An FDA Inspection of Manufacturing Company Leads to CRL for Lebrikizumab

The FDA has issued a complete response letter for Lilly’s biologic license application (BLA) for lebrikizumab to treat patients with moderate-to-severe atopic dermatitis. At issue are findings from the agency’s inspection of a third-party manufacturing company. The FDA indicated there were no concerns about the safety or labeling of lebrikizumab.

Patrik Jonsson

"We are confident in lebrikizumab's potential to help people living with eczema and in the clinical data that supports our submission package for the medicine,” Patrik Jonsson, Lilly executive vice president, president of Lilly Immunology and Lilly USA, and chief customer officer, said in a press release.

Atopic dermatitis is a chronic skin disease characterized by inflammation of the skin and skin barrier defects, and it can cause an abnormal immune response beneath the skin. About one in three adults and one in three children and adolescents have moderate-to-severe atopic dermatitis.

Recent research indicates that Interleukin-13 (IL-13) is overexpressed in atopic dermatitis and modifies the skin microbiome. This causes itching, skin thickening, and susceptibility to infection.

Lebrikizumab is monoclonal antibody that inhibits IL-13. The FDA submission was based on data from several trials, including ADvocate 1, ADvocate 2 and ADhere studies, which assess patients 12 years and older with moderate-to-severe eczema. ADvocate 1 and ADvocate 2 are 52-week are placebo-controlled phase 3 studies designed to evaluate lebrikizumab as monotherapy in adult and adolescent patients. ADhere is a 16-week placebo-controlled phase 3 study to evaluate lebrikizumab in combination with topical corticosteroids.

In May 2023, Lilly presented data from these trials at the 5th annual Revolutionizing Atopic Dermatitis (RAD) Congress. A post-hoc analysis based on data from the 16-week induction periods of the three studies showed a 58% to 73% of patients treated with lebrikizumab experienced improvement or clearance of face or hand dermatitis. Improved or cleared skin was seen with and without the use of topical corticosteroids.

In the ADvocate 1 study, 58% of lebrikizumab-treated patients reported an adverse event. In ADvocate 2, it was 68%. Most adverse events in the two studies were mild or moderate and did not lead to treatment discontinuation. The most commonly reported adverse events were conjunctivitis, common cold and headache.

Lilly has also initiated a clinical study of lebrikizumab in people of color living with atopic dermatitis to generate additional data. It is expected to be completed in March 2024.