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.