In an interim analysis of the ongoing phase 3 ALLEGRO-LT trial, the investigational JAK3/TEC kinase inhibitor ritlecitinib demonstrated remarkable scalp hair regrowth in both adult and adolescent patients with alopecia areata (AA) over a treatment period of up to 36 months. The safety profile was consistent with the primary ALLEGRO study results and treatment effects were already noted after 3 months.
AA is a T cell-mediated autoimmune disease with an underlying immune-inflammatory pathogenesis characterised by non-scarring hair loss of the scalp, face, and/or body. Ritlecitinib is a selective inhibitor of JAK3 and the TEC kinase that previously showed efficacy in AA in the ALLEGRO phase 2b/3 study (NCT03732807) . At this year´s EADV meeting, Dr Athanasios Tsianakas (Fachklinik Bad Bentheim, Germany) reported interim results from the de novo arm of ALLEGRO-LT (NCT04006457), an ongoing phase 3 study investigating the long-term safety and efficacy of ritlecitinib in patients with AA .
Included in the ALLEGRO-LT study were either roll-over participants from previous trials or de novo participants. De novo participants were first treated with 200 mg ritlecitinib, once daily, for 4 weeks (induction dose) followed by the maintenance dose of 50 mg. Key inclusion criteria of de novo participants were an age of ≥12 years and a diagnosis of AA with a ≥25% scalp hair loss due to AA. Dr Tsianakas presented the results of the de novo arm up to month 36.
The median range of exposure was about 17 months. “All in all, 85% of the included participants were taking the drug for more than 12 months,” Prof Tsianakas said. At data cut-off, 21.6% of participants had discontinued, but only 3% due to adverse events. Regarding efficacy, the proportion of participants showing a maximum of 20% hair loss in the Severity Alopecia Tool (SALT) score, a global severity score, was evaluated up to month 24. “We can see that the curve nicely goes upwards until a year and stays steady at about 70%,” Prof Tsianakas elucidated (see Figure). The more stringent SALT 10 results level out at about 56% after a year. The high efficacy seen in ALLEGRO-LT is mirrored in the positive participant-reported outcome, the proportion of participants who moderately or greatly improved their Patient Global Impression of Clinical Status (PGI-C) score. Already after 5 months, 57% of participants felt their hair growth had moderately or greatly improved, this percentage went up to about 78% at month 24.
Figure: Response to ritlecitinib therapy based on SALT ≤20 up to month 24 
SALT, Severity of Alopecia Tool; QD, once daily; N, number of patients with observed data; n, number of patients achieving SALT score ≤20.
Among the 447 participants included in the safety analysis, a total of 1,448 adverse events were recorded. From the de novo group, 78% developed adverse events but 94.6% of those were mild-to-moderate in severity. The most frequent adverse events were headache, positive SARS-CoV-2 test, and acne. Importantly, no opportunistic infections and no clinically relevant median changes from baseline in haematological parameters were observed.
Taken together, these long-term data are consistent with the primary ALLEGRO study results. In contrast with the 2 other JAK inhibitors developed for AA, baricitinib and deuruxolitinib which both target JAK1 and 2, ritlecitinib is only targeting JAK3. This high selectivity may have advantages regarding the safety profile.
Also effective in alopecia totalis
In a post-hoc analysis of the ALLEGRO study presented as a poster, the efficacy of ritlecitinib at weeks 24 and 48 was assessed across different subgroups based on the presence of alopecia totalis (AT; complete loss of scalp hair) or alopecia universalis (AU; complete loss of scalp, face, and body hair), subgroups that can be challenging to treat . Of the 718 participants randomised in the ALLEGRO trial, 151 (21%) and 147 (20%) had AT and AU, respectively. Across all ritlecitinib treatment arms, SALT ≤20 response rates were higher in the non-AT/non-AU participants at weeks 24 and 48. However, ritlecitinib was also effective in the AT/AU group with up to 30% of this difficult-to-treat group achieving a SALT ≤20 response at week 48 .
- King B. Efficacy and safety of ritlecitinib (PF-06651600) in patients with alopecia areata and ≥50% scalp hair loss: results from the international ALLEGRO phase 2b/3 randomised, double-blind, placebo-controlled study (NCT03732807). D3T01.1C, EADV Congress 2021 – Virtual, 29 September – 2 October.
- Tsianakas A. Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata: interim results from the ALLEGRO-LT phase 3, open-label trial. D3T01.1G, EADV Congress 2022, Milan, Italy, 7‒10 September.
- Kassira S, et al. Int J Dermatol. 2017;56:801‒10.
- Zhang X, et al. Efficacy of ritlecitinib (PF-06651600) in patients with alopecia totalis and alopecia universalis: post hoc analysis of the ALLEGRO phase 2b/3 study. P0486, EADV Congress 2022, Milan, Italy, 7‒10 September.
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What Is Hot in Hair Disorders?
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Long-term improvement in alopecia areata with ritlecitinib therapy