- After five years of testing, Novartis said Monday its heart medication Entresto "narrowly" failed a study that could have added a valuable indication to the drug's label.
- The PARAGON-HF trial enrolled more than 4,800 patients who had heart failure with preserved ejection fraction (HFpEF), a condition for which there are no approved treatments. Topline results found Entresto didn't significantly outperform valsartan, a common medicine for high blood pressure and heart failure, on the study's composite primary endpoint of heart failure hospitalizations and cardiovascular death.
- Novartis built up the PARAGON readout as an important near-term catalyst for both the drug and the overall company. Entresto has become a key drug for Novartis, with second quarter sales up 81% year over year to $421 million.
Entresto (sacubitril/valsartan) first gained approval in 2015, as a treatment for patients with or chronic heart failure and reduced ejection fraction. Sales from that indication ticked over the $1 billion mark last year, and Novartis expected another blockbuster opportunity in HFpEF.
Company executives, speaking earlier this month on a second quarter earnings call, sounded optimistic of PARAGON-HF's chances of success. Yet Wall Street analysts remained skeptical, since no drugmaker has been able to lock down an approval in the HFpEF setting.
The apprehension now appears justified.
Novartis didn't provide any data points from the study in a July 29 release. It is possible Entresto "narrowly missed" because of the composite primary endpoint — as in, the drug's effect may have been dragged down by either the cardiovascular death measure or the hospitalization measure.
John Tsai, global head of drug development, previously signaled the hospitalization endpoint is particularly important for this condition.
"For us what we think would be success, really is dependent on hospitalizations or sometimes a subsequent readmission into the hospital," he said on the July 18 earnings call. "So, that's something that we're looking at very closely, and knowing that this is a significant burden for that population of patients."
More details about Entresto's performance should come at the European Society of Cardiology meeting in early September, when data from the study will be presented. Investors in the meantime didn't take the news well, as Novartis shares dipped 1% in Monday morning trading.