Sanofi, Regeneron's Praluent pulls off PCSK9 coup with 29% cut to death risks in most vulnerable patients

ORLANDO, Fla.—As the American College of Cardiology's annual meeting kicked off in Orlando Saturday, all eyes turned to Sanofi and Regeneron, who reported that their PCSK9 drug Praluent reduced the risk of cardiovascular events by 15%—as well as all-cause mortality by 15%—in the outcomes trial Odyssey. 

In conjunction with the data announcement, Sanofi disclosed it'll incorporate a new cost-effectiveness review by ICER in future payer negotiations as it fights for market share with rival Amgen and its PCSK9 treatment Repatha. The analysis concludes that Praluent is worth $4,460 to $7,975 for certain patients. 

If payers are willing to reduce barriers to access, Sanofi said it will lower the drug's net price to within ICER's range. The program will use a "precision medicine approach" to home in on high-risk patients. 

“Too many patients in urgent need of additional treatment options on top of statins have faced tremendous hurdles to gain access to this important medicine," Sanofi CEO Olivier Brandicourt said in a statement. "We are prepared to change this by improving access and affordability, eliminating these burdensome barriers for high-risk patients in need." 

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In the much anticipated Odyssey trial, Praluent reduced the risk of a composite endpoint of heart attack, stroke, death from coronary heart disease or unstable angina requiring hospitalization by 15%, investigators reported Saturday, meeting its primary endpoint. The drug also cut the risk of death from any cause by 15%. For high-risk patients with LDL levels of 100 mg/dL or higher, the benefit was larger: a 24% reduction in risk of MACE and a 29% drop in all-cause mortality.  

Speaking with FiercePharma, principal investigator Philippe Gabriel Steg, M.D., Ph.D., said the benefit in high-risk patients is particularly important, because it fits what "clinicians would want to do in real practice" and will allow the healthcare system to get the most "bang for the buck." He argues it's a "no-brainer" more patients should be on the Sanofi and Regeneron drug than currently are. 

Gregory Schwartz, M.D., Ph.D., another lead researcher for the trial, said that after working in the field for "nearly a quarter of a century, it's very gratifying to find something that will have a great impact on the patients that we treat and see every day in our work." 

Odyssey tested Praluent in nearly 19,000 patients who experienced an acute coronary event the year before their enrollment. The participants were on the highest statin dose they could tolerate and received either placebo or Praluent in addition to their statin therapy. Investigators followed the patients for an average of 33 months. 

All told, the data will be important for Sanofi to grow Praluent's uptake against Amgen's market-leading Repatha in a class that's already far behind initial projections, largely because of payer barriers. Last year, Amgen presented Repatha's outcomes data at the ACC conference in Washington, D.C., but analysts thought the results weren't good enough to make a big impact on sales and use.

In that trial, Repatha reduced heart attack risks by 27%, stroke risks by 21% and coronary revascularizations by 22%, but it didn't provide a mortality benefit. It's important to note that a comparison between the two trials isn't apples to apples due to differences in design and patient base. Still, analysts and others will be looking to both sets of results to weigh the drugs' benefits.

Following the results announcement, Bernstein analyst Ronny Gal, Ph.D., speculated that Regeneron's payer strategy could be to accept that only high-risk patients who are on statins will qualify for Praluent. Then, he wrote, the company could reduce its prices and argue that Praluent's mortality benefits justify added costs. Lastly, the company could "threaten to raise hell if the drug is not covered," according to Gal. 

The partners will submit a supplemental application to the FDA around the middle of this year for a potential label update early next year, according to Jefferies analyst Michael Yee. 

While cautioning against direct cross-trial comparisons, SunTrust analyst Yatin Suneja wrote that the mortality benefit seen in Odyssey will likely be seen as a "key differentiator" between the PCSK9 outcomes trial results. Looking ahead, Suneja wrote that important considerations are whether Praluent's mortality benefit will be included in a potential FDA label update and the timing for new treatment guidelines.

RELATED: Court tosses Praluent ban, gives Sanofi and Regeneron a new trial in Amgen patent battle 

In December, Repatha won an FDA label saying it can reduce the risk of cardiovascular events, becoming the first PCSK9 drug boasting the indication. On Amgen's fourth-quarter conference call, commercial chief Tony Hooper said it's "still early days since the approval," but that the drugmaker has heard positive feedback. According to a Friday note from Mizuho analysts, Repatha holds more than 60% of the PCSK9 market, compared with less than 40% for Praluent.

Meanwhile, the drugmakers are locked in a patent dispute that could make the discussion moot. Last October, a judge tossed a ban on Sanofi and Regeneron's Praluent sales, setting up a new trial between the rivals. Amgen claimed Sanofi and Regeneron infringed its patent, leading to a short-lived injunction on sales.

While Amgen and Sanofi and Regeneron battle it out with the PCSK9s, another competitor could be lurking in Esperion. The drugmaker's cholesterol met phase 3 endpoints in results released this week, and CEO Tim Mayleben has previously said the company is planning to charge $9 or $10 per day, which would fall below the low end of the range ICER suggested for Sanofi's Praluent. Sanofi, Regeneron and Amgen initially rolled their drugs out with prices of more than $14,000 per year before rebates and discounts.

Editor's note: This story was updated with comments from analysts.