Brepocitinib Shows Promising Results for Treatment of Cicatricial Alopecia

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Brepocitinib was safe and well tolerated in patients with cicatricial alopecia (CA), according to a recent study.¹ The TYK2/JAK1 inhibitor reduced CCL5 and inflammatory biomarker expression while improving clinical severity scores.

The randomized, double-blind, single-center, phase 2a trial (NCT05076006) occurred from June 2021 to September 2024. The study included qualifying adults 18 years of age and older who were diagnosed with lichen planopilaris, frontal fibrosing alopecia, or central centrifugal cicatricial alopecia and had a disease duration of 6 months to 7 years.

Participants were randomized into groups 3:1. For 24 weeks, patients took either 45mg of brepocitinib (n = 37) or the placebo (n = 12) daily. Following this period, all patients received brepocitinib for another 24 weeks with a safety follow-up 4 weeks later. The mean age of patients receiving brepocitinib was 54 years compared to 59 years in placebo.

Scalp biopsies were taken at baseline, week 24, and week 48. The investigators measured changes in inflammation, fibrosis legions, and CCL5 expression while assessing Lichen Planopilaris Activity Index (LPPAI), Frontal Fibrosing Alopecia Severity Index (FFASI), Change in Hair Loss Grade (CHLG), and Dermatology Life Quality Index (DLQI) scores. Clinical photos of the scalp and eyebrows were taken throughout the trial.

Patients receiving brepocitinib showed significant downregulation in CCL5 expression at week 24 compared to both baseline and the placebo group (p = 0.004). There was also reduced lesional scalp expression of key inflammatory markers belonging to Th1/IFNγ, T cell activation/Th1, and Th2 pathways at week 24, which remained lowered through week 48 compared to baseline. These numbers were also significantly less than those of the placebo group.

By week 24, patients receiving brepocitinib showed substantial mean percent change in LPPAI (-51.0%), FFASI (-33.6%), and CHLG (-11.9%). Greater improvement was shown at week 48. Placebo patients who crossed over into the brepocitinib group also observed numerical reduction when they began the drug.

While no improvement in DLQI was noted in the placebo group, patients taking brepocitinib saw a decrease starting at week 8 (p = 0.004). They also noted a decline in patients’ subjective measure of itch/pruritus. Researchers noted that patients with shorter disease duration (less than 5 years) had greater percent improvement in clinical scores when compared to patients with long disease duration.

Mild to moderate adverse events were reported in 29 brepocitinib patients and 5 placebo patients. The most common were acne, anemia, COVID-19 infection, and elevation in serum creatinine levels. Only two patients experienced severe adverse reactions (anemia and pneumonia with gastroenteritis) and discontinued the drug. This safety profile is comparable to what was observed in previous trials.

“No significant difference in AE rates was found between the placebo cross-over group and the brepocitinib group,” the authors wrote. “Rates of mild, moderate, severe, and life-threatening AE were not significantly different between placebo and brepocitinib groups in either study phase. No cardiovascular events, thrombotic events, malignancies, or deaths in any treatment group were reported through week 52. “

The researchers also noted some study imitations including the single-dose regimen and a small placebo group. Further trials with altered design can find more sound comparisons between brepocitinib and the placebo.

The subtype of CA represents 7% of total alopecia cases seen in specialized clinics.² The promising potential of brepocitinib solves an unmet need as there are currently no FDA-approved, well-tolerated therapies for cicatricial alopecia.³ Larger studies are needed to move towards formal approval of brepocitinib for the treatment of CA.

References

1. David E, Shokrian N, Del Duca E, et al. A phase 2a trial of brepocitinib for cicatricial alopecia. J Am Acad Dermatol. Published online October 24, 2024. doi:10.1016/j.jaad.2024.09.073

2. Whiting DA. Cicatricial alopecia: clinico-pathological findings and treatment. Clin Dermatol. 2001;19(2):211-225. doi:10.1016/s0738-081x(00)00132-2

3. Larrondo J, McMichael AJ. Scarring Alopecia. Dermatol Clin 2023;41(3):519-537. (In 446 eng). DOI: 10.1016/j.det.2023.02.007.