New developments in Advanced Pancreatic Cancer from ASCO GI 2013 – Part 2
Mar01

New developments in Advanced Pancreatic Cancer from ASCO GI 2013 – Part 2

The following is a guest post from Sally Church (known to many in the twittersphere as @MaverickNY), from the Pharma Strategy Blog. In my last post on The Haystack, we discussed the phase III data from the Abraxane MPACT trial in advanced pancreatic cancer that was presented at the recent ASCO GI meeting in San Francisco. Two other late-stage studies in pancreatic cancer caught my eye—fresh data for AB Science’s kinase inhibitor masitinib and Sanofi’s multidrug pill S1. Masitinib is an oral tyrosine kinase inhibitor from AB Science that targets KIT, PDGFR, FGFR3 and has shown activity in gastrointestinal stromal tumours (GIST). A different version of the drug (Masivet, Kinavet) is also approved in France and the US for the treatment of a dog mast cell (skin) cancers, which are also known to be KIT-driven. S1 is multidrug pill from Sanofi and Taiho that consists of tegafur (a prodrug of 5FU), gimeracil (5-chloro-2,4 dihydropyridine, CDHP) which inhibits dihydropyrimidine dehydrogenase (DPD) enzyme, and oteracil (potassium oxonate, Oxo), which reduces gastrointestinal toxicity. Previous Japanese studies have demonstrated effectiveness of this agent in gastric and colorectal cancers, so a big unaswered question is whether it is effective in pancreatic cancer. So what was interesting about the latest data at this meeting? At the ASCO GI conference in 2009, French oncologist Emmanuel Mitry presented data from a small Phase II study of the effect of combining masitinib and Eli Lilly’s Gemzar in advanced pancreatic cancer. The study had just 22 patients, but the median overall survival of 7.1 months in was not a large improvement over what is often seen with the standard of care, Gemzar given alone, or with a combination of Gemzar and Genentech’s Tarceva. Over the years, many combination therapies based on Gemzar have failed to show superiority over single agent therapy. It’s both a high unmet medical need and a high barrier to beat.  Thus, the phase III data for the combination of masitnib and Gemzar was highly anticipated at this year’s ASCO GI meeting. Gael Deplanque and colleagues compared masitinib plus Gemzar to Gemzar plus placebo.  Although the overall trial results for median overall survival were slightly higher than in the phase II study, they were not significant (7.7 versus 7.0 months, P=0.74; HR=0.90). Some promising data was observed, however, in a subset of the population identified by a profile of biomarkers that the authors vaguely described as, “a specific deleterious genomic biomarker (GBM) consisting of a limited number of genes.” No other details on the actual genes or biomarkers were was provided, but the subset was described as having an improved MOS to 11.0 months compared to the Gemzar...

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Genzyme R&D Layoffs Today
Jan31

Genzyme R&D Layoffs Today

The other shoe has dropped at Genzyme, which last year was acquired by Sanofi, but had yet to experience the kind of major research restructuring that typically accompanies the integration of two pharma companies. Today, Genzyme scientists were told whether their job was being shed or moved. Here's an excerpt from the official statement: As part of the integration process between Sanofi and Genzyme, R&D activities were reviewed and assessed. On January 31, 2012, the results of the review of U.S. R&D Genzyme activities were announced, including synergies that unfortunately make some positions redundant. All US R&D Genzyme employees impacted by the integration received notice regarding whether their position would be relocated or eliminated. The job cuts are separate from the latest round of R&D layoffs at Sanofi. As readers might recall, Sanofi announced last November that it was closing its Bridgewater R&D site, and move discovery and early development activities to Boston. A Sanofi spokesperson tells the Haystack that despite today's cuts at Genzyme, the company is committed to its presence in Massachusetts, and to maintaining a stable level of jobs there. While R&D is falling under the axe, the company is hiring in manufacturing and multiple sclerosis, she says. The company has not provided details on how many R&D scientists will be shed, but once more information comes to light, we'll update...

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Genentech Says Experimental Cancer Combo is Safe
Apr05

Genentech Says Experimental Cancer Combo is Safe

Genentech this week unveiled promising results from a Phase I study suggesting it is possible to safely combine two cancer drug candidates, its MEK inhibitor GDC0973 and its PI3K inhibitor GDC0941. In addition to a relatively clean safety profile, there were also early signs that the combination is combating cancer. Genentech is one of several companies running a trial to test the safety of combining inhibitors of the lipid kinase PI3K, part of the PI3K/AKT/mTor pathway, and drugs blocking the protein kinase MEK, part of the KRas/MAP signalling pathway. As we discuss in our upcoming April 11th cover story on PI3K inhibitors, the rationale for knocking down both pathways  is compelling: both are considered to be crucial in cancer cells’ survival, and blocking only one pathway has more often than not proven ineffective. As Robert Abraham, CSO of Pfizer’s oncology research unit, explains in Monday’s story: “KRas mutations are associated with many of the deadliest cancers,” including colorectal and pancreatic, Pfizer’s Abraham says. Yet they are incredibly resistant to conventional chemotherapy, and based on preclinical studies of the mutations, are expected to be resistant to the new batch of mTor/PI3K inhibitors as well, he adds. The working hypothesis is that knocking out two of the major drivers of cancer—the KRas and PI3K pathways—could have a significant effect on the most recalcitrant tumors. To date, there are at least six Phase I trials planned or ongoing that combine MEK inhibitors with compounds that block some aspect of the mTor/PI3K pathway. Merck and AstraZeneca made headlines in 2009 when they said they would partner to test Merck’s AKT inhibitor with AstraZeneca’s MEK inhibitor. Sanofi-Aventis has meanwhile teamed with Merck Serono to explore the potential of combining two of its PI3K inhibitors in combination with Merck Serono’s MEK inhibitor. GlaxoSmithKline has two of its own drugs in a combination trial, and its MEK inhibitor GSK1120212 is also being tested in combination with Novartis’ PI3K inhibitor BKM120. And while Pfizer has yet to initiate such a study, Abraham said the company is “keeping two eyes on that combination.” We go into much more detail in Monday’s cover story about the efforts to match PI3K inhibitors with other drugs, and the rationale behind different flavors of compounds (mTor/PI3K inhibitors vs. pan-PI3K inhibitors vs. single-isoform inhibitors). Stay...

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Another Week in Pharma Job Cuts
Jan28

Another Week in Pharma Job Cuts

This week brought a stream of bad news on the pharma job front, with at least four companies announcing substantial cutbacks. Worse, scientists were the main target for layoffs at three of those companies—Sanofi-Aventis, Arena, and Elan. As everyone's favorite employment watchdog Chemjobber commented on an In the Pipeline post about cuts at Abbott: When, when, when will it stop? Here’s a look back at the news from this week: --Sanofi is shedding 90 research jobs at its Bridgewater, N.J., site as part of “the evolution of the R&D portfolio towards more biologic-based therapies,” the company told C&EN. The French pharma firm is ceasing chemical library and chemical development activities, including pharmaceutical development and analytical science. Meanwhile, discovery-stage laboratory activities within several groups, including Lead Identification Technologies, Structure, Design & Informatics, and Analytical Sciences, will be reduced. Some people will be shifted over to the company’s Molecular Innovative Therapeutics group, which will be transformed into “a cluster of small multidisciplinary biotechs with specialized expertise in key diverse therapeutic approaches.” This new approach sounds an awful lot like what GlaxoSmithKline has been doing over the last two years—creating smaller, more independent units in the hopes of mimicking the culture and innovative spirit of small biotechs. --Arena Pharmaceuticals is cutting 25% of its staff, or 66 employees, by the end of March. The move isn’t unexpected. Last fall, FDA gave the San Diego-based biotech a thumbs down for its obesity drug lorcaserin based on concerns that it had caused tumors in rats. Now, FDA is asking for a slew of new data, meaning Arena will be unlikely to refile its application for approval until 2012, analysts say. See here and here for more on its lorcaserin trials and tribulations. --Abbott is slashing 1,900 jobs in the U.S., mirroring layoffs it made last year in Europe following its acquisition of Solvay Pharmaceuticals. The cuts will come from its commercial and manufacturing operations, with over half the job losses concentrated in Northern Illinois. In a conference call, Abbott CEO Miles D. White blamed the restructuring on several factors: the slow recovery of the global economy, costs associated with healthcare reform, European pricing pressures, and a harsher regulatory environment that has made it tough for drugs to get approved. --And last but not least, Elan has laid off 10% of its staff, or about 130 workers, with its R&D site in South San Francisco most heavily impacted. Researchers accounted for about half of the job losses. If we've missed any layoffs that chemists should be aware of, drop us a note or leave a...

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Big Pharma Talks Emerging Markets Strategy
Jan14

Big Pharma Talks Emerging Markets Strategy

Last year’s JP Morgan Healthcare conference brought a flood of proclamations and projections about growth in emerging markets. Although the topic is now more of a given rather than a new arm of drug companies’ strategies, it seemed worth compiling some of the comments on emerging markets made at this year’s event. Of note? With many of the best assets in developing countries already snatched up and so much attention on what remains, prices are rising. Several big pharma CEOs underscored the need to grow at a profit, instead of just for the sake of growing. Time will tell if companies can heed their own advice. GlaxoSmithKline is very deliberately shifting resources away from the U.S. and into emerging markets. In just a few years, the number of sales reps in the U.S. is down to 5,000 from 9,000, while the number of reps in emerging markets has grown from about 8,500 to 13,000, said GSK’s chief strategy officer David Redfern. Of the 17 significant M&A deals undertaken by GSK since mid-2008, nine were in emerging markets. When asked whether that pace would continue, Redfern said the company no longer needed acquisitions to gain entry into those markets. And while bolt-on deals are still possible, he notes that “There’s no doubt prices are going up in emerging markets and we’ll maintain our discipline,” Redfern said. “In 2008 we did quite a few deals. We’ve walked away from a lot more deals last year.” Sanofi-Aventis is also bolstering its sales force in emerging markets at the expense of jobs in the U.S. and Europe. Chris Viehbacher said there has been a 40% reduction in pharmaceutical operations between 2009 and 2011, and a significant overhaul of its European operations is underway. Meanwhile, headcount in emerging markets is expected to increase by 40% in that same timeframe. As a result, “in 2011, we expect to sell more in emerging markets than we do in Europe or the U.S.” Merck said it had also “significantly reduced” the number of sales reps in developed markets. The company’s goal is to grow sales in emerging markets from 18% to 25% by 2013. “We’ve been frank to say that companies are ahead of us,” Merck’s CEO Ken Frazier said. However, he pointed out that it’s still an open field: the leading player in China only has about 3% of the market share. Frazier also stressed the importance of achieving profitable growth in those regions, a nod to the rising prices for assets. “We think value-creating partnerships are the right way to go, because that way our partners have a strong stake in the growth and success...

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