- Regeneron Pharmaceuticals Inc. and Sanofi SA's cholesterol drug Praluent significantly lowered the risk of major adverse heart events in a major study of nearly 19,000 patients, a result which the drugmakers hope will convince insurers to pay for the pricey medicine.
- Treatment with Praluent, one of a powerful class of drugs known as PCSK9 inhibitors, was also associated with fewer overall deaths, nominally cutting the risk of so-called all-cause mortality by 15% when compared to those patients who only received statin therapy.
- In an unusual step aimed at reversing the drug's commercial woes, Sanofi and Regeneron signaled willingness to reduce the net price of Praluent for certain high-risk patients if U.S. payers agree to ease restrictions that have so far limited access to the drug.
Regeneron and Sanofi's study, called ODYSSEY, pitted Praluent (alirocumab) against placebo in patients who had recently experienced an acute coronary syndrome and were already receiving a maximally tolerated dose of a statin such as Lipitor (atorvastatin).
Over the three-year trial, treatment reduced the risk of major adverse cardiovascular events (MACE) by 15% — a similar effect to what was observed in a large study of Amgen Inc.'s rival PCSK9 blocker Repatha (evolucumab) last year.
Importantly, however, Praluent also demonstrated a mortality benefit. In the overall study, fewer patients died in the treatment group versus the placebo group, but the 15% risk reduction reported is only considered a nominal result due to how the data was analyzed. Among higher risk patients with baseline LDL cholesterol levels at or above 100 mg/dL, a post-hoc analysis found treatment with Praluent reduced the risk of death from any cause by 29%.
Results were presented Saturday at the American College of Cardiology's annual conference. The findings could help Regeneron and Sanofi convince insurers to cover Praluent more broadly and better communicate to physicians who should receive the drug.
"We believe this is practice-changing data which we expect in due course to be incorporated in treatment guidelines," said Sanofi CEO Olivier Brandicourt on a March 10 call with investors.
Yet the study's findings could also serve to weaken the rationale to prescribe or cover PCSK9 inhibitors in lower-risk patients.
"ODYSSEY also suggests that patients achieving LDL <100 mg/dL on statins get only a modest cardiovascular event and mortality benefit and likely do not justify the cost and inconvenience of PCSK9 therapy," wrote Leerink analyst Geoffrey Porges in a March 11 note to investors.
Blockbuster estimates fall flat
Praluent and Repatha arrived on the market in 2015 to blockbuster sales expectations fueled by the drugs' powerful effect in lowering LDL cholesterol.
Since then, however, both treatments have struggled to find a commercial footing, hamstrung by access restrictions put in place by insurers unwilling to pay for the expensive drugs — both of which carry list prices of more than $14,000 a year.
Hopes of a sales turnaround have hinged on whether the drugs could be shown to reduce the risk of MACE like heart attack or stroke. Since Repatha's cardiovascular benefit was proven last spring, Amgen's drug has captured about 65% of the market as physicians mostly prescribed Repatha over Praluent.
The data from Odyssey will help Sanofi and Regeneron even that playing field and, given the mortality finding, could spur more physicians to start patients on Praluent instead.
"As a physician, I am unlikely to change somebody who has already been prescribed the Amgen drug, because I think the drugs are basically the same," said Ethan Weiss, a cardiologist and associate professor at the University of California San Francisco School of Medicine. "But I am very unlikely to write a new prescription for it."
Sanofi and Regeneron also aim to win over payers. Along with the data, the companies announced an offer to reduce the net price of Praluent for payers that lower barriers to access for high-risk patients.
The Institute for Clinical and Economic Review, which has consistently called for the PCSK9 makers to reduce prices, on Saturday released an update to its cost-effectiveness analysis for Praluent. For high-risk patients, such as those with LDL cholesterol levels greater than 100 mg/dL even after maximum statin treatment, a net price of between $4,500 and $8,000 would be cost-effective, ICER said.
That would represent a 45% to 70% discount to Praluent's list price of $14,560. Sanofi and Regeneron didn't specify exactly what level of discount they would offer to payers, only noting it would be within a "cost-effective range, leveraging a new ICER analysis."
The companies gave ICER early access to the ODYSSEY data in order for the group to revise its analysis of the drug's cost-effectiveness.
"We challenge payers to respond by making Praluent accessible to high-risk patients," said Regeneron CEO Len Schiefler, who has been outspoken in his frustration at payers unwillingness to cover Praluent, on an investor call Saturday.
Sanofi and Regeneron said they expect to file a supplementary Biologics License Application to the Food and Drug Administration by the end of the second quarter in hopes of adding the Odyssey data to Praluent's label.