Clean safety and efficacy data tee Medicines Company up for PCSK9 scrap

E-Tattoo takes the hassle out of heart monitoring
An exploratory endpoint tied use of The Medicine Company's inclisiran to a lower rate of heart attack and stroke in patients with high LDL cholesterol. (Pixabay)

The Medicines Company looks to have the data it needs to compete for the PCSK9 market. In a close look at the top-line readout shared last week, Medicines Company showed its siRNA inclisiran has a clean safety profile and is as effective as incumbent drugs sold by Amgen, Regeneron and Sanofi.

Medicines Company revealed the phase 3 trial of inclisiran in patients with high LDL cholesterol met its primary endpoints late last month. Yet that release lacked key details that would point to whether the drug has a shot at superceding the anti-PCSK9 antibodies, namely Amgen’s Repatha and Sanofi and Regeneron’s Praluent. A presentation (PDF) given Monday provided those missing details.

The full data set shows inclisiran can compete with the 50%-plus placebo-adjusted LDL-C lowering achieved by Repatha and Praluent. Inclisiran achieved a time-averaged reduction in LDL-C of 50%.  

As importantly, the safety issues some observers feared would torpedo inclisiran are yet to materialize. The readout features no evidence that inclisiran suffers from the same liver toxicity problems as Alnylam’s givosiran, despite using the same delivery platform, and otherwise shows the siRNA looks little more dangerous than placebo. 

Barring a surprise, Medicines Company looks to be on track to win approval for inclisiran next year. If that happens, attention will then turn to whether payers, providers and patients find the price and clinical data associated with inclisiran compelling enough for the drug to usurp Repatha and Praluent. Neither Repatha nor Praluent has sold as well as expected, leading to steep price reductions. 

Initially, efforts to position inclisiran as a better option than the incumbents will likely focus on dosing convenience. The antibodies are given at least every month. Inclisiran was given every six months in the phase 3, although the LDL-C charts suggest levels of the cholesterol started rising again before the end of that period.

In the longer term, inclisiran may be able to compete on outcomes. An exploratory endpoint tied use of inclisiran to a lower rate of heart attack and stroke than placebo, giving analysts confidence in the prospects of an ongoing cardiovascular outcomes trial (CVOT).

“Although the trial is not powered for detecting CV benefit, the trend is encouraging and supports our confidence for the ongoing ORION-4 CVOT trial, as similar patients are being recruited,” analysts at Jefferies wrote in a note to investors. 

Whether responsibility for making a success of inclisiran falls on Medicines Company or another company remains to be seen. Medicines Company is preparing to commercialize inclisiran itself, but the prospect of acquiring a near-approval cardiovascular drug could prove attractive to larger players.