Posts Tagged → Takeda
For those keeping track, yesterday’s layoffs at AstraZeneca add to an already substantial list of cuts in the pharma and biotech industries since the beginning of the year. By our tally, nearly 13,000 job cuts, many in R&D, have been announced so far–and we’re barely into February. Here’s where we’re at (and do let us know if we’ve missed any):
–AstraZeneca is chopping 7,300 jobs, including 2,200 R&D positions, by 2014. Neuroscience research is being revamped and focused on external partnerships; the company’s Montreal R&D site will be shuttered, and research activities ended at its Södertälje site in Sweden.
–Genzyme gave the pink slip to an unspecified number of R&D scientists this week. The layoffs come as Sanofi integrates its big biotech acquisition.
–Alnylam is trimming 61 jobs, or 33% of its workforce, in order to save roughly $20 million this year.
–BioSante Pharmaceuticals is shedding 25% of its staff, or 21 employees and contractors, after disappointing Phase III results for its female sexual dysfunction treatment LibiGel.
–Takeda is axing 2,800 jobs, or 9% of its workforce, following its acquisition of Swiss drugmaker Nycomed. The bulk of the layoffs, which cut across R&D, commercial, operations, and administrative positions, will occur in Europe.
–Novartis unveiled plans to shed some 1,960 positions in the U.S. as it braces for generic competition for Diovan, a blood pressure medicine that brought in more than $6 billion in 2010, and an expected drop in demand for its renin inhibitor Rasilez following questions about the drug’s safety.
–Human Genome Sciences said it would cut 150 jobs, or about 14% of its workforce, in a move that affects manufacturing, R&D, and administrative activities.
–Xoma is shedding 84 workers, or 34% of its staff, as it shifts to outsourcing late-stage and commercial manufacturing, as well as some research.
–SkyePharma is cutting 20% of the 101 employees at its site in Muttenz, Switzerland.
–Sanofi plans to layoff 100 workers at its Monteal site as part of an overhaul of its Canadian operations.
–J&J will trim 126 workers as it closes its Monreal R&D center.
Takeda Pharmaceutical today announced it has begun Phase III clinical trials of TAK-875, a first-in-class drug candidate for treating type 2 diabetes. The experimental therapy activates GPR40, a G-protein-coupled receptor that resides in pacreatic islet cells.
The TAK-875 story is as much about the biology of the target as it is about the molecule itself. And it’s a story that owes much to the company’s willingness to delve into uncharted territory.
In the early 2000s, scientists knew GPR40 existed, but didn’t know what GPR40′s purpose was in the body. Plenty of proteins fit this description– they’re called “orphan receptors” in the industry parlance. Much of Takeda’s drug discovery strategy is based on figuring out what orphan receptors do.
In a 2003 paper in Nature (DOI: 10.1038/nature01478), Takeda laid out what it learned about GPR40. The receptor responds to a variety of long-chain fatty acids. In response to fatty acid binding, GPR40 activates and boosts insulin secretion from pancreatic beta cells.
GPR40 became a viable drug target for Takeda for several reasons. First, one of the hallmarks of type 2 diabetes is a reduction in insulin secretion from pancreatic beta cells, something GPR40 activation could help counter. Second, G-protein-coupled receptors are established drug targets– and GPR40 happens to be in the class of GPCRs for which researchers know the most about structure– the Class A, or rhodopsin-like, GPCRs. (Note: other GPR-type receptors are diabetes targets as well– C&EN contributing editor Aaron Rowe has written about Arena Pharmaceuticals’ activators of GPR119 as diabetes drug candidates.)
Takeda used structural knowledge to its advantage in the discovery of TAK-875 (ACS Med. Chem. Lett., DOI: 10.1021/ml1000855). Researchers were able to build a model of GPR40 based on its similarity to GPCRs of known structure, and dock potential drug candidates inside to see how well they could bind.
This is far from the only drug discovery story that has to do with “de-orphanizing” orphan receptors. In fact, as far back as 1997, pharmaceutical company researchers were writing about orphan receptors as a neglected drug discovery opportunity (Trends Pharmacol. Sci., DOI: 10.1016/S0165-6147(97)90676-3). And of course, just because researchers have “de-orphanized” a receptor doesn’t mean all of the complex biology is pinned down. Case in point: the PPAR receptors (J. Med. Chem., DOI: 10.1021/jm990554g). Despite these receptors’ promise as targets for obesity and diabetes, drugs designed to target them have tanked in development or had unexpected problems after arrival on the market (read: Avandia).
