram. A pharmacodynamic in vitro bioassay which evaluates the utility of different antibiotics to treat a specific infection in a patient. Antibiograms are used extensively in clinical practice, as a very valuable tool in guiding antimicrobial therapy for each patient. It provides the profile of susceptibility or resistance patterns of pathogens to antimicrobials commonly used. Even though some antibiotics can have synergistic effects, this synergy can take place at different levels. It can be related with their mechanism of action,  pharmacokinetic and pharmacodynamic issues (cytochrome P450), isoenzyme liver metabolism, route of elimination, and others.  Therefore, it is not possible to predict their whole synergistic potential based on the analysis of their in vitro combination only.

An antibiogram does not test the combination of antibiotics. Final antibiotic selection takes into account the pathogen susceptibility to each antibiotic from the antibiogram, and those with a better potential combination in clinical practice are selected.

A concomitant evaluation of pharmacodynamics and pharmacokinetics of the drugs can be an advisable tool to perform successful patient-tailored immunosuppressive therapy.

Even so, as it is possible to study the in vitro effect of IMSs combinations with the IMMUNOBIOGRAM®, usual combinations of them will be tested in the future as a complementary information.

When will the doctor use this test? How many will be necessary for the patient?2019-12-26T17:30:59+01:00

The test has been clinically tested in patients after more than one year after transplant. The reason is that currently the major challenge for clinicians is to improve the graft survival after one year, reducing the risk of chronic allograft injury due to rejection, and avoiding at the same time the adverse effects of immunosuppression like infections and malignancies. It is planned to be studies in patients before transplantation as well.

The IMMUNOBIOGRAM® can be used to identify and monitor patients at risk of rejection (who might require an increase of immunosuppression or a change in the immunosuppressive regime prescribed), and in patients with low risk who could profit from a gradual reduction of immunosuppression to avoid severe side effects. The estimated monitorization frequency is twice/three times a year. This estimation is based in the frequency of DSA de novo determinations in routine clinical practice. The development of de novo (dn) DSA beyond one-year post-transplantation has been demonstrated to be strongly associated with graft loss through antibody-mediated rejections.

Why THE IMMUNOBIOGRAM® has been tested initially in patients > 1-year post RT?2019-12-26T17:29:01+01:00

Significant progress has occurred over the decades in renal transplantation, mostly driven by improvements in short-term (one year) graft and patient survival. Further improvement, which has to come mainly from long-term survival improvements, has been more difficult to achieve.

The multifactorial nature of chronic renal allograft loss makes specific interventions difficult. In the absence of any good tools to individualize immunosuppression to each patient, modest progress has occurred in long-term graft attrition, resulting in longer kidney allograft half-lives.  An adequate immunosuppression regimen can decrease graft rejection rates. On the other hand, increased immunosuppression can lead to more graft loss driven by opportunistic infections.

Which is the differential value of the IMMUNOBIOGRAM®, what is unique in the IMMUNOBIOGRAM® biotechnology or in the IMMUNOBIOGRAM® software?2019-12-26T17:15:40+01:00

There are some papers supporting that the in vitro study of the pharmacodynamic effect of immunosuppressive drugs (IMS) on stimulated PBMCs derived from each patient, can provide a useful way for the differentiation of patients who show clinical resistance to immunosuppressive therapies.

However,  previous approaches have not evaluated all IMs within the same bioassay (experiment), and have not used easy methods for commercialization. They use 96-Well Assay Plates and progressive dilutions of IMs to test the effect over PBMCs; that, severely complicates the handling and evaluation of up to 7 IMs in terms of time and costs.

Also, results rely on the discrete number of concentration points of the same drug (predefined by the researcher) and not in a continuous concentration gradient. Therefore, it is difficult to build reliable dose/response curves. Further, this approach implies a lot of variability in the  results with little precision,  and it is difficult to standardize.

The value of the IMMUNOBIOGRAM® relies on the design of a bio model that:

  • Simplifies considerably the IMs efficacy evaluation in terms of handling, costs and time
  • Simultaneously adds precision and robustness.
  • The results also consider clinical variables.

The IMMUNOBIOGRAM® is a model similar to antibiograms in the infectious disease area to guide the prescription of antibiotics.

This bio model is based on a novel design of a “channelled well”, a 3D semisolid matrix to hold the PBMC culture and a simple device to release the IMs into the cell culture. These are the basis for our patent, which was published by the European Patents Agency in January 2019.

  • The development of a biotech standardized method (IVD) to quantify this effect in a valid, reliable and comparable way
  • The definition of mathematical algorithms that not only evaluate dose/response curves but also is capable of clustering patients in sensitive/resistant groups combining biological results with clinical data

Altogether, the IMMUNOBIOGRAM® has become an innovative in vitro immune assay that combines a biotechnological kit and a software for data interpretation that cannot be duplicated in a normal reference lab unless having access to all the biotechnological and mathematical development reached by Biohope.

Does the whole test need a specific instrument?2019-12-26T17:14:25+01:00

To process the IMMUNOBIOGRAM® NO specific instrument is needed. Any standard clinical lab (cell incubator (37ºC, 5% CO2), biosafety cabinet for cell culture and blood processing, microscope, centrifuge, small bath and a fluorimeter) can run the test, provided they follow the instructions that are part of our CE Mark and ISO 13485 Quality Certification.

What are the components of the whole system?2019-12-26T17:13:35+01:00

A cell incubator (37ºC, 5% CO2), a biosafety cabinet for cell culture and blood processing, a microscope, a centrifuge, a small bath and a fluorimeter. In addition, all small devices for cell manipulation.

Is a biosafety cabin absolutely required?2019-12-26T14:27:52+01:00

Yes. It is not only to prevent sample contamination from the operator, but also for the operator safety taking into account that blood samples are potentially hazardous.

The IMMUNOBIOGRAM® includes separation and culture of PBMCs cells, how is it solved the contamination problem? Is there any specific requirement for the laboratory?2019-12-26T14:26:58+01:00

In order to keep sterility and workers’ safety during the IMMUNOBIOGRAM® process, it is necessary to work within a biological safety cabinet, to sterilize all the materials used, to filter all the reagents, and to ensure a proper hygiene and training of the lab technicians. In case of a cultured PBMCs’ contamination, the sample should be discarded, regardless of the step of the process when the contamination appears. It is crucial to discard this kind of samples to avoid a potential influence in the IMMUNOBIOGRAM® results.

How is the IMMUNOBIOGRAM® performed?2019-12-26T14:26:02+01:00

The IMMUNOBIOGRAM® is an endpoint bioassay. It is done with a 10 ml peripheral blood sample per patient. The readout of the bioassay translates in numbers the inhibition of the patient´s T cells proliferative response after exposure to each immunosuppressive drug.

This bioassay is done with a sample of 3D cell culture of PBMCs, one part is physiologically stimulated (control +), and the other part is not stimulated and serve as control (control -).

A hydrogel containing the PBMCs is loaded in longitudinal channels and immunosuppressive (IMS) drugs delivery devices are placed at the edge of the different channels.  In each channel a IMSs concentration gradient takes place due to a passive diffusion process.

After 18-20h of exposure to IMSs, an indicator of cell proliferation/viability reveals the capacity of IMSs gradient to inhibit the activation of T cells. A quantifiable signal is obtained and properly measured with fluorimetry.

A mathematical model and a software for the data interpretation have been developed to  evaluate the IMMUNOBIOGRAM® dose/response curves to IMSs and obtain the patient sensitivity /resistance profile to each of the IMS tested.

