Novartis announced that the phase III RELAX-AHF study has shown  investigational RLX030 (serelaxin) improved symptoms and reduced deaths by one-third at the end of six months in patients with acute heart failure (AHF). Most of these deaths were due to cardiovascular causes. RLX030 is the first in a new class of medicines and is believed to act through multiple mechanisms on the heart, kidneys and blood vessels.

RELAX-AHF demonstrated that RLX030 significantly reduced dyspnea (i.e. shortness of breath), the most common symptom of AHF and the primary endpoint of the study. As one of two co-primary endpoints was met, the study achieved its primary objective based on pre-specified protocol criteria.

Results of the study were presented at the American Heart Association (AHA) Scientific Sessions in Los Angeles and published simultaneously in The Lancet.

"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," said Professor John R Teerlink, of the Section of Cardiology, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, the co-lead investigator of the RELAX-AHF study.

Professor Marco Metra, Director of the Institute of Cardiology at the University and Civil Hospital of Brescia, Italy, the other co-lead investigator of the study, said: "The reduction in mortality seen with serelaxin is supported by the decreases in episodes of worsening of heart failure, as well as by the biomarker data collected during the study, suggesting that the clinical effects of serelaxin may be linked to a beneficial effect on organs such as the heart and kidneys."

Novartis has begun discussing the results of this single phase III study with health authorities worldwide.

"The survival results with RLX030 are encouraging for patients, their families and society at large," said Tim Wright, Global Head of Development, Novartis Pharma. "Novartis is committed to significantly improving treatment outcomes for patients with heart failure, and these results support our research into this therapeutic area which may lead to better management of the disease."

RELAX-AHF was an international randomized, double-blind study involving 1,161 patients and was designed to compare the efficacy and safety profile of RLX030 to placebo in addition to standard therapy for the treatment of AHF. RLX030 was given upon hospitalization in the form of an intravenous infusion (30 mcg per kg per day) for 48 hours in addition to conventional therapy for AHF, i.e. loop diuretics and other medicines.

The study had two primary endpoints using different scales to measure reduction in dyspnea. The visual analog scale (VAS) showed a significant benefit up to day five (p=0.0075), whereas the Likert scale (a baseline-related short-term assessment of dyspnea relief) did not reach significance at 6, 12 and 24 hours (p=0.702). As one of the primary endpoints was met the study was positive according to protocol criteria.

The study did not meet its secondary efficacy endpoints, namely days alive and out of hospital up to day 60 (p=0.37), and cardiovascular death or re-hospitalization due to heart or kidney failure up to day 60 (p=0.89).

Results showed that 7.3% of patients died from all causes in the RLX030 group compared to 11.3% in the placebo group (p=0.02)at 180days of follow-up. All-cause mortality up to day 180 was a safety endpoint of the study. The number of deaths due to cardiovascular causes to day 180 (an additional pre-specified efficacy endpoint) was also significantly lower with RLX030 than placebo (6.1% vs. 9.6%, p=0.028). RLX030 was therefore associated with a 37% reduction in all-cause and cardiovascular mortality at the end of six months.

In addition to its effects on mortality and symptoms, RLX030 met several other efficacy endpoints including significantly reducing the worsening signs and symptoms of heart failure up to day 14 (p=0.024), thereby decreasing the need for intensified heart failure treatment. RLX030 also reduced the mean length of stay in hospital by 0.9 days (p=0.039) and in the intensive/cardiac care unit by 0.4 days (p=0.029).

RLX030 was well tolerated and adverse events (AEs), including low blood pressure (hypotension), were generally comparable between RLX030 and placebo. There was a lower incidence of adverse events related to renal impairment with RLX030 than placebo (4.6% vs. 8.6%). The most common AEs in both treatment groups were cardiac disorders, metabolism and nutrition disorders, and gastrointestinal disorders. No clinically significant differences in the incidence of serious adverse events were seen between treatment groups.

Heart failure is a disease in which the heart is unable to supply enough blood to meet the body's needs. The disease leads to a spiral of physical decline, often leading to acute episodes in which patients' symptoms suddenly become worse and urgent hospital treatment is needed. Acute heart failure (AHF) places an enormous burden on healthcare systems and is estimated to account for more than 15 million days in hospital each year in the EU and US. Patients with AHF have a poor prognosis following hospitalization. Nearly a quarter of people admitted to hospital with AHF die within a year.

Novartis and its wholly owned subsidiary Corthera Inc. have the exclusive worldwide rights to RLX030 (except in Canada).