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Takeda Announces Outcome of FDA Advisory Committee Meeting to Review Uloric® (febuxostat) Cardiovascular Outcomes Trial Results

January 11, 2019

Deerfield, IL, January 11, 2019Takeda Pharmaceuticals, U.S.A., Inc. (“Takeda”), today announced the outcome of a joint meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss the “Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES)” trial results and the benefit-risk assessment of febuxostat. Members of the committees voted 19 to 2, with 1 abstention, that based on available data, there are patient populations in which the benefit-risk profile for Uloric® (febuxostat) is favorable for the treatment of hyperuricemia in patients with gout. The committees held a widely varied discussion about the appropriate patient populations and potential regulatory actions. CARES was conducted by Takeda as a post-marketing requirement by the U.S. Food and Drug Administration (FDA) following its approval in 2009 to evaluate the cardiovascular (CV) safety of Uloric compared to allopurinol in subjects with gout.

“Many believe that gout is a condition that comes and goes for patients, but it is a chronic disease that can be severe and potentially debilitating, and many patients require pharmacologic treatment options to manage their disease,” said Lawrence Edwards, MD, rheumatologist, University of Florida Health. “Today’s vote from the Advisory Committees reflects the continued importance of having treatment options available for patients with gout.”

In the CARES trial, Uloric met the primary endpoint, demonstrating that the rate of major adverse CV events (MACE: CV death, non-fatal myocardial infarction (MI), non-fatal stroke, and unstable angina with urgent coronary revascularization) in patients treated with Uloric was non-inferior to that of allopurinol. When analyzing the individual components of MACE as secondary endpoints, the individual rates for MI, stroke, and unstable angina with urgent coronary revascularization were similar with Uloric compared to allopurinol. However, the rate of CV death was higher among patients assigned to Uloric compared to allopurinol, which also contributed to a higher rate of death from all causes. Based on analyses conducted to date, a reason for this finding has not been identified. There were no significant differences in rates of other serious CV events such as hospitalization for heart failure or arrhythmias.

“Patient safety has always been our first priority at Takeda, and we appreciate that common purpose and the thoughtful discussion today with the Advisory Committee members about CARES,” said Tom Harris, Senior Vice President, Head of Global Regulatory Affairs, Takeda Pharmaceuticals. “We have studied the safety of Uloric for more than 15 years, and remain confident in Uloric as an important option for the chronic management of hyperuricemia in gout. We look forward to additional discussions with the FDA regarding these CARES data.”

In 2009, Uloric was approved by the FDA as a once-daily, oral prescription medication for the treatment of hyperuricemia in adults with gout. The approval made Uloric the first new treatment for this indication in more than 40 years. Since approval, the Prescribing Information for Uloric has included a warning and precaution that a higher rate of adverse CV events was observed in patients treated with Uloric when compared with allopurinol in clinical trials.

CARES was initiated in 2010 and completed in 2017. In October 2017, Takeda submitted the preliminary CARES results to the FDA and followed with the full study results in January 2018.

The outcome of the Advisory Committee meeting is non-binding and will be taken into consideration by the FDA.


Use of ULORIC (febuxostat)

ULORIC is a prescription medicine used to lower blood uric acid levels in adults with gout. ULORIC is not for the treatment of high uric acid without a history of gout.


Important Safety Information

Do not take ULORIC if you are taking azathioprine or mercaptopurine.


ULORIC may cause serious side effects, including:

Gout Flares. Gout flares can happen when you first start taking ULORIC. Your healthcare provider may give you other medicines to help prevent your gout flares.

Heart Problems. People who take ULORIC can have serious heart problems including heart attacks, strokes and heart-related deaths. It is not known that ULORIC caused these problems. Call your healthcare provider right away or get emergency medical help if you have any of the following symptoms: chest pain, shortness of breath, dizziness, numbness or weakness on one side of your body, trouble talking or headache.

Liver Problems. Liver problems can happen in people who take ULORIC. Your healthcare provider may do blood tests to check how well your liver is working before and during your treatment with ULORIC.

Severe Skin and Allergic Reactions. Serious skin and allergic reactions that may affect different parts of the body such as your liver, kidneys, heart or lungs, can happen in people who take ULORIC. Call your healthcare provider right away or get emergency medical help if you have any of the following symptoms: rash, red and painful skin, severe skin blisters, peeling skin, sores around the lips, eyes or mouth, swollen face, lips, mouth, tongue or throat, or flu-like symptoms.

The most common side effects of ULORIC include liver problems, nausea, gout flares, joint pain, and rash. Tell your healthcare provider if you have any side effect that bothers you, or that does not go away.


Please see the accompanying complete Prescribing Information and talk to your healthcare professional.


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.


About Gouty Arthritis

Gout is caused by a buildup of uric acid in the body. Uric acid forms crystals in the joints, which can lead to the inflammation and pain of a gout attack. As the uric acid level rises, so does the chance for gout and gout attacks. Over time, these attacks, or flares, can involve more joints, last longer, and happen more often.

An estimated 8.3 million Americans have gout, which may be increasing. Half of gout patients have three or more attacks per year; a typical gout attack can last at least 4 days.

Takeda Pharmaceuticals, U.S.A., Inc.

Takeda has maintained a strong and growing commitment to the United States for more than 50 years. On January 8, 2019, Takeda completed its acquisition of Shire, PLC, becoming a global, values-based, R&D-driven biopharmaceutical leader. In the U.S., Takeda employs more than 18,000 employees across multiple business units, and as of August 2019, will be headquartered out of the greater Boston area.

Additionally, Takeda also has a research facility in San Diego, California, specialty products manufacturing facilities in Brooklyn Park, Minnesota and plasma fractionation manufacturing facilities in Covington, Georgia.

As one of the world’s leading biopharmaceutical companies, Takeda is committed to bringing Better Health and a Brighter future to people worldwide. We aspire to bring our leadership in translating science into life-changing medicines to the next level, in our core focus areas; oncology, gastroenterology, neuroscience, rare diseases, plasma-derived therapies, and vaccines.

For more information, visit https://www.takeda.com



Kara Hoeger                                        
Takeda Pharmaceuticals U.S.A., Inc.                            

TEL: 224-554-1277                                         

[email protected]