So as TAK-875 enters Phase III trials, the news might be about the drug candidate’s clinical performance, but you can be sure that Takeda’s researchers are still working hard to unravel as much of GPR40′s basic biology as they can behind the scenes.
This year’s additions to the pile of setbacks in the obesity drug arena are enough to make anybody wonder whether big pharma companies will continue to invest in the field (was it already two years ago that Pfizer exited obesity research entirely?!). But news today of a pact between Takeda and Sanford-Burnham Medical Research Institute suggests the Japanese drug maker is in it for the long haul.
Takeda’s agreement with Florida Hospital and Sanford-Burnham Medical Research Institute creates a partnership to evaluate potential new obesity drug targets.
Today’s deal is the latest in a string of obesity-related investments for Takeda. Haystack readers may recall that Takeda is Orexigen’s partner for the development of Contrave, the weight-loss drug that is awaiting a decision from FDA in the wake of a thumbs-up from the agency’s advisory panel. The company also has a stake in peptides from Amylin Pharmaceuticals as potential obesity treatments, and it is conducting clinical development in Japan for Alizyme’s lipase blocker cetilistat, a next-generation pill to Xenical (orlistat), the drug sold over-the-counter as alli.
Takeda’s interest in obesity makes sense given its strong history with type 2 diabetes drugs, a class with close ties to the obesity area. A quick look at Takeda’s pipeline is a whirlwind tour of diabetes drug targets, like glucokinase activators and dipeptidyl peptidase-4 inhibitors. The company has also discovered a protein, TGR5, that could be a target for drugs that mimic gastric bypass surgery‘s ability to control diabetes. And they are behind Actos, the well-known diabetes medication which shares its mechanism of action with Avandia. Unlike Avandia, Actos remains on the market, although FDA is currently investigating its safety.
After years of plugging away at antibody-drug conjugates, Seattle Genetics has finally secured significant validation for its technology. This morning, Seattle-based biotech announced impressive results from a pivotal trial of brentuximab vedotin, an anti-CD30 antibody linked to an auristatin, a small molecule that blocks the formation of microtubules.
Brentuximab, also known as SGN-35, shrank or got rid of tumors in 75% of Hodgkin’s lymphoma patients who had failed to respond to other treatments. Further, that response to SGN-35 lasted for over six months in many of those patients. In this patient population, medical experts had felt that anything more than a 30% response rate would have been solid, Needham & Co. analyst Mark Monane said in a note to investors.
The results “underscore the importance of targeting CD30 in the treatment of Hodgkin’s lymphoma and provide strong validation for our proprietary antibody-drug conjugate technology,” Seattle Genetics’ CEO Clay Seagall said in a conference call this morning.
With today’s data, Seattle Genetics appears to be succeeding in an area that has proven challenging for many. In theory, designing an antibody-drug conjugate (ADC) is straightforward: tether a powerful chemotherapeutic to a cell-specific antibody that can deliver it directly to tumors. And voila, the therapeutic window is opened on chemo drugs that are excellent cancer killers but too toxic to healthy cells.
But developing an ADC has turned out to be tougher than anticipated. The biggest hurdle for scientists has been finding the right link between the antibody and the small molecule–the link after all enables scientists to control where and when that toxic payload is released. Continue reading →
This morning Orexigen Therapeutics became the second of the three leaders in the obesity drug race to partner with a larger company. They’ve successfully courted Takeda, which now gets exclusive marketing rights to obesity drug Contrave in the U.S., Canada, and Mexico, if the drug gets regulatory approval. Orexigen’s shares soared on the news, first released in the pre-dawn hours this morning.
In the deal, Orexigen gets $50 million upfront from Takeda and could nab up to $1 billion more, depending on whether Contrave meets certain regulatory and sales milestones. Further details about the agreement are available on an Orexigen press release.
Contrave refresher: Contrave is a combination of two drugs already on the market: naltrexone, which is typically used to manage alcohol or opioid dependence, and the antidepressant bupropion. Orexigen’s developed a sustained-release formulation of those active ingredients. This is thought to alleviate the nausea that cropped up in clinical trials, but also could come in handy in terms of real-world prescriptions if the drug is approved. People might want to save money by taking the generic versions of Contrave’s two components but it isn’t clear how that would work for them.
In July we covered the first partnership deal in the obesity drug race, that of Eisai and Arena Pharmaceuticals, which is developing the obesity drug candidate lorcaserin. It’s worth stepping back to compare and contrast the deals. Continue reading →