Which are the conceptual basis for the IMMUNOBIOGRAM®?2019-12-26T14:24:26+01:00

Previous scientific studies have shown that “cellular pharmacodynamics of immunosuppressive drugs is an efficient strategy to predict the clinical efficacy of drugs in many immunological disorders and organ transplantations. Unexpectedly large individual deviations in PBMC sensitivity to the drugs, paralleled with deviations in the clinical efficacy of the drugs have been observed in most cases of immunological disorders”

“Therefore, the examination in vitro of drug sensitivity before drug administration can be a valuable tool to predict the clinical efficacy of drugs in these patients” (Hirano T, 2007)

The logic behind the development of the IMMUNOBIOGRAM® is the same one as  in the antibiograms. A pharmacodynamic in vitro bioassay to evaluate the utility of different antibiotics to treat a specific infection in a patient. Antibiograms are extensively used in clinical practice, as they are very valuable in guiding antimicrobial therapy for each patient. An antibiogram provides the profile of susceptibility or resistance patterns of pathogens to antimicrobials commonly used.

The IMMUNOBIOGRAM® has been designed to test the patients´ sensitivity/resistance profile  to each immunosuppressant. It is a tool that, taken together with other important variables, can help physicians to make more precise therapeutic decisions.

To what extent diagnostics/biomarkers are used in current medical practice concerning RT to tailor treatments to improve outcomes and reduce costs?2019-12-26T14:23:24+01:00

The search for predictive markers associated with allograft rejection is a key focus in transplant research. Post-transplant monitoring relies mainly on serial serum creatinine (Cr) measurements and in biopsies.

  • Serum Cr level is a highly insensitive indicator of the degree of damage in the kidney. It has a lag time of weeks to months while on-going damage is occurring, and changes are non-specific with regards to the cause of the injury.
  • Surveillance biopsies are the gold standard to detect graft rejection, but they are performed infrequently after kidney transplantation. Biopsies are invasive, expensive, and subject to inter-grader variability of approximately 30%; therefore, performing invasive biopsies is not suitable for frequent monitoring.
  • To date, the only validated and accepted marker by the clinical community is the -de novo – appearance of DSA (Donor Specific Antigens), which advise about the risk of graft rejection.
  • Currently, there is no validated test to measure or monitor the adequacy of the immunosuppression regimen. The lack of this test may result in under-immunosuppression and cause graft rejection, or in over-immunosuppression causing a higher risk of opportunistic infections and malignancies.
  • Immuknow® is an IVD approved by the US Food and Drug Administration (FDA) (not in the EU) under the 510K pathway in 2002. This bioassay quantifies the amount of intracellular ATP that is released from CD4+ T cells in response to a non-specific mitogenic stimulus. It only identifies if there is a certain risk of rejection (due to underimmunosuppression), but it doesn´t provide a specific result regarding the sensitivity/resistance profile of each patient to the IMSs they are taking.
  • Other tools (like Trugraf) have been developed to tests on gene-expression “signatures”, but again they only identify if there is a certain risk of rejection and only differenciate between a state of trasplant eXcellence (TX= adequately immunosuppressed) from a not-TX situation.
  • Molecular biomarkers have been studied in the graft, urine and blood of kidney transplant recipients, but recent reviews have highlighted the need for robust multicenter validation studies, and underscored the potential role for biomarker monitoring of immunosuppressive therapy and transplant outcomes. They are not used in daily clinical practice (Menon 2017).
Which clinical need can help to solve the IMMUNOBIOGRAM® in renal transplantation (RT)?2019-12-30T12:10:37+01:00

Kidney transplantation is the treatment of choice for patients with end stage renal failure. It has demonstrated, by large, to improve the patients QoL, and decrease treatment costs. However, these patients have a persistent risk of graft rejection due to immune-mediated kidney injury.

The donor´s graft is from the same species but genetically different from the recipient. The immune system of the recipient will inevitably recognize donor-specific antigenic (DSA) determinants (i.e., alloantigens) expressed by the graft, mainly from the human leukocyte antigen (HLA) complex. The alloimmune response that is developed against donor-specific HLA molecules of the graft is responsible for tissue damages which lead to the failure of the transplanted organ, a process named rejection.

To limit the risk of rejection, transplanted kidney patients require long term treatment with different immunosuppressive (IMSs) drugs and doses.  Currently, IMSs are prescribed empirically and based on standard clinical guidelines, but there is a lack of biomarkers to help health professionals to stablish a personalized therapeutic immunosuppression plan for each patient.

The IMMUNOBIOGRAM® is a valuable tool that help physicians to individualize immunosuppression based on the patients´ response to immunosuppressive treatment (IMSs).

Which is the value of having a tool that can predict the clinical efficacy of drugs in immunological disorders and organ transplantations?2019-12-26T14:05:18+01:00

Precision Medicine is the current major trend in chronic medical conditions to maximize the chance of saving lives and improving quality of life. This means that days of “one drug fits all” are over, instead, human diversity responses must be considered. Different patients need different drugs, and this is the driver of new medical management.

Chronic inflammation is the “poor sister” of the large family of human diseases. Infectious diseases, cancer, and many other diseases have been managed under precision medicine protocols for decades. Nowadays, antibiograms are mandatory to prescribe antibiotics, and nobody thinks of cancer treatment without biomarkers and targeted therapies. On the contrary, chronic inflammation remains treated with immunosuppressant drugs, which are mostly used following clinical guidelines, drug blood levels, and trial/error approaches.

Inflammatory diseases are clearly lacking a tool to determine the potency (efficacy) of immunosuppressant drugs over the immune cells of the patients.  An assay to identify those immunosuppressants that may be more efficacious for each patient at a certain point of time was needed.

What is the IMMUNOBIOGRAM®?2019-12-26T14:04:08+01:00

The IMMUNOBIOGRAM® is an In Vitro Diagnostic immunoassay that combines a biotechnological KIT and a software for data interpretation.

The IMMUNOBIOGRAM® is a tool that helps physicians to adapt the immunosuppressive therapy in patients with a kidney transplant, allowing them to select for each patient the most adequate combination of  immunosuppressive drugs (IMS) and doses, to avoid kidney rejection and reduce the side effects of treatments.

The IMMUNOBIOGRAM® is performed with a 3D-cell culture of peripheral blood mononuclear cells (PBMCs) subdued to a specific immune stimulation which replicates the physiological immune response of each patient. The PBMCs are included in a hydrogel and exposed to each IMSs in different channels. The hydrogel is capable of a spontaneous generation of IMSs concentration-gradient due to a passive-diffusion process. An indicator of cell-proliferation/viability reveals the capacity of the IMSs-gradient to inhibit the patient´s immune activation cells state.

Cellular pharmacodynamics of immunosuppressive drugs is an efficient strategy to predict the clinical efficacy of drugs in many immunological disorders and organ transplantations (Hirano T 2007, Francis DM 1988). A concomitant evaluation of pharmacodynamics/ pharmacokinetics of the drugs would be useful to perform successful patient-tailored immunosuppressive therapy.

This endpoint immunoassay offers a personalized comparative evaluation of a patient´s sensitivity/resistance profile to a panel of the most commonly prescribed IMSs, allowing to predict and monitor the patients ‘response to IMSs.

Bibliography RA2019-03-21T17:42:43+01:00

Kirkham BW, Corkill MM, Davison SC, Panayi GS. Response to glucocorticoid treatment in rheumatoid arthritis: in vitro cell mediated immune assay predicts in vivo responses. J Rheumatol

1991;18:821–5.

