Fezakinumab

Months after Leo Pharma said its drug candidate for atopic dermatitis delivered positive results in a Phase 2b trial, the company finally revealed details of its success. The highest three doses of the company’s temtokibart significantly improved patients’ Eczema Area and Severity Index (EASI) score from baseline at 16 weeks versus placebo in the study’s primary endpoint, according to results presented Wednesday at the European Academy of Dermatology and Venereology’s annual meeting in Paris. In the highest 600 mg dose cohort, the average EASI score improved about 62% compared with 42% for placebo. Meanwhile, the 450 mg dose led to a 57% improvement in the score. But patients who received the 300 mg dose did best, achieving an average 64% reduction in the same metric. Further, those treated with the 600 mg and 300 mg doses of temtokibart maintained significant improvements in their scores up to 32 weeks, even though they stopped receiving treatment at around 14 weeks. The Phase 2b trial enrolled 262 adults with moderate-to-severe eczema. Although Leo said the trial was positive in May, this is the first time the company reported data. Chief scientific officer Jacob Pontoppidan Thyssen told Endpoints News in an interview that Leo is currently evaluating the best temtokibart dose to advance into a potential Phase 3 study. The company believes the drug’s safety profile could differentiate it from Sanofi and Regeneron’s blockbuster Dupixent. Temtokibart was generally well tolerated in the Phase 2b, with fewer discontinuations or withdrawals due to side effects (2.4%) compared with the placebo group (3.8%). “We did not see conjunctivitis, which you see with Dupixent,” Thyssen said. “We did not see vomiting or nausea to a high degree, or acne, which has been associated with JAK inhibitor use,” he added. Temtokibart works by blocking a subunit of the IL-22 receptor called IL-22RA1. This inhibits the effect of several inflammatory cytokines, including IL-22, IL-20 and IL-24, according to Leo. IL-22 receptors are only found on a type of skin cell called keratinocytes, Thyssen said. “We do not target or hit any of the immune cells, and that’s why we see such a beautiful safety profile at this point.” Dupixent, which targets the IL-4 and IL-13 cytokines, has dominated the atopic dermatitis market to date. The drug reached €3.8 billion ($4.5 billion) in second-quarter sales. But not all patients respond well to the treatment, Thyssen said. Pfizer also tried to develop an IL-22 antibody called fezakinumab, but it failed a mid-stage trial in atopic dermatitis. Fezakinumab targets the free cytokine, whereas temtokibart acts on the receptor, Thyssen said. “What we’ve shown [with the Phase 2b data] is that when you target the receptor, you actually get very good efficacy, which is meaningful for patients,” he added. Leo obtained exclusive rights to temtokibart from Dutch drugmaker argenx in 2022. The partners had previously developed the drug together as part of an exclusive option and research agreement. Editor’s note: This article was updated to clarify that Leo Pharma is headquartered in Denmark.