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Experimental Heart Failure Drug Cuts Death Rate by 37%
Phase III trial evaluates recombinant human hormone (Nov. 7)
The phase III RELAX-AHF study has shown that the investigational drug RLX030 (serelaxin, Novartis) improved symptoms and reduced deaths by one-third at the end of 6 months in patients with acute heart failure (AHF). Most of the deaths were due to cardiovascular causes.
RLX030 is a recombinant form of the human hormone relaxin-2 — the first in this new class of medicines — and is believed to act through multiple mechanisms on the heart, kidneys, and blood vessels. Relaxin-2 occurs naturally in both men and women.
The RELAX-AHF trial demonstrated that RLX030 significantly reduced dyspnea — the most common symptom of AHF and the study’s primary endpoint.
Results of the new study were published in The Lancet.
RELAX-AHF was a phase III, international, randomized, double-blind trial involving 1,161 heart-failure patients. The study was designed to compare the efficacy and safety of RLX030 with that of placebo in addition to standard therapy for the treatment of AHF. RLX030 was administered upon hospitalization in the form of an intravenous infusion (30 mcg/kg/day) for 48 hours in addition to conventional therapy for AHF (i.e., loop diuretics and other medicines).
The study used two different scales to measure the primary endpoint of a reduction in dyspnea. The visual analog scale (VAS) showed a significant benefit up to day 5 (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).
The study did not meet its secondary efficacy endpoints, namely days alive and out of the hospital up to day 60 (P = 0.37), and cardiovascular death or rehospitalization due to heart or kidney failure up to day 60 (P = 0.89).
The results showed that 7.3% of patients died from all causes in the RLX030 group compared with 11.3% in the placebo group (P = 0.02) after 180 days of follow-up. All-cause mortality up to day 180 was one of the study’s safety endpoints. The number of deaths due to cardiovascular causes up to day 180 (an additional prespecified efficacy endpoint) was also significantly lower with RLX030 than with placebo (6.1% vs. 9.6%, respectively; P = 0.028). RLX030 was therefore associated with a 37% reduction in all-cause and cardiovascular mortality at the end of 6 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 the hospital by 0.9 days (P = 0.039) and in the intensive/cardiac care unit by 0.4 days (P = 0.029).
Adverse events (AEs), including hypotension, were generally comparable between RLX030 and placebo. A lower incidence of AEs related to renal impairment was observed with RLX030 than with placebo (4.6% vs. 8.6%). The most common AEs in both treatment groups were cardiac, metabolic, nutritional, and gastrointestinal disorders. No clinically significant differences in the incidence of serious adverse events were seen between the two groups.
Patients with AHF have a poor prognosis after hospitalization. Nearly 25% of people admitted to a hospital with AHF die within 1 year.
Source: Novartis; November 7, 2012.