- Amgen on Friday revealed its PCSK9 drug Repatha (evolocumab) reduced the risk of major adverse cardiovascular events but had no effect on cardiovascular death, mixed results which could spell continued sluggish uptake for the cholesterol-lowering medicine.
- But Amgen is willing to cut a deal with payers who will drop barriers to coverage which have limited Repatha's commercial success to date. Options on the table include a refund of the drug's cost for any eligible patient which suffers a heart attack or stroke while on the drug.
- The results from the FOURIER outcomes trial, presented at the annual meeting of the American College of Cardiology, definitively proved Repatha's cardiovascular benefit. Yet investors had been hoping for a greater risk reduction than the 15% seen on the trial's primary endpoint. Amgen's shares slid more than 5% Friday morning.
Proving Repatha's cardiovascular benefit was a major hurdle to clear for Amgen. Repatha, and the PCSK9 drug class as a whole, rode to market on high expectations ginned up by strong efficacy in lowering LDL cholesterol.
Sales for the drug have been modest as payers have balked at the high price tags for Repatha and its rival Praluent (alirocumab) — developed by Sanofi and Regeneron. Demonstrating positive cardiovascular outcomes, then, had become a crucial test to justify the drugs' costs.
In FOURIER, Amgen demonstrated Repatha lowered a composite of cardiovascular risks, including heart attack, stroke and other related events, by 15% — meeting the study's primary endpoint. On a more narrow basis looking at just cardiovascular death, heart attack or stroke, treatment with Repatha reduced risk by 20%.
In addition, Repatha's benefit grew over time, suggesting the effect of LDL cholesterol reduction takes time to impact cardiovascular outcomes. Risk reduction as measured by the primary endpoint rose from 12% in the first year to 19% beyond that time period.
Yet the drug failed to show a statistically significant effect on cardiovascular death, and the risk reductions observed on the primary and secondary endpoints checked in lower than some had hoped to see. Given the low cost of statin treatment, payers could still limit coverage for Repatha to higher risk patients.
So far, payers have thrown up utilization barriers to block coverage for a "significant number" of patients who have been prescribed Repatha, Amgen has indicated in filings with the Securities and Exchange Commission.
Amgen, though, clearly believes Repatha can meet expectations. The offer of refund contracts to payers willing to open up coverage shows that. And the biotech emphasizes that the absolute benefit of Repatha will likely be higher outside of trials, noting the cardiovascular event rate in clinical practice is higher than in the controlled environment of an outcomes study.
Repatha also showed a clean bill of health from a safety standpoint. Rates of new onset diabetes, cataracts and neurocognitive effects were similar between treatment and placebo arms. Injection site reactions were more common with Repatha than placebo, but remained at low levels.
FOURIER is the first outcomes trial to read out for the PCSK9 class. Sanofi and Regeneron are conducting their own study, dubbed ODYSSEY, to test Praluent's cardiovascular benefit. That trial is expected to read out sometime this year and will give a better sense of how high of a bar Amgen has set with Repatha.
Judging by the market reaction to FOURIER, investors appear to see the two drugs as broadly similar with Sanofi and Regeneron stock dropping in value. Shares in The Medicines Company, which is pushing towards submitting its PCSK9 synthesis inhibitor for U.S. approval, sold off in dramatic fashion, falling more than 20% Friday.
Praluent is also still at risk of legal action, which could give Amgen a more secure market position down the road. In January, a U.S. district court placed an injunction against sales of Praluent in the U.S., surprising many. An appeals court overturned the ban, but legal proceedings between Amgen and the Sanofi/Regeneron team are still ongoing.