Study results published in the NEJM showed that experimental PCSK9 inhibitors under development by Amgen, Sanofi and Regeneron Pharmaceuticals reduce the risk of cardiovascular events by around half, while cutting LDL cholesterol levels by more than 60 percent.
The OSLER-1 and -2 studies of Amgen's Repatha (evolocumab) included 4465 patients who were randomised to treatment with the drug dosed either bi-weekly or monthly, or placebo and followed up for a median of 11.1 months. Patients in both arms also received standard therapy, which included diet modification and statin therapy. Results, which were also presented at the American College of Cardiology annual scientific session, showed that the cardiovascular event rate was 0.95 percent at one year in the Repatha arm, compared to 2.18 percent for standard therapy alone. Meanwhile, the drug reduced LDL cholesterol levels by 61 percent versus standard therapy alone.
Study author Marc Sabatine suggested that the data "are very consistent...it appears that cutting LDL by 61 percent translates to a roughly 50 percent reduction in cardiovascular events." The researchers noted that the adverse event rate was similar in both study arms, although Repatha was associated with a three-fold higher neurocognitive event rate. However, Scott Wasserman, Amgen's head of cardiovascular and metabolic therapies," stated "we have been looking at this throughout our clinical programme," adding "we have not identified what we believe is a safety issue."
Meanwhile, the ODYSSEY LONG TERM study randomised 2341 people at high risk of cardiovascular events who had LDL cholesterol levels of at least 70 milligrams per decilitre despite statin therapy to treatment with Sanofi and Regeneron's Praluent (alirocumab) or placebo every two weeks. The primary endpoint of the study was the percent change in LDL cholesterol levels from baseline at 24 weeks.
Results illustrated that Praluent cut LDL cholesterol levels by 62 percentage points versus placebo at 24 weeks, with the reduction being sustained for 78 weeks. Meanwhile, a post-hoc analysis revealed that Praluent lowered the risk of major cardiovascular events, including cardiac death, nonfatal myocardial infarction, stroke or unstable angina requiring hospitalisation, to 1.7 percent, versus 3.3 percent for the placebo arm. The investigators noted that higher rates of injection-site reactions, myalgia, neurocognitive events and ophthalmologic events were recorded in the Praluent arm.
Lead investigator Jennifer Robinson stated "to see a reduction in cardiovascular events already is very encouraging that we're on the right track." In a related editorial, Neil Stone and Donald Lloyd-Jones commented that the results for Repatha and Praluent "whet our appetites for further results that show cardiovascular benefit and documented safety" of PCSK9 inhibitors. However, the authors cautioned "it would be premature to endorse these drugs for widespread use before the ongoing randomised trials…are available."
The FDA accepted Amgen's application for Repatha in November last year, with the agency anticipated to render a decision by August 27. Meanwhile, in January, the FDA granted priority review to Praluent, with a decision expected by July 24. Amgen has filed a lawsuit in the US against Sanofi and Regeneron claiming that Praluent infringes several of its patents (for related analysis, see ViewPoints: Sanofi/Regeneron succeed in plan to leapfrog Amgen in PCSK9 race – will they be willing to compete on price?).
Analysts estimate that PCSK9 inhibitors could generate $12 billion in peak annual sales. Meanwhile, CVS Health has warned that the drug class could increase healthcare spending in the US by as much as $150 billion annually.
For additional analysis on the PCSK9 inhibitor class, see ViewPoints: Scrutiny of PCSK9 inhibitor competitive positioning set to increase. See also Spotlight On: Where will US payers strike next?
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