On Thursday, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10-0 with one abstention against approving Xarelto (rivaroxaban) to help prevent heart attacks and strokes 90 days after patients experience serious chest pain or cardiac illness (a condition known as acute coronary syndrome).
On Thursday, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10-0 with one abstention against approving Xarelto (rivaroxaban) to help prevent heart attacks and strokes 90 days after patients experience serious chest pain or cardiac illness (a condition known as acute coronary syndrome). This is the company’s third attempt to gain FDA clearance for such patients.
FDA panelists appeared skeptical that data submitted by Johnson & Johnson (Janssen Pharmaceuticals) proves its anticoagulant, Xarelto, is effective at reducing the risk of further heart problems in patients who have recently suffered a heart attack. Additionally, FDA reviewers highlighted the risk of bleeding that increases the longer patients take Xarelto. Thus as a compromise, the 90-day treatment period was set. The agency said the data on the effectiveness of the drug were not strong enough to make up for this increased risk of bleeding for longer duration use. Panelist Sanjay Kaul urged the FDA not to set a precedent that allows drugmakers to cherry-pick treatment times.
The FDA initially approved Xarelto in July 2011 to prevent blood clots in patients undergoing knee and hip surgeries. The drug’s use has since been extended to reduce the risk of stroke and blood clots in patients with irregular heartbeats not caused by heart problems and deadly leg and pulmonary embolism (blood clot of the lung).
Previously, in 2012 and last March, the FDA rejected Xarelto as a treatment to prevent heart attack and stroke in patients with acute coronary syndrome (ACS). J&J disputed the FDA’s decision after the latest rebuff and while the agency denied the appeal, the FDA offered a path forward that included limiting how long patients use the drug.
The FDA’s latest review suggests the agency remains skeptical regarding expanding the user population.
“It’s not just that the data are fragile, it’s that the therapy has both benefits and harms and in that context the quality of the data becomes increasingly important,” Steven Nissen, a panelist and chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic Foundation, said during the meeting.
“It is unclear how to choose the metric for determining when the benefit of rivaroxaban is greatest,” reviewers found. “Not only does the effect of rivaroxaban not appear to be greater earlier, but an effect in the first 90 days or so is not apparent at all.”
The reviewers also questioned whether the benefit of the drug outweighs the heightened risk of bleeding as two other drugs, Eli Lilly & Co’s Effient and AstraZeneca Plc’s Brilinta, are currently approved for ACS.
J&J’s proposed prescribing information would warn that treatment in combination with the Effient, known also as prasugrel, and Brilinta, also known as ticagrelor, has not been studied and is not recommended because of the risk of bleeding.
Xarelto would therefore only be available as an add-on to Bristol-Myers Squibb Co’s antiplatelet Plavix, or clopidogrel. Reviewers noted that there are no data demonstrating that ACS patients treated with clopidogrel plus rivaroxaban will have superior outcomes compared to treatment with prasugrel or ticagrelor. Thus, rivaroxaban does not provide therapy for an unmet medical need.
Additionally, reviewers mentioned that while treatment for a limited duration has an intuitive appeal, the task for the analyses of the effect of rivaroxaban over time is not to pick a time period in which the benefit-risk is acceptable.
Xarelto and its competitors are trying to replace the 50-year-old blood-thinner warfarin, which is commonly used against the condition. Xarelto was approved in Europe in May to prevent heart attacks and strokes in acute coronary syndrome patients.
Acute coronary syndrome is an umbrella term for any condition brought on by a sudden, reduced blood flow to the heart, including heart attack and chest pain. ACS leads to 1.2 million hospitalizations each year.
The FDA is not bound by the CRDAC’s decision but normally follows its recommendation.
ISS has over a decade of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact firstname.lastname@example.org.
Do you want a more detailed analysis of this drug’s FDA AdComm meeting? Great news – ISS can help you! Click on the link below in order to receive a detailed post-meeting outcome report!
Over the past few years, the number of ex-US manufacturers submitting a Class II exempt 510k device registration has increased substantially. For companies with medical devices that are approved and successful in a foreign market, the logical next step is to introduce their product into the US, which has one of the most lucrative healthcare markets in the world. Read more
FDA advisory committee meetings are important regulatory events for many manufacturers on the path to marketing approval. These meetings can quite literally result in the approval or rejection of a product based on the panel’s vote. Read more
One of the main challenges our clients face is determining which regulatory pathway is best for their products. For example, what if an OTC product has a Monograph active ingredient but that ingredient is present at a different amount than the permitted amount? Or what if the label claims a novel indication not specified in a Monograph? If you are debating pursuit of either regulatory pathway for your OTC drug, it is critical to consider cost, timeline, and label claims to ensure your products has a unique stance in today’s market. Read more
US distributors and agents trying to import rapid antibody tests for coronavirus face a number of obstacles. The good news is that FDA has opened up the Emergency Use Authorization (EUA) program to include SARS-CoV-2 (the virus) and COVID-19 (the disease), expediting time to market. Read more
The journey to scientific and commercial success is often complex and always critical, if you are looking for an expert partner to help steer you to confident solutions, contact us todayContact us