The Phase 2B/3 Trial Data for Ritlecitinib: Does it point to the next FDA approved JAK Inhibitor?

Phase 2b-3 Trial of Ritlecitinib Shows Benefits for Treating Severe Alopecia Areata

A new study shared the results of a much awaited phase 2b/3 trial of the JAK3/TEC kinase inhibitor “ritlecitinib” in patients aged 12 years and older with severe alopecia areata.

Patients in the study had at least 50% scalp hair loss (ie the definition of severe AA) and were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose. The different study groups are shown in the image below.

At the end of the 24 weeks there was a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24.

The mean age of patients was around 32-34 years of age and 15 % were adolescents. 55 % were female. 68% were white, 26% Asian and 4% Black. The mean SALT score was around 90 indicating that patients had advanced forms of AA in this study. The mean duration of the current AA episode was 2.7 to 3 years.

Results

I’ve summarized results of the study in the three columns to the right of the figure. The number of patients in each group is shown first followed by the number of patients age 12-17. Finally, the proportion of patients achieving the primary end point (SALT Score Less than or equal to 20) is shown in the final column).

Side effects of Ritlecitinib

Ritlectinib was generally well tolerated. Side effects seemed to match typical side effects seen in other JAK trials. Adverse events that required stoping the drug occurred in around 2 %. There was 1 case of breast cancer in the 50 mg group, felt to be related to treatment. 1 case of breast cancer occurred in the 200 mg loading dose /50 mg group but was not felt to be treatment related. There were no deaths, no opportunistic infections, no major cardiac events. There was 1 pulmonary embolism but it was not felt to be related to the treatment. 12 % had headaches, 6 % acne, <2 % had zoster.

Conclusion

This is an important study and will likely form the basis for what the company submits to the FDA for consideration of FDA approval. The drug helps about one quarter patients achieve fairly reasonable regrowth (SALT 20) at week 24 and even a greater proportion by week 48. The drug does not help everyone. There were about 100 adolescents in the study but only a small number in each individual group. We’ll just need to wait to see whether this will influence how the FDA views the approval in those 12-17 years of age and what dose goes up for approval. Long term studies will be needed to evaluate safety beyond 48 weeks and to further clarify the significance of the cases of breast cancer and if other side effects appear in longer term studies.

REFERENCE

King B et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial. Lancet. 2023 May 6;401(10387):1518-1529.