Radner H, Smolen JS, Aletaha D. Remission in rheumatoid arthritis: benefit over low disease activity in patient reported outcomes and costs. Arthritis Res Ther 2014; 16: R56.

Bernard Combe, Robert Landewe, Claire I Daien, Charlotte Hua, Daniel Aletaha, Jose María Álvaro-Gracia. 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis 2017;76:948–959. doi:10.1136/annrheumdis-2016-210602

Smolen, J.S. et. al. 2016 EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update Ann Rheum Dis 76(6):960-977

Schipper, L.G.; van Hulst, L.T.; Grol, R.; van Riel, P.L.; Hulscher, M.E.; Fransen, J. Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome Rheumatology 2010, 49(11):2154-64 doi: 10.1093/rheumatology/keq195. Epub 2010 Jul 29.

Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations

for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis 2009;68:1086–93.

Which impact can IMBG have in the outcomes and costs of follow-up in patients in RA?2019-03-21T17:42:35+01:00

A pharmacoeconomic model will be developed to estimate the potential impact of IMBG in clinical outcomes and cost savings in the follow-up of patients with RA. Direct medical costs in RA are mainly driven by pharmacological treatment and disease activity.  The availability of IMBG can largely contribute to adequate the drug regimen for each patient to the individualized profile of sensitivity/resistance to DMARDs as shown in IMBG and can have a great potential for better clinical outcomes and cost savings.

When will be IMBG commercially available for use in RA?2019-03-21T17:42:26+01:00

We expect IMBG will be available for RA in 2021.

Do IMMUNOBIOGRAM® have CE mark for Rheumatoid Arthritis?2019-03-21T17:42:18+01:00

Biohope expects to achieve CE marking Self-Certification in 2021, when the company will accomplish all the needed legal requirements. We also have a QA team fully dedicated to the development of the technical file regarding our Kit, which will be produced according to the ISO13485 standard, already in place.  ®

Why IMBG currently doesn´t test other dmards (such as biologic dmards)2019-03-21T17:42:11+01:00

Biological DMARDs aren´t currently tested with the IMBG due that they are monoclonal antibodies with a larger molecular size, what hamper the passive diffusion process in the hydrogel through the IMBG channels to create a concentration gradient. An adaptation in the diffusion process is being developed to adjust IMBG to the physicochemical features of these compounds is currently ongoing. For the Rheumatoid Arthritis indication, we have added JAK inhibitors, which demonstrates that such adaptations to other products are possible.

 

When and to whom should the IMBG be performed?2019-03-21T17:42:02+01:00

The IMBG is being currently clinically tested in patients with early disease (2010 classification criteria for RA from American College of Rheumatology (ACR). The objective is to test if IMBG can be used to identify the patients´ sensitivity/resistance profile to first line treatments for RA before treatment is begun and to advise over the treatment adequacy after 3/6 months of follow-up when remission is not achieved. One important goal is to demonstrate if IMBG can be used to identify and monitor patients with a higher probability of resistance to methotrexate to allow physicians to take a quicker treatment change orientation to achieve remission.

It is also being tested in patients with a chronic AR when they are treated with the IMS tested, to facilitate therapeutic decisions.

What are the IMS tested by IMBG Rheumatid Arthritis?2019-03-21T17:41:54+01:00

The immunosuppressive drugs tested by IMBG in rheumatoid arthritis are the following:

– Methotrexate

– Sulfasalazine

– Leflunomide

– Hydroxychloroquine

– Azathioprine

– Methylprednisolone

– Tofacitinib

– Baricitinib

The recipients where IMSs are included for the exposure in channels to PBCMs in IMBG are prepared by Biohope following a standardized method.

What is the intended use of the IMBG in clinical practice?2019-03-21T17:41:45+01:00

The clinical program has been designed to cover the essential aspects of the technology that provides the data needed to use the IMBG in a reliable way in clinical practice. It is very important to consider that the IMBG will not directly guide physician prescription. This means that the tool does not ambition to tell the doctor what medicine should be used; we offer efficacy/potency information to be added to other variables, which altogether combined, will drive the clinical decision.

Clinical decisions will have always to be made taking into account other important patient variables (like immunological patients´ profile, baseline disease activity, clinical evolution and treatment side effects) to help physicians to make more precise therapeutic decisions.

Which is the publication plan for the ongoing clinical studies in RA?2019-03-21T17:41:38+01:00

Final results of BH-Pilot Study 2018 IN RHEUMATOID ARTHRITIS are planned to be presented 2019/2020 in EULAR Annual European Congress of Rheumatology and in ACR/ARHP American College of Rheumatology Annual Meeting

It is planned to publish a paper with the results of RA BH-Pilot Study 2018

Which are the next steps in IMBG clinical development?2019-03-21T17:41:29+01:00

TRANSBIO study in Renal Transplantation is an ongoing, international study (conducted in 10 Europe and USA hospitals) that will allow to confirm the results of the PoC study in Renal Transplantation, and that will also allow to test IMBG reproducibility. Final results are expected in September 2019.

Regarding Rheumatoid Arthritis, once the feasibility and robustness of IMBG in this disease have been demonstrated with the BH-Pilot Study 2018, a subsequent validation study is planned to be carried out at international level.

Which have been the clinical results of IMBG studies in other indications?2019-03-21T17:41:18+01:00

BH-Pilot 2015 in renal transplant was a clinical study performed in 2015-2016 in “La Paz” and “Puerta de Hierro” University Hospitals (Madrid) as a proof of concept study in patients with a renal transplantation. The study included 70 renal transplanted patients at least 1 year after the transplant (immunosuppression maintenance period).

The study outcomes indicated a positive proof of concept for IMBG that can be summarized in the following points:

1) Immunobiogram provided an individualized patient response pattern to immunosuppressive medication.

2)  Sensitivity ranges could be determined in each patient for each of the drugs and doses tested.

3) Significantly associated low-sensitivity patterns to IS in IMBG have been observed in patients with high risk immunological-profile and who present worse clinical evolution.

4) Patients with a low-risk profile showed better sensitivity scores to IS in IMBG compared with other patients.

The classification of immunoassay profiles could be reproduced accurately by a neural network and thus completely automatized.

The outcomes of the study indicated that in renal transplantation IMBG enables to measure the sensitivity/resistance profile of patients to immunosuppressant medication, and it can detect patients with bad prognosis due to IS low sensitivity.

Which clinical studies are taking place with IMMUNOBIOGRAM® in Rheumatoid Arthritis?2019-03-21T17:41:13+01:00

IMBG is being studied in Rheumatoid Arthritis under a comprehensive clinical plan program, which includes an already running first proof of concept clinical study in 100 patients (BH-Pilot Study 2018 in Rheumatoid Arthritis) and a it is planned to be followed by a subsequent validation study

BH-Pilot Study 2018 in Rheumatoid Arthritis aims to evaluate the feasibility and potential clinical utility of a specifically-developed IMBG for Rheumatoid Arthritis. This first-in-clinic study is being done in collaboration with the Rheumatology Unit of “Reina Sofía” Hospital (Córdoba) and “Maimonides Institute of Biomedical Research” (IMBIC).

