Swiss drug giant Novartis has reported a mixed bag of Phase III data for its first-in-class heart drug serelaxin, but seems confident of a regulatory approval.
On the plus side, the drug, which is also known as RLX030, hit one of two primary endpoints, by inducing a significant cut in dyspnoea (shortness of breath) in patients with acute heart failure (AHF) up to day five, using a particular method known as the visual analog scale (VAS).
But the RELAX-AHF study failed to meet the co-primary goal of a significant reduction when using a different assessment – the Likert scale – at timepoints of six, 12 and 24 hours.
It also failed on secondary efficacy endpoints of days alive and out of hospital and cardiovascular death or re-hospitalisation due to heart or kidney failure, the firm reported.
More encouragingly, however, on the safety target of all-cause mortality 7.3% of patients died from all causes in the serelaxin group versus 11.3% in the placebo arm at 180 days of follow-up.
Deaths due to cardiovascular causes at day 180 was also significantly lower with the drug compared to placebo (6.1% vs. 9.6%), and it was concluded that serelaxin was associated with a 37% cut in all-cause and cardiovascular mortality after six months, the Swiss group said.
Serelaxin is a recombinant form of the hormone relaxin-2, which, despite being widely known as a pregnancy hormone, as it helps the body stretch to accommodate a growing baby, occurs naturally in both men and women.
The drug, which is believed to act through multiple mechanisms on the heart, kidneys and blood vessels, was found to be well tolerated in the trial and adverse events were generally comparable between the treatment and placebo arms.
Regulatory filing on the horizon
Novartis is already in discussion with regulators with a view to filing the drug next year. Ameet Nathwani, head of Novartis’ critical care products, said there shouldn’t be the need to conduct an extra trial to receive marketing approval, according to Bloomberg, noting: “Our perspective is that our data is robust”.
AHF places an huge burden on healthcare systems around the globe, accounting for more than 15 million days in hospital each year in the EU and US.
But despite available therapies, patients with AHF have a poor prognosis following hospitalisation, with nearly a quarter of dying within a year.
“This study with serelaxin is important because it may offer the prospect of a much-needed new medicine for acute heart failure, where the death rate remains high and there have been few new therapies for several decades,” noted trial investigator Professor John Teerlink, Section of Cardiology, San Francisco Veterans Affairs Medical Center, University of California.
QVA149 filed in Japan
Meanwhile, in other news Novartis has submitted an application in Japan for the registration of QVA149, an investigational fixed dose combination of two long-acting inhaled bronchodilators (indacaterol maleate and glycopyrronium bromide) as a once-daily treatment for chronic obstructive pulmonary disease (COPD).
The product was filed in Europe in October 2012, and an application to US regulators is scheduled for 2014.
