Merck & Co delays rolofylline in heart failure
This article was originally published in Scrip
Merck & Co's acute heart failure drug rolofylline (MK-7418) has failed in a Phase III trial, preliminary results show. The company no longer plans to seek regulatory approval for the drug this year.
The 2,033-patient Phase III trial of the adenosine A1 receptor antagonist failed to meet its primary endpoint – the drug, which increases blood flow and urine output, at a 30mg dose, did not improve symptoms of heart failure compared with placebo. It also failed to meet secondary endpoints, including reduction of the risk of death or cardiovascular or renal re-hospitalisation 60 days after treatment. Merck Research Laboratories' executive director of cardiovascular research Dr Dan Bloomfield admitted the results were disappointing. "We had been hopeful that blocking the adenosine A1 receptor with rolofylline would prove to be a useful new approach for these patients."
Merck said it would continue to analyse the data with outside experts and present its results at a medical meeting later this year. Merck gained the product candidate through its 2007 acquisition of NovaCardia, which had previously licensed it from Kyowa Hakko Kogyo.
The results will also cast some doubt over the adenosine A1 receptor antagonist strategy in heart failure. Biogen Idec and CV Therapeutics (Gilead Sciences) have a similar product Adentri (BG-9928) also in Phase III for patients with acute decompensated heart failure with renal insufficiency. Meanwhile, Solvay is investigating its candidate SLV320 in Phase II.
pipeline problems
The setback with rolofylline is not Merck's first pipeline problem this year. It delayed plans to file an NDA for telcagepant, a calcitonin gene-related peptide antagonist for the treatment of migraine, following safety concerns – this had been considered by analysts at Credit Suisse as its largest near-term pipeline opportunity. The analysts had forecast sales for rolofylline in 2012 reaching $85 million following a 2010 launch.
Financially, Merck suffered a poor first quarter (scripnews.com, April 22nd, 2009). In addition, it discontinued its Phase III anti-obesity candidate taranabant late last year, following concerns over its safety at its higher, more effective doses.
Merck still has several products in late-stage development, including MK-0524A (ER niacin/laropiprant for primary hypercholesterolaemia), which is already approved in some markets, the CETP inhibitor anacetrapib (in Phase III for coronary heart disease), and MK-0822 (for osteoporosis). And, it plans to finalise its $41 billion acquisition of Schering-Plough by the end of this year, which would reinvigorate its pipeline.