Novartis' acute heart failure (AHF) drug serelaxin (RLX030), which both the FDA and the European regulator knocked back in 2014, failed in a global, 6600-patient Phase III study. The 3.5-year RELAX-AHF-2 trial evaluating serelaxin in addition to standard of care fell short of its primary endpoints of a reduction in cardiovascular death through to day 180, or a reduction in worsening heart failure through to day 5. Serelaxin is a recombinant form of the human relaxin-2 hormone, which is produced in higher levels in pregnant women and is thought, Novartis says, to support the increased demands put on the body's cardiovascular system during pregnancy.
“We are disappointed this study did not confirm the efficacy of RLX030 in acute heart failure, especially given the urgent need for effective new treatments for this condition,” admitted Vas Narasimhan, M.D., global head, drug development, and CMO Novartis. “We will continue to further analyze the data to better understand and learn from these results as well as evaluate next steps for the overall program.
FDA refused to approve serelaxin in May 2014, stating that it wanted further evidence of efficacy. Earlier that year, the European Commission’s Committee for Medicinal Products for Human Use (CHMP) advisory panel recommended against approving the drug, stating that the original, much smaller Phase III RELAX-AHF study didn’t demonstrate benefits for short-term relief of dyspnea over 24 hours, and also requesting further studies to demonstrate the drug's effectiveness. At that time, the RELAX-AHF-2 trial was already in progress.
Novartis’ heart failure drug Entresto™ (sacubitril/valsartan) was approved in the U.S. and Europe in 2015 and made global sales of $170 million in 2016. The drug is indicated for reducing the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (New York Heart Association Class II–IV) and reduced ejection fraction. Earlier this month, Novartis reported data from a post hoc analysis of subgroups of patients in the global PARADIGM-HF study, indicating that Entresto may also help improve glycemic control among heart failure patients with diabetes.
The firm is separately evaluating Ilaris® (canakinumab), a selective interleukin-1β-targeting monoclonal antibody that is approved for autoinflammatory disease indications, in the Phase III CANTOS trial in patients who have previously had a heart attack and are at risk of further cardiac problems due to high vascular inflammation. Data from CANTOS are expected during 2017.