Biotech Strategy Blog

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

Posts tagged ‘pharma strategy blog’

A diagnosis of stage IV pancreatic cancer is pretty much a death sentence.

People are often diagnosed in the advanced stage of the disease – 49.5% are diagnosed in stage IV – and the prognosis is generally not good.  Sadly most don’t live long, even with the latest treatments.

According to the National Cancer Institute (NCI) SEER survival monograph, the relative survival rates are extremely poor. Across all types of pancreatic cancer, only 5% of people live for 5 years, and only 23% survive 1 year.  Three to five months is the median survival time for those with untreated metastatic pancreatic cancer.

In the United States, there were 33,730 new cases of pancreatic cancer in 2006 and 32,300 deaths!  There is, therefore, an unmet need for effective new pancreatic cancer treatments.

Lake Tahoe Pancreatic Cancer ConferencePreclinical data presented by Nicole Teichmann and colleagues at the recent American Association for Cancer Research (AACR) special conference on Pancreatic Cancer in Lake Tahoe, NV suggests that BAY 86-9766 may be an interesting compound to watch as it moves forward in clinical development.

“We showed in our endogenous mouse model that our novel chemotherapeutic agent leads to dramatic tumor shrinkage after only one week of treatment,” said Nicole Teichmann, Ph.D., of the Klinikum rechts der Isar at the Technische Universität München in Munich, Germany in an AACR press release.

Although impressive tumor shrinkage was seen in the preclinical trial of BAY 86-9766, a novel MEK1/2 inhibitor, “in most animals the tumors relapsed typically after 3 weeks of treatment,” according to Teichmann’s abstract.  This suggests that there is an escape pathway that may also need to be targeted for the drug to be more effective.

One of the signaling pathways involved in pancreatic cancer is the Raf-MEK-ERK pathway (75-90% of pancreatic cancers have a K-ras mutation), which is why a MEK inhibitor such as BAY 86-9766 that targets this pathway may be effective.

However, pancreatic cancer represents a challenge for drug development and many drugs have failed in clinical development.

Sorafenib despite being an inhibitor of Raf-1 kinase and EGFR2, failed to show any effect in pancreatic cancer.  Adding sorafenib to gemcitabine did not improve survival significantly.

Recently, Infinity Pharmaceuticals terminated a pancreatic cancer phase 2 trial with their Hedgehog inhibitor, saridegib (IPI-926).

Despite scientific evidence suggesting that hedgehog signaling plays an important role in pancreatic cancer, patients receiving saridegib with gemcitabine did worse (i.e. lived for a shorter period) than they would if they had just received gemcitabine alone.

The Infinity news release noted that “the median survival for patients receiving saridegib plus gemcitabine was less than the historical median survival for single-agent gemcitabine of approximately six months.” Not surprisingly, the trial was terminated.

Other Hedgehog compounds being evaluated in pancreatic cancer include Roche’s vismodegib (Erivedge), which was initially approved in advanced, refractory basal cell carcinoma last year.  The drug is also being tested in trials for pancreatic cancer, including one with gemcitabine and another with gemcitabine plus nab-paclitaxel (Abraxane).

Interestingly, Celgene are waiting for the final data to mature on their phase III trial in pancreatic cancer with nab-paclitaxel and gemcitabine.  The interim results were encouraging, but it is too early to tell if the outcomes will be significantly improved by the combination. You can read more about the scientific rationale for nab-paclitaxel in pancreatic cancer on Pharma Strategy Blog.

The efficacy and safety of BAY 86-977 in combination with gemcitabine is currently being evaluated in a phase 2 trial of patients with non-resectable, locally advanced or metastatic pancreatic cancer.

Caution must, therefore, be expressed as to whether BAY 86-9766 will be effective given that so many promising pancreatic cancer drugs have failed in drug development.

It remains to be seen whether BAY 86-9766 will live up to the promise of the preclinical data presented at the AACR pancreatic meeting in Lake Tahoe.

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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.

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.

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.

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