A phase 3 trial of AbbVie’s lutikizumab in hidradenitis suppurativa (HS) has hit its primary endpoint. But with the drug candidate beating placebo by a narrower margin than expected, the readout raises questions about AbbVie’s chances of cracking a competitive market.
The phase 3 Intrepid study randomized 1,400 patients to receive lutikizumab subcutaneously or placebo. At Week 16, 31.4% of people with lutikizumab met the HiSCR75 criteria—including at least a 75% reduction in abscesses and inflammatory nodules—compared to 23.4% of their peers on placebo. The HiSCR75 result was statistically significant, achieving the trial’s primary endpoint.
In phase 2, AbbVie reported HiSCR75 rates up to 45.9% on lutikizumab, compared to 17.5% for placebo. Based on the phase 2 data and rivals’ results, H.C. Wainwright analysts last week set their threshold for competitive differentiation at a 45% to 50% HiSCR75 rate with at least a 25-point benefit over placebo.
AbbVie’s failure to come close to either threshold sent shockwaves through the HS race. Shares in Avalo Therapeutics, which is developing a rival drug candidate, fell 35% to $8 in early trading on Nasdaq. The biotech is developing an antibody that binds to IL-1β. Lutikizumab targets IL-1α and IL-1β.
BMO Capital Markets analysts were sanguine about the readout. In a note to investors on Thursday, the analysts acknowledged that lutikizumab’s efficacy “may be lower than other competitive agents.” Yet the analysts still concluded that the data “could expand the treatment landscape in HS for patients in need of an alternative mechanism.”
AbbVie plans to file for approval once it has additional data from the Intrepid study. The company expects to report results from a 36-week blinded extension period in 2027 and file for approvals in HS in the second half of the year.
The planned filing is supported by hits on eight ranked secondary endpoints. AbbVie saw statistically significant reductions in HS-related pain and flares compared to placebo. Patients experienced declines in HS-related skin pain as early as Week 1. The results “are likely to resonate with physicians given the substantial burden of pain and recurrent flares commonly seen in HS,” the analysts said.
Lutikizumab could face more efficacious rivals if it comes to market. Merck & Co. recently reported placebo-adjusted HiSCR75 rates of up to 27% in a phase 2b trial of tulisokibart, its anti-TL1A antibody. UCB’s Bimzelx achieved a 20% placebo-adjusted improvement in HiSCR75, BMO analysts said.
Safety and tolerability may help AbbVie win share, with BMO analysts predicting that “lutikizumab’s clean profile could support broad utilization across diverse HS patient populations, even if efficacy is less differentiated.” Lutikizumab’s safety and tolerability profile could also support combinations, for example, with AbbVie’s anti-TL1A antibody, ABBV-701. Combinations could improve responses, the analysts said.