New Safety and Efficacy Data of Ritlecitinib for Alopecia Areata Published in The Lancet

Data from the randomized, double-blind, multicentre, ALLEGRO phase 2b-3 clinical trial (NCT03732807) evaluating the safety and efficacy of ritlecitinib (Pfizer) for adult and adolescent patients with alopecia areata was recently published in The Lancet. King et al found that ritlecitinib was effective and well-tolerated among patients aged 12 years and older with alopecia areata, and it may be a potential treatment option for patients who are candidates for systemic therapy.¹

Lynne Napatalung, MD, MA

“We believe there is a clear need for ritlecitinib and are working to bring this potential new treatment option to patients living with alopecia areata as soon as possible. Based on results from the ALLEGRO phase 2b/3 trial and other studies, we believe that ritlecitinib has a favorable benefit-risk profile and may be appropriate for adults and adolescents,” said Lynne Napatalung, MD, MA, one of the ALLEGRO investigators, a board-certified dermatologist, a clinical instructor of dermatology at Mount Sinai in New York, and a senior medical director at Pfizer.

Physicians are eager to have another treatment option for alopecia areata, as baricitinib (Olumiant; Eli Lilly and Company) is the only other FDA-approved treatment for adults, and there are no currently FDA-approved treatments for adolescents.

Background

“Ritlecitinib is the first in a new investigational class of oral kinase inhibitors, which has a selectivity profile distinct from currently approved JAK inhibitors. It is a dual inhibitor of the TEC family kinases and of JAK3, while remaining devoid of JAK1, JAK2, and TYK2 inhibition. We are proud to be part of the emerging science in the alopecia areata space and to potentially bring ritlecitinib to adults and adolescents suffering with this autoimmune disease,” said Napatalung.

The pathophysiology of alopecia areata includes immune privilege collapse of the hair follicle, which is believed to leave the hair follicle vulnerable to attack by natural killer and autoreactive CD8+ T cells. The activation and proliferation of immune cells involve multiple cytokines such as interferon-γ and interleukin (IL)-15, which have been cited as major drivers of alopecia areata.

Study Methods

The phase 2b-3 ALLERGO clinical trial enrolled 718 patients which included adult patients aged 18 years and older and adolescent patients aged 12 to 17 years with a confirmed diagnosis of alopecia areata with at least 50% scalp hair loss (including alopecia totalis and alopecia universalis) measured using the Severity of Alopecia Tool (SALT). According to the study, patients were randomly assigned (2:2:2:2:1:1:1) to receive oral ritlecitinib 200mg loading dose for 4 weeks followed by 50mg (n=132), 200mg loading dose for 4 weeks followed by 30mg (n=130), 50mg (n=130), 30mg (n=132), 10mg (n=63), placebo for 24 weeks followed by 200mg loading dose for 4 weeks then 50mg (n=66), or placebo for 24 weeks followed by 50mg (n=65).

“Patients enrolled were required to have 50% or less of their scalp hair at baseline and many experienced significant hair regrowth. Of note, approximately 46% of patients had either alopecia totalis or alopecia universalis, indicating no scalp hair with or without eyebrow, eyelash, or body hair at baseline, respectively,” said Napatalung.

The selected treatments were administered orally once a day for 24 weeks during the placebo-controlled period and for 24 weeks during the extension period. Evaluations were completed at screening, baseline, and week 4, 8, 12, 18, 24, 28, 34, 40, and 48 (or at the end of treatment) and included SALT score, eyebrows and eyelashes hair loss (eyelash assessment or eyebrow assessment by the investigator with 4-point scales from 0 (none) to 3 (normal), and patient self-administered Patient Global Impression of Change (PGI-C).

In total, 105 patients (15%) were adolescents and 613 patients (85%) were adults.

Results

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The primary endpoint of ALLEGRO was response based on SALT score 20 or less (20% scalp hair loss or less), defined as a clinically meaningful treatment outcome by both the clinicians and patients, and the more "stringent" key secondary endpoint was response based on SALT score 10 or less (10% scalp hair loss or less). Other secondary endpoints included a PGI-C score of moderately improved or greatly improved to week 48, response based on SALT score 20 or less and 10 or less to week 48, change from baseline in SALT scores to week 48, measures of eyebrow and eyelash regrowth, and exposure response based on SALT score 20 or less.

“Results demonstrated ritlecitinib 30mg and 50mg (with or without an initial 4-week treatment of 200mg once-daily) achieved the primary efficacy endpoint of the study at Week 24, namely a statistically significantly greater proportion of patients experienced hair regrowth (SALT score ≤20) with ritlecitinib versus placebo. The treatment effect of ritlecitinib was consistent between participants with alopecia totalis or alopecia universalis and those without, as well as between adolescents 12 through 17 years of age and adults at week 24,” said Napatalung.

King et al noted that the proportions of patients with response based on SALT score 20 or less and 10 or less were much higher among patients receiving ritlecitinib than in patients receiving placebo at week 24. Additionally, response rates continued to increase up to week 48.

“In terms of safety data, through week 48 the most common [adverse events] (AEs) of any grade occurring in at least 10% of patients in any treatment group were headache, nasopharyngitis, upper respiratory tract infections, nausea, and acne. Most AEs were mild or moderate in severity. Serious adverse events were experienced by 0% to 3% of patients across treatment groups,” said Napatalung.

The study authors stated that hair regrowth seen with ritlecitinib may imply restoration of hair follicle immune privilege. Overall, the authors concluded that ritlecitinib doses of 50mg and 30mg once a day, with or without the loading dose of 200mg once a day, were efficacious, safe, and well-tolerated over 48 weeks.

“Additionally, patient-reported improvement, measured as the proportion of patients achieving greatly or moderately improved on the Patient’s Global Impression of Change (PGI-C) scale ("1=greatly improved" to "7=greatly worsened"), was also significantly greater among patients receiving ritlecitinib than those receiving placebo (not multiplicity controlled),” said Napatalung.

A long-term study, ALLERGO-LT (NCT04006457) is currently ongoing to further investigate the efficacy and safety of ritlecitinib.

“Alopecia areata is an often-misunderstood autoimmune disease with underlying immuno-inflammatory pathogenesis that targets hair follicles, which results in hair loss. It is a devastating and complex disease that can affect all ages, genders, and people of any race or ethnicity, and for which there have been limited treatment options. An estimated 6.8 million people in the US and 147 million people globally are living with alopecia areata,” concluded Napatalung.

Lynne Napatalung joined Pfizer in 2017 and works as a senior medical director, where she serves as the ritlecitinib asset lead on the global medical affairs dermatology team, covering alopecia areata and vitiligo. She is a board-certified dermatologist and continues to enjoy seeing both pediatric and adult patients at the Mount Sinai Hospital in New York, New York.

Reference

1. King B, Zhang X, Harcha WG, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2B–3 trial. The Lancet. April 2023. doi:10.1016/s0140-6736(23)00222-2