July FDA Approvals to Watch

The FDA plans on deciding whether to approve abrocitinib (PF-04965842; Pfizer) for the treatment of atopic dermatitis (AD) on July 27.

Abrocitinib is a once-daily, oral Janus kinase 1 (JAK1) inhibitor for moderate to severe AD in patients 12 years and older. Inhibition of JAK1 is said to influence interleukin (IL)-4, IL-13, IL-22, IL-31 and interferon gamma–all of which are thought to be involved in the pathophysiology of AD.

The drug was granted a Breakthrough Therapy designation from the FDA in February 2018¹ and given Priority Review designation in October 2020.² Originally set for April 2021, the FDA extended the review of abrocitinib’s New Drug Application (NDA) by 3 months to July.³

Fillings for the drug are supported by positive results from studies in the abrocitinib JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global development program. The submitted studies include JADE MONO-1 and JADE MONO-2, which investigated abrocitinib as a monotherapy; and JADE COMPARE, which evaluated the drug compared to placebo in patients on background topical therapy while also comparing the drug to an active control arm consisting of dupilumab (Dupixent; Sanofi and Regeneron) vs placebo.

In JADE COMPARE⁴, abrocitinib met all co-primary endpoints and both doses (100 mg and 200 mg) of abrocitinib demonstrated superiority over placebo at week 16 and was sustained until week 16.

Meanwhile, results from JADE MONO-1⁵ also met all co-primary and secondary endpoints, including a proportion of patients who achieved an IGA score of 0 or 1 and at least a 2-point improvement, and a proportion of patients who achieved 75% or more change from baseline in their Eczema Area and Severity Index (EASI) score. Secondary endpoints included a proportion of patients achieving a 4-point or more reduction in itch severity measured with the pruritus numerical rating scale (NRS) and the magnitude of decrease in the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD).

Additionally, results from JADE MONO-2⁶ met all primary and secondary endpoints while demonstrating statistical superiority to placebo. Investigators reported both doses (100 mg and 200 mg) of abrocitinib subjects achieved EASI-75, EASI-90, PP-NRS and IGA responses in a greater proportion vs placebo.

References:

1. PFIZER ANNOUNCES POSITIVE TOP-LINE RESULTS FROM THIRD PHASE 3 TRIAL OF ABROCITINIB FOR MODERATE TO SEVERE ATOPIC DERMATITIS, WHICH SHOWED IMPROVEMENTS IN SKIN CLEARANCE, DISEASE EXTENT AND SEVERITY, AND ITCH. Pfizer. Published March 18, 2020. Accessed July 6, 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_positive_top_line_results_from_third_phase_3_trial_of_abrocitinib_for_moderate_to_severe_atopic_dermatitis_which_showed_improvements_in_skin_clearance_disease_extent_and_severity_and_itch
2. FDA grants priority review and ema accepts regulatory submission for pfizer’s abrocitinib, an oral once-daily jak1 inhibitor, for patients 12 and up with moderate to severe atopic dermatitis. Published October 27, 2020. Accessed July 6, 2021. https://www.businesswire.com/news/home/20201027005434/en/FDA-Grants-Priority-Review-and-EMA-Accepts-Regulatory-Submission-for-Pfizer%E2%80%99s-Abrocitinib-an-Oral-Once-Daily-JAK1-Inhibitor-for-Patients-12-and-Up-with-Moderate-to-Severe-Atopic-Dermatitis
3. Pfizer announces extension of review of new drug application of abrocitinib for the treatment of moderate to severe atopic dermatitis. pfizerus.com. Accessed July 6, 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-extension-review-new-drug-application
4. Pfizer reports positive results from third Phase III study of JAK1 inhibitor abrocitinib in atopic dermatitis. FirstWord Pharma. Published March 18, 2020. Accessed July 6, 2021. https://www.firstwordpharma.com/node/1709141?al=3a2380-a882871cf1564cc5f229595ac3bb61d7^|^MTEwOTcyOA==^|^NQ==&cp1=bmV3c2xldHRlcl9yZWdpb25faWQ9dG9wX25ld3M
5. Pfizer’s experimental drug abrocitinib hits all primary, secondary goals of Phase III study for atopic dermatitis. Accessed July 6, 2021. https://www.firstwordpharma.com/node/1641083
6. Complete Results from Second Pivotal Monotherapy Study of Abrocitinib Published in JAMA Dermatology. Published June 2, 2020. Accessed July 6, 2021. https://investors.pfizer.com/investor-news/press-release-details/2020/Complete-Results-from-Second-Pivotal-Monotherapy-Study-of-Abrocitinib-Published-in-JAMA-Dermatology/default.aspx