The failure of Novartis’ acute heart failure therapy serelaxin to hit its objectives in a second phase III trial is somewhat embarrassing for the company, which has been talking up the programme in recent months.
Earlier this week, Novartis revealed that serelaxin missed two main endpoints in the RELAX-AHF2 trial – worsening of heart failure at day five after starting treatment and cardiovascular death at day 180.
It follows an earlier trial (RELAX-AHF) which was able to show that serelaxin improved symptoms such as shortness of breath (dyspnoea) in AHF patients, but also failed on hard clinical endpoints including cardiovascular death or re-admission to hospital for heart or renal failure.
The dyspnoea data weren’t compelling enough to win over regulators in the US and EU, which refused to back the drug in 2013 and 2014m respectively, but a later analysis showing a trend towards reduced cardiovascular death at six months encouraged Novartis to add that endpoint to its second, much larger study.
Novartis’ chief medical officer Vasant Narasimhan isn’t calling time on the drug just yet, saying the company will take a decision after a complete look at the dataset. However, analyst Seamus Fernandez at Leerink said the failure to hit the main endpoints in RELAX-AHF2 “essentially terminates all enthusiasm for the drug”.
It’s a big disappointment for Novartis – which just recently was talking about blockbuster sales potential for the drug and signals of a mortality benefit – as well as a massive blow to cardiologists and their patients, who have an urgent need for effective drugs for AHF as it has a very high death rate and has seen no new therapies for decades.
Bernstein analyst Tim Anderson said that the high level of confidence in serelaxin at Novartis could lead some investors to see the news as “the latest blow to management R&D credibility”. Novartis had been hoping to build a valuable heart failure franchise around serelaxin for AHF and Entresto (sacubitril and valsartan) for chronic heart failure (CHF).
The slow uptake of the latter drug due to payer resistance as well as problems at eyecare unit Alcon are cited by Anderson as a signal of some operational problems at Novartis, although he stressed that overall the firm’s R&D engine is running pretty smoothly given recent launches such as psoriasis drug Cosentyx (secukinumab) and Kisqali (ribociclib) for breast cancer.
Deutsche Bank analyst Tim Race said: “The failure of serelaxin will refocus the importance of Entresto to meet consensus long-term sales expectations as well as the importance for management to bolster its pipeline.”