Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Alain Moussy’

AB Science confirms the filing for the Marketing Authorization Application to the European Medicines Agency of Masitinib in the treatment of Pancreatic Cancer.

AB Science LogoParis based biopharmaceutical company AB Science announced in an October 16 news release that the company has applied to the European Medicines Agency (EMA) for approval of masitinib in pancreatic cancer.

Masitinib is a tyrosine kinase inhibitor of PDGF, PDGFR, FGFR, FAK, c-KIT. A phase 3 clinical trial (NCT00789633) in pancreatic cancer is underway that compares masitinib with gemcitabine to placebo with gemcitabine.  The trial started in November 2008 with an estimated enrollment of 320 patients at 68 study locations. As far as I am aware no data has yet been presented for this trial.

The phase 2 trial results for mastinib in pancreatic cancer were, however, extremely promising.

Alain Moussy, CEO of AB Science in an interview on Pharma Strategy Blog, A leap of faith: AB Science & mastinib in pancreatic cancer, stated that masitinib “is unique its ability to resensitize the pancreatic cell that has become resistant to gemcitabine.

Strangely, the AB Science news release today offers no top line results, and merely states the “communication of results was delayed to allow the filing for patent applications aimed at extending the period of marketing exclusivity.

The presumption from the filing and today’s announcement is that the data for mastinib in pancreatic cancer is positive, which is good news for patients. I look forward to hearing more about the overall survival benefit for masitinib when more data becomes available.

This news also adds to the excitement building in pancreatic cancer, with the Celgene Abraxane data expected before year end.

Update November 1, 2012: Phase 3 Trial Results Announced

In an October 30, 2012 news release, AB Science finally shared the data for their Phase 3 clinical trial (NCT00789633): A Study to Compare Efficacy and Safety of Masitinib in Combination With Gemcitabine, to Placebo in Combination With Gemcitabine, in Treatment of Patients With Advanced/Metastatic Pancreatic Cancer.

I don’t plan to rehash the self-explanatory news release, but the results are mixed. The Principal Investigator, and leading pancreatic cancer experts I contacted (who were not involved with the trial) did not respond to requests for comment. This suggests that we will have to wait till the data is presented at the ASCO GI symposium in San Francisco next year to fully understand the implications for clinical practice.

Bad news: Study failed to meet it’s primary endpoint of showing that masitinib increased overall survival (patients lived longer) when used in combination with gemcitinabine versus gemcitabine alone.

  • Median OS was 7.7 months in the masitinib plus gemcitabine treatment arm versus 7.0 months in the placebo plus gemcitabine treatment arm (p=0.74; hazard ratio=0.90).

The company news release states:

“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.”

However, there is some positive news for AB Science, and that is a subset of the 320 patients in the study did significantly live longer with masitinib.

Good news: a subset of pancreatic cancer patients with a novel genetic biomarker for tumor aggressiveness, identified using RNA expression from whole blood samples, lived significantly longer with masitinb.

  • Patients in the subset with this biomarker (65% of the study population) had a median overall survival (OS) of 5 months on gemcitabine alone, while those on masitinib and gemcitabine had an OS of 11.0 months (hazard ratio of 0.29, p=0.000038).

A survival advantage of 6 months with mastinib is a dramatic result!

If mastinib can be used in conjunction with a predictive biomarker that identifies those patients who may likely respond, it is hard not to imagine that some form of regulatory approval would be forthcoming, despite the failure of the trial to meet it’s primary endpoint. However, more clinical data and another clinical trial may be needed to validate the biomarker, if as it appears, the biomarker was identified retrospectively.

There are also many unanswered questions:

  • what is the technology needed to detect the biomarker?
  • is this a test that can be routinely performed?
  • is there a diagnostic kit available?
  • How might such a genetic biomarker be used in clinical practice by non-academic physicians?
  • What is the extent to which the biomarker has been shown to be valid and reproducible?

I look forward to hearing more about the masitinib data at the ASCO GI 2013 meeting.

Update November 6, 2012: Skuldtech identified as diagnostics partner

Another piece of the jigsaw has been provided in a November 3 news release from AB Science that french company, Skuldtech is the company they are working with on a companion diagnostic test for masitinib in pancreatic cancer. As usual, I found the news out first on Twitter:

The AB Science news release states that:

Skuldtech and AB Science plan to exploit these new markers for commercialization of a future companion test associated with masitinib, a molecule developed by AB science for treating pancreatic cancer.

It goes on to say:

“From a simple drop of blood, Skuldtech and AB Science were able to identify specific markers – transcriptomic markers – that can distinguish between the different populations treated during the phase III study and select the predictive markers for pancreatic cancer survival associated with masitinib treatment.”

We await further information on the cost, availability and validation of the companion diagnostic.

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It’s been a bad week for vitamins, especially with the publication of data from the SELECT trial that showed healthy men taking 400 IU/day of Vitamin E had a 17% increased risk of prostate cancer.

However, there is some evidence in support of tocotrienols (unsaturated form of Vitamin E) having a potential role to play in anti-cancer therapy.  One paper that caught my attention was the work by Kazim Husain and colleagues from the Moffitt Cancer Center and Research Institute in Tampa.

