FDA Rejects Incyte’s PD-1 For Anal Cancer

 

The U.S. Food and Drug Administration (FDA) issued Incyte Corporation with a Complete Response Letter (CRL) over its Biologics License Application (BLA) for retifanlimab 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 drug is the company’s intravenous PD-1 checkpoint inhibitor. The BLA was specifically for adults with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) whose disease has progressed after receiving platinum-based chemotherapy or in patients who, for whatever reason, were intolerant of platinum-based chemotherapy.

Hervé Hoppenot, Incyte’s chief executive officer, noted that patients with SCAC for this indication don’t have approved treatment options, adding, “While we are not surprised with the FDA decision given the ODAC recommendation, we are disappointed. We remain committed to advancing science to find solutions for patients with unmet medical needs, and we will ensure close coordination with the FDA in order to address feedback and determine next steps for the review of retifanlimab.”

The BLA was accepted under Priority Review. The drug also was granted Orphan Drug Designation by the FDA for anal cancer.

The CRL indicated, according to Incyte, that the agency needs “additional data” for proof of clinical benefit.

The submission was based on the Phase II POD1UM-202 trial results, which enrolled 94 patients, including several with well-controlled HIV infection. 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.

Incyte picked up global rights to retifanlimab from MacroGenics in 2017 for $150 million upfront. The National Comprehensive Cancer Network has added Merck’s checkpoint inhibitor Keytruda (pembrolizumab) and Bristol Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) to its guidelines for second-line treatment of metastatic anal cancer in 2018. However, there is not that much data in support of it. They conducted small studies in anal cancer, with 24 patients for Keytruda and 37 patients for Opdivo. Merck then evaluated Keytruda in 112 anal cancer patients.

On July 16, Incyte and Eli Lilly announced that the FDA would not meet the target action date for their supplemental New Drug Application (sNDA) for Olumiant (baricitinib) for adults with moderate to severe atopic dermatitis (AD). They said the delay was associated with the agency’s ongoing assessment of JAK inhibitors.

Barcitinib is an oral JAK inhibitor discovered by Incyte and licensed to Eli Lilly and is approved for adults with moderately to severely active rheumatoid arthritis (RA) in more than 75 countries. It is also approved in more than 40 countries for adults with moderate to severe AD who are candidates for systemic therapy. It is also approved in Japan for certain hospitalized COVID-19 patients. The drug is also being tested in alopecia areata (AA), systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA).

“We are confident in the efficacy and safety of baricitinib data supporting a favorable benefit-risk profile for the treatment of atopic dermatitis and look forward to continuing to work with the FDA during the remainder of the review process,” said Ilya Yuffa, senior vice president and president of Lilly Bio-Medicines.