The Medicines Company was up about 6% in early trading on positive top-line, interim Phase II data for its PCSK9 inhibitor to treat hypercholesterolemia. The idea is to use the candidate to offer three-times, or even twice, yearly injections in addition to statin use, which would be an improvement on Amgen’s monthly PCSK9 Repatha (evolocumab) that was just approved by the FDA in July.
The company’s candidate is a first-in-class proprotein convertase subtilisin/kexin type 9 synthesis inhibitor (PCSK9si); it’s designed to work in the liver to inhibit PCSK9 synthesis rather than binding to PCSK9 in the blood like existing anti-PCSK9 monoclonal antibodies.
It’s being developed under a 2013 deal with Alnylam Pharmaceuticals ($ALNY), which has seen its valuation slashed roughly in half in recent weeks as it was forced to pull a Phase III candidate after patient deaths.
“Based on the results from our ORION-1 Day 90 interim analysis, PCSK9si has again demonstrated robust and durable knockdown of LDL-C, as well as impressive safety and tolerability,” said Medicines Co. VP and Global Medical Director David Kallend in a statement. “These results validate a triannual, and potentially biannual, low volume subcutaneous dose regimen, which we believe represents a compelling, highly-differentiated approach for treating patients with hypercholesterolemia.”
The company will present detailed data at the American Heart Association's (AHA) annual scientific conferences in mid-November. For now, it only said the Phase II results have “significantly exceeded” study objectives and confirmed Phase I data. The data demonstrate significant and durable LDL-C reduction strong enough to make a triannual or biannual dose possible.
The AHA data will include interim 90-day follow-up data for 501 patients as well as top-line 180-day follow-up data for up to 200 patients. The Medicines Co. plans to disclose the 180-day follow-up, top-line data for all 501 patients before year end.
The trial is a placebo-controlled, double-blind, randomized and dose-finding in patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents such as diabetes or familial hypercholesteremia and elevated LDL-C despite maximum tolerated doses of LDL-C lowering therapies.
“The potential for management of hypercholesterolemia with two or three low volume injections per year could open a new, transformative and affordable pathway for patients and physicians in the treatment of atherosclerotic cardiovascular disease,” summed up Dr. John Kastelein, Professor of Medicine and Chairman of the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam.
Ultimately, Medicines Co. expects it could develop its PCSK9si into a heart attack prevention and maintenance tool. That would be a next step beyond the current indication of reduction of LDL-C in hypocholesteremia patients.
“We know with high, high dose stanching over three years or four years, you can see some modest … plaque regression, tumor regression,” noted Medicines Co. CEO Clive Meanwell on the company’s most recent earnings call. “But it takes forever and you have to take your products very carefully and regularly. So, our theory here is could you rapidly shrink the tumor, the plaque in a matter of a few weeks with this drug. And then, of course, you would hope that if the patient was at appropriate risk that you have to put them on lifetime LDL lowering therapy and lifestyle improvement.”