- The Medicines Company on Wednesday unveiled ambitious plans for a pivotal Phase 3 study to support regulatory submission of its PCSK9 drug inclisiran by the end of 2019, seeking to catch Amgen and Sanofi/Regeneron in the closely watched but still commercially disappointing space.
- The biotech, along with its partner Alnylam Pharmaceuticals, said they had reached agreement with the Food and Drug Administration on the clinical program, which will study the PCSK9 synthesis inhibitor's effect on LDL-C levels in about 3,000 patients with atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia (FH).
- Also on the agenda: a 14,000 patient cardiovascular outcomes study of inclisiran aimed at proving the drug's cardio-protective benefit. In March, Amgen revealed its rival PCSK9 drug Repatha (evolocumab) reduced the risk of major adverse cardiovascular events, but the level of effect disappointed some.
Having cleared the decks to speed development of inclisiran, the Medicines Company is quickly plunging into an aggressive late-stage clinical program.
Complete results from the biotech's mid-stage ORION-1 study, released in March, showed two 300 mg injections of inclisiran lowered LDL-C levels by an average of nearly 53% after six months — a reduction competitive with that seen from Amgen's Repatha and Sanofi and Regeneron's Praluent (alirocumab).
Since the company hopes to establish biannual or triannual dosing, the planned Phase 3 trial will run for 18 months to adequately assess the drug's effect and safety over time. Both Repatha and Praluent are administered once to twice monthly.
While a successful Phase 3 study will be sufficient to clear the bar for submission of a New Drug Application to the FDA, the Medicines Co. believes a cardiovascular outcomes study is key to making inclisiran competitive with the existing PCSK9 options.
At the American College of Cardiology (ACC) meeting in March, Amgen unveiled the results of its closely watched FOURIER study, demonstrating treatment with Repatha lowered a composite of cardiovascular risks, including heart attack, stroke and other related events, by 15%.
While a landmark result for the PCSK9 market, some investors and analysts had hoped to see a greater effect. Repatha also failed to show a statistically significant effect on cardiovascular death.
Even so, the standard to compete in the LDL-lowering space has now been set. Sanofi and Regeneron are racing to complete their own cardiovascular outcomes study, dubbed ODYSSEY, later this year.
Both existing PCSK9 drugs have struggled to get off the ground commercially, but the FOURIER results could begin to change payer's reluctance to pay for the pricey new drugs. Equal or stronger results from ODYSSEY would only make it more difficult to restrict coverage tightly.
Inclisiran, then, will likely be well behind both drugs if it reaches market in 2019. One advantage Medicines Co. has, though, is the ability to incorporate lessons from FOURIER into the design of its own cardiovascular outcomes study.
In FOURIER, the clinical benefit of Repatha grew over time, suggesting that an outcomes trial with a longer follow-up could pick up stronger efficacy. At the ACC meeting, Medicines Co. CEO Clive Meanwell said a longer follow-up in inclisiran's trial could help show a greater cardiovascular benefit.
While the company didn't indicate a specific study length Wednesday, the statement noted that "the duration of the outcomes trial will be long enough to accumulate a sufficient number of events to provide overwhelming statistical power to ascertain treatment group differences."