Eyeing one of the first RNAi therapies and cholesterol blockbuster, MedCo shows detailed inclisiran data
The main question was not whether it would work; it was if it would be safe.
The Medicines Company is out with new data on its LDL cholesterol drug inclisiran, and they confirm the first, tentative answers: Yes. They also keep MedCo on track for an imminent FDA submission for one of the first RNAi therapies and a drug that could flip the cholesterol market. An EU application will follow in the first quarter of 2020.
Presenting detailed results from the second of three Phase III inclisiran trials at the American Heart Association Congress, MedCo showed the drug had similar safety metrics as a placebo in patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL cholesterol. MedCo announced in September the trial had met all efficacy endpoints and appeared safe but released no data.
The new results showed adverse events rates equal to or smaller than the placebo group. The ORION-10 results also showed a greater degree of LDL-C lowering than the earlier ORION-11 trial. At day 510, LDL-C reductions were at 58%, compared with the 54% displayed in ORION-11, a difference that may reflect slightly different patient populations.
“ORION-10 results met our high expectations,” SVB Leerink’s Joseph Schwartz wrote.
The new data comes not long after Regeneron and Amgen slashed prices on two drugs once billed as the next generation blockbusters of cholesterol therapies. Praluent and Repatha, both monoclonal antibodies that blocked the PCSK9 enzyme, dramatically lowered LDL in Phase III trials, but payers balked at the initial cost: A little over $14,000.
SVB Leerink’s Mani Foroohar has modeled inclisiran at a price around $5,000, or slightly less than what the PCSK9 inhibitors are now going for. Analysts have also predicted it will become the top seller by virtue of its dosing schedule: twice per year. The antibodies are administered twice per month.
“We believe this dosing schedule is attractive to patients and can improve adherence since currently, only 55-60% of patients are compliant on PCSK9 Ab therapy,” Jefferies has noted.
But first, it had to clear safety hurdles, particularly given the newness of the RNAi tech. The ORION-10 study of 1,561 patients showed similar rates of serious adverse events in the two arms (26.3% in placebo vs. 22.4% in treatment), death incidence (1.4% vs 1.5%), and malignancies (3.3% in both).
Details from the final study, ORION-9 in patients with heterozygous familial hypercholesterolemia will be presented later today. Topline data from that study released in September showed the drug meeting all primary and secondary efficacy endpoints and displaying an “excellent” safety profile.
As one of the first small RNA interference therapies, an approval would have significance beyond the cardiovascular world. Based on a process first hinted at in a 1990 experiment on petunia, it uses a built-in process, cells have to dice up virus RNA or messenger RNA it doesn’t want to code. (For an explanation of the basic science at play for you or your 5th grader, see this food-based Ted Ed.)
Rather than block the LDL-building PCSK9 protein, MedCo injects patients with little bits of RNA that impedes cells from creating the protein altogether. The first RNAi therapy was approved last year: a rare disease treatment from Alnylam.