It will include 100 Rheumatoid Arthritis patients classified in the following categories:

  1. Naïve patients
  2. Chronic patients under treatment with DMARDs with low disease activity
  3. Chronic patients under treatment with DMARDs with high disease activity

We expect BH- Pilot Study 2018 in Rheumatoid Arthritis to be a clinical study that will demonstrate:

1) IMBG -RA will be feasible in patients with Rheumatoid Arthritis at various disease stages and clinical scenarios

2) IMBG-RA will offer an in vitro potency evaluation of Immunosuppressant drugs (IS) that will correlate with sensitivity grades of the patient to a panel of IMs

3) A significant proportion of patients with non-controlled RA will show low-sensitivity patterns in IMBG -RA to the medication they are taking

What clinical needs can IMBG contribute to solve in Rheumatoid Arthritis (RA)?2019-03-21T17:41:03+01:00

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes chronic inflammation of the synovial membrane of multiple joints, generating swelling, pain and stiffness, and that can lead to a progressive cartilage and bone destruction resulting in severe joint deformities and disability. The disease can have also systemic manifestations.

The clinical evolution of RA is fluctuating with periods of exacerbation and remission; the prognose differs a lot from one patient to another and in some cases can be rapidly progressive.

The treatment paradigm of RA has changed a lot in the last years due to new concepts in the diagnosis and in the treatment goals, and since more successful treatment options are now available. The main goal of disease-modifying anti-rheumatic drugs (DMARD) treatment is to achieve remission.

Currently the mainstay of RA treatment includes conventional synthetic drugs (csDMARDS), biological, and novel potential small molecule DMARDs (called tsDMARDS, targeted synthetic DMARDs), which have allowed a significant progress to attenuate disease activity and decrease joint deformity. But even with a medical treatment, 40% of patients will develop some type of functional disability after 10 years of evolution.

Patients with early arthritis should be treated as soon as possible (ideally within 3 months after onset of symptoms) in order to reduce and even prevent the risk of joint damage and disability. DMARDs have been shown to slow disease progression in RA. However, there is a wide variation in patient clinical response to current therapies. Among the DMARDs, Methotrexate (MTX) monotherapy should be part of the first treatment strategy (unless contraindicated), with or without Glucocorticoids (GC) as bridging therapy for most patients.

However, it fails to control the disease activity in 30-40% of patients (Rau R 2010).

The optimum treatment goal is remission, or at least low disease activity in patients irresponsive to earlier treatments. Until the desired treatment target is reached, drug therapy should be reviewed at least every 3 to 6 months.

Due to the heterogeneity of patients´ clinical evolution and treatment response, it is important to adjust the treatment at a patient basis. EULAR recommends “a regular monitoring of disease activity, treatment adverse events and comorbidities to guide decisions on choice and changes in treatment strategies to reach this target”.

The availability of diagnostic tools that allow to evaluate for each patient the clinical efficacy of the drugs before administration can help clinicians to take treatment informed decisions to prevent delays in the use of the more effective treatments for each patient and to avoid the risk of unnecessary adverse events and costs.

IMBG can support clinicians to individualize immunosuppressive treatment based on the patients´ immune profile of response to the disease-modifying antirheumatic drugs (DMARDs) tested.

What is IMMUNOBIOGRAM® in Rheumatoid Arthritis?2019-03-22T10:03:37+01:00

INMUNOBIOGRAM® (IMBG) is an In Vitro Diagnostic immunoassay that combines a biotechnological KIT and a software for data interpretation.

IMBG is a service provided by BH  that will help physicians to adapt the immunosuppressive drugs (IS) in patients with Rheumatoid Arthritis (RA), allowing to select for each patient the most adequate IS and doses to reach clinical remission and reduce the side effects of treatment.

IMBG offers a personalized comparative evaluation of patient sensitivity/resistance profile to a panel of IS most commonly used in RA in clinical practice, allowing to predict and monitor patients‘ response to IS and supporting clinicians to take informed decisions to optimize the immunosuppressive therapy.

Bibliography RT2019-03-21T17:40:29+01:00
  1. E. Lamb, S. Lodhi and H.-U. Meier-Kriesche Long-Term Renal Allograft Survival in the United States: A Critical Reappraisal. American Journal of Transplantation 2011; 11: 450–462
  2. Wang JH, Skeans MA, Israni AK. Current Status of Kidney Transplant Outcomes: Dying to Survive. Adv Chronic Kidney Dis. 2016 Sep;23(5):281-286.
  3. Trends in 1-, 5-, & 10-year kidney transplant graft survival, 1999-2015 (unadjusted) USA- Anual Report 2018. USRDS Figure 6.25. Volume 2: End-Stage Renal Disease in the United States. Accessed on January 2019
  4. Registre de malalts renals de Catalunya. Informe estadístic 2016. Barcelona: Servei Català de la Salut. Organització Catalana de Trasplantaments (OCATT)
  5. Madhav C. Menon, Barbara Murphy, and Peter S. Heeger. Moving Biomarkers toward Clinical Implementation in Kidney Transplantation. J Am Soc Nephrol 2017 28: 735–747
  6. Kurata Y, M Kato, T Kuzuya, Y Miwa, K Iwasaki, M Haneda. Pretransplant Pharmacodynamic Analysis of Immunosuppressive agents using CFSE based T cell proliferation assay. Clinical Pharmacology & Therapeutics 2009; 86 (3): 285-289
  7. Gulimire Muhetaer, Hironori Takeuchi, Sakae Unezaki, Shigeyuki Kawachi, Hitoshi Iwamoto, Yuki Nakamura et al.Clinical Significance of Peripheral Blood Lymphocyte Sensitivity to Glucocorticoids for the Differentiation of High-risk Patients With Decreased Allograft Function After Glucocorticoid Withdrawal in Renal Transplantation. Clinical Therapeutic 2014;36 (8): 1264-1272
  8. Francis DM, Dumble LJ, Bowes L, Clunie GJ, Macdonald IM. Adverse influence of recipient lymphoid resistance to in vitro immunosuppression on the outcome of kidney transplants. 1988 Dec;46(6):853-7.
  9. Aurelie Premaud, Matthieu Filloux, Philippe Gatault , Antoine Thierry , Matthias Büchler, Eliza Munteanu  et al.  An adjustable predictive score of graft survival in kidney transplant patients and the levels of risk linked to de novo donor-specific anti-HLA antibodies.  PLoS ONE 12(7): e0180236. https://doi. org/10.1371/journal.pone.0180236
Which impact can IMGB have inoutcomes and costs of follow-up in patients with RT?2019-03-21T15:04:23+01:00

A pharmacoeconomic model has been developed to estimate the potential impact of the IMBG in clinical outcomes and cost savings in the follow-up period of patients with RT. Cost savings are expected to happen :

  • In patients with high immunological risk that show low-sensitivity patterns to the IS they are taking . They will benefit from a change in IS regimen to decrease the graft rejection risk.
  • In patients with good clinical evolution and a high sensitivity pattern their IS regimen. They will benefit from dose adjustments/reductions to decrease the risk of IS adverse reactions like metabolic disorders, opportunistic infections or malignancies.

The pharmacoeconomic model was based in the following assumptions:

  • Probabilistic second-order Monte Carlo simulation
  • Hypothetical cohort of 1,000 patients 1 year after renal transplantation
  • Spanish NHS Perspective
  • Time horizon of 5 years
  • Only Direct Costs are included*
  • All model assumptions were validated by a Spanish clinical experts’ panel

Direct costs associated with graft failure (dialysis, retransplantation), IS therapy, and Adverse Events management were obtained from Spanish sources

Key results of the analysis were

  • The use of the the IMBG would entail a potential risk reduction of graft failure with a saving of costs per HR patient in 5 years of € 20,279 (95% CI € 17,512-23,105) and a 100% saving probability
  • The use of the IMBG would entail an expected reduction in the AE rate that would generate savings per non-HR patient in 5 years of € 3,328 (95% CI € 451-7,957) and a 99.5% saving probability

This pharmacoeconomic model will be presented in the next congress of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR 2019)

This model can be easily adapted for different countries and health care systems as long as data of transplantation maintenance costs are available

 

When will be the IMBG commercially available in kidney transplant?2019-03-06T18:40:45+01:00

We expect the IMBG will be available in 1Q 2020

Does the Immunobiogram has a CE mark for kidney transplant?2019-03-06T18:39:43+01:00

Biohope expects to achieve CE marking Self-Certification on June 2019, as the company will accomplish all the needed legal requirements. The TRANSBIO study results (ongoing International Study) will be more than enough to get it by that date. We also have a QA team fully dedicated to the development of the technical file regarding our Kit, which will be produced according to the already in place ISO13485 standard.

