Leaders in Pharmaceutical Business Intelligence (LPBI) Group

SILVER SPRING, MD — The Cardiovascular and Renal Drugs Advisory Committee of the US Food and Drug Administration (FDA) voted 9 to 2, with one member abstaining, that the injectable antiplatelet agent cangrelor (the Medicines Company, Parsippany, NJ) should be approved for reducing thrombotic events in PCI—a reversal from the committee’s vote last year.

Today’s “yes” votes included acting chair Dr Philip Sager (Stanford University School of Medicine, CA). He told heartwire from Medscape after the meeting there was “a lot of good discussion,” and he was impressed that the sponsor responded several times with additional data when asked.

“Everyone was committed to making this a good meeting. And I’d say in the end that the data, taken in totality, showed that cangrelor will have an important role in the armamentarium for a subset of patients undergoing PCI,” said Sager.

Some of the “good discussion” he mentioned sounded more like hearty debate as questions and concerns were brought up throughout the day regarding the trial at the center of the new drug application. CHAMPION-PHOENIX showed positive results in its cangrelor-vs-clopidogrel comparison. However, the previousCHAMPION-PLATFORM and CHAMPION-PCI trials were both negative.

Last year, the committee voted 7 to 2 against recommending cangrelor for PCI because of data problems and they felt that the risk/benefit profile was not sufficiently strong enough. The Medicines Company then underwent further sensitivity analyses and supplied a more simplified application.

Earlier this week, FDA reviewers gave a favorable review that the agent now be approved “in patients in whom treatment with an oral P2Y₁₂ platelet inhibitor prior to PCI is not feasible and when glycoprotein IIb/IIIa receptor antagonists are not anticipated to be used.” They also noted that PHOENIX was sufficient enough as a stand-alone trial to warrant approval of cangrelor^[1].

However, several panel members voiced concerns both last year and this year that PHOENIX was successful only after the failure of the other two trials. “Is this a pivotal trial or just a third attempt?” asked Dr Scott Emerson (University of Washington, Seattle). “If we don’t like the results, can we just fish through essentially the same population to get a better efficacy point?”

Emerson, along with Dr Julia Lewis (Vanderbilt University School of Medicine, Nashville, TN), cast the two “no” votes today. Lewis also voiced her displeasure with looking only at PHOENIX. “I have a lot of concerns that make me unwilling to accept a single trial for approval,” she said.

The one abstaining vote came from Dr Thomas Fleming (University of Washington, Seattle). “Specifically in this case, it felt more comfortable to abstain because there are issues on both sides of this,” he explained.

Even several of the “yes” voters did so after asking many, many questions throughout the day about the study and treatment procedures, population, and especially the statistical data. Still, the bottom line is that the majority of the committee voted its approval for the medication.

“I think it was important that these different sensitivity analyses were done and that more conservative approaches were statistically examined. It showed that there really is a clinically meaningful benefit of using cangrelor as compared with clopidogrel the way it was administered in the study,” said Sager.

Reference

FDA Briefing Document for the Cardiovascular and Renal Drugs Advisory Committee (CRDAC)

Meeting Date: 15 April 2015

NDA: 204958

Sponsor: The Medicines Company

Drug: KENGREAL (cangrelor) for Injection Proposed Indication KENGREAL is an intravenous P2Y12 platelet inhibitor indicated for for Use: reduction of thrombotic cardiovascular events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI – PCI refers to the opening of narrowed blood vessels supplying the heart muscle by a balloon inserted through an artery puncture with or without a stent) who have not received an oral P2Y12 inhibitor prior to the PCI procedure and in whom oral therapy with P2Y12 inhibitors is not feasible or desirable (P2Y12 is a protein involved in blood clotting. Inhibiting this protein is a key mechanism of action of cangrelor). Title of Study: PHOENIX – A randomized, double-blind, parallel group, superiority study comparing cangrelor to clopidogrel in subjects who require PCI.

The primary objective was to demonstrate that cangrelor reduces the risk of a composite of all-cause mortality, myocardial infarction, ischemia driven revascularization, and stent thrombosis compared to clopidogrel.

SOURCE

http://www.medscape.com/viewarticle/843236