Affecting an estimated 100,000 adults in the United States, LPP causes the body’s immune system to attack the stem cell-rich “bulge” region of the hair follicle, leading to permanent baldness, intense scalp pain, and burning sensations. By utilizing a dual-action mechanism that blocks two key inflammatory enzymes simultaneously, brepocitinib aims to shut down the destructive immune cascade before permanent scalp scarring occurs.
What Is It and How Does It Work?
Brepocitinib is an oral, once-daily investigational medication being developed for lichen planopilaris and other severe autoimmune skin conditions. LPP is a form of cicatricial (scarring) alopecia where aggressive immune cells specifically target the hair follicle’s bulge region—the permanent reservoir where hair stem cells reside to regenerate new hair fibers. When this area is destroyed by inflammation, the follicle is replaced by scar tissue, making natural hair regrowth impossible.
The treatment works through an advanced process called Dual TYK2 and JAK1 Inhibition:
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The Inflammatory Cascade: In LPP, immune cells flood the scalp tissue with destructive signaling proteins (interferons and cytokines such as IL-6 and IL-12) that command T-cells to assault the follicle bulge.
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Dual-Locking the Pathways: While standard Janus kinase blockers target only JAK enzymes, brepocitinib acts as a dual-action blocker, disabling both Tyrosine Kinase 2 (TYK2) and Janus Kinase 1 (JAK1) simultaneously.
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Saving the Stem Cell Bulge: By blocking both TYK2 and JAK1 pathways, brepocitinib cuts off the multiple overlapping cytokine signals driving the attack. This rapid suppression halts tissue destruction, calms severe scalp burning and pain, and protects the remaining stem cell bulge so hair follicles can survive.
The Science: Halting Follicle Destruction in Phase 2a and Launching Registrational Phase 2b/3 Trial
The expansion into the Phase 2b/3 registrational program follows positive results from an investigator-initiated Phase 2a trial published in the Journal of the American Academy of Dermatology.
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Phase 2a Biomarker Suppression: The 52-week Phase 2a trial in patients with scarring alopecias (including LPP and frontal fibrosing alopecia) demonstrated that daily brepocitinib significantly suppressed key Th1/IFN$\gamma$ inflammatory gene expression in lesional scalp biopsies compared to placebo.
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Symptom Relief: Patients experienced marked reductions in painful scalp inflammation, burning, itching, and redness (erythema), halting active disease progression.
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The ALPINE Phase 2b/3 Trial: Launched in March 2026, the ALPINE study (NCT07532603) is enrolling adult patients with biopsy-confirmed active LPP. The trial evaluates oral brepocitinib against placebo to measure reductions in the Lichen Planopilaris Activity Index (LPPAI) and hair loss stabilization.
“Lichen planopilaris is what my colleagues and I refer to as a ‘trichologic emergency.’ Absent early diagnosis and aggressive intervention, patients experience rapid hair loss that is generally irreversible and often accompanied by erythema, scaling, pain, itching, and burning sensations… Efficacious FDA-approved treatments are urgently needed.” — Dr. Kristen Lo Sicco, Chief of the Skin and Cancer Unit at NYU Langone Health and Board Member of the Scarring Alopecia Foundation.
When Will It Be Available?
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Current Stage: Brepocitinib is actively recruiting participants across clinical trial sites in the United States and internationally for the Phase 2b/3 ALPINE study.
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Priority Regulatory Track: The drug platform holds FDA Priority Review in other autoimmune indications. If the ALPINE trial confirms efficacy in halting scarring hair loss, brepocitinib could become the first-ever FDA-approved medication for lichen planopilaris by 2028 or 2029.
How you can benefit from this treatment now
If you or someone you know is experiencing symptoms of scarring hair loss, the launch of the ALPINE trial highlights urgent steps you can take today:
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Recognize LPP as a “Trichologic Emergency”: Because LPP permanently destroys hair stem cells, early intervention before scarring sets in is critical. If you experience sudden patchy hair loss accompanied by scalp burning, intense itching, redness, or painful tenderness, seek an immediate evaluation from a specialist dermatologist or hair clinic.
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Obtain an Early Scalp Biopsy: Diagnosis of LPP requires a small scalp biopsy. Confirming active inflammation around the hair bulge early allows doctors to initiate aggressive anti-inflammatory therapies before permanent follicle loss occurs.
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Explore ALPINE Trial Recruitment: Because there are currently no approved LPP drugs on the market, participating in clinical trials is a primary way to access targeted TYK2/JAK1 therapy. You can search for the ALPINE study (NCT07532603) on ClinicalTrials.gov to locate active medical centers accepting eligible patients.
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