Biohope expects to present the IMBG file for FDA approval in 2020.

Will the IMBG replace ims therapeutic drug monitoring (TDM)?2019-03-06T18:38:23+01:00

The IMBG is not meant to replace the therapeutic drug monitoring (TDM), as TDM measure pharmacokinetics of the drugs but gives no information about the pharmacodynamic effect of them in the immune system. A concomitant evaluation of pharmacodynamics and pharmacokinetics of the drugs can be an advisable tool to perform successful patient-tailored immunosuppressive therapy.

The IMBG can support clinicians in the selection of the optimal combination/posology of immunosuppressant drugs and it will be a complementary tool to TDM, which allows that a selected drug reaches in blood the therapeutic levels needed to be effective.

How will the IMBG results be reported to physicians in the clinical practice?2019-03-06T18:37:09+01:00

A report will be provided with the patient´s sensitivity/ resistance profile to each of IS tested.

Results are obtained by clusterization in categories under a semi-quantitative method, which includes the result of the bioassay and some common clinical data.

Why IMBG currently doesn´t test other advanced immunology products (such as il-2 inhibitor products)?2019-03-06T18:35:56+01:00

The IMBG has been clinically tested in the renal transplantation maintenance period (after >1 year post RT). The reason is that currently the major challenge for clinicians is to improve the graft survival after one year, reducing the risk of chronic allograft injury due to rejection and avoiding at the same time immunosuppressive adverse effects like infections and malignancies. Graft survival during first year has reached very good results.

That´s why the IS tested in IMBG are Tacrolimus, Cyclosporin, Mycophenolate, Sirolimus, Everolimus, Azathioprine and Methylprednisolone, which are the ones used for renal maintenance therapy in clinical practice.

It is planned to test the use of the IMBG in patients just before transplantation in the near future. The inclusion of the IL-2 inhibitor products will be approached in this phase of IMBG development.

 

What are the IMS tested by the IMBG in renal transplantation?2019-03-21T15:02:08+01:00

The immunosuppressive drugs tested by the IMBG in renal transplantation are the following:

  • Tacrolimus
  • Ciclosporin
  • Mycophenolate mofetil
  • Sirolimus
  • Everolimus
  • Azathioprine
  • Methylprednisolone
Does the imbg test the combination of several ims in patients with RT?2019-03-22T13:34:07+01:00

The rationale behind the IMMUNOBIOGRAM® (IMBG) resembles the one of an antibiogram, a pharmacodynamic in vitro bioassay which evaluate the usefulness of different antibiotics to treat a specific infection in a patient. Antibiogram is used extensively in clinical practice, as it is a very valuable tool in guiding antimicrobial therapy for each patient. It provides the profile of susceptibility or resistance patterns of pathogens to antimicrobials commonly used. Even though some antibiotics can have synergistic actions, this synergy can take place at different levels:  it can be related with their mechanisms of action, with their pharmacokinetic and pharmacodynamic issues like cytochrome P450 isoenzyme liver metabolism, with their route of elimination and with other factos.  Therefore, it is not possible to predict their whole synergistic potential only based on the analysis of their combination in vitro.

An antibiogram does not test the combination of antibiotics. Final antibiotic selection is decided by taking into account the pathogen susceptibility to each antibiotic from the antibiogram and selecting those with a better potential combination in clinical practice.

A concomitant evaluation of pharmacodynamics and pharmacokinetics of the drugs can be an advisable tool to perform successful patient-tailored immunosuppressive therapy.

Even so, as it is possible to study in vitro the effect of IS combinations with the IMBG, combinations of them will be tested in a further step as a complementary information.

When and to whom should the IMBG be performed?2019-03-06T18:44:29+01:00

The test has been clinically tested in patients after more than one year of the transplant. The reason is that currently the major challenge for clinicians is to improve the graft survival after one year, reducing the risk of chronic allograft injury due to rejection, and avoiding at the same time immunosuppressive adverse effects like infections and malignancies. It is planned for the IMBG to be tested as well for its use in patients before transplantation.

It can be used to identify and monitor patients at risk of rejection (who might require an increase of immunosuppression or a change in the immunosuppressive regime prescribed), and in patients with low risk to profit from a gradual reduction of immunosuppression and avoidance of severe side effects.

Estimated monitoring frequency will depend on the patient profile. An IMBG should be done to all patients at baseline, once the immunological system has got stabilized after the induction therapy (6 months post RT). In the maintenance phase it is estimated that 1 IMBG per year should be performed in high immunological risk patients. Patients who present immunological events (ie. dnDSA) or adverse events which can lead to a change in immunosuppressive regimen can require an additional IMBG before undertaking a treatment change. The development of de novo (dn) DSA beyond one-year post-transplantation has been demonstrated to be strongly associated with graft loss through antibody-mediated rejections, and is often related with underimmunosuppression.

What is the intended use of the IMBG in clinical practice?2019-03-06T18:44:48+01:00

The clinical program has been designed to cover all the essential aspects of the technology to generate the data needed for the IMBG to be used in a reliable way. It is very important to consider that IMBG will NOT directly guide the physician prescription. The IMBG offers efficacy/potency information to be used with epidemiological, immunological, clinical and pharmacokinetic (TDM) variables, which altogether combined, will drive the decision.

To improve patients showing a RT hard outcome (in terms of graft failure or proven signs of immune rejection by a biopsy) the physician will have to consider not only the clinical decisions about the IS regimen to be used,  but also a pool of epidemiological (ie donors age, type-death or living donor-, recipient characteristics), clinical,  and immunological variables (ie level of HLA mismatch,  dnDSA appearance). Clinical decisions have always been made taking into account these important variables, and pharmacodynamic (IMBG) and pharmacokinetic (TMD) data will complement them, and help physicians to make more precise therapeutic decisions.

Which is the publication plan for the ongoing clinical studies in RT?2019-03-06T18:30:40+01:00

Final results of the TRANSBIO STUDY in RENAL TRANSPLANTATION are to be presented in 2019/2020 in the European Society for Organ Transplantation Congress (ESOT), American Transplant Congress (ATC), and the International Congress of The Transplantation Society (TTS).

It is planned to publish a paper with the results of the BH-PILOT and TRANSBIO studies.

Are there any publications of the studies results?2019-03-22T13:33:12+01:00

Final results from the BH-PILOT STUDY 2015 were first presented at the 27th International Congress of the Transplantation Society, TTS 2018 (1-5th July, Madrid) by Prof. Julio Pascual from Hospital del Mar, Barcelona:  “IMMUNOBIOGRAM® : A Novel Precision Medicine Tool to Help Guidance of Immunosuppression in Renal Transplantation. Results of “BH-Pilot 2015” Proof-of-Concept Clinical Study”

A poster and an oral communication were presented at the 5th European Congress of Immunology 2018, (2-5th September 2018, Amsterdam).

Oral presentation: ‘IMMUNOBIOGRAM®  a new immunological tool to personalize immunosuppressive therapy in kidney transplant recipients”.

