Sonelokimab

Avalo Therapeutics surged 35% on Wednesday after reporting mid-stage data for its experimental antibody abdakibart in hidradenitis suppurativa (HS). The results were released alongside the pricing of a $375-million public offering intended to bankroll the drug's progression into a pivotal Phase III programme and through to its topline readout.The LOTUS study tested two dosing regimens of abdakibart, a monoclonal antibody targeting IL-1β, in 253 patients with moderate-to-severe disease. The primary endpoint measured HiSCR75, defined as a ≥75% reduction in total abscess and inflammatory nodule count with no increase in abscess or draining tunnel count relative to baseline.'De-risking data'Both arms succeeded on that metric, with week-16 HiSCR75 response rates of 42.2% for the 150-mg regimen and 42.9% for the 300-mg regimen, versus 25.6% for placebo. The results were statistically significant (p=0.004) across both doses. Avalo noted that HiSCR75 response was similar in patients regardless of prior biologic exposure.Abdakibart also demonstrated statistically significant benefit across key secondary endpoints such as HiSCR50 response, reductions in the International HS Severity Score System (IHS4) and declines in draining tunnel counts.No safety signals were observed related to neutropenia, serious infections, or opportunistic infections during the 16-week treatment period. Side effects were typically mild or moderate, with headache and nausea being the most common. Full results from LOTUS will be shared at an upcoming medical congress."This de-risking data set gives us tremendous confidence to advance abdakibart into a pivotal Phase III registrational programme," said CEO Garry Neil. "With a differentiated and patient-friendly potential monthly dosing regimen, we aim to offer a truly innovative mechanism of action."Clinical hurdlesHowever, the HS space has been marked by several instances of candidates showing promising results, only to face challenges in later stages of testing.Insmed last month ended development of Brinsupri (brensocatib) in HS after the DPP1 inhibitor failed a mid-stage study. In 2023, Acelyrin's IL-17A inhibitor came up short in a Phase IIb/III study of HS patients after a "marked increase" in placebo response seen in the trial.Meanwhile, MoonLake Immunotherapeutics is evaluating a trispecific IL-17A/F nanobody called sonelokimab in a pair of Phase III trials involving more than 800 patients. VELA-1 met its primary endpoint at 16 weeks, with HiSCR75 achieved in 34.8% of sonelokimab-treated patients versus 17.5% on placebo, though VELA-2 fell short of statistical significance despite a 35.9% response rate because of a high placebo response. However, the company recently reported longer-term readouts hinting at deepening responses.Martina Porter, an assistant professor of dermatology at Harvard Medical School and an investigator on Incyte's STOP-HS programme testing the oral JAK1 inhibitor povorcitinib, recently told FirstWord that predicting treatment response remains a challenge."What we'll want to see over the next five years are clinical or demographic features or other biomarkers that will enable us to figure out what will help us predict response to therapy so we can make more informed decisions about treatment, so that patients don't need to cycle through so many drugs before they find one that works for them," she said (see – KOL Views Q&A: Better