AB Science confirms the filing for the Marketing Authorization Application to the European Medicines Agency of Masitinib in the treatment
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.
Husain, 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
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.
Image by Anirudh Koul via Flickr
An emerging French biotech company, AB Science has plans for an IPO on the Paris based Euronext exchange. The company is reported to be seeking €50 million. What makes AB Science interesting is not only that it has a tyrosine kinase inhibitor that has particular promise in pancreatic cancer, but the company has grand designs to follow the growth strategy of biotech companies such as Genentech, Celgene and Biogen Idec.
In the initial company filing with the French Autorité des Marchés Financiers (AMF), the stated corporate strategy is to become a “fully integrated pharmaceutical company (FIPCO)” in order to preserve as much of the potentlal value of the drugs in the pipeline. Very few biotech companies have been able to succeed with this busienss model, so it will be interesting to see if AB Science makes it.
The CEO of AB Science, Alain Moussy provided insight on his plans for the company in the interview he did last year with Sally Church of the Pharma Strategy Blog.
In the interview he states why AB Science has not pursued alliances or partnerships with large pharma companies:
“Biotechs are owned by venture capitalists, who have a 5 to 7 year cycle to make money, but the cycle of drug development is 10-12 years, so in the middle of the cycle they have to sell where the risk is not too high. Typically, venture capitalists do not care whether the product ends up being approved or not. Most biotechs end up following this strategy because they are owned by VC firms. AB Science is owned by entrepreneurs, and we have chosen to dedicate our life to developing products that make a difference. We have to stay independent, because if we try to make money in the middle of the drug development cycle, then we will just select drugs that we can sell to a big pharma, and this is not what we want. What we want is stability for the long-term to have time to take the necessary risks to make the right products.”
AB Science is a company to watch, not only because the CEO has a passion for wanting to make a difference to the lives of patients, but their business model is different from many other biotech companies who instead have adopted a licensing and shared risk approach with major pharma companies.
Ultimately, AB Science’s success will rest on clinical data and in particular the phase 3 clinical trial results for mastinib in pancreatic cancer. Recruitment is set to end in this study in mid-2010 with results in 2011.