Poster: “IMMUNOBIOGRAM®  as a diagnostic assay for detection of resistance to immunomodulatory treatment in patients with chronic inflammatory diseases”

An abstract was presented at the Basic Science Transplantation Congress BST 2018: “IMMUNOBIOGRAM®: a new immunological tool to personalize immunosuppressive therapy in kidney transplant recipients”, that took place in 11-13 October 2018, Rotterdam.

 

Is there any registration of Transbio clinical study?2019-03-06T18:45:08+01:00

Find attached the link to clinicaltrials.gov, where main milestones of the study are described

https://clinicaltrials.gov/ct2/show/NCT03562845

Have any kol’s discussed clinical program results and the imbg value in clinical practice?2019-03-06T18:27:23+01:00

In September 2017 a meeting was held with the main investigators of the TRANSBIO validation study and very positive feedback was received. The attendees were 7 renowned nephrologists of the following hospitals in Europe and USA:

  • Hospital Puerta de Hierro (Spain)
  • Hospital Vall d´Hebron (Spain)
  • Hospital del Mar (Spain)
  • Hospital La Paz (Spain)
  • Universitätsklinikum Essen (Germany)
  • Medical University Borowska (Poland)
  • University Hospital of Copenhagen (Denmark)
  • Massachusetts General Hospital, Harvard Medical School (Boston).

During the TTS 2018 congress presentation encouraging comments from several top KOL ( Charité Universitätsmedizin Berlin,  Germany; University Hospitals Leuven, Belgium; Necker Hospital in Paris, France) were received.

The TRANSBIO study results will be discussed in an investigator meeting during ESOT 2019

What are the indicators to evaluate the clinical results?2019-03-06T18:26:22+01:00

In the TRANSBIO study bad clinical evolution will be considered when patients show a progressive deterioration in renal function (with a significative increase of creatinine and/or proteinuria), show signs attributable to any kind of immunological response compatible with a rejection in biopsy, or an increase in strength of DSA expressed as Luminex MFI and with titters of more than 3000 UI.

Good clinical evolution will be considered for patients without rejection episodes, with a negative DSA, with a stable renal function and with no changes in their treatment.

Which are the clinical results of the IMBG studies?2019-03-06T18:45:23+01:00

BH-Pilot 2015 was a clinical study performed during 2015-2016 in “La Paz” and “Puerta de Hierro” University Hospitals (Madrid). The study included 70 patients at least 1 year after the renal transplant (immunosuppression maintenance period). They were classified into three categories depending on their immunological risk evaluation:

  • High-risk patients (history of rejection, positive HLA antibodies, impaired renal function, or any combination of the previous criteria)
  • Controlled patients (with conventional maintenance immunosuppression)
  • Low-risk patients (lack of risk criteria and treated with low levels of IS for years).

Data of patients’ clinical and immunological history were collected; an extensive battery of biomarkers (proteomics, metabolomics and cell phenotyping) was performed to complement the risk information, and 10 ml of blood was taken to be tested with the IMBG

The study outcomes indicated a positive proof of concept for the IMBG that can be summarized in the following points:

1) IMBG  provides an individualized patient response pattern to immunosuppressive medication.

2)  Sensitivity ranges can be determined in each patient for each of the drugs and doses tested.

3) Significantly associated low-sensitivity patterns to IMSs in IMBG have been observed in patients with high risk-profile who present worse clinical evolution.

4) Patients with a low-risk profile show better sensitivity scores to IS in IMBG compared with standard patients and high-risk patients.

The classification of the immunoassay profiles can be reproduced accurately by a neural network and be completely automatized.

The outcomes of the study indicate that the IMBG  enables the measurement of the sensitivity/resistance profile of patients to immunosuppressant medication, and can detect patients with bad prognosis due to IS low sensitivity.

Which clinical studies have been done with the IMBG in renal transplantation (RT)?2019-03-21T14:45:12+01:00

IMBG has been initially tested in an observational, proof of concept study, which included patients with kidney transplant and with proven bad clinical evolution due to active rejection mechanisms, and patients with good clinical evolution.

We have two studies in place:

  • BH Pilot 2015: published results show that there is a direct correlation between high risk patients (patients with active rejection mechanisms) and drug resistance in IMBG, as well as there is a correlation between low risk patients and drug sensitivity patterns.
  • TRANSBIO study: it is an ongoing international study that will allow to test the correlation between drug resistance in IMBG and bad clinical evolution (defined as a progressive deterioration in renal function plus rejection signs in biopsy or an increase in DSA strength by Luminex). Also, it allows to test a correlation between drug sensitivity in IMBG and good clinical evolution (patients without rejection episodes, negative DSA, stable renal function and no changes in treatment). IMBG reproducibility will be also tested.

BH-PILOT STUDY 2015 and TRANSBIO STUDY will allow to ensure that IMBG is ready for implementation in the clinical laboratory and reproducible. TRANSBIO will allow to compare IMBG in kidney transplanted patients with good vs bad clinical evolution.

Additionally, 2 local studies are planned to be conducted during 2019/2020. The first one will allow to get prospective data about the clinical evolution of the patients included in BH-Pilot 2015 and to analyze the correlation between the sensitivity/resistance profile detected in IMBG and the patients´ clinical evolution 2 years later. The second one will compare the IMBG from the same patients when performed from a fresh or a frozen blood sample and between two different centers.

Why has the IMBG been tested initially in patients > 1-year post rt?2019-03-06T18:45:51+01:00

Significant progress has occurred over the decades in renal transplantation, mostly driven by improvements in short-term (one year) graft and patient survival. Further improvements in long-term survival have to come through improvements in long-term graft maintenance.

The multifactorial nature of chronic renal allograft loss makes specific interventions difficult. In the absence of any good tools to individualize immunosuppression to each patient, modest progress has occurred in long-term graft survival.  An individualized immunosuppression regimen based on the patients´ response to IS can contribute notably to decrease graft rejection rates and to avoid the appearance of severe adverse events.

To what extent are diagnostic/ biomarkers used in rt medical practice to tailor treatment and improve outcomes?2019-03-06T18:21:31+01:00

The search for predictive markers associated with allograft rejection is a key focus in transplant research. Post-transplant monitoring relies mainly on serial serum creatinine (Cr) measurements and in biopsies.

 

  • Serum Creatinine level is a highly insensitive indicator of the degree of damage in the kidney. It has a lag time ranging from weeks to months while on-going damage is occurring, and changes are non-specific with regards to the cause of the injury.
  • Surveillance biopsies are the gold standard to detect graft rejection, but they are performed infrequently after kidney transplantation. Biopsies are invasive, expensive, and subject to inter-grader variability; performing invasive biopsies is not suitable for frequent monitoring.
  • To date, the only validated and accepted marker by the clinical community is the -de novo – appearance of DSA (Donor Specific Antigens), which advises about the risk of graft rejection.
  • Currently there is no validated test to measure or monitor the adequacy of the immunosuppression regimen. The failure of the regimen may result in under-immunosuppression and cause graft rejection, or in over-immunosuppression and increase the risk of opportunistic infections and malignancies.
  • Immuknow® is an IVD approved by the US Food and Drug Administration (FDA) (not in the EU) under the 510K pathway in 2002. This bioassay quantifies the amount of intracellular ATP that is released from CD4+ T cells in response to a non-specific mitogenic stimulus. It only identifies if there is a certain risk of rejection (due to underimmunosuppression), but it doesn´t provide a specific result regarding the sensitivity/resistance profile of each patient to the IS they are taking.
  • Other tools (like Trugraf) that test on gene-expression “signatures” have been developed, but again only identify if there is a certain risk of rejection, and only differentiate between a state of transplant eXcellence (TX= adequately immunosuppressed) from not-TX
  • Molecular biomarkers have been studied in the graft, urine and blood of kidney transplant recipients, but recent reviews have highlighted the need for robust multicenter validation studies, while underscoring the potential role for biomarker monitoring of immunosuppressive therapy and transplant outcomes. They are not used in daily clinical practice (Menon 2017).
Which clinical need adresses the IMMUNOBIOGRAM® in renal transplantation (rt)?2019-04-01T17:48:15+02:00

Kidney transplantation is the treatment of choice for patients with end stage renal failure. It has by large demonstrated to improve patients QoL and decrease treatment costs.

