The Medicines Co. (NSDQ:MDCO) and Alnylam Pharmaceuticals (NSDQ:ALNY) said today that they’ve reached a deal with the FDA over a Phase III trial for the companies’ RNA-based cholesterol-lowering drug, inclisiran. If approved, it would be the 1st RNA-interference therapy on the market.
The drug is a part of a new group of drugs called PCSK9 inhibitors. Anti-PCSK9 drugs from Amgen (NSDQ:AMGN) and Regeneron (NSDQ:REGN) have been on the market since 2015 and despite their ability to reduce low density lipoprotein cholesterol in clinical trials, the products have had trouble commercially.
Although the drugs provide an alternative to statins, which many patients can’t tolerate or don’t respond to, insurers and consumers are hesitant thanks to the $14,000 per patient annual price-tag. Combined, Amgen and Regeneron’s products made about $80 million globally in the last reported quarters.
Alirocumab, Regeneron’s drug, and Amgen’s evolocumab are antibodies that bind to PCSK9 and block its activity. Inclisiran, on the other hand, uses RNA interference to stop the liver from producing PCSK9. Inclisiran might help boost patient compliance since it potentially could be injected just 2 or 3 times a year, compared to alirocumab and evolocumab, which have to be given once or twice every month, according to Xconomy.
The Medicines Co. and Alnylam said that they plan to enroll 3,000 patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia in multiple Phase III trials. Half of the group will receive a 300 milligram dose of inclisiran 4 times a month over an 18 month period, while the other half will get a placebo. The primary goal of the trials is to lower LDL-cholesterol.
The 2 companies also said they plan to run a 14,000-patient outcomes trial, which will evaluate the drug’s ability to lower heart attacks and strokes. The study is not required for FDA approval, but insurance companies have been hesitant to cover the 2 approved PCSK9 inhibitors without evidence that the drugs improve cardiovascular outcomes.
Medicines Co. and Alnylam anticipate that they will submit a New Drug Application by 2019, as long as all goes well in their Phase III program.
“Based on data from our Phase II ORION-1 study and the previous Phase I study – both published in The New England Journal of Medicine – we are confident that inclisiran reduces LDL-C meaningfully,” Medicines Co. CEO Dr. Clive Meanwell said in prepared remarks. “We have also been highly encouraged by the safety data in these prior studies. Furthermore, inclisiran’s highly-differentiated dosing schedule has the potential to transform the burden placed on millions of patients who so badly need to lower LDL-C levels. We anticipate completing the LDL-C lowering program quickly and expect to submit an NDA for ASCVD and FH at or around the end of 2019. We believe our agreement with the FDA on the Phase III clinical development program for inclisiran is highly favorable and adds significantly to inclisiran’s strategic value.”
“Although not required for the NDA, we will also perform an aggressive cardiovascular outcomes trial in high-risk subjects with ASCVD and/or risk-equivalents, such as diabetes. We believe that positive outcomes data, with primary outcome clinical effects greater than those reported for anti-PCSK9 monoclonal antibodies, will drive a high level of competitiveness in the worldwide market – which we expect to become very large.”
“The Medicines Company’s agreement with the FDA supports a clear path forward for further inclisiran development and regulatory review. Indeed, we’re pleased with the excellent progress made by our colleagues at The Medicines Company to advance this potential, innovative medicine to patients in need, and we intend to fully support them in their efforts,” Alnylam CEO John Maraganore added. “Moreover, we believe the planned development path for inclisiran positions this promising potential medicine to contribute meaningfully to our Alnylam 2020 goals.”