Sorry, Praluent: Sanofi, Regeneron's PCSK9 med misses boat on early outcomes data boost

Praluent and Repatha
A much-anticipated trial of Sanofi and Regeneron's Praluent in heart patients didn't deliver results overwhelming enough to stop early.

Sanofi and Regeneron might have had a chance to take the lead in the PCSK9 sales race, but that fuel injection didn’t come through.

A cardiovascular outcomes trial on Praluent, widely seen as key to the drug’s success, will go ahead as planned, rather than stopping early as the companies might have hoped. Final results aren’t due till late 2017 or early 2018, leaving Sanofi and Regeneron to wait for the marketing boost an early success would have offered.

The announcement wasn’t unexpected; the ODYSSEY OUTCOMES trial had set ambitious benchmarks for an early halt, analysts said. And it doesn’t necessarily indicate that the trial won’t deliver the positive results Praluent needs.

“We do not see this result as suggesting higher odds of trial failure,” Bernstein analyst Ronny Gal said in a Thursday investor note. “The bar for interim stop is intentionally set very high,” he added, at a 20.2% reduction in cardiovascular events such as heart attack and stroke, with similar results across the various patient groups enrolled.

Still, overwhelming results in the study would have been welcome news as Praluent and its Amgen-made rival Repatha cajole payers and doctors to adopt their high-tech, expensive drugs. And Amgen expects to unveil Repatha outcomes numbers in early 2017.

In the meantime, Sanofi and Regeneron on the one hand, and Amgen on the other, have been building their case for the meds with additional data, including a couple of trials demonstrating other clinical benefits. This week, Amgen’s study of Repatha’s effect on clogged arteries—which showed the drug could reduce the size of arterial plaques—was presented at the American Heart Association annual meeting. The results fell short of a threshold that might have made a difference to payers, however, some analysts said, though Amgen contended insurers should take notice.

Sanofi and Regeneron had previously unveiled a study of Praluent’s ability to reduce pricey apharesis treatments required in some patients with extremely high cholesterol; the drug cut the number and frequency of those treatments, which mechanically pull cholesterol out of the blood. That trial was directly aimed at showing that, even at a premium list price of more than $14,000, Praluent could save payers money.

The companies have also turned to data mining to help identify patients whose PCSK9 scripts are most likely to win payer approval, those with a rare disorder that pushes cholesterol to sky-high levels. And they have inked performance-based deals with several insurers, which link rebates and discounts to the drugs' real-world cholesterol-lowering results.

It’s the big outcomes trials that would make a real difference, however. Sanofi and Regeneron’s Praluent trial enrolled 18,000 patients, while Amgen’s is testing Repatha in 27,000. Physicians and payers are looking for rather dramatic reductions in cardiovascular risk—a tough task—but the companies believe they can deliver.

Analysts aren’t so sure; though the smaller PCSK9 trials that weren’t designed to measure CV benefits have suggested even bigger reductions in risk than the 20% to 25% investors appear to be expecting, the outcomes studies may not follow suit. For instance, Bernstein is expecting a 15% improvement for Praluent, Gal said.

The two drugs’ results could diverge as well, because their primary endpoints are slightly different. In the Praluent study, the composite endpoint encompasses heart attack, stroke, death from cardiovascular causes and hospitalization for angina. The Repatha study includes those, but adds coronary revascularization procedures.

“We will need to wait and see Amgen’s data to get a sense for what effect, if any, the inclusion of revascularization ... has on the primary outcome,” Evercore ISI analyst John Scotti said in a Thursday note.

Some information could be on tap soon. Top-line data from the Repatha trial could come as early as January, Scotti said, with details presented at the American College of Cardiology meeting in March.