Merck looks to ditch the needles with its next-gen oral PCSK9 inhibitor for high cholesterol

15 Nov 2021
endpts.com
CollaborateGeneric DrugAHA
After winning approval about six years ago, the first wave of PCSK9 inhibitors largely failed to muster the blockbuster sales analysts had predicted. Now Merck is hoping its oral option will find better success. The pharma giant unveiled on Monday what it says are the first in-human results for an oral PCSK9 inhibitor. The candidate, MK-0616, was well-tolerated in men and women with high cholesterol at doses up to 300 mg, with no deaths or serious side effects, the company said at the American Heart Association conference. In addition, the experimental drug reduced blood levels of free PCSK9 by more than 90% from baseline when administered as a single dose between 10 and 300 mg, Merck announced. In a multiple-dose study, LDL-cholesterol (also known as bad cholesterol) decreased by about 65% from baseline in patients who took MK-0616 on top of their current statin therapy for 14 days. “The initial results are encouraging; however, more clinical studies are needed to confirm these findings, given limited clinical experience with the molecule MK-0616,” lead study author Douglas Johns said in a statement. PCSK inhibitors work by blocking a liver protein that helps to destroy LDL-C receptors on the surface of cells. Those receptors are responsible for taking cholesterol out of the blood stream. Therefore, more active receptors means less bad cholesterol. Sanofi and Regeneron’s Praluent and Amgen’s Repatha were the first to secure approvals here, marking the first big cholesterol drugs since Lipitor. Analysts had predicted megablockbuster sales — but payers, weary of funding a chronic treatment for a large patient population, did everything possible to keep patients on cheap generics. That led to major price cuts, and in 2019, Sanofi lopped off its cardio division altogether. Novartis shelled out $9.7 billion for The Medicine Company’s PCSK9 drug inclisiran that same year, planning for a swift US approval. But after getting slapped with a CRL last year, the company released more post-hoc data this week at AHA in the hopes of finally getting it past the goal line. Novartis touts inclisiran (which is injected twice a year) as an easier option than Repatha and Praluent, which require dosing every two weeks or monthly, respectively. Merck, on the other hand, thinks it can skip the needles altogether. “I believe this is the first report of successful oral absorption of a synthesized cyclic peptide like MK-0616 in people,” Johns said. “We were pleased that it appeared to be consistently absorbed and concentrated in patients’ blood, and that it reduced cholesterol levels so effectively.”
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