RARE Daily

FDA Rejects Mallinckrodt’s Treatment for Advanced Liver Disease that Causes Kidney Failure

September 14, 2020

Rare Daily Staff

The U.S. Food and Drug Administration notified Mallinckrodt that it would not approval the company’s therapy for adults with hepatorenal syndrome type 1, a life-threatening condition for people with advanced liver disease that causes kidney failure.

Hepatorenal syndrome type 1(HRS-1) is an acute and life-threatening syndrome involving acute kidney failure in people with cirrhosis for which there is currently no FDA-approved treatment. HRS-1 is estimated to affect between 30,000 and 40,000 Americans annually, and often is a challenge to effectively diagnose in a timely manner due to its diagnosis of exclusion. If left untreated, HRS-1 has a median survival time of approximately two weeks and greater than 80 percent mortality within three months.

Terlipressin is a potent vasopressin analogue selective for V1 receptors being investigated for the treatment of HRS-1 in the U.S. and Canada. It is an investigational product in these countries as the safety and efficacy have not been established with, nor has approval been granted by, regulatory authorities in either country. Terlipressin is approved for use outside the United States and Canada.

A complete response letter from the FDA said based on the available data, the agency cannot approve the terlipressin in its current form and requires more information to support a positive risk-benefit profile for terlipressin for patients with HRS-1.

“HRS-1 is a complex disease that affects a critically ill patient population with no approved treatment in the U.S. at present,” said Steven Romano, executive vice president and chief scientific officer at Mallinckrodt. “We are surprised by and disagree with the FDA’s decision and remain committed to pursuing all available options as we continue working with the FDA toward approval of terlipressin in order to help address this difficult and life-threatening syndrome.”

In 2005, the FDA granted Fast Track designation to terlipressin. The designation provides for expedited review to facilitate development of drugs intended to treat serious or life-threatening conditions and fill an unmet medical need. In 2016, Mallinckrodt and the FDA reached agreement on the phase 3 CONFIRM trial protocol design and data analysis under the agency’s special protocol assessment process. A SPA is an advance agreement with the FDA for the acceptability of the clinical design, endpoints and statistical data analyses for a phase 3 trial before the start of the trial.

On July 15, 2020, the Cardiovascular and Renal Drugs Advisory Committee of the FDA voted to recommend approval of its terlipressin to treat adults with HRS-1 based, in part, on results from the phase 3 CONFIRM trial.

Photo: Steven Romano, executive vice president and chief scientific officer at Mallinckrodt

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