Pfizer's JAK3/TEC Inhibitor Ritlecitinib Achieves Phase 2b/3 Clinical Trial Success in Alopecia Areata with Significant Hair Regrowth

On August 4, 2021, Pfizer announced that its oral JAK3/TEC inhibitor ritlecitinib achieved positive topline results in the Phase 2b/3 ALLEGRO clinical trial for the treatment of patients with alopecia areata. In the trial, both doses of ritlecitinib (50 mg and 30 mg) met the primary efficacy endpoint of improved scalp hair regrowth. Specifically, after 6 months of treatment, the proportion of patients in the ritlecitinib group with ≤20% scalp hair loss was significantly higher than that in the placebo group.

Ritlecitinib is an oral, once-daily, selective JAK3/TEC inhibitor. It inhibits the signaling pathways of IL-15 and CD8+ T cells, which are critical factors driving the immune system to attack hair follicle cells. In September 2018, ritlecitinib was granted Breakthrough Therapy Designation by the U.S. FDA for the treatment of alopecia areata. The drug is also currently under clinical evaluation for vitiligo, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. This innovative therapy was also proposed for inclusion in China's Breakthrough Therapy Drug list in December last year, and four clinical trials are currently underway in China.

▲Phase 2 Clinical Trial Results of Ritlecitinib (Image source: Pfizer official website)

This randomized, double-blind, placebo-controlled Phase 2b/3 clinical trial enrolled 718 patients aged 12 years and older with alopecia areata, all of whom had at least 50% scalp hair loss at baseline.

The trial met its primary efficacy endpoint. At Week 24 of treatment, the proportion of patients with ≤20% scalp hair loss was significantly higher in those receiving 30 mg or 50 mg ritlecitinib (with or without an initial 4-week once-daily 200 mg ritlecitinib lead-in treatment) compared with the placebo group.

Subjects will subsequently enter a 24-week extension study. The ritlecitinib group will continue to receive the same treatment regimen, while the placebo group will be randomized to one of two regimens: 200 mg ritlecitinib for 4 weeks followed by 50 mg ritlecitinib for 20 weeks; or 50 mg ritlecitinib for 24 weeks.

In terms of safety, the safety profile observed in this trial was consistent with that of previous studies. Overall, the proportions of patients experiencing adverse events (AEs), serious AEs, and treatment discontinuation due to AEs were similar across all treatment groups. The most common AEs in the study were nasopharyngitis, headache, and upper respiratory tract infection. No major adverse cardiovascular events (MACE), deaths, or opportunistic infections occurred during the trial. Mild to moderate herpes zoster occurred in 8 patients receiving ritlecitinib. In the 50 mg group, one case of pulmonary embolism occurred on treatment day 169, and two cases of malignancy (both breast cancer) were reported on days 68 and 195; both subjects discontinued the study.

Alopecia areata is the second most prevalent hair loss condition globally, affecting approximately 147 million people worldwide, with about 4 million patients in China. It is an autoimmune disease in which the immune system attacks hair follicles, resulting in partial or complete hair loss on the scalp, face, or other parts of the body. The average age of onset ranges from 25 to 35 years, and the condition can affect individuals of any age, sex, or race. The disease can cause severe psychological distress, including depression and anxiety. Currently, there are no FDA-approved therapies for this condition.

Note: The original text has been abridged.

References:

[1] Pfizer Announces Positive Top-Line Results From Phase 2b/3 Trial Of Ritlecitinib In Alopecia Areata. Retrieved August 4, 2021, from https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-results-phase-2b3-trial

▽Follow 【WuXi AppTecGermany】WeChat Official Account