Recently the makers of two novel cholesterol-lowering drugs in development provided important updates on their progress.
On Tuesday, the Medicines Company announced positive top-line results for a trial of its unusual PCSK9 synthesis inhibitor scheduled to be presented in November. Last week, Esperion announced details of its phase III program with bempedoic acid, its unique cholesterol-lowering drug.
ORION-1
In August 2015, The Medicines Company attracted positive coverage from myself and others when it announced initial phase I results for a drug, initially created by Alnylam Pharmaceuticals, which uses RNA interference technology to inhibit the synthesis of PCSK9 in the liver. The main theoretical advantage of PCSK9si, as it is now being called, is that it would yield reductions in LDL cholesterol similar to that achieved with PCSK9 inhibitors but with only two to four injections a year.
Preliminary results from ORION-1, a phase II trial of the drug, will be presented on November 15 at the American Heart Association meeting in New Orleans. ORION-1 is a dose-finding study in 501 patients with cardiovascular disease or at high risk for cardiovascular disease. The primary endpoint is the LDL-lowering effect at 180 days. The company said it will present 90-day results from all 501 patients in the trial and top-line 180-day results from 200 patients at the AHA meeting. The company said that it expects to disclose top-line results from the full trial by the end of 2016.
In its press release on Tuesday, the Medicines Company said that the interim analysis of the results "confirm results up to day 90 from PCSK9si Phase 1 study and significantly exceed ORION-1 study objectives." The company said the results demonstrate "significant and durable LDL-cholesterol reduction" and support a triannual and perhaps even a biannual dosing regimen.
"The thoughtful and robust design of the ORION-1 study has delivered highly impressive interim data," said John Kastelein, MD, PhD, of the University of Amsterdam, in the press release. "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."
The company has previously reported that PCSK9si reduced LDL cholesterol from 50% to 80%.
Bempedoic Acid
Last week, Esperion announced new details about its phase III program for bempedoic acid, its unique oral, once-daily cholesterol-lowering compound. The company said the phase III program would include patients with hypercholesterolemia on any statin at any dose, including those with LDL levels not adequately controlled on current statin therapy and "statin intolerant" patients unable to take even low doses of statins.
Esperion also announced that it had expanded the size of its CLEAR Harmony trial, a 52-week long-term safety study, from 900 patients to 1,950 patients, "to further support the Company's expected first half 2019 regulatory submission for an LDL-cholesterol lowering indication." The company hopes to announce top line results from the trial by mid-2018.
But the ultimate success of bempedoic acid will likely depend on how it does in the cardiovascular outcomes trial announced earlier this year. Clear Outcomes is expected to randomize 12,600 statin intolerant patients with a history of or at high risk for cardiovascular disease. Steve Nissen, MD, of the Cleveland Clinic, is the study chairman. Results are expected in 2022.