FDA Action Alert: Incyte, Iterum and Ardelyx

FDA_Sarah Silbiger/Getty Images

Sarah Silbiger/Getty Images

The U.S. Food and Drug Administration (FDA) had several PDUFA dates on their calendar for the last week of July, but in two cases, there were problems with the submissions ahead of time. Here’s a look.

Incyte’s Retifanlimab for Anal Cancer

Incyte has a target action date of July 25, 2021, for its Biologics License Application (BLA) for retifanlimab for adults with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) who have progressed on, or who are intolerant of, platinum-based chemotherapy. The BLA was accepted under Priority Review. The drug is an intravenous PD-1 checkpoint inhibitor. The submission was based on results from the Phase II POD1UM-202 trial, which enrolled 94 patients, including several with well-controlled HIV infections. There was an objective response rate (ORR) of 14% for retifanlimab monotherapy, regardless of PD-L1 status, presence of liver metastases, age or HIV status. The drug also was granted Orphan Drug Designation by the FDA for anal cancer.

On June 24, the FDA’s Oncologic Drugs Advisory Committee (ODAC) met to discuss the drug and voted 13-4 that a regulatory decision for the drug for this indication should be deferred until more data was available from the POD1UM-303 confirmatory trial. The FDA is not required to follow the advice.

The drug was developed in partnership with Zai Labs.

Iterum’s Sulopenem Etzadroxil/Proenecid for Urinary Tract Infections

Iterum Therapeutics has a target action date of July 25 for its New Drug Application (NDA) for sulopenem etzadroxil/probenecid (oral suylopenem) for treatment of uncomplicated urinary tract infections (uUTIs) in patients with a quinolone non-susceptible pathogen. It was accepted under Priority Review. The NDA was based on data from the SURE-1, -2, and -3 Phase III clinical trials, where the drug was well tolerated. The SURE-1 trial demonstrated statistical superiority over the widely used comparator, ciprofloxacin.

On July 1, Iterum announced they had received a letter from the FDA that stated that as part of the agency’s ongoing review of the NDA, it had identified deficiencies that prevent the continuation of the discussion of labeling and post-marketing requirements. No details were disclosed by the FDA at that time.

“While we are disappointed by this news, we continue to believe in the potential of sulopenem to help address the growing challenge of antibiotic resistance,” said Corey Fishman, chief executive officer of Iterum. “Our goal now is to work with the FDA to identify and resolve the issues as expeditiously as possible in order to continue advancing this much needed antibiotic.”

Ardelyx’s Tenapanor for Chronic Kidney Disease

Ardelyx has a target action date of July 29 for its NDA for tenapanor for control of serum phosphorus in adults with chronic kidney disease (CKD) on dialysis. The company originally had a target action date in April, but after discussions with the FDA and the submission of additional analyses, the FDA decided they needed more time to analyze the new data and pushed it back three months.

The NDA was built on a comprehensive development program with more than 1,000 patients, including three Phase III studies, all of which hit their primary and key secondary endpoints.

Tenapanor acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3). This causes a conformational change of the epithelial cell tight junctions, which decreases paracellular permeability of phosphate, decreasing phosphate absorption.

On July 13, the company received a communication from the FDA saying the agency had identified deficiencies that preclude discussion of the NDA at this time. Ardelyx has immediately requested a meeting to discuss the issue, but the meeting was denied.

“This is an extremely disheartening and disappointing communication from the FDA, particularly following the weeks of label discussions that occurred in early April, the fact that our NDA submission included three pivotal trials across 1,000 patients, all of which met their primary and key secondary endpoints, as well as the additional data analyses we submitted in late April in response to the FDA’s requests,” said Mike Raab, president and chief executive officer of Ardelyx. “We plan to work with the FDA to learn more about the identified deficiencies and will seek to resolve them as quickly as possible.”

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