Novartis’s announcement today that its late-stage acute heart failure drug Relaxin (serelaxin) met one of its two primary endpoints in reducing breathlessness in patients with heart failure is really only really an entrée. The really interesting main course is that the drug met its secondary endpoint of reducing all-cause mortality at six months.
While the full magnitude of this benefit is tantalisingly set to be revealed at the American Heart Association conference in November, if the numbers around mortality benefit are strong it could catapult Relaxin into the blockbuster stratosphere and continue Novartis’s run of coming up with pipeline winners.
Currently there are few treatments for acute heart failure (AHF), a disorder where sufferers can often feel not only dyspnoea – breathlessness – but as if they are drowning because of the build-up of fluid in the lungs due to the weakened heart.
Questions have been asked of the effectiveness of the available treatments, Natrecor and Simdax.
UBS estimates that 2 million people are hospitalised every year in Europe and the US because of AHF, creating a big market opportunity for a drug that can successfully crack the space.
As such, industry observers had been eagerly awaiting the outcome of the 1,161-patient Relax-SHF-1 trial pitching Relaxin against standard of care and placebo. Relaxin is a recombinant form of a naturally occurring peptide hormone that is released during pregnancy, which helps increase cardiac output and renal blood flow.
Although only topline data have been released today, they do seem to back the results seen in a smaller phase II trial where a faint trend towards mortality benefit appeared.
Consensus sales forecasts in 2018 for Relaxin are at present $229m, and it is Novartis’s second most-valuable pipeline drug after the infant vaccine Bexsero, according to EvaluatePharma.But if the drug does come good in AHF, UBS analysts are optimistically expecting sales of more than $5bn.
The question now will be whether meeting only one of the two primary endpoints will allow the drug to be approved. Novartis, which had paid $120m initially with future payments of up to $500m to get the drug through its 2009 takeout of Corthera, is confident thanks to a pre-agreed protocol with the FDA.
But given the number of AHF patients who are readmitted to hospital within three months of first diagnosis – 30% – and that about 9% of patients die within that timeframe, the appropriateness of an endpoint that helps with breathlessness is debatable.
As such the mortality benefit for the drug could be the thing that helps it get past regulators thanks to the paucity of existing treatments and the questionable clinical benefit for those that are not diuretics.
The passage of the drug might be slightly easier in Europe, where the European Medicines Agency has published guidelines indicating that a mortality benefit remains the gold standard for approval, but that improvement in symptoms without excess mortality could also be a criterion for marketing authorisation.
The situation is less clear in the US, so Novartis will almost certainly be relying more heavily on the mortality data.
However, this reliance could be an issue in both Europe and the US. The relatively small size of the study means that it might not have sufficient power to detect anything other than large treatment effects, so anything other than a home run on mortality might not be picked up.
Since it now looks like it might all come down to the magnitude of mortality benefit, this year’s AHA meeting has significantly gained in importance for Novartis.
To contact the writer of this story email Lisa Urquhart in London at firstname.lastname@example.org