AbbVie is eyeing regulatory filings in 2027 for the skin disease drug lutikizumab after clearing multiple endpoints in a late-stage trial, but the results have disappointed some analysts, raising questions about its commercial prospects.
AbbVie’s investigational IL-1α/β inhibitor designed to treat a painful inflammatory skin condition reduced abscesses and other symptoms, meeting the main goal of a Phase 3 trial, though the result fell below analyst expectations set by earlier data.
AbbVie’s Phase 3 INTREPID study evaluated lutikizumab, a dual-variable-domain immunoglobulin taking aim at IL-1α and IL-1β—two key inflammatory cytokines. The trial recruited about 1,400 patients with hidradenitis suppurativa (HS), a chronic disease that causes painful cysts and abscesses and can lead to irreversible skin damage.
Patients receiving lutikizumab demonstrated a 31.4% response rate in abscess and nodule count reduction at week 16. The reduction compares to a 23.4% decrease seen for patients on placebo, a statistically significant difference of 8%.
Analysts with Guggenheim Partners called the placebo-adjusted response rate “disappointing,” citing significant degradation from mid-phase data, when lutikizumab elicited a 28% improvement over placebo.
Analysts at BMO Capital Markets were more bullish, writing in a Thursday note to investors that AbbVie’s late-stage findings validate “efficacy of IL-1α/β inhibition in HS, potentially expanding treatment with a new mechanism.” The current leading HS treatment is UCB’s Bimzelx, an IL-17 targeting antibody that led to a 20% placebo-adjusted response rate at week 16. Meanwhile, Merck recently shared competitive mid-stage data for its anti-TL1A tulisokibart, achieving about a 25% placebo-adjusted reduction in HS.
Despite the lower response rate than competitors, the achievement of eight secondary endpoints for lutikizumab strengthen its overall profile, with BMO analysts citing reductions in both pain and flares. The drug’s clean safety profile also supports potential broad use as a chronic therapy, BMO added.
Overall, the Phase 3 efficacy demonstrated by lutikizumab “could expand the treatment landscape in HS for patients in need of an alternative mechanism,” BMO said.
Both analysts were intrigued by AbbVie’s newly announced plans to combine lutikizumab with its long-acting amylin analog ABBV-295 later this year, plus the potential to pair with the anti-TL1A antibody ABBV-701 “to address multiple disease pathways that may improve outcomes for patients living with HS,” according to the pharma’s Thursday release.
AbbVie is expected to share 36-week blinded extension data for lutikizumab next year—findings the pharma said could be used to support regulatory filings in the second half of 2027. Analysts are looking to the additional data to provide clarity on the drug’s durability, long-term safety and commercial positioning.
“While the results could be sufficient to support regulatory approval, we think that given the topline Phase 3 data reported today, commercial uptake for luti monotherapy in HS will likely be limited,” Guggenheim wrote.
Making waves for other HS developers
The mixed data sent waves across the market for other drugmakers in the space.
“While the study was technically positive, results were disappointing relative to Phase 2 and investor expectations,” Leerink Partners analysts wrote, citing the AbbVie readout as “a key external catalyst” for Avalo Therapeutics, which is developing abdakibart, an IL-1β antagonist, for HS.
Given the partial overlap between the two candidates’ mechanisms of action, Avalo’s shares sunk more than 36% on Thursday, a reaction Leerink called “overdone.” The analysts instead view the “underwhelming lutikizumab results as an opportunity for greater differentiation and competitive positioning for abdakibart.”
Avalo’s most advanced asset, abdakibart is expected to enter Phase 3 testing in the first half of 2027. Avalo’s drug has the potential to be dosed less frequently than lutikizumab. In a Phase 2 trial, abdakibart reduced HS abscesses and nodules by about 42% as compared to 25.6% for placebo.
