ALLEGRO-LT shows long-term benefit of ritlecitinib for alopecia areata
In the interim analysis of the ongoing phase III ALLEGRO-LT trial, the investigational oral JAK3*/TEC inhibitor ritlecitinib demonstrated long-term safety and remarkable scalp hair regrowth in adults and adolescents with alopecia areata (AA).
“AA is a T-cell mediated autoimmune disease with an underlying immune-inflammatory pathogenesis characterized by non-scarring hair loss of the scalp, face, and/or body [that can significantly impact patients’ lives],” said Dr Athanasios Tsianakas from Fachklinik Bad Bentheim, Germany, at EADV 2022.
This open-label study enrolled 1,052 AA patients** who rolled over from ALLEGRO phase IIa or IIb/III who had received the study intervention, or who had not received treatment (de novo patients). The de novo cohort comprised 449 participants (mean age 33 years, 17 percent adolescents, 64 percent female, mean SALT*** score 74.5 percent). Of these, a third had alopecia totalis (total scalp hair loss) and/or alopecia universalis (total body hair loss). Participants received a loading dose of ritlecitinib 200 mg QD for the first 4 weeks, followed by a maintenance dose of 50 mg QD. [EADV 2022, abstract 3454]
Median ritlecitinib exposure among de novo patients is ~17 months. Overall, 86 percent of participants have taken the drug for ≥12 months (32 percent with ≥15 to <18 months’ exposure). About 20 percent of participants discontinued the trial prematurely (3 percent due to adverse events [AEs]).
More than three-quarters of de novo patients reported AEs, but most (95 percent) were mild or moderate in severity. Only 4 percent had serious AEs. The most common AE was headache (16 percent) followed by positive SARS-CoV-2 test (13 percent) and acne (12 percent).
Regarding AEs of special interest, there were only four cases of mild-to-moderate herpes zoster. There were no opportunistic infections reported.
Apart from one case of grade 3 anaemia, there were no other clinically relevant changes from baseline in haematologic parameters. “All reductions did not result in study discontinuation,” noted Tsianakas. “Despite the slight increase in liver values in some patients, which was very typical for JAK inhibitors, none led to study discontinuation.”
At 24 months, about two-thirds of participants in the de novo cohort achieved SALT score ≤20 (ie, ≤20 percent scalp without hair; 70 percent) and the more stringent SALT score ≤10 (ie, ≤10 percent scalp without hair; 62 percent). “The curves of the proportions of patients achieving [both endpoints] went upwards for 12 months and stabilized by month 24,” said Tsianakas.
There was a substantial jump in the fraction of patients with PGI-C# response. From a baseline rate of 16 percent, more than half (57 percent) of participants had a PGI-C response by month 3, which continued to increase throughout the trial, stabilizing at 78 percent by month 24.
“[These] interim results from the de novo cohort of ALLEGRO-LT are consistent with those of the pivotal ALLEGRO phase IIb/III study,” said Tsianakas. “Following an induction dose of 200 mg, ritlecitinib 50 mg showed a very good efficacy and safety profile in adolescent and adult patients with AA.”
A potential new treatment alternative
“AA … can impact people of all ages, genders, and ethnicities, often having an impact on day-to-day life that goes beyond the hair loss itself,” said Dr Michael Corbo, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development, in a press release.
“[If approved, ritlecitinib may] be an important new treatment option [for AA],” continued Corbo. “[W]e are continuing to work closely with regulatory authorities to bring ritlecitinib to adults and adolescents in the US and EU.”
Based on the ALLEGRO phase IIb/III results and the current findings, the US FDA has accepted the NDA## filing for ritlecitinib for adults and adolescents ≥12 years with AA. The EMA has similarly accepted the MAA## for ritlecitinib for the same patient subgroup. [www.pfizer.com/news/press-release/press-release-detail/fda-and-ema-accept-regulatory-submission-pfizers, accessed September 17, 2022]