Second positive read-out tees up regulatory filings for Lilly, Incyte's baricitinib in alopecia

Eli Lilly and Incyte announced Tuesday that a second Phase III study of baricitinib in adults with severe alopecia areata met its primary endpoint, paving the way for regulatory submissions for the oral JAK inhibitor in this indication. The companies said that in the BRAVE-AA1 trial, a significant proportion of patients treated with baricitinib achieved the main goal of hair regrowth across the two dosing regimens at week 36 compared to placebo.

"The positive results from our Phase III trials…bring us one step closer to potentially providing an approved treatment option to people affected by this serious autoimmune disease," commented Lotus Mallbris, head of immunology development at Eli Lilly. In addition to BRAVE-AA1, the development programme for baricitinib in alopecia areata also consists of the BRAVE-AA2 trial, for which the companies reported top-line results last month showing it had met its primary endpoint as well.

BRAVE-AA1 and BRAVE-AA2 randomised about 725 and 476 adults, respectively, to receive once-daily doses of baricitinib 2 mg or 4 mg, or placebo. Participants had severe alopecia, defined as a Severity of Alopecia Tool (SALT) score ≥50, signifying hair loss over half their scalp, in addition to a current episode of alopecia areata lasting at least six months, but no more than eight years. Both trials measured the percentage of patients achieving a SALT score of ≤20 at week 36 as a primary endpoint.

In BRAVE-AA1, results demonstrated that 35% of patients given baricitinib 4 mg achieved ≥80% scalp hair coverage at week 36, compared to 22% in the 2-mg dose group, and 5% for placebo. Also released Tuesday, additional results from BRAVE-AA2 showed that the main goal was met by 33% of subjects in the baricitinib 4-mg dose group, 17% of those treated with the 2-mg dose and 3% for placebo. Eli Lilly and Incyte added that across both studies, the proportion of patients self-reporting at least 80% scalp hair coverage was significantly greater in the 2-mg and 4-mg groups versus placebo by week 36.

'Consistent' safety profile amid class concerns

The companies said the safety profile for baricitinib is consistent with its known profile in rheumatoid arthritis and atopic dermatitis, two other indications it is already approved for. The most common treatment-emergent adverse events in BRAVE-AA1 and BRAVE-AA2 included upper respiratory tract infections, headache and acne, but there were no deaths or venous thromboembolic events reported in either study. Eli Lilly says it plans to present detailed findings from the BRAVE-AA programme at scientific meetings later this year and also submit results to peer-reviewed journals.

The drug is marketed in the US and more than 70 countries as Olumiant for the treatment for adults with moderately-to-severely active rheumatoid arthritis, as well as in Europe and Japan for certain adults suffering from moderate-to-severe atopic dermatitis. Earlier this month, the FDA extended its review of an application seeking to include atopic dermatitis to Olumiant's US label, with a decision now expected early in the third quarter, as the regulator continues to scrutinise the safety of the drug class (see ViewPoints: FDA continues to hold JAKs after class). Eli Lilly recently said Olumiant sales were up 50% in the fourth quarter of 2020 to $192.2 million.

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