ADA Wrap-Up: Where's The Chocolate?

Trying to understand all that data released at the American Diabetes Association’s 68th Scientific Sessions in San Francisco? Attempting to make sense of the company posturing and resulting fallout in the marketplace? It’s enough to make anyone a little hypoglycemic.

But getting a handle on the market potential of the various medicines in the lucrative Type II diabetes space, such as Januvia and Byetta, is worth a potential sugar low.

Here's a quick review for those who need it. By 2012 a gazillion people in the US will have Type II diabetes--actually only about 25 million but you get the point. BIG MEDICAL PROBLEM. Januvia, the first FDA-approved DPP-4 inhibitor, is proving to be a useful weapon--or at least a highly prescribed one. In 2007, the drug racked up worldwide sales of $668 million. And Catherine Arnold, an analyst at Credit Suisse, projects global sales will grow to $3.1 billion by 2010. But there's competition. (See below.)
The curve for Amylin/Lilly’s Byetta, a GLP-1 analog on the U.S. market since 2005, hasn’t been so steep. At $158 million in revenue for the first quarter, twice-daily Byetta missed its mark due to a number of factors – among them lack of up-take by primary care physicians. That’s one reason why Amylin told the street in January it would speed up its filing for once-weekly Byetta LAR to the second quarter of 2009.

At ADA this week, Amylin reported data showing its Byetta LAR injection improved glucose control at or below ADA’s 7% goal for 72% of patients, with an average weight loss of 9.5 lbs. Jim Reddoch of FBR Capital Markets said, “We think LAR is a potential best-in-class drug, well ahead of the competition.” He’s modeling $2 billion-plus in peak sales for the drug in 2012. But the news did little to help Amylin's share price, which slid June 9 on news from Novo Nordisk and Roche.

Novo released new Phase III results pitting its once-daily GLP-1 analog liraglutide against Byetta. Liraglutide was significantly more effective at lowering A1c and resulted in slightly more weight loss. JPMorgan’s Cory Kasimov noted, “With liraglutide’s approval expected by 1H09, we believe the drug could take significant market share from Byetta.”

Amylin isn't taking the news sitting down--but it will likely have to invest considerable money and resources to keep a leadership position. The biotech's CEO, Daniel Bradbury, told “The Pink Sheet” DAILY the firm is considering head-to-head trials of Byetta vs. liraglutide.

Meanwhile, Roche and partner Ipsen’s taspoglutide (R1583) also demonstrated impressive A1c control. Rate of nausea, however, appeared high at 52% with the 20 mg once-weekly dose, although patients weren’t titrated. The firm announced at ADA that it will begin a head-to-head trial of taspoglutide vs. Byetta. It plans an NDA filing in 2010. Maybe Amylin needs to add another arm to that trial its considering?

(We understand if you are getting a bit dizzy. Great summaries of all the news are available at our sister publication, "The Pink Sheet" DAILY.)

But the news wasn't all GLP-1. The DPP-4 class is looking more crowded as two contestants vie for the prize of being second to market. The Bristol-Myers Squibb/AstraZeneca drug, Onglyza, when taken alone, apparently significantly improves A1c levels compared to baseline in just three doses. Bristol plans to file an NDA for the compound mid-year. Meanwhile, Takeda issued a slew of reports about its alogliptin, widely expected to be approved later this year. Good news for Merck--analysts don't seem to think either drug looks superior to Januvia.

And that's definitely bad news for Takeda. The company has a thin pipeline and is counting on this compound to generate sales to offset the revenue losses caused by the 2011 patent expiration of its blockbuster Actos. (We'll have more on Takeda's strategy in an up-coming IN VIVO feature. )

Which brings us to our final point. How much should we care about HbA1c anyway? In a previous post, we wrote about the ACCORD trial’s finding that lowering hemoglobin A1c levels doesn’t correlate with a lowered risk of adverse events such as heart disease and stroke. Amylin CEO Daniel Bradbury told IN VIVO Blog that he believes the finding won’t result in modified endpoints. HbA1c is still a valid endpoint because it’s directly proportional to microvascular complications of type 2 diabetes, Bradbury said. But if that's just wishful thinking, it could spell trouble for any company currently playing in this arena, necessitating the expensive redesign of clinical trials.

Time for some chocolate while we ponder that issue.

--Pamela Taulbee

(Photo courtesy of Flikr user the Princess of Ilyr via a creative commons license.)