FDA Action Alert: Incyte and Ascendis

Incyte had a particularly big week scheduled with the U.S. Food and Drug Administration (FDA), which included two PDUFA dates and an advisory committee meeting. In addition, Ascendis had a target action date. However, the agency had a chance of plans. Read on for more information.

Incyte’s Ruxolitinib Cream for Atopic Dermatitis

Incyte has a target action date of June 21, 2021, for its New Drug Application (NDA) for ruxolitinib cream, a selective JAK1/JAK2 inhibitor designed for topical application for atopic dermatitis (AD), a type of eczema. The NDA included data from the Phase III TRuE-AD clinical trial program of more than 1,200 people ages 12 and older. The company submitted a priority review voucher (PRV) with the NDA. The use of the PRV shortens the review period by four weeks. On June 11, the company reported the FDA had extended the review period for the NDA by three months to September 21, 2021. The agency indicated it needed time to review additional analyses the company submitted in response to an information request.

At the company’s first-quarter financial report on May 4, Herve Hoppenot, Incyte’s chief executive officer, said, “We expect an exciting year ahead for Incyte with the potential for multiple approvals, including ruxolitinib cream in atopic dermatitis, and several regulatory filings, notably parsaclisib in NHL and ruxolitinib cream in vitiligo. We are also initiating pivotal trials across key development programs for both tafasitamab and LIMBER this year.”

Incyte’s Ruxolitinib for Steroid-Refractory Chronic Graft-Versus-Host Disease

Incyte also has a target action date of June 22 for its supplemental NDA for ruxoliltinib (Jakafi) for treatment of steroid-refractory chronic graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older. This sNDA is built on data from the Phase III REACH3 trial comparing ruxolitinib with best available therapy (BAT) in this patient population. In that study, patients receiving ruxolitinib had a significantly greater overall response rate (ORR) compared to BAT at Week 24, which was the primary endpoint of the study. The ORR was 49.7% in the ruxolitinib group compared to 25.6% in the BAT cohort. On June 8, 2021, Incyte announced the FDA had also extended the review period for the sNDA for Jakafi for this indication until September 22, 2021. Again, it was in response to additional information submitted as part of an FDA information request.

“Chronic GVHD is a life-threatening complication following stem cell transplant that burdens a vulnerable patient population, which today has limited treatment options,” said Peter Langmuir, Group Vice President, Oncology Targeted Therapies, Incyte, in a February 2021 statement. “The acceptance of this sNDA represents an important milestone for Incyte as we continue our work towards helping more people living with GVHD, particularly for those who do not respond to steroids. We look forward to working closely with the FDA to bring this innovative therapy to patients and to providing continued support to the GVHD community in the United States.”

FDA’s AdCom to Review Incyte’s BLA for Retifanlimab Injection for Anal Cancer

In what is clearly a busy week for Incyte, the FDA’s Oncologic Drugs Advisory Committee is holding a meeting on June 24 to discuss the company’s Biologics License Application (BLA) for retifanlimab injection for the treatment of adults with locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) who have progressed on or who are intolerant of platinum-based chemotherapy.

The BLA was accepted for Priority Review on January 21, 2021, and has a target action date of July 25, 2021. The submission was based on data from the Phase II POD1UM-202 trial. It enrolled 94 patients, including several with well-controlled HIV infection. There was an ORR of 14% for retifanlimab monotherapy.

“Patients with SCAC who have progressed after first-line chemotherapy treatment currently have no approved treatments available, and we are encouraged that the FDA’s acceptance of this BLA for Priority Review brings us one step closer to addressing this historically neglected, yet important, tumor,” said Lance Leopold, Group Vice President, Immuno-Oncology Clinical Development, Incyte, in a January 21 statement. “Despite SCAC being a rare disease, its incidence is increasing, and its impact is profound. We look forward to working with the FDA to potentially fill an unmet need and advance progress in SCAC for patients.”

Ascendis’s TransCon hGH for Pediatric GHD

Ascendis Pharma has a target action date of June 25 for its BLA of TransCon hGH (lonapegsomatropin) for the treatment of pediatric Growth Hormone Deficiency (GHD). The drug is designed to release somatropin with the same action and distribution as once-a-day somatropin products, but with a once-a-week injection. The BLA is based on a clinical development program including eight clinical trials in more than 400 patients with GHD. In pediatric GHD, the pituitary gland does not generate enough growth hormone. The children are short, but may also experience metabolic abnormalities, psychosocial challenges and poor quality of life. The standard of care for GHD is a daily subcutaneous injection of hGH. On June 11, the FDA pushed back the PDUFA date until September 25, 2021. Ascendis indicated, like with the previous Incyte announcements, that after an FDA information request, the agency decided it was a major amendment and extended the target action date in order to provide more time to review the data.

During the company’s first-quarter financial report on May 27, Jan Mikkelson, Ascendis Pharma’s president and chief executive officer stated, “With potential U.S. FDA approval for TransCon hGH now less than a month away, we believe we are one step closer to fulfilling our Vision 3x3 to build a leading biopharma company. Guided by our values of patients, science and passion, we have built a pipeline of three differentiated endocrinology rare disease product candidates by applying our TransCon technology to clinically validated parent drugs and/or targets. Each candidate targeting substantial unmet medical needs in larger markets where we have the potential to become the market leader.”

At the new deadline, Mikkelsen stated, “We have responded to all outstanding questions from the FDA and believe the complete package we have submitted satisfies all of FDA’s requests and will enable a complete review of the application of lonapegsomatropin for pediatric GHD. We are committed to making lonapegsomatropin the market-leading therapy for treating pediatric GHD and look forward to continuing interactions with the FDA during the remainder of the review process.”