ADC Reviews

FDA and EMA accept review of JAK3/TEC inhibitor ritlecitinib

alopecia areata

On September 19, 2022, Pfizer announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for the oral JAK3/TEC inhibitor ritlecitinib for adolescent and adult patients 12 years of age and older. Alopecia areata. In addition, the European Medicines Agency (EMA) has also accepted a Marketing Authorization Application (MAA) for ritlecitinib in the same patient population. The FDA and EMA are expected to make a review decision in the second and fourth quarters of 2023, respectively.

Rilecitinib, an investigational once-daily oral drug, is the first in a new class of oral highly selective covalent kinase inhibitors, dual inhibition of the TEC family of tyrosine kinases and Janus kinase 3 (JAK3) agent. In laboratory studies, ritlecitinib has been shown to block the activity of signaling molecules and immune cells thought to be responsible for hair loss in people with alopecia areata.

Alopecia areata is an autoimmune disease with an intrinsic immune-inflammatory pathogenesis. The disease occurs when the immune system attacks the body’s hair follicles, causing the hair to fall out. This hair loss usually occurs on the scalp, but can also affect eyebrows, eyelashes, facial hair, and other parts of the body. It is estimated that alopecia areata affects approximately 6.8 million people in the United States and approximately 147 million people worldwide.

In September 2018, the U.S. FDA granted Breakthrough Therapy Designation (BTD) to ritlecitinib for the treatment of alopecia areata. In addition to alopecia areata, ritlecitinib is currently being evaluated for vitiligo, rheumatoid arthritis, Crohn’s disease and ulcerative colitis.

“Alopecia areata is an autoimmune disease that affects people of all ages, genders and ethnicities, often affecting everyday life beyond hair loss itself,” said Michael Corbo, Ph.D., Chief Development Officer, Inflammation and Immunity, Pfizer Global Product Development. “We believe that, If ritlecitinib is approved, it will be an important new treatment option. We will continue to work closely with regulatory agencies to bring ritlecitinib to adults and adolescents with alopecia areata in the US and EU.”

Regulatory filing for ritlecitinib in alopecia areata based on top-line results from the pivotal and dose-ranging Phase 2b/3 ALLEGRO study (NCT03732807) and the ongoing Phase 3 ALLEGRO-LT (NCT04006457) open-label long-term study. Among them, the results of the ALLEGRO study have been presented at the 2021 European Academy of Dermatology and Venereology (EADV) Congress and the 2022 American Academy of Dermatology (AAD) Annual Meeting. Preliminary data from the ALLEGRO-LT study will be presented at the 2022 EADV Congress.

ALLEGRO was a randomized, placebo-controlled, double-blind study in patients with alopecia areata 12 years and older (n=718). The study enrolled patients with ≥50% scalp alopecia, including those with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss) who were experiencing alopecia areata , Duration 6 months to 10 years. In the study, patients were randomly assigned to receive ritlecitinib 50 mg or 30 mg (with or without a one-month initial treatment, ritlecitinib 200 mg orally once daily), ritlecitinib 10 mg, and placebo for 24 weeks. This was followed by a 24-week expansion period, during which all patients initially randomized to receive ritlecitinib continued on the same regimen, while those who received placebo for the initial 24 weeks received one of 2 regimens: 200mg for 4 50 mg for 20 weeks, or 50 mg for 24 weeks.

The primary endpoint of the study was the proportion of patients with scalp hair regrowth in response to ritlecitinib treatment, as determined by an absolute SALT score of ≤20 at week 24 of treatment. SALT is a tool used to measure the amount of hair loss on the scalp. The scalp is divided into multiple standard areas and each area has a total SALT score of 0-100. A score of 0 means no hair loss on the scalp and a score of 100 means there is no hair on the scalp at all.

Results showed that after 24 weeks of treatment, 2 doses of ritlecitinib (50mg, 30mg) met the primary efficacy endpoint of improving scalp hair regrowth compared to placebo: a significantly higher proportion of patients achieved scalp hair growth compared to placebo Hair loss ≤20% (absolute SALT score ≤20). A 10 mg treatment group was also included in the study, which was evaluated for a dose range and was not tested for statistical significance with the placebo group.

The safety profile of ritlecitinib in this study was consistent with previous studies. Overall, the proportion of patients who experienced adverse events (AEs), serious adverse events (SAEs), and discontinuation due to adverse events was similar across all treatment groups. The most common adverse events in the study were nasopharyngitis, headache and upper respiratory tract infection. No major adverse cardiac events (MACE), deaths, or opportunistic infections occurred in the study. Eight patients treated with ritlecitinib developed mild to moderate herpes zoster. One case of pulmonary embolism in the ritlecitinib 50 mg group was reported on day 169. There were 2 malignancies (both breast cancer) in the ritlecitinib 50 mg group, which occurred on days 68 and 195, respectively. Both patients have discontinued the study.

FDA and EMA Accept Regulatory Submission for Pfizer’s Ritlecitinib for Individuals 12 Years and Older with Alopecia Areata