Published Online First (October 4, 2011) in the American Association for Cancer Research (AACR) journal, “Molecular Cancer Therapeutics” they showed that δ- tocotrienol may have potential to improve the effectiveness of gemcitabine in pancreatic cancer.

In their laboratory and animal based research, the authors showed that δ-Tocotrienol:

  • “augments inhibition of pancreatic cancer cell proliferation by gemcitabine”
  • “augments gemcitabine-induced apoptosis in pancreatic cancer cells”
  • down-regulates constitutively activated NF-κB in gemcitabine-treated pancreatic cancer cells”
  • “enhances the in vivo therapeutic effects of gemcitabine in a pancreatic tumor model in SCID nude mice”

Pancreatic cancer patients have a poor prognosis with less than <5% of patients surviving 5 years.  Current treatment revolves around the chemotherapy gemcitabine, but as the authors note in their Molecular Cancer Therapeutics paper, “tumor resistance is common.”

Various researchers are working on how to improve treatment options for pancreatic cancer.  One company I’m watching is AB Science and their phase 3 trial for masitinib.  You can read more about this on Pharma Strategy Blog and Sally Church’s excellent interview with CEO, Alain Moussy.

The work on the δ-tocotrienol form of Vitamin E shows that it may have a role to play in cancer treatment, notwithstanding the negative data that was published earlier this week in prostate cancer.

Husain and colleagues from Moffitt showed for the first time that δ-tocotrienol inhibited NF-κB activity and the expression of NF-κB regulated gene products. They note that inflammatory transcription factor NF-κB is involved in tumorigenesis, so inhibition of NF-κB may be how tocotrienols exert their anti-cancer effects.

These preclinical results are promising and show that:

“δ-tocotrienol is the most bioactive tocotrienol against human pancreatic cancer cells and provide the rationale for selecting δ-tocotrienol as the lead tocotrienol compound for further studies of the use of tocotrienols for pancreatic cancer prevention and treatment.”

A phase I clinical trial is ongoing (NCT00985777) evaluating the use of δ-tocotrienol in patients with pancreatic tumors.

While Vitamin E supplementation may yet be of benefit to healthy individuals, it could have benefit in patients with pancreatic cancer, so it will be interesting to see how this develops.

ResearchBlogging.orgHusain, K., Francois, R., Yamauchi, T., Perez, M., Sebti, S., & Malafa, M. (2011). Vitamin E  -Tocotrienol Augments the Anti-tumor Activity of Gemcitabine and Suppresses Constitutive NF- B Activation in Pancreatic Cancer Molecular Cancer Therapeutics DOI: 10.1158/1535-7163.MCT-11-0424

Following on from yesterday’s news that Gilead had acquired Calistoga and CAL-101, another company that is exploring the interface between cancer and inflammation is Paris based AB Science.

Pharma Strategy Blog has an excellent interview with the CEO, Alain Moussy.  AB Science is an emerging French biopharmaceutical company, and I previously wrote about its IPO.

The company has adopted a unique market entry strategy of obtaining approval first in animal health for their tyrosine kinase inhibitor, masitinib.  In 2008, AB Science gained European approval for canine mast cell tumors and in December 2010 FDA approval.

The company recently announced that on February 8, 2011 it had its first US sale of masitinib to vets.

Masitinib is in fact a multi-kinase inhibitor that inhibits wild type and mutant forms of stem cell factor receptor (c-KIT, SCFR), platelet-derived growth factor (PDGFR), fibroblast growth factor 3 (FGFR3) and to a lesser degree, focal adhesion kinase (FAK).

Sally Church on the Pharma Strategy Blog has written about how AB Science’s strategy makes sense – if you look at Pfizer, they obtain more revenue from animal health than they do from oncology.  AB Sciences’ Masivet® in Europe, Kinavet® in the United States competes against Pfizer animal health’s tyrosine kinase inhibitor, Palladia® (toceranib), which also targets mast cell cancer in dogs.

Not only does this growth strategy generate revenue for an early-stage company like AB Science, it also allows the company to build a sales and marketing infrastructure in the United States and Europe while waiting for the results of pivotal phase 3 studies in humans.

The phase 2 clinical trial data for masitinib in combination with gemcitabine in pancreatic cancer were impressive (28% survival at 18 months).  The phase 3 clinical trial results are expected this year.  The clintrials.gov listing shows the date for the estimated primary completion date (Overall Survival) as November 2010 with study completion in November 2011.  Obviously the exact timing depends on how fast subjects were accrued, but I would be surprised if we didn’t see some data presented at ASCO or ESMO, especially if positive.

In terms of targeting inflammation, masitinib is in phase III development for mastocytosis, rheumatoid arthritis (RA) and asthma.  AB Science announced on January 27, 2011 the first patient recruited into their phase 3 study in severe asthma.

The company’s new product development strategy is way ahead of many of its competitors in identifying the links between cancer and inflammation, and choosing to target market opportunities in both areas.

AB Science is an exciting company to watch, and I expect that we will see important new data come out at major scientific meetings this year.

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