AB Science SA is providing a summary of the live webcast held on June 3, 2021 following the voluntary hold in the clinical studies of masitinib.
PRESS RELEASE
SUMMARY OF THE WEBCAST HELD ON JUNE 3, 2021 FOLLOWING THE VOLUNTARY HOLD IN THE CLINICAL STUDIES OF MASITINIB
RESUMPTION OF TRADING ON WEDNESDAY JUNE 9, 2021
Paris, June 8, 2021, 8.30am
AB Science SA (NYSE Euronext - FR0010557264 - AB) is providing a summary of the live webcast held on June 3, 2021 following the voluntary hold in the clinical studies of masitinib.
The presentation of the webcast, which includes the most frequent questions, is available on the company’s website.
The presentation has been delivered by AB Science Medical and Safety team:
- Christian Fassotte, MD, Chief Medical Officer of AB Science
- Peter De Veene, MD, Head of Pharmacovigilance and Global Safety of AB Science
- Olivier Hermine, MD, PhD, Chief of Adults Hematology staff at Hospital Necker in Paris, France, president of AB Science scientific committee and member of the French Académie des Sciences
AB Science’s shares, suspended from trading since June 1st, 2021, will resume trading on Euronext Paris on Wednesday June 9th, 2021 at the opening of its session.
Summary
- Studies continue for patients already under treatment subject to documentation by the investigator of the individual benefit/risk. These patients continue to be dosed.
- AB Science took the decision to temporarily hold the inclusions of new patients because of a potential signal of ischemic heart disease.
- Investigations continue in close collaboration with the agencies.
- Reinforced risk management plan is a possible classic mitigation approach in such situations.
- This decision to suspend inclusions reflects the priority of AB Science to protect patient’s safety while investigations continue.
Overview
AB Science reiterated that patient safety is its priory and justifies the decision to voluntarily put a temporary hold on recruitment and randomization in the on-ongoing studies.
After unblinding the phase 2B/3 studies with masitinib, AB Science ran multiple safety analyses in a continuous effort to detect signals. In one of the exploratory analyses, pooling a subset of studies and a subset of patients, an imbalance of events of Ischemic Heart Disease (IHD) between masitinib and the control arm was detected, which might be interpreted as a signal of increased risks of IHD.
As a consequence, the company consulted with external experts and decided to perform a series of analysis called meta-analysis on all available data from controlled and unblinded study data:
- This meta-analysis was based on Relative Risks (RR) of cardiovascular events based on multiple categorizations of events from all studies
- This analysis relied on the methodology described by the Cochrane Library (gold-standard according to experts)
This meta-analysis did not confirm the signal. These results were shared with national competent authorities across the world. The French competent authority (ANSM) requested some additional analyses and data to finalize its own investigation.
Out of precaution, AB Science decided to hold inclusions in on-going studies pending completion of these investigations.
AB Science will communicate when investigations are completed. In the meantime, AB Science works in close relationship with ANSM, and also other agencies in the world, to provide in a timely manner the requested additional analyses and data.
Most frequent questions
What happens for the patients under treatment?
Patients already under treatment at the time of the decision can stay in the study at the investigator’s decision, provided positive individual benefit/risk is documented. This request has been approved by the ANSM, pending the completion of on-going investigations.
Is this potential risk new?
Cardiotoxicity: Cardiotoxicity is an identified risk with certain tyrosine kinase inhibitors (TKIs). This has been identified at the beginning of the clinical development program as a potential risk with masitinib based on TKI class-risk and data from one animal toxicology study. This potential risk is already described in the Investigator’s Brochure and the Informed Consent for the patient.
Ischemic heart disease (IHD): IHD is the new signal we have detected and not an identified risk.
Were deaths reported from ischemic heart disease (IHD) under masitinib?
Deaths from IHD have been reported both under masitinib and placebo. Some patients present with comorbidities that can lead to IHD in the course of the disease itself, and so when patients enter a clinical study, such IHD events can happen and also sometimes lead to major adverse cardiac events including death, whether the receiving masitinib or the placebo. The role of the pharmacovigilance is to continuously evaluate these events when they occur, to analyze the medical history of the patients and many other parameters to know if the drug may be involved in the more frequent occurrence of these events.
