Novartis has held high hopes for cardiovascular med Entresto, pegging peak sales at $5 billion. Now, a major trial setback is hurting the drug's prospects, but Novartis is trying to looking at the bright side: Entresto may have flopped, but it was a “narrow miss.”
Entresto reduced the combined rate of heart failure hospitalizations and cardiovascular death among heart failure patients by 13% over valsartan, according to data from the phase 3 Paragon-HF trial presented Sunday at the European Society of Cardiology Congress in Paris. But that improvement didn't reach the threshold for statistical significance.
Novartis, though, pointed to smaller subgroups that showed even stronger results. Patients with a left ventricular ejection fraction equal to or below the median of 57% saw a 22% reduction in total CV events, and female patients showed a 27.5% reduction in the same measure.
Entresto “narrowly missed” its primary endpoint, but the drug still showed promising improvements in patient quality of life and renal function, David Soergel, Novartis’ global head of cardiovascular, renal and metabolic drug development, said.
“What we see in the data is clear evidence that Entresto has drug effects and potentially beneficial effects just based on the totality of the data,” Soergel said. “This syndrome is a huge unmet need, and it’s been a really difficult puzzle to crack for many years.”
Entresto sought to become the first drug approved to treat HFpEF, which affects an estimated 13 million patients globally. Soergel said the drugmaker would present its data to global health authorities to determine the next step in the indication.
Despite the setback, Entresto has seen a long-awaited surge in sales in recent months—including the $1.03 billion it hit in 2018—after a sluggish launch following its 2015 approval. Novartis had high hopes the drug would become a cash cow, predicting $5 billion in peak sales.
In the second quarter, Entresto posted an 81% jump in quarter-over-quarter sales to hit $421 million. Novartis said booming uptake helped the drug beat analyst consensus by 9% and boost the drugmaker’s total sales to $11.8 billion on the quarter.
Entresto’s trial flop is only the most recent of Novartis’ worries in cardiology: The FDA rejected another candidate to treat patients with prior heart attacks, canakinumab, in October. In that case, the FDA knocked 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."
Entresto’s setback is also just one of a suite of struggles Novartis has faced recently. In early August, Novartis admitted that clinical data for gene therapy Zolgensma had been manipulated by researchers at the drugmaker’s AveXis unit. The unraveling prompted penalty promises from the FDA and a tepid response from CEO Vas Narasimhan, who in a call with investors said that management “did the best we could."