Bristol-Myers Squibb’s novel diabetes therapy, Pargluva (muraglitazar), comes before a US Food and Drug Administration advisory panel today and is widely expected to win a positive recommendation despite the number of cautions surrounding the drug class – according to a briefing paper posted on the agency’s website this week [[04/08/05e]].
Pargluva belongs to the peroxisome proliferator-activator agonist class of drugs, and is designed have a dual mechanism of action by tackling both insulin resistance and high blood lipids in type 2 diabetes [[14/06/05d]]. However, caution surrounds the class, with side effects including weight gain and oedema, as well as infrequent reports of heart failure. Concerns have also abounded over the potential of PPAR agonists to cause cancer, after findings from rat studies showed a carcinogenic effect of several PPAR agonists. For this reason, Pargluva has been rigourously evaluated and the FDA’s briefing paper states it: “should not pose a carcinogenicity risk to humans at clinical doses and exposures.”
In one 24-week, Phase III study, involving 1,160 type 2 diabetes patients, Pargluva was linked to a significant reduction in blood glucose levels versus Lilly/Takeda's Actos (pioglitazone). However, oedema rates were 9.2% amongst Pargluva receivers, compared to 7.2% in the Actos group, while three cases of heart failure were observed versus one amongst patients given the Lilly/Takeda drug. In the Phase II trial, 15 cases of heart failure were reported in the Pargluva arm with none in the Actos arm. However, the FDA says “the clinical presentations, underlying risk factors, management and outcome of heart failure events were in line with the clinical experience gained with [Actos and GlaxoSmithKline’s Avandia (rosiglitazone)] over the past several years.”
Overall, though, the FDA briefing paper says composite results of five pivotal clinical trials have “consistently demonstrated that [Pargluva] has significant efficacy for improving both glycaemic and lipid control in type 2 diabetes mellitus. In addition, fatty acid elevations, fasting and postprandial hyperinsulinemia, and overall insulin sensitivity improved during [Pargluva] treatment.”
Pargluva – which B-MS hopes will prove a shining star for its fortunes – is expected to win a nod of approval for use as an adjunct to diet and exercise in patients with type 2 diabetes, and as either a combination therapy or monotherapy. However, as a precautionary measure, the drug will not be indicated in patients with heart failure, those using insulin, or those under 18 years of age.
If approved, B-MS would split any profits with partner Merck & Co, with Pargluva widely expected to pull in peak revenues of $3 billion dollars.