- In data presented at the 86th European Atherosclerosis Society Congress (EAS 2018), The Medicines Company's RNAi-based PCSK9 inhibitor inclisiran lowered atherogenic lipoproteins, which are implicated in an increased risk of heart attack and stroke.
- Dose-dependent reductions were most clear at the 300 mg dose, which was given on day one and day 90, and were sustained at 180 days and beyond, to at least 210 days.
- Phase 3 trials of the 300 mg dose are expected to read out in the second half of 2019, and will include LDL-C as the primary endpoint and other atherogenic proteins as secondary endpoints.
One of the reasons that MedCo is working so hard at proving inclisiran's value is that all its eggs are in one basket. In October 2017, The Medicines Company cut its headcount to below 60 people, and in November 2017, sold its infectious disease business to Melinta Therapeutics for $255 million in cash and $55 million of Melinta common stock, as well as tiered royalty payments. These moves followed a fall in sales of the company's legacy portfolio, and a strategic review that began in 2015. MedCo management said these transactions should provide enough money to advance inclisiran through its pivotal trials.
But the success of inclisiran is far from guaranteed. Even if inclisiran proves safe and effective in clinical trials, it faces a tough commercial landscape.
Other PCSK9 inhibitors already on the market haven't had an easy ride. Neither Amgen's Repatha (evolocumab) nor Sanofi and Regeneron Pharmaceuticals' Praluent (alirocumab) has performed well commercially. The market is flooded with cheap, generic statins that generally work well in lowering cholesterol. The high-priced PCSK9 inhibitors also have administrative hurdles that have deterred physicians from prescribing them.
While these companies have taken steps to prove the effectiveness of their drugs and show their value, it has made little difference. Most recently, Regeneron and Sanofi dropped the price of Praluent for Express Scripts in return for placement on the pharmacy benefit manager's national formulary.
While there is no suggestion yet of a price point for inclisiran, the drug's long-acting profile and the associated compliance benefit could be a useful differentiator in the market.
"Patient compliance is a huge issue in medicine, and there can be great variability in cholesterol levels when patients are required to take a treatment every day. However, inclisiran continues to work for months after each injection, with additional effects from follow-up doses," said John Kastelein, professor of Medicine at the Academic Medical Center of the University of Amsterdam, and chair of the ORION studies steering committees.
"Some patients may get sufficient effects with a single dose, while those who need the most cholesterol reduction can be given two doses per year. Inclisiran could eventually become like a vaccine shot for people with high cholesterol," Kastelein said.