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Takeda Announces Additional Analyses of Results from Uloric® (febuxostat) Cardiovascular Outcomes Trial in Patients with Gout and Cardiovascular Disease

October 21, 2018
Two abstracts analyzing general safety and kidney disease population data from the Phase 3b trial results being presented at the 2018 American College of Rheumatology Meeting

Deerfield, IL, October 21, 2018Takeda Pharmaceuticals, U.S.A., Inc. (“Takeda”), todayannounced the presentation of two abstracts at the 2018 American College of Rheumatology (ACR) Meeting, being held October 19-24 in Chicago. The presentations provide further analyses of data from a Phase 3b cardiovascular (CV) outcomes trial of Uloric® (febuxostat), which was previously published in the New England Journal of Medicine (NEJM) and presented at the American College of Cardiology’s (ACC) 67th Annual Scientific Session & Expo earlier this year. The trial, titled “Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Comorbidities (CARES),” was conducted by Takeda to evaluate the CV safety of Uloric compared to allopurinol in subjects with gout and CV disease.

In that trial, Uloric met the primary endpoint of CARES, demonstrating that the rate of major adverse cardiovascular events (MACE: CV death, non-fatal myocardial infarction (MI), non-fatal stroke, and urgent revascularization due to unstable angina) 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 urgent revascularization for unstable angina 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.

The CARES data to be presented at ACR include new analyses meant to provide additional insight into the secondary endpoint of CV death rates observed in the trial. The first analysis reviews the general safety of febuxostat and allopurinol in patients with gout and CV disease. Overall, febuxostat and allopurinol treatments had comparable safety and tolerability for patients with gout and CV disease. There was also no distinct relationship between CV mortality and reduction of sUA levels or gout flares. The second presentation at ACR includes results from an analysis in patients with chronic kidney disease (CKD) that showed rates of CV mortality were comparable for CKD patients who received febuxostat or allopurinol treatments. In this analysis, the patients with moderately impaired kidney function (53% of the CARES cohort), who required up-titration of febuxostat or allopurinol to reach the target serum urate levels, had greater gout and CV disease burden at baseline.

“These analyses from the CARES trial do not explain the differences, in terms of mortality rates between febuxostat and allopurinol. However, the data provide important context for physicians who treat patients with gout, including those with moderate kidney disease and greater CV disease burden,” said William B. White, M.D., Professor, Calhoun Cardiology Center, University of Connecticut School of Medicine, and lead investigator of the CARES study.

In 2009, Uloric was approved by the U.S. Food and Drug Administration (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 as a post-marketing requirement by the FDA to determine if the use of Uloric had similar CV risk compared to allopurinol and was 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. In early 2019, Takeda will have an additional opportunity to review the CARES results in an open scientific forum at an FDA Advisory Committee Meeting.

“These complex data have been extensively discussed with the medical community and analyzed by Takeda to fully understand and disclose the results appropriately, with patient safety as our first priority,” said Beth-Anne Knapp, Vice President, Global Regulatory Affairs Development, Takeda Pharmaceuticals. “We look forward to the continued discussion to ensure that physicians have comprehensive and accurate information to make educated treatment decisions.”

Full details of the presentations follow:

Abstract 873: General Safety of Febuxostat and Allopurinol in a Cardiovascular Outcomes Study in Patients with Gout

Session: Metabolic & Crystal Arthropathies: Comorbidities & Outcomes

Date: Sunday, October 21, 2018

Time: 2:30 – 4:00 pm


Abstract 2242: Cardiovascular Outcomes of Treatment with Febuxostat and Allopurinol in Gout Patients with Kidney Disease

Session: Metabolic and Crystal Arthropathies – Basic and Clinical Science Poster

Date: Tuesday, October 23, 2018

Time: 9:00 – 11:00 a.m.


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.


About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda’s presence in emerging markets, are currently fueling the growth of Takeda. Around 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda’s partners in health care in more than 70 countries. For more information, visit https://www.takeda.com/newsroom/.

Takeda Pharmaceuticals U.S.A., Inc. is located in Deerfield, Ill., and is the U.S. marketing and sales organization of Takeda Pharmaceutical Company Limited.

Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Pharmaceuticals U.S.A., Inc. is available through its website, www.takeda.us.



Kara Hoeger                                        
Takeda Pharmaceuticals U.S.A., Inc.
TEL: 224-554-1277
[email protected]