Dual PPARs   (September 25, 2013)

Unless you’ve been involved with diabetes drug development, the phrase “Dual PPARs” or the term “glitazars” probably doesn’t ring a bell. But for those of us who have monitored drugs in development as a career or as a hobby, the phrase is a warning of disaster: it represents an entire class of diabetes drugs that has failed in clinical development. Until now.

The class of drugs that activate both PPAR-alpha and PPAR-gamma has been a will-of-the-wisp for drug companies for years: a single molecule that both improves blood glucose and lipid levels. At least three “Dual PPARs” have been in clinical development for the US and world-wide market, and have failed for safety reasons: aleglitazar (trials halted by Roche earlier this year); muraglitazar (development terminated by Bristol-Myers Squibb in 2006) and tesaglitazar (discontinued by AstraZeneca in 2006).

But, as Alexander Pope once said, hope springs eternal in the breasts of drug manufacturers. A Dual PPAR has been under development in India since 2000 by a company called Zydus Cadila, and has just been approved there: saroglitazar (brand name Lipaglyn).

Is it safe? The only data I can find on saroglitazar’s adverse events is at the manufacturer’s website and really doesn’t indicate anything of concern, but there’s no detailed review of the product’s safety profile. A press release does say that  “the new drug application for Lipaglyn was based on a comprehensive clinical development programme spanning eight years” but they don’t say how many subjects were involved. The press release also claims that the studies “did not show adverse events like edema, weight gain, myopathies or derangement of liver and/or kidney functions, thus making it safe and efficacious.”

There’s no apparent evidence that the manufacturer is interested in the global diabetes market, and I don’t see anything to imply that they are doing any trials outside of India. For instance, there are no studies of saroglitazar registered with ClinicalTrials.gov (which is not a requirement if the company is not seeking world-wide approval, but is required for potential FDA review).

So, there’s an apparently safe Dual PPAR on the market in India. But, I must remain skeptical: if it does have a satisfactory safety profile, why isn’t the company seeking partnerships with other drug companies to eventually gain approval in the rest of the world? And if it hasn’t done studies with the rigor that’s required for US and European approval, I must wonder if we’ll see the drug withdrawn at some future time after diabetic consumers in India are harmed by adverse events.