Promising phase II data from The Medicines Company's inclisiran have paved the way for phase III trials of a long-acting oligonucleotide-based PCSK9 inhibitor. Although the FDA has already approved two PCSK9 blockers — Amgen's evolocumab and Sanofi and Regeneron's alirocumab — these subcutaneously delivered lipid-lowering antibodies are administered every 2–4 weeks for the treatment of hyperlipidaemia. If data hold up, inclisiran might only require two or three injections per year.

The Medicines Company presented the new data at the American Heart Association (AHA) Scientific Sessions 2016 in New Orleans in November. Preliminary data from the first 189 patients in a phase II study of the RNA interference (RNAi)-based drug showed that one injection reduced low-density lipoprotein cholesterol (LDL-C) levels by 59% compared with placebo at day 60, and that two injections reduced LDL-C by 57% at day 120. Treatment was well tolerated. There was one death and one case of increased liver enzyme levels, but investigators said neither were related to treatment.

But even as The Medicines Company prepared to move its proprotein convertase subtilisin/kexin type 9 (PCSK9) programme forward, Pfizer discontinued development of its would-have-been competitor bococizumab. The antibody had been in phase III trials in more than 27,000 patients. Safety data showed, however, that it was more immunogenic than the competition. Pfizer also cited “the evolving treatment and market landscape”, referencing disappointing sales for the approved PCSK9 inhibitors.

Payers are pushing back against the high cost of these drugs — around US$14,000 per patient per year — because of the absence as yet of definitive data proving that they reduce cardiovascular events.

The field is awaiting the results of large cardiovascular outcomes studies that could open up the market. Another study that was presented at that AHA meeting provided some encouragement. Researchers dosed 968 patients with evolocumab or statins, and used ultrasound to measure the size of atherosclerotic plaques, a risk factor for heart attacks. Plaques shrank in 64% of evolocumab patients, and in 47% of statin-treated patients.