Novartis’ phase 3 trial of serelaxin in acute heart failure has missed its primary endpoint. The Swiss pharma saw the 6,600-patient trial as a way to bounce back from FDA’s 2014 rejection, but instead the study cast further doubts over the efficacy and future of a drug previously tipped to rack up blockbuster sales.
For the trial, dubbed RELAX-AHF-2, Novartis enrolled 6,600 patients with acute heart failure and randomized them to receive either placebo or the recombinant peptide vasodilator serelaxin. Patients were assessed against two primary endpoints: reduction in cardiovascular death over 180 days, and occurrence of worsening heart failure over five days. The drug failed to move the needle on either count, wiping up to 2% off Novartis’ share price in early trading in Switzerland.
Novartis has yet to formally give up on the drug—it is still analyzing data and deciding on the next steps—but given the scale and design of the study were expected to fix the problems it faced last time it pitched regulators, the setback shrinks its chances of ultimately prospering.
When Novartis sought FDA approval of serelaxin in 2014, an advisory committee unanimously rejected it. The committee’s criticism of the design of the trial and gaps in the data—which made assessing safety and efficacy difficult—led to the rejection. European officials also rejected the drug that year.
With the size of RELAX-AHF-2 dwarfing the previous study, it was expected to have the heft needed to link serelaxin to statistically significant improvements in health outcomes. That it has failed to do so makes it harder to argue that serelaxin is a good drug undone by a bad trial.
The setback leaves Novartis lacking an anticipated cornerstone of its cardiovascular division. After Diovan lost patent protection in 2012, Novartis looked to serelaxin and Entresto to ensure the unit prospered. Neither drug has lived up to expectations. With sales of $170 million last year, Entresto has made a slow start to commercial life. And with RELAX-AHF-2 coming up short, serelaxin may now never deliver any return on Novartis’ investment in the program.
Novartis’ data drop comes four months after fellow Swiss drug developer Cardiorentis posted its own set of lackluster heart failure results. The phase 3 trial of Cardiorentis’ ularitide, which like serelaxin is a vasodilator, failed to link the drug to reduced myocardial injury or lower long-term risk of death.