Can you quantify the number of cases and the seriousness of the cases?
Number of cases and difference between masitinib and control vary across studies. Some ischemic events are of grade 1 such as pain in chest and others are grade 5 (death), both in control and masitinib treatment arms. This is the analysis of all studies and all parameters that give a signal.
What additional analyses requested by ANSM need to be done?
Health Authorities usually do not rely solely on sponsors’ analyses and request data to perform their own assessment. Such data and analyses typically include raw data and listings, detailed narratives, sensitivity analyses. AB Science is actively cooperating in all transparency with all agencies and will timely provide the requested information so that on-going investigations can be completed.
When will you know the conclusion of the investigation of this potential risk?
AB Science will communicate when investigations are completed. In order to be conservative, we do not provide forecasts. We work in close relationship with ANSM but also other agencies in the world. Our current expectation is to be able to address rapidly the requests from ANSM. Agencies, like us, are patient-driven and reactive on this topic, in particular in conditions with high unmet medical need.
Given the nature of this potential risk, does it modify or prevent the benefit/risk in non-oncology indications to be positive?
First, we don’t have the position of the agency. Second, there is an expected benefit in each of the indications pursued due to the positive clinical phase 2B/3 results, and based on expected mechanism of action in COVID-19. Therefore, if this potential risk is materialized, an assessment will be done indication by indication. Moreover, the risk mitigation plan can be adapted.
Safety was a strength of masitinib. Does it mean the program is jeopardized?
Expected benefits are unchanged and still present. What is at stake today is to determine if there is an increased risk and how to protect the patients, including with risk management measures such as new exclusion criteria and cardiology preventive measures during the studies.
What is the probability that the studies do not restart?
There will be a specific decision for each study. The decision to restart for each study will depend on the conclusion of the investigation of this risk. The Benefit/Risk ratio will have to be analyzed based on these conclusions, separately for each of the current and future development programs. The Benefit/Risk ratio takes into account the existence or not of a new risk, the risk management plan, the medical need, and the benefit based on existing results.
Why you did not see this potential risk in previous studies?
For each study, predefined analyses were performed and did not identify any signal. When phase 2B/3 studies were unblinded and large amount of safety data were pooled, there was one analysis in a subset of studies and a subset of patients that might be interpreted as a signal of increased risks of IHD. After we generated this exploratory analysis, we performed multiple other analyses, which did not at this time confirm the initial signal. The situation is therefore contradictory at this stage and that is why, since there is some doubt, we suspended the inclusions.
Does this potential risk come from the on-going studies?
This potential risk comes from a retrospective analysis of subset of completed, controlled and unblinded studies, not from on-going studies in ALS, mastocytosis, and COVID-19.
Why do you take these precautionary measures only now?
After an initial analysis which detected a signal on a study group, meta-analyzes performed on all the studies did not confirm this signal. These analyzes are therefore contradictory. The ANSM has requested additional data and analyzes. Therefore, we concluded that a certain level of uncertainty remains and that is why we suspended inclusions.
Why this potential risk has never been seen in the past. You never did such analysis?
Cardiovascular events, including IHD, have occurred in masitinib clinical studies. This potential risk has been analyzed in the past but was not previously detected. This potential signal comes after the unblinding of the phase 2B/3 studies.
Does this situation affect the data of past studies?
The efficacy and safety data of completed studies and study results remain unchanged. The Benefit/Risk will be reassessed in each indication if the signal was confirmed and depending on its magnitude.
Suspension of inclusion or discontinuation of patients will delay by how much the program?
First, patients are not discontinued, subject to documentation by the investigator of the individual benefit/risk. The program will be extended by the duration between the hold and the restart.
What is the position of other agencies apart from ANSM?
We shared all the analyzes with all the agencies and we will collaborate with these agencies in the same way as we do with the ANSM.
About masitinib
Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and microglia and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases.
About AB Science
Founded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment.
AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB).
Further information is available on AB Science’s website:
www.ab-science.com.
Forward-looking Statements - AB Science
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These forward-looking statements can often be identified by the words “expect”, “anticipate”, “believe”, “intend”, “estimate” or “plan” as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations.
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