Big stage for diabetes hopeful

August 28, 2009 – 6:05 pm by Michael Christel

Recent regulatory setbacks aside, Takeda Pharmaceutical Co. is plowing full steam ahead on its quest to win approval for the company’s key type 2 diabetes drug alogliptin, another potential entrant into the suddenly competitive field of DPP-4 inhibitors.

The Japanese drug giant said today that it received the “all-clear� from FDA on the design for the company’s monster cardiovascular outcomes trial for alogliptin, a move made necessary after the agency, in June, issued a complete response letter for the drug, requesting an additional CV safety test.

Takeda will begin the placebo-controlled trial, called EXAMINE, next month, with hopes of reporting data in about two years, which could mean U.S. approval for alogliptin in 2012.

No further examination of EXAMINE is needed to realize its magnitude. The trial will enroll about 5,400 patients at a total of 1,000 sites in the United States, Europe, and Asia. The primary outcome, as stated by Takeda, is “time from randomization to the occurrence of the primary major adverse cardiac events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.”

Takeda partners with contract research company PPD Inc. on the development of alogliptin, which, like other dipeptidyl peptidase-4 inhibitors, works by stimulating the pancreas to make more insulin after eating a meal. Takeda San Diego, a unit of Takeda, and PPD originally launched the collaboration on alogliptin, also called SYR-322, in November 2003.

“We continue to believe alogliptin is a safe and effective drug to treat type 2 diabetes,� William Sharbaugh, PPD’s chief operating officer, told me recently. “The whole DPP-4 class is a great addition to the armamentarium for physicians. We think this drug will eventually make it to the market. We’re working closely in collaborating with Takeda to help that happen and perform the testing required by the FDA.�

DDP-4 inhibitors first burst on to the U.S. market in 2006 with the approval of Merck & Co.’s Januvia. There have been several candidates from the class in clinical testing, but it wasn’t until late July, with the approval of of Bristol-Myers Squibb’s and AstraZeneca’s Onglyza, that Januvia finally got some competition. The approval of another DPP-4 inhibitor, Galvus, made by Novartis, is presently delayed by the FDA, pending further kidney disease data, although the drug was approved in Europe in 2007.

According to this detailed analysis, DPP-4 inhibitors work in a way entirely unique from any previous diabetes treatments. The author notes that the drug class was inspired by early 20th century discoveries made by researchers examining the relationship of the intestines and the pancreas in diabetes.

The request for an additional study of alogloptin was no surprise. Late last year, FDA sent companies new guidance regarding approvals for diabetes drugs. The agency made clear it wants more information about a product’s heart risks, which could mean the need for more long-term CV safety studies.

Tags: alogliptin, diabetes, DPP-4, FDA, insulin, PPD, Takeda