A Comprehensive Report on the Investigational Drug Serelaxin (DB05794)

Section 1: Executive Summary

Serelaxin (DrugBank ID: DB05794) is an investigational biotech drug developed as a recombinant form of human relaxin-2, a pleiotropic peptide hormone. It was investigated by Novartis, under the codename RLX030 and the proposed brand name Reasanz, primarily for the treatment of acute heart failure (AHF).[1] The scientific rationale for its development was compelling, based on its mechanism as a relaxin receptor (RXFP1) agonist that mimics the profound cardiovascular and renal adaptations observed during pregnancy. Its proposed benefits in AHF stemmed from its multifaceted physiological effects, including systemic and renal vasodilation, anti-inflammatory actions, and anti-fibrotic properties, driven by the activation of nitric oxide and cAMP signaling pathways.[4]

The clinical development program for Serelaxin in AHF was defined by two pivotal, large-scale Phase III trials with starkly contrasting outcomes. The initial trial, RELAX-AHF, produced ambiguous results on its primary dyspnea endpoints but generated significant optimism due to a promising, albeit exploratory, 37% reduction in 180-day mortality.[7] This finding prompted the initiation of a much larger confirmatory trial, RELAX-AHF-2, which was designed to definitively establish this mortality benefit. However, RELAX-AHF-2 failed to meet either of its co-primary endpoints, showing no statistically significant effect on cardiovascular mortality at 180 days or on the incidence of worsening heart failure through day 5.[9]