A diagnosis of stage IV pancreatic cancer is pretty much a death sentence. People are often diagnosed in the advanced
Academic institutions are now bringing pharma/biotech companies together and facilitating rational combination trials that make solid scientific sense.
Combining at least two targeted drugs looks to be increasingly necessary in order to develop innovative new cancer treatments, where turning off one target may stimulate another, thus both need to be targeted for there to be an overall effect.
However, one company may not have all the pathways and drug targets covered by their portfolio. The result is that companies may have to work together in combination trials with each providing one drug from their portfolio.
That was one of the key messages I took from Gordan Mills (UT MD Anderson Cancer Center) in his recent video interview with Sally Church from Pharma Strategy Blog:
Sally Church’s video interview with Professor Mills is well worth watching if you have not already done so.
Not only are universities and research institutions well placed to judge the scientific merits, but as Mills points out they can facilitate things as an independent third party and actively help bring partnerships together. Given that combination therapies may be needed in order to turn off different parts of signaling pathways and cross-talk, I think we are likely to see more of this approach.
It’s going to be new territory for many companies – how to enter into a potential joint venture or alliance? However, if it results in a therapy that works, it is going to be win-win for all parties. It may also improve efficiency in drug development and lead to better use of patients in early stage development.
Some examples of where this is happening already in oncology include AstraZeneca and Merck with their MEK-AKT approach and GSK (MEK) with Novartis (PI3K), to name a couple. This is a new trend we are likely to see more of in the future.
I can see universities hiring alliance managers who have industry experience to ensure these collaborations run smoothly.
The topic of the industry/academia interface in rational cancer drug development will also be discussed in a plenary session at the forthcoming American Association for Cancer Research (AACR) meeting on Molecular Targets and Cancer Therapeutics (November 12-16, 2011) in San Francisco.
How academia can better help the pharma/biotech industry bring innovative, rational drug combinations to market is a topic that I think we will be reading more about in coming months.
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.
In an acquisition that highlights the importance of cancer and inflammation, Gilead Sciences today announced the acquisition of Seattle based Calistoga Pharmaceuticals for $375M.
Calistoga’s pipeline is focused on the development of PI3 kinase inhibitors for cancer and inflammation. Sally Church on Pharma Strategy Blog has written extensively about “The potential of the PI3K pathway inhibitors in lung cancer”, and discussed Calistoga’s CAL-101 compound and its development for hematological malignancies in her report on “What’s hot at ASH in 2010”.
I encourage you to read (if you already don’t) Sally’s excellent Pharma Strategy Blog for further information on the science and mechanism of action of the PI3K pathway (way beyond my pay grade) and her view on CAL-101’s potential.
Sally will also be at the timely AACR meeting on targeting PI3K/mTOR signaling in cancer that is being held in San Francisco later this week.
What makes CAL-101 interesting to me is its potential in targeting inflammatory mediators. CAL-101 is a first in class PI3K delta specific inhibitor; the delta isoform of phosphoinositide-3 kinase (PI3K) is expressed in leukocytes involved with a variety of inflammatory, autoimmune and hematological cancers. Increasingly I think we will see companies investigating the cross-talk between inflammation and other diseases.
In addition to the upfront payment of $375M, there are potential milestone payments of $225M. The deal is set to close in the second quarter of 2011.