Cardiovascular med Entresto’s blockbuster turn in 2018 was a long time coming for Novartis, which held on to a $5 billion vision for the drug even as its launch lagged. But those dreams took another hit Monday with a major phase 3 trial flop.
Entresto “narrowly missed” its trial goal of reducing deaths and emergency hospitalizations in heart failure patients with preserved ejection fraction (HFpEF) as a combo treatment with valsartan, the company said.
Entresto, which has an FDA approval to treat heart failure patients with reduced ejection fraction (HFrEF), had been poised for a first-ever drug approval in HFpEF. That indication could have brought along a global patient pool of 13 million people, Novartis said.
Novartis R&D chief John Tsai said in a release the drugmaker would present the findings from the phase 3 trial, dubbed Paragon-HF, at the European Society of Cardiology Congress in September.
Entresto’s trial flop will take some of the shine off the drug’s recent sales surge after an FDA approval—and slower-than-expected rollout—in 2015. Novartis had hoped a new approval in HFpEF would help the drug power toward top-end sales of $5 billion a year, but now that forecast could be out the window.
More importantly, Entresto's shortfall is now the second recent setback for Novartis’ cardiovascular portfolio alongside the FDA’s rejection of canakinumab for patients with prior heart attacks back in October.
In that case, the FDA knocked down the drug’s application after requesting more information on its phase 3 trial responder population. Canakinumab, marketed as Ilaris, posted moderate results in that study with a 15% reduction in cardiovascular risks and 10% cut in cardiovascular deaths—figures one analyst said wouldn’t be "fully compelling to payers."
Taken together, the two failures have set Novartis back in its cardiovascular pursuits, particularly after its arduous journey to ramp up Entresto’s sales to $1.03 billion in 2018.
In late 2017, Novartis pegged slow sales of Entresto to warier-than-expected cardiologists more familiar with traditional cardiovascular meds like warfarin and statins. Once Entresto received positive clinical guidelines from the American College of Cardiology, however, drug sales began to ramp up after repeatedly undershooting analyst and company expectations.
Those positive results continued in the second quarter after Entresto posted an 81% jump in sales quarter over quarter to hit $421 million. Novartis said booming uptake helped the drug beat analyst consensus by 9% and boost the drugmaker’s total sales of $11.8 billion on the quarter.