A week before highly anticipated Phase III data are to be presented at a key scientific meeting, Roche announced it is taking a step backward in the development program for its GLP-1 analog taspoglutide, a move that sent Amylin's stock up almost 20 percent and gave Novo Nordisk comfort it will be fending off only one potential competitor in the space for the near term.

Roche announced June 18 that after consulting with FDA it has decided to implement a risk management plan in the taspoglutide Phase III program in reaction to the possibility some patients are developing anti-drug antibodies (ADAs) that are causing hypersensitivity reactions. The most frequently reported symptoms were skin reactions and gastrointestinal symptoms, while some patients experienced cardiovascular and respiratory symptoms. All patients recovered without complications, Roche said.

Under the risk mitigation plan, patients in the studies will have their ADA levels monitored and those who develop a pre-specified level will be dropped from treatment and followed for symptoms. Antibodies are a known class effect with GLP-1s, Robert W. Baird analyst Thomas Russo pointed out in a June 18 note. However, he added, "we are not aware of any significant hypersensitivity concerns associated with the drugs" so far.

The development will set back taspoglutide's regulatory timeline at least 12 to 18 months, pushing a filing into 2012 or 2013. Roche had planned to file taspoglutide in 2011 as the lynchpin of its move to establish itself in the metabolic and cardiovascular disease markets (Also see "With One Foot Firmly Planted In Oncology, Roche Moves The Other Into CV/Metabolic" - Pink Sheet, 18 March, 2010.).

Roche's decision not to push forward with a drug that isn't showing a clear advantage in the class reflects the growing awareness of comparative effectiveness in drug development. The fact the Swiss drug giant took the step voluntarily is probably a nod to FDA's mood of heightened safety vigilance, particularly around anti-diabetics.

Competitors gain time advantage

The setback puts taspoglutide well behind Bydureon , Lilly/Amylin/Alkermes' pending once-weekly formulation of exenatide (currently dosed twice daily as Byetta ) and potentially behind even GlaxoSmithKline/Human Genome Sciences' Phase III GLP-1 candidate Syncria (albiglutide). Phase IIb data for Syncria are to be presented at the upcoming American Diabetes Association scientific sessions in Orlando, June 25-29.

Amylin turned around a "complete response" on Bydureon in just a month and now has an Oct. 22 action date on the NDA (Also see "GLP-1 Showdown Set For Fall: Bydureon Gets New October Review Deadline" - Pink Sheet, 6 May, 2010.). The company's stock closed June 18 at $19.80, up 19.93 percent over the previous day.

Novo Nordisk's once-daily Victoza (liraglutide) was approved in January and now has even more time to gain market share from twice-daily Byetta.

Taspo may not be able to overcome its side-effect profile

Roche is set to present data from five of the eight trials in the Phase III T-emerge program at the ADA meeting, and analysts already looking forward to clarity on the drug's clinical performance now seek understanding of this new wrinkle in the development plan.

The hypersensitivity reactions are relatively uncommon, appearing in less than 1 percent of patients, but the prospect of the drug going to market with the burden of an ADA monitoring requirement did not sit well.

The testing would have to be done in a clinical setting, putting taspoglutide at "a significant disadvantage," Piper Jaffray analysts observed in a June 18 note. They called the safety issues a "significant negative," pointing out that "it would take only one or two severe hypersensitivity reactions to kill the program" should the testing prove less than 100 percent effective.

Roche licensed the glucagon-like peptide-1 analogue from the French biopharma group Ipsen in 2006 and has exclusive worldwide rights, except for Japan, where the rights are shared with Teijin, and France, where Ipsen retains co-marketing rights.

-Shirley Haley (s.haley@elsevier.com)

Roche's Wildcard GLP-1 Not A Spoiler After All; Amylin Stock Soars On Taspoglutide Setback

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