‘Better things are coming’: Brepocitinib improves scarring alopecia biomarkers, severity
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Key takeaways:
- Brepocitinib downregulated key inflammatory biomarkers in cicatricial alopecias.
- Brepocitinib also improved clinical severity scores allowing hair regrowth.
SAN DIEGO — Brepocitinib induced clinical improvement in patients with cicatricial alopecia and attenuated scalp inflammatory biomarkers, according to a presentation at the American Academy of Dermatology Annual Meeting.
“Scarring alopecias are really considered an epidemic recently,” Emma Guttman-Yassky, MD, PhD, the Waldman Professor and System Chair of the Kimberly and Eric J. Waldman Department of Dermatology at Icahn School of Medicine at Mount Sinai and one of the study investigators, told Healio.
“We see a very large portion of patients that come to our clinic for hair loss having scarring alopecia,” Guttman-Yassky, who is also a member of the Healio Dermatology Peer Perspective Board, continued. “And really, until now, we don’t have anything to give them because there is nothing FDA approved for scarring alopecia.”
According to the late-breaker presentation cicatricial alopecias (CA) are chronic, progressive, scarring hair loss conditions. The subtypes of CA, which include lichen planopilaris (LPP), frontal fibrosing alopecia (FFA) and central centrifugal cicatricial alopecia (CCCA), often occur in women, particularly women with skin of color.
As Healio previously reported, an earlier study in alopecia found that type 1 T-helper (Th1) cells were upregulated in patients with CA. This discovery provided the rationale for the phase2a, double-blinded study in which the investigators evaluated the effect of brepocitinib (Priovant Therapeutics), an oral tyrosine kinase 2 and Janus kinase 1 inhibitor, on the biomarkers of inflammation and clinical scores in CA.
The primary endpoint of the study was changes in Th1 markers, specifically chemokine ligand 5 (CCL5) and interferon gamma, as well as data on brepocitinib’s safety profile and tolerability in this indication. The secondary endpoint focused on the clinical scores at weeks 24 and 48.
Researchers randomly assigned patients 3:1 to receive brepocitinib 45 mg once daily or placebo for the first 24 weeks followed by all patients receiving brepocitinib from week 24 through week 48. Of the patients that received brepocitinib, five had FFA (mean age, 57 years; 100% women; 100% white), 13 had LPP (mean age, 51 years; 85% women; 62% white) and 13 had CCCA (mean age, 54 years; 100% women; 100% Black). Of the patients that received placebo, four had FFA (mean age, 63 years; 100% women; 50% white), three had LPP (mean age, 58 years; 100% women; 100% white) and five had CCCA (mean age, 55 years; 100% women; 80% Black).
At weeks 24 and 48, results showed that the FFA and LPP groups treated with placebo experienced an uptick in interferon gamma, CCL5, C-X-C motif chemokine ligand 10 and signal transducer and activator of transcription 1, whereas the groups treated with brepocitinib saw downregulations of these biomarkers (P value range = < .001 to < .05). The CCCA groups followed a similar, but smaller, trend that achieved significance.
Clinical severity scores decreased across all patient groups, with some patients regrowing their hair. A shorter disease duration of less than 5 years was also associated with better clinical improvement in CA at week 24 (P = .024) and week 48 (P = .029), emphasizing that early treatment is imperative for positive results.
“If you do not have the disease for long, then we can intervene and grow hair,” Guttman-Yassky told Healio. “We found that 4 years is the sweet spot.”
No new safety signals, deaths, thrombotic, deep vein thromboses or cardiovascular events were reported. Most of the adverse events were mild to moderate, and four were severe. Five patients discontinued the study due to adverse events.
“The key take-home message to practitioners is that better things are coming for the treatment of our patients with scarring alopecia,” Guttman-Yassky told Healio.
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Meariman M, et al. S026 late-breaking research: session 1. Presented at: American Academy of Dermatology Annual Meeting; March 8-13, 2024; San Diego.
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