Lilly and Incyte Announce Positive Topline Results from Second Phase 3 Trial of Olumiant (baricitinib) in Severe Alopecia Areata

April 20, 2021 /BioValleyBIOON/ --Eli Lilly(Eli Lilly) and its partner Incyte recently announced positive topline results from BRAVE-AA1, the second Phase 3 study evaluating the oral JAK inhibitor Olumiant (baricitinib) for the treatment of adults with severe alopecia areata (AA). The study assessed the efficacy and safety of two doses of Olumiant (2 mg and 4 mg, once daily). These data are consistent with the results from the first Phase 3 study, BRAVE-AA2, which were announced earlier this year. The data showed that at Week 36 of treatment, both studies met their primary efficacy endpoints: compared with patients receiving placebo,Patients treated with two doses of Olumiant showed statistically significant improvements in scalp hair regrowth.

The active pharmaceutical ingredient of Olumiant is baricitinib, an oral JAK1/JAK2 inhibitor discovered by Incyte,Eli LillyDeveloped under license from Incyte. In November 2020, Olumiant received EU approval for a second indication: the treatment of adult patients with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy. Notably, Olumiant is the first JAK inhibitor approved globally for the treatment of atopic dermatitis (AD).

Alopecia Areata (AA) is a devastatingAutoimmunityalopecia areata, which can cause patchy hair loss on the scalp, face, and sometimes other areas of the body, and can also have a significant psychological impact on patients. Currently, there are no drugs approved by the U.S. FDA for the treatment of AA. Previously, in the United StatesFDABaricitinib has been granted Breakthrough Therapy Designation (BTD) for the treatment of AA.

Data from the BRAVE-AA study will support the regulatory submission for Olumiant in the treatment of severe alopecia areata (AA). If approved,Olumiant Has the Potential to Become the First Drug for Treating Alopecia Areata, and AA will also become the second therapeutic indication for Olumiant in the field of dermatology, following atopic dermatitis (AD).

“Given that existing topical agents and steroids fail to provide meaningful improvement for many patients, there is an urgent need for effective alopecia areata treatments that have received regulatory approval,” said Dr. Maryanne Senna, Assistant Professor of Dermatology at Harvard Medical School and an investigator in the BRAVE-AA1 study. “I am pleased to see such positive results from these pivotal baricitinib trials, which will offer a much-needed potential breakthrough treatment option for this condition.”

Alopecia Areata (Image source: bing.com)

The BRAVE-AA clinical trial program was designed to evaluate the efficacy and safety of baricitinib in adult patients with severe alopecia areata (AA). The program comprised two trials: BRAVE-AA1 and BRAVE-AA2. BRAVE-AA1 was a multicenter, randomized, double-blind, placebo-controlled, adaptive Phase 2/3 trial. Based on the interim results from the Phase 2 portion of BRAVE-AA1 at Week 12, once-daily doses of 2 mg and 4 mg of baricitinib were selected for further evaluation in the Phase 3 portion of the study. BRAVE-AA2 was a multicenter, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of baricitinib 2 mg and 4 mg dosing regimens versus placebo. Both studies enrolled adult patients with severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score ≥50 (i.e., ≥50% scalp hair loss) and a current severe AA episode lasting at least 6 months but no more than 8 years. The program included diverse patient populations from multiple countries, including China.

In both studies, during the 9-month treatment period, patients treated with two doses of baricitinib showed statistically significant improvements in scalp hair regrowth compared to those receiving placebo, as assessed by physicians. The results of the BRAVE-AA1 study demonstrated that at Week 36, the proportion of patients achieving ≥80% scalp hair coverage was 35% in the baricitinib 4 mg group (p≤0.001), 22% in the 2 mg group (p≤0.001), and 5% in the placebo group, thereby meeting the primary endpoint. The results of the BRAVE-AA2 study showed that at Week 36, the proportion of patients achieving ≥80% scalp hair coverage was 33% in the baricitinib 4 mg group (p≤0.001), 17% in the 2 mg group (p≤0.001), and 3% in the placebo group, also meeting the primary endpoint. In both studies, by Week 36, the proportion of patients self-reporting at least 80% scalp coverage was significantly higher in the 2 mg and 4 mg groups than in the placebo group (p≤0.001).

The most common treatment-emergent adverse events (TEAEs) in BRAVE-AA1 and BRAVE-AA2 included upper respiratory tract infection, headache, and acne. No deaths or venous thromboembolism (VTE) events were reported in the trials. The safety profile of baricitinib in these two studies was consistent with its known safety profile in patients with rheumatoid arthritis (RA) and atopic dermatitis (AD).

Eli Lilly will be at the scientific conference later this yearMeetingprovide detailed data from these studies and submit the results to peer-reviewed journals. Based on these results,Eli LillyPlanned for the second half of 2021 in the United StatesFDASubmitted a supplemental New Drug Application (sNDA) for baricitinib in the treatment of severe alopecia areata (AA), followed by submissions to other regulatory authorities globally. In the first quarter of 2020, baricitinib was granted Breakthrough Therapy Designation (BTD) by the U.S. FDA for the treatment of AA.

Eli LillyImmunologyLotus Mallbris, M.D., Vice President of Development, stated: “Phase 3 baricitinib treatment for alopecia areataClinical TrialThe positive results of the project bring us closer to helping those suffering from this severeAutoimmunityThis brings us one step closer to providing an approved treatment option for patients affected by this condition. We look forward to discussing data from the BRAVE-AA clinical program with regulatory authorities worldwide. Baricitinib has the potential to become the first therapy for alopecia areata.”

The active pharmaceutical ingredient of Olumiant is baricitinib, a selective, reversible JAK1 and JAK2 inhibitor administered orally once daily, currently in clinical development for various inflammatory diseases andAutoimmunityTreatment of sexually transmitted diseases, includingRheumatoid Arthritis(RA), psoriasis,DiabetesRenal disease, atopic dermatitis, systemicLupus Erythematosus(SLE), etc. There are four JAK enzymes: JAK1, JAK2, JAK3, and TYK2. JAK-dependent cytokines are involved in the pathogenesis of various inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be widely used for the treatment of diverse inflammatory conditions. In kinase assay tests, baricitinib demonstrated 100-fold greater inhibitory potency against JAK1 and JAK2 than against JAK3.

Baricitinib was discovered by Incyte and licensed toEli Lilly. In the United States and more than 70 countries, baricitinib has been approved for marketing under the brand name Olumiant for the treatment of moderate to severe active rheumatoidRheumatoid Arthritis(RA) adult patients. In the EU and Japan, Olumiant is also approved for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD).

In the treatment of RA, the approved doses of Olumiant are 4 mg and 2 mg in the European Union, and 2 mg in the United States. For administration, Olumiant is taken orally once daily, either as monotherapy or in combination with methotrexate (MTX) or other non-biologic disease-modifying antirheumatic drugs (non-biologic DMARDs). Concomitant use of Olumiant with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants (such as azathioprine and cyclosporine) is not recommended. Notably, the U.S. prescribing information for Olumiant includes a Boxed Warning regarding serious infections and malignancyTumorand the risk of thrombosis.

Currently, baricitinib is also being evaluated in clinical studies for the treatment of systemicLupus Erythematosus(SLE), juvenile idiopathic arthritis (JIA), and coronavirus disease 2019 (COVID-19). (Bioon.com)

Original Source: Lilly and Incyte's Baricitinib Improved Hair Regrowth for Alopecia Areata Patients in Second Phase 3 Study