Out to shake up PCSK9 market, Medicines Co boasts of pivotal PhIII win for inclisiran
The Medicines Company’s first pivotal Phase III results for inclisiran are in, and the biotech can’t wait to highlight the cholesterol-lowering potential of its long-acting drug.
Ahead of a data presentation of ORION-11 at next week’s European Society of Cardiology, The Medicines Company is putting out word that inclisiran — an RNAi therapeutic licensed from Alnylam that works by preventing PCSK9 from being synthesized in the liver — met all primary and secondary endpoints. The efficacy was “consistent with findings from Phase 1 and 2 studies” and the safety profile was “at least as favorable” as in previous Phase II studies.
Baird’s Madhu Kumar added that in speaking with management, the results were “consistent with modeling work previously described to represent a 50%-55% reduction in LDL-C” — though he emphasized data at the ESC will be needed to confirm a win here.
Meanwhile, Umer Raffat of Evercore ISI zeroed in on the claim about a clean safety profile, which was “by and far the biggest issue” heading into Phase III, calling the topline results possibly “the single most important piece of validation for RNAi safety.”
Shares $MDCO rose 12.79% to $38.03 pre-market.
Patients who have completed ORION-11 will now join cohorts from ORION-9 and -10 for ORION-8, an open-label extension study to evaluate the dosing of inclisiran over three years.
ORION-11 and -10 both enrolled patients with atherosclerotic cardiovascular disease and elevated LDL cholesterol despite statin therapy; the former was conducted in seven countries ex-US while the latter took place in the US. The results for ORION-10 as well as -9 — which target patients with heterozygous familial hypercholesterolemia — are expected later this quarter.
That bulky data package — with each trial involving more than a thousand patients — will be sent to the FDA by the end of this year and to the EMA in Q1 2020.
The data presentation at ESC can also bode well for Alnylam $ALNY, Mani Foroohar of SVB Leerink noted, especially with regards to applying its GalNAc-conjugated RNAi platform in large population, primary care indications.
While monoclonal antibodies from Regeneron/Sanofi and Amgen have beat inclisiran to the market, Baird analysts have predicted the drug will be “ascending the Iron Throne of PCSK9 drugs” due mostly to its dosing schedule. Unlike Praluent and Repatha, which are administered monthly or twice-monthly, inclisiran can be given just twice a year after an initial interval of three months.
“We believe this dosing schedule is attractive to patients and can improve adherence, since currently only 55-60% patients are compliant on PCSK9 Ab therapy,” Jefferies analysts have noted.
Notably, ORION-11 excluded patients with active liver disease, which the company said is “not uncommon for studies of dyslipidemia medications.” While a case of liver enzyme elevation cropped up in Phase II, it was deemed unrelated to the drug. Recent studies comprising renally impaired patients also suggested inclisiran is safe for that group, and that they do not require dose adjustment.
“This is a momentous occasion that further reinforces our confidence in the tremendous potential of inclisiran to fundamentally change the treatment of cardiovascular disease,” said CEO Mark Timney, who succeeded longtime chief Clive Meanwell in December 2018.