Positive results from its Angiomax coronary angioplasty and stenting trial flashing across the big screen, The Medicines Co. sent American Heart Association conference attendees scrambling for their cameras.
"It was really exciting, it was sort of like being at the first pitch of the World Series," President and CEO Dave Stack told BioWorld Today. "Every time we put a slide up, there were several hundred flashes in the room. It was very interesting."
Given the reaction to such results, it should come as no surprise that the Parsippany, N.J.-based company plans to submit to the FDA a supplement to update product labeling for Angiomax (bivalirudin) - an outcome that therapeutically and financially could benefit coronary angioplasty patients currently relying on heparin.
The Medicines Co. expects the added labeling to include data from the post-marketing REPLACE-2 trial, which met all of its primary and secondary objectives. Results from the 6,002-patient, double-blind study, presented at this week's meeting in Chicago, could signal a transition from heparin to Angiomax as an anticoagulant in the procedures.
Specifically, Angiomax was found to be superior to heparin on its own, yielded clinical outcomes similar to current standards of care when combined with a provisional IIb/IIIa blockade and its use reduced bleeding and a need for transfusion. At the same time, Angiomax might lower costs associated with today's standard therapy.
"If you use data from the first quarter of this year, 38 percent of U.S. patients still receive heparin alone," Stack said. "So we were able to report on how this drug could be compared to both the 38 percent of patients who get heparin alone and the 62 percent who get heparain plus the IIb/IIIa inhibitor. The design was such that we were able to report that Angiomax was the same as heparain plus the IIb/IIIa, better than heparin alone, safer, less expensive and less complicated than either one of them. That's a pretty powerful message."
Angiomax, a small-molecule, reversible, direct thrombin inhibitor, was approved in the U.S. two years ago for use as an anticoagulant in patients with unstable angina undergoing percutaneous translumenal coronary angioplasty, along with aspirin. Its potential in a broader indication sent the company's shares (NASDAQ:MDCO) into a marked climb - The Medicines Co.'s stock closed Monday up 26 percent, or $3.29, to finish at $15.99.
Stack cited 2000 data showing there were 1.1 million coronary angioplasties, a number growing between 5 percent and 7 percent. He added that the company estimates 175,000 peripheral angioplasties annually. "We think should have all of those, or at least we should be considered for all of those."
The study, which enrolled three-quarters of its patients in the U.S., was designed to evaluate whether patients receiving Angiomax plus provisional glycoprotein IIb/IIIa inhibitors would have outcomes that were better than a heparin historical control arm (based on heparin event rates from prior angioplasty trials).
Data showed the study met its primary quadruple composite outcomes endpoint of death, myocardial infarction, urgent revascularization and major bleeding at 30 days. Angiomax was superior to heparin alone and equal to heparin plus a GP IIb/IIIa inhibitor.
The study also was designed to evaluate whether patients in the randomized trial receiving Angiomax plus provisional GP IIb/IIIa inhibitors would have outcomes that were the same as patients in the trial receiving heparin plus GP IIb/IIIa inhibitors.
Findings indicated the study reached its secondary triple composite outcomes endpoint of death, myocardial infarction and urgent revascularization at 30 days. Again, Angiomax was superior to heparin alone and the same as heparin plus GP IIb/IIIa inhibitors. The Angiomax group demonstrated a significant decrease in bleeding complications, as compared to heparin plus GP IIb/IIIa inhibitors. The Angiomax group demonstrated a significant decrease in thrombocytopenia. The provisional use rate of GP IIb/IIIa inhibitors in the Angiomax treatment group was 7.2 percent.
Such comparisons demonstrate some significant benefits to patients, Stack said.
"If you're using a IIb/IIIa inhibitor, the average time of infusion is between 12 and 18 hours," he said. "The average time on drug in the Angiomax arm of this trial was 24 minutes. From a patient's perspective with the discomfort associated with having a sheath inserted, there are major comfort and patient care issues being addressed here."
Results from the study, which is continuing beyond its primary results to examine patient outcomes at six months and a year, will be used as the basis for regulatory updates and submissions in international markets, including Europe.
"If you look at the Kaplan-Meier curves, they're already flat," Stack said. "I think the vast majority of these events, other than death, happen in the first 48 hours. But the nonsignificant benefit in the composite endpoint of death was in favor of Angiomax. So over the next six months and year, we expect that if this follows normal Kaplan-Meier curves, the benefits would be maintained."
Beyond therapeutic well being, the study points to a cost benefit associated with Angiomax. The Medicines Co. said that given dosing and administration data for the study, it estimates the Angiomax regimen to save an average of $448 vs. the heparin plus GP IIb/IIIa regimen, though a more thorough cost analysis is under way.
The drug is being studied in a number of other indications as well. Stack said the FDA has approved Angiomax trials in coronary artery bypass graft procedures - a 50-patient, single-arm study in off-pump CABG, and a separate 50-patient trial for on-pump CABG. The Medicines Co. is studying Angiomax in a neonate trial, a study Stack said would grow into a pediatric trial next year, as well as several other areas.
Elsewhere in the company's pipeline, Stack said The Medicines Co. is in the process of out-licensing CVT-05, a candidate being investigated for a range of urogenital and reproductive health applications that is in Phase II trials designed to determine its safety and efficacy in bacterial vaginosis.
But The Medicine Co. licensed from London-based AstraZeneca plc a candidate called clevidipine, a calcium channel blocker with a 36-second half-life.
"We intend to study it for blood pressure control during cardiac surgery," Stack said. "It maps very closely to where we're going to be with CABG, and it's another critical care product for the sales force to carry in the hospital."
He said the company is completing a Phase III protocol and entering patients into a proof-of-principle trial.
"I think we're building a real company here," Stack said. "It's pretty exciting."