However, these patients have a persistent risk of graft rejection due to immune-mediated kidney injury.  The immune system of the recipient can recognize as strange the donor-specific- antigens expressed by the graft, mainly from the human leukocyte antigen (HLA) complex (alloantigens). An alloimmune response is developed in the recipient against the donor graft alloantigens that is responsible for graft tissue damages, and can lead to the failure of the transplanted organ.

To limit the risk of rejection, transplanted kidney patients require long term treatment with different immunosuppressive drugs (IS) and doses.  Treatment with IS has driven overall improvements in graft survival, mainly during the first-year after kidney transplantation, but long-term survival has improved only slightly over decades.  Recent data from registers show that graft failure at 10 years from transplant occurs in about 57 % patients in USA (Annual Report 2018 USRDS) and in about 50% in Spain, (Registre de malalts renals de Catalunya) (deceased donors, unadjusted).1,2,3,4

On the other hand, immunosuppression can lead to different side effects that cause a substantial clinical burden for the patients, and negatively affect patient and allograft survival,  metabolic toxicities (hypertension, hyperlipidemia, diabetes, bone loss), and serious adverse events like malignancies and opportunistic infections.

Currently, prescribed IS regimens are based on standard clinical guidelines, drug blood levels and empirical use. There is a lack of biomarkers to help health professionals to stablish a personalized therapeutic immunosuppression plan for each patient according to the individual response profile to IS.

IMBG has been developed to test the patient´s profile of sensitivity/resistance to each immunosuppressant. It is a tool that, taken together with other important variables, can help physicians to make more precise therapeutic decisions, and contribute to decrease the risk of rejection due to under-immunosuppression, and decrease the burden of IS adverse events due to over-immunosuppression.

IMMUNOBIOGRAM® RT2019-03-22T13:03:03+01:00

IMMUNOBIOGRAM® (IMBG) is an In Vitro Diagnostic immunoassay that combines a biotechnological KIT and a software for data interpretation.

IMBG is a service provided by BH  that will help physicians to adapt the immunosuppressive drugs (IS) in patients with Rheumatoid Arthritis (RA), allowing to select for each patient the most adequate IS and doses to reach clinical remission and reduce the side effects of treatment.

IMBG offers a personalized comparative evaluation of patient sensitivity/resistance profile to a panel of IS most commonly used in RA in clinical practice, allowing to predict and monitor patients‘ response to IS and supporting clinicians to take informed decisions to optimize the immunosuppressive therapy

Bibliography2019-03-06T18:09:31+01:00

Hirano T. Cellular pharmacodynamics of immunosuppressive drugs for individualized medicine. International Immunopharmacol 2007, 7: 3-22

Kurata Y, M Kato, T Kuzuya, Y Miwa, K Iwasaki, M Haneda. Pretransplant Pharmnacodynamic Analysis of Immunosuppressive agents using CFSE based T cell proliferation assay. Clinical Pharmacology & Therapeutics 2009; 86 (3): 285-289

Gulimire Muhetaer, Hironori Takeuchi, Sakae Unezaki, Shigeyuki Kawachi, Hitoshi Iwamoto, Yuki Nakamura et al.Clinical Significance of Peripheral Blood Lymphocyte Sensitivity to Glucocorticoids for the Differentiation of High-risk Patients With Decreased Allograft Function After Glucocorticoid Withdrawal in Renal Transplantation. Clinical Therapeutic 2014;36 (8): 1264-1272

Francis DM, Dumble LJ, Bowes L, Clunie GJ, Macdonald IM. Adverse influence of recipient lymphoid resistance to in vitro immunosuppression on the outcome of kidney transplants. Transplantation. 1988 Dec;46(6):853-7.

Madhav C. Menon, Barbara Murphy, and Peter S. Heeger. Moving Biomarkers toward Clinical Implementation in Kidney Transplantation. J Am Soc Nephrol 2017 28: 735–747

Which clinical studies have been performed and what are the next steps in the IMMUNOBIOGRAM® clinical development?2019-04-01T17:50:47+02:00

IMBG has being studied in KIDNEY TRANSPLANT under a comprehensive clinical plan program, which includes a first proof of concept clinical study in 70 patients (BH-PILOT STUDY 2015), and in a multicenter international validation study, to be finished in 2Q 2019 (TRANSBIO STUDY). The BH-PILOT STUDY 2015 and the TRANSBIO STUDY will ensure that the IMMUNOBIOGRAM®  is ready for implementation in a clinical laboratory and reproducible.

IMBG is also being studied in RHEUMATOID ARTHRITIS under a clinical plan program, which includes an ongoing first proof of concept clinical study in 100 patients (BH-PILOT STUDY 2018 IN RHEUMATOID ARTHRITIS).  This clinical study aims to evaluate the feasibility and clinical utility of a specifically-developed IMBG for Rheumatoid Arthritis.

It is foreseen to conduct a subsequent validation multicenter and international study in Rheumatoid Arthritis.

The clinical program has been designed to cover the essential aspects of the technology for the IMBG to be used in a reliable way. It is very important to consider that IMBG is not aimed to guide directly the physician prescription. The kit offers efficacy/potency information to be considered along with epidemiological, immunological, clinical and pharmacokinetic variables, which altogether combined, will drive the decision.

 

Which is the differential value of the IMMUNOBIOGRAM® (IMBG) technology?2019-04-01T17:51:24+02:00

Some papers support that the study in vitro of the pharmacodynamic effect of IS on stimulated PBMCs derived from each patient, can provide a useful way to differentiate patients in relation to who shows clinical resistance to immunosuppressive therapies.

Previous approaches have not evaluated all IS within the same bioassay (experiment) and do not use methods easy to commercialize. They use 96-Well Assay Plates and progressive dilutions of IS to test the effect over PBMCs. That severely complicates the handling and evaluation of up to 7 IS in terms of time and costs. Results also rely on the discrete number of concentration points of the same drug (predefined by the researcher) and not in a continuous concentration gradient, so it is complicated to build reliable dose/response curves. Further, this approach provides much variability in results with little precision, and difficult to standardize.

The value of IMBG relies on the design of a biomodel that:

  • Simplifies considerably the IS efficacy evaluation in terms of handling, costs and time.
  • Simultaneously adds precision and robustness.
  • Allows IMBG to be interpreted also considering clinical variables.

IMBG is a model similar to the antibiograms used in the infectious diseases to guide the prescription of antibiotics.

This biomodel is based on:

  •  A novel design of a “channeled well”, a 3D semisolid matrix to hold the PBMC culture, and a simple device to release the IMs into the cell culture. These are the basis for our patent, which was published by the European Patents Agency in January 2019.
  • The development of a biotech standardized method (IVD) to quantify this effect in a valid, reliable and comparable way
  • The development of mathematical algorithms that evaluate dose/response curves AND are capable of clustering patients in sensitive/resistant groups combining biological results with clinical data

Altogether, IMBG has become an innovative in vitro immune assay that combines a biotechnological kit and a software for data interpretation that currently cannot be duplicated in a normal reference lab unless having access to all the biotechnological and mathematical development proven by Biohope.

