The Grateful Dead seem to best encapsulate the labyrinthine FDA approval process for two different cardiovascular therapies—the Sapien transcatheter heart valve (Edwards Lifesciences) and the antiplatelet drug ticagrelor (Brilinta, from AstraZeneca)—that seek to treat severe aortic stenosis and acute coronary syndrome, respectively.
The FDA is held to the congressional expectation to prove the safety and effectiveness of new therapies, before they become available to U.S. patients. This, in addition to the heightened scrutiny that the agency endures from a variety of press and governmental sources, has led to a longer and more stringent approval process.
In the case of ticagrelor, AstraZeneca originally submitted its new drug application to the FDA in late 2009, when it was already widely used in Europe, based on the results of the PLATO trial. In July 2010—one year ago—the FDA’s Cardiovascular and Renal Drugs Advisory Committee recommended the FDA approve ticagrelor for the reduction of thrombotic events in patients with acute coronary syndromes (ACS).
Since then, the FDA has twice delayed making a decision, requesting additional data on the PLATO trial, which has enrolled nearly 19,000 patients. Yet, the agency put an end to the delays yesterday, when it decided to approve the new anticoagulant to the U.S. market for ACS patients.
Of course, there’s a caveat, as the FDA is requesting that the company add a boxed warning to the drug's label outlining that a maintenance dose of more than 100 mg aspirin may decrease the effectiveness of the drug and should be avoided. Additionally, the company must conduct educational outreach to physicians to alert them about the use of higher doses of aspirin (above 100 mg) with the drug.
For the Sapien heart valve, the jury is still out on how the FDA will decide, but the device is one step closer, as yesterday's Circulatory System Devices Panel voted a resounding yes for the device.
Despite the positive final verdict, the panel debated for more than nine hours about the merits of the PARTNER trial—which received multiple compliments—as well as the risk of stroke and the appropriate patient selection for this inoperable population. Also, there was much discussion about the design of the post-approval studies.
Many questions still remain: How will the technology actually rollout in real-life clinical practice? How many centers will be performing these procedures? Will the FDA take advice of some physicians and add a warning label about stroke? But stay tuned, as we traverse these long, strange trips. On these topics, or any others, please feel free to contact me.