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RELAX-AHF-2: Serelaxin does not reduce risk for CV death, worsening HF

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A phase 3 trial of serelaxin, a relaxin receptor agonist, failed to meet its primary endpoints. Data from the trial were presented at Heart Failure 2017, confirming previously announced negative results from Novartis.

Serelaxin, also known as RLX 030, was studied in the RELAX-AHF-2 trial to assess safety and efficacy, following the RELAX-AHF trial, which met its primary endpoint of improving dyspnea in participants with acute HF (n = 1,161). The present study was a multicenter trial enrolling patients hospitalized for acute HF (n = 6,600).

John R. Teerlink, MD, FACC, FAHA, FESC, FRCP(London), professor of medicine, University of California, San Francisco, Marco Metra, MD, professor of cardiology, University of Brescia, Italy, and colleagues randomly assigned participants to 48-hour IV infusions of serelaxin (30 µg/kg per day) or placebo within 16 hours of presentation. Inclusion criteria included hospitalization for acute HF requiring IV therapy with persistent dyspnea and pulmonary congestions, systolic BP 125 mm Hg and mild to moderate renal impairment (estimated glomerular filtration rate 25 mL/min/1.73 m² and 75 mL/min/1.73 m²).

John R. Teerlink

Primary endpoints were 180-day CV death and worsening HF through day 5. Secondary endpoints included all-cause death at 180 days, length of hospital stay and composite of CV death or rehospitalization due to HF or renal failure at 180 days.

After 180 days of follow-up, 575 CV deaths occurred; in 8.7% of participants randomly assigned serelaxin (n = 285) and 8.9% of the placebo group (n = 290; HR = 0.98; 95% CI, 0.83-1.15).

In the serelaxin group, 6.9% had worsening HF through day 5 vs. 7.7% of the placebo group (HR = 0.89; 95% CI, 0.75-1.07).

None of secondary endpoints were statistically significant (HR for all-cause mortality = 0.94; 95% CI, 0.81-1.08; HR for CV death or rehospitalization = 0.97; 95% CI, 0.88-1.07; mean difference in hospital length of stay = –0.183; 95% CI, –0.645 to 0.28; P = .4408).

There were no significant safety concerns during the trial.

“In RELAX_AHF-2, we continued to show that serelaxin was safe, but unfortunately, we did not find that it was also efficacious,” Metra said in a press release. “It is concerning that the findings of this trial should be so disparate from the prior RELAX-AHF trial.”

“These are truly late-breaking results, and we are still analyzing the data to understand these disparate findings,” Teerlink said in the release. “Were we misled by the results from the moderate number of events in RELAX-AHF, or is there still a group of patients in RELAX-AHF-2 who benefited from serelaxin?” – by Cassie Homer

Reference:

Teerlink JR, Metra M. Late-breaking trials I: Focus on acute heart failure. Presented at: Heart Failure 2017 and the 4th World Congress on Acute Heart Failure; April 29-May 2, 2017; Paris.

Disclosure: Metra reports consulting for Amgen, AstraZeneca, Fresenius, Novartis, Relypsa, Servier and Trevina and speaking for Abbott Vascular, Fresenius, Novartis and Servier. Teerlink reports receiving research contracts from and/or consulting for Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celyad, Cytokinetics, Medtronic, Merck, Novartis, St. Jude, Stealth and Trevena.