Which are the requirements to perform the IMMUNOBIOGRAM® (IMBG)?2019-04-01T17:51:55+02:00

The whole IMBG procedure takes 3-4 days, plus the time needed for the physiological stimulation of LT cells, which depends on the immunological state of each patient (4-5 days time frame).

-LAB COMPONENTS

Cell incubator (37ºC, 5% CO2), biosafety cabinet for cell culture and blood processing, microscope, centrifuge, small bath, and a fluorimeter. In addition, all small devices and  components for cell manipulation.

-SPECIFIC NEEDS

To process de IMBG NO specific instrument is needed. Any standard clinical lab can run the test, provided they follow the “instructions” included in our CE Mark and ISO 13485 Quality Certification.

-CONTAMINATION PROBLEM

In order to keep sterility and workers’ safety during the IMBG process, it is necessary to work within a biological safety cabinet, to sterilize all the materials, to filter all the reagents and to ensure a proper hygiene and training of lab technicians. In case of a cultured PBMCs’ contamination, the sample should be discarded to avoid a potential influence on the IMBG-test’s results.

-BIOSAFETY CABIN

A biosafety cabin is absolutely required. Not only to prevent sample contamination from the operator, but also for the operator safety considering that blood samples are potentially hazardous.

-WHICH QUALIFICATION IS REQUIRED FOR A LAB TECHNICIAN? 

The Laboratory Technician, should have a basic/mid-level knowledge or experience in a laboratory setting and in cell culture management. Under Biohope supervision, only one month is needed to train a lab technician to run the test.

How long does it take the INMUNOBIOGRAM® (IMBG) procedure?2019-03-22T12:55:43+01:00

The whole IMBG procedure takes 3-4 days, plus the time needed for the physiological stimulation of LT cells, which depends on the immunological state of each patient (4-5 days time frame).

How does the INMUNOBIOGRAM® (IMBG) works?2019-03-22T12:54:43+01:00

IMMUNOBIOGRAM® is an endpoint bioassay. It is done with a 10 ml peripheral blood sample per patient. The readout of the bioassay translates in numbers the inhibition of the patient´s T cells proliferative response after exposure to each immunosuppressive drug.

This bioassay is done with a sample of 3D cell culture of PBMCs, some are physiologically stimulated (control +) and the other are not stimulated and serve as control (control -).

A hydrogel containing the PBMCs is loaded in longitudinal channels and immunosuppressive drugs (IS) delivery devices are placed at the edge of the different channels.  In each channel an IS concentration gradient takes place due to a passive diffusion process.

After 18-20h of exposure to IS, an indicator of cell proliferation/viability reveals the capacity of IMSs gradient to inhibit the activation of T cells. A quantifiable signal is obtained and properly measured with fluorimetry.

A mathematical model and a software for the data interpretation has been developed to

evaluate the IMBG dose/response curves to IS, and toperform a cluster analysis of patients based on this cellular response.

Overall, this software can qualify the patient´s sensitivity /resistance profile to each IS tested.

What is the rationale behind the INMUNOBIOGRAM® (IMBG)?2019-03-22T10:13:03+01:00

The logic behind IMBG resembles the one of an antibiogram, a pharmacodynamics in vitro bioassay that evaluates the usefulness of different antibiotics to treat a specific infection in a patient. The antibiogram is extensively used in clinical practice, as a very valuable tool in guiding antimicrobial therapy for each patient. It provides the profile of susceptibility or resistance patterns of pathogens to commonly used antimicrobials.

Previous scientific studies have shown that “cellular pharmacodynamics of immunosuppressive drugs is an efficient strategy to predict the clinical efficacy of drugs in many immunological disorders and organ transplantations. Unexpectedly large individual deviations in PBMC sensitivity to the drugs, paralleled with deviations in the clinical efficacy of the drugs have been observed in most cases of immunological disorders”

“Therefore, the examination in vitro of drug sensitivity before drug administration can be a valuable tool to predict the clinical efficacy of drugs in these patients” (Hirano T, 2007)

Which is the added value of the INMUNOBIOGRAM® (IMBG) in immunological disorders?2019-03-22T10:08:53+01:00

Precision Medicine is the current major trend to maximize health outcomes in chronic medical conditions. This means that the time of “one drug for all” is over, instead, human diversity responses must be considered. Different patients need different drugs, and this is the driver of new medical management.

Chronic inflammation is the “poor sister” of the big human diseases family. Infectious diseases, cancer, and many other diseases have been managed under precision medicine protocols for decades. Culture and antibiograms are mandatory to prescribe antibiotics, and nowadays nobody thinks of cancer treatment without biomarkers and targeted therapies. On the contrary, chronic inflammation remains treated with immunosuppressive drugs mostly based on clinical guidelines, drug blood levels and trial/error approaches.

Inflammatory diseases are clearly lacking a tool to determine the potency (efficacy) of immunosuppressive drugs over the immune cells of the patients, which are actually the target cells of the immunosuppressants/ immunomodulators. This assay is able to identify those immunosuppressants that may be more efficacious for each patient at a specific point in time.

What is INMUNOBIOGRAM®?2019-03-22T10:07:27+01:00

INMUNOBIOGRAM® (IMBG) is an In Vitro Diagnostic (IVD) immunoassay that combines a biotechnological KIT and a software for data interpretation and report elaboration.

IMBG provides information that will help physicians to personalize the immunosuppressive therapy in patients with inflammatory diseases, and help them to take informed decisions to select the most adequate immunosuppressive drugs (IS) for each patient to improve clinical outcomes.

IMBG offers a personalized comparative evaluation of the patient´s sensitivity/resistance profile to a panel of the most commonly used IS in clinical practice, allowing physicians to predict and monitor the patients‘ response to a specific IS.

The immunoassay is performed with a 10 ml peripheral blood sample, and allows to measure the response of immunologically stimulated PBMCs to a panel of  IS used for the treatment of an inflammatory disease in clinical practice. PBMCs are included in a hydrogel that is distributed into several channels in a plate, and IS delivery devices are placed in the edge of those channels. The hydrogel is capable of generate a spontaneous IS concentration-gradient due to a passive-diffusion process. An indicator of cell-proliferation/viability reveals the capacity of IS-gradient to inhibit the patient´s immune activation cells state.

INMUNOBIOGRAM® has been designed to test the patient´s profile of sensitivity/resistance to each immunosuppressant as a tool that, taken together with other important variables, can help physicians to make more precise therapeutic decisions.

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    “Closer to the personalization of renal transplant treatment.
    First study to evaluate the functionality of the IMMUNOBIOGRAM® to predict the immunosuppressive response.”
    “Closer to the personalization of renal transplant treatment.
    First study to evaluate the functionality of the IMMUNOBIOGRAM® to predict the immunosuppressive response.”
    “Closer to the personalization of renal transplant treatment.
    First study to evaluate the functionality of the IMMUNOBIOGRAM® to predict the immunosuppressive response.”
    “Closer to the personalization of renal transplant treatment.
    First study to evaluate the functionality of the IMMUNOBIOGRAM® to predict the immunosuppressive response.”
    “Closer to the personalization of renal transplant treatment.
    First study to evaluate the functionality of the IMMUNOBIOGRAM® to predict the immunosuppressive response.”
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