European Medicines Agency accepts Marketing Authorization Application for conditional approval of masitinib in the treatment of pancreatic cancer.
AB Science reports phase 3 study results of masitinib in combination with Gemzar® for treatment of pancreatic cancer.
AB Science - Financial Communication & Press RelationsLaurent Guy01 47 20 00 14
(NYSE Euronext - FR0010557264 - AB), a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors, announced today the results from a phase 3 study evaluating the effect of masitinib in combination with Gemzar® (gemcitabine, Eli Lilly and Company) on overall survival (OS) in patients with pancreatic cancer. Briefly, masitinib in combination with Gemzar® significantly extended median OS by 6 and 2.7 months in two independent patient populations, representing 65% and 45% of the overall population; namely, patients with a genetic biomarker - collected from simple blood sample - indicative of aggressive disease progression, and patients with cancer pain. Pain intensity and the discovered genetic biomarker were shown to be of prognostic value for survival under Gemzar® alone and at the same time predictive of increased survival with masitinib in combination with Gemzar® for those patients identified as having a poor prognosis with Gemzar® alone.
AB Science also announced that the European Medicines Agency (EMA) has accepted to review a Marketing Authorization Application (MAA) for conditional approval of masitinib in combination with Gemzar® in the treatment of pancreatic cancer, following filing of this dossier.
Full data has been submitted for presentation at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium (24-26 January 2013, in San Francisco, California).
Filing for the conditional approval of masitinib in combination with Gemzar® in the treatment of non resectable, advanced adenocarcinoma pancreatic cancer was accepted by EMA on the basis of results from a phase 3 study that showed masitinib in combination with Gemzar® significantly extends overall survival in two independent patient populations having the worst prognosis. These populations consisted of patients with a gene expression profile (or genetic biomarker) indicative of aggressive disease progression (65% of pancreatic cancer patients), and patients with cancer pain (45% of pancreatic cancer patients). In this prospective, international, randomized, double-blinded clinical trial, 348 patients received either masitinib in combination with Gemzar®, or placebo in combination with Gemzar®. A planned ancillary pharmacogenomic study, based on RNA extracted from whole blood samples before treatment start, was also conducted to identify genetic expression patterns predictive for overall survival and/or treatment benefit.
AB Science made two important discoveries based on data from these studies.
Besides being predictive for masitinib plus Gemzar® treatment efficacy, these two factors were also of prognostic value for overall survival in patients treated with Gemzar® as a single agent. Regarding the genetic biomarker, patients harboring this ‘aggressive genetic fingerprint’ had a median OS of 5.0 months whilst patients without this fingerprint had a median OS of 14.3 months. Regarding the prognostic factor of ‘pain intensity’, patients exceeding a certain threshold of pain at baseline had a median OS of 5.4 months versus 15.4 months in patients without pain.
Results in the overall study population did not show a significant advantage for masitinib in combination with Gemzar® as compared with Gemzar® treatment alone. Median OS was 7.7 months in the masitinib plus Gemzar® treatment arm versus 7.0 months in the placebo plus Gemzar® treatment arm (p=0.74; hazard ratio=0.90). This finding of a non significant survival improvement in the overall population is explained by the fact that masitinib is not indicated when Gemzar® is highly efficient; namely, the situation defined by an absence of both pain and genetic biomarker detecting “aggressiveness”.
Olivier Hermine, MD, PhD, President of the Scientific Committee of AB Science commented:
Alain Moussy, CEO of AB Science declared:
Masitinib received orphan drug designation in the treatment of pancreatic cancer from both FDA and EMA.
Incidence of pancreatic cancer has markedly increased over the last few decades with more than 230,000 patients worldwide diagnosed with this condition. Patients diagnosed with pancreatic cancer often have a poorer prognosis compared with other cancers in part because early detection is difficult. At the time of diagnosis, most patients with pancreatic ductal adenocarcinoma present with locally advanced or metastatic disease and only 10-20% of cases are candidates for curative surgery. Median overall survival from diagnosis is around 3 to 6 months; 5-year survival is much less than 5% and complete remission is extremely rare [American Cancer Society, 2008].
Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells, important cells for immunity, as well as a limited number of kinases that play key roles in various cancers. Owing to its novel 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. Through its activity of inhibiting certain kinases that are essential in some oncogenic processes, masitinib may have an effect on tumor regression, alone or in combination with chemotherapy. Through its activity on the mast cell and certain kinases essential to the activation of the inflammatory cells and fibrosing tissue remodeling, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases.
Founded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a new class of targeted molecules whose action is to modify signaling pathways within cells. Through these PKIs, the Company targets diseases with high unmet medical needs (cancer, inflammatory diseases, and central nervous system diseases), in both human and veterinary medicines. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine in Europe and in the USA, and is pursuing 8 on-going phases 3 studies in human medicine in GIST, metastatic melanoma expressing JM mutation of c-Kit, multiple myeloma, mastocytosis, severe persistent asthma, rheumatoid arthritis, and progressive multiple sclerosis. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB).
Further information is available on AB Science’s website: