Merck Seals Hepatitis C Pact with Roche
May17

Merck Seals Hepatitis C Pact with Roche

Merck is going bare knuckles in the marketing battle for Hepatitis C patients. Just days after receiving FDA approval to market its protease inhibitor boceprevir, now known as Victrelis, it revealed Roche has signed on to co-promote the drug alongside its pegylated interferon drug Pegasys, a cornerstone of HCV treatment. Competition in the HCV arena is expected to be fierce, as Vertex Pharmaceuticals is expected to get the FDA nod to market its own protease inhibitor for HCV telaprevir, to be marketed as Incivek, no later than Monday. Both the Merck and Vertex drugs will need to be taken in combination with the current standard of care, pegylated interferon and ribavirin. Although the two drugs have never gone head to head in the clinic, telaprevir is widely considered to have a better dosing regimen and a slight safety and efficacy edge over Victrelis. As such, analysts have believed that Merck’s main advantage in the HCV market would be its ability to promote Victrelis alongside its own pegylated interferon PegIntron. Now, it will also have Roche’s sales force out there hawking Victrelis with Pegasys, as well. No financials for the deal were announced, so its hard to say at this point how much Merck is giving up in its quest for a bigger piece of the HCV market. It’s also important to note that this is a non-exclusive pact, so time will tell whether Roche and Vertex establish a similar alliance. The deal also allows Merck and Roche to “explore new combinations of investigational and marketed medicines.” As readers will recall, the ultimate goal is to eliminate the need for interferon and ribavirin, which have harsh side effects, and treat HCV using only a cocktail of pills. Roche and Merck each have promising small molecules against HCV in their pipelines: Merck has vaniprevir, an NS3/4a protease inhibitor in Phase II trials, while Roche has the polymerase inhibitor RG7128, the protease inhibitor RG7227, and the earlier-phase polymerase inhibitor RG7432. Read here for past coverage of the race to get new HCV drugs to...

Read More
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...

Read More
Drug Candidate Structures Revealed At #ACSAnaheim
Mar27

Drug Candidate Structures Revealed At #ACSAnaheim

1PM Pacific: There's one hour left before chemists will pack a ballroom in Anaheim to see potential new drugs' structures unveiled for the first time. Watch this space for updates. 2:39PM Pacific: CEP-26401 This drug candidate now has a name: irdabisant company: Cephalon meant to treat: deficits in cognition and/or attention in diseases such as Alzheimer's and schizophrenia mode of action: inverse agonist of histamine H3 receptor, which regulates several neurotransmitter pathways involved in cognition, attention, memory medicinal chemistry tidbits: Cephalon's goal was to bring a high quality compound to the clinic to define the utility, if any, of H3 antagonists for these indications. The team studied compounds in this area that failed. Among the things they learned was that several adverse events could be tied to drug candidates' lipophilicity. So the team prioritized lipophilicity and other such characteristics in its discovery workflow. status in the pipeline: completing Phase I in the beginning of April 2011, advancing to Phase II structure coming soon! UPDATED 3/29 with structure: 3:16PM Pacific: BMS-663068 company: Bristol-Myers Squibb meant to treat: HIV mode of action: inhibits HIV attachment to host cells by binding to the viral envelope gp120 protein and interfering with its attachment to host CD4 receptors medicinal chemistry tidbits: potency and getting the drug candidates to reach the bloodstream efficiently were key. Replacing a methoxy group on with heterocycles, such as triazoles, gave a big boost in potency. status in the pipeline: Completed Phase IIa clinical trials. Phase IIb studies are planned for later this year. 4:24PM Pacific:LX1031 company: Lexicon meant to treat: irritable bowel syndrome mode of action: blocks a subtype of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, in the gut. medicinal chemistry tidbits: Lexicon started their medchem program with an open mind. They could have made a molecule that was exquisitely selective for the subtype of tryptophan hydroxylase in the gut, they could avoid hitting the other subtype by making their molecule stay out of the brain, or both. They ultimately ended up using the latter strategy, making molecules slightly on the heavy side (above 500 or 550 molecular weight) and adding groups like a carboxylic acid, that tend to keep things out of the brain. status in the pipeline: Completed Phase IIa clinical trials. 5:30PM Pacific: MK-0893 company: Merck meant to treat: type 2 diabetes mode of action: blocks the receptor for the hormone glucagon. Glucagon is released by the pancreas in response to falling glucose levels. medicinal chemistry tidbits: Merck kept several chemical scaffolds in play during this research program. But the team's big breakthrough was adding a methyl group to the benzylic position of a...

Read More
First Time Drug Disclosures at #ACSAnaheim
Mar25

First Time Drug Disclosures at #ACSAnaheim

Medicinal chemists, it's that time of year once again. Time for the ACS National Meeting, and the accompanying symposium where drug companies reveal the structures of drug candidates in clinical trials for the first time. I'll be on the ground in Anaheim and will be posting from that session (which lasts from 2PM-5PM Pacific Sunday the 27th) and others. Here is the Anaheim Division of Medicinal Chemistry program (pdf). And here is the list of disclosures: Discovery and characterization of CEP-26401: A potent, selective histamine H3 receptor inverse agonist: R. Hudkins, Cephalon Discovery of BMS-663068, an HIV attachment inhibitor for the treatment of HIV-1: J. Kadow, Bristol-Myers Squibb Discovery and development of LX1031, a novel serotonin synthesis inhibitor for the treatment of irritable bowel syndrome: A. Main, Lexicon Discovery of MK-0893: A glucagon receptor antagonist for the treatment of type II diabetes: E. Parmee, Merck Discovery of ELND006: A selective γ-secretase inhibitor: G. Probst,...

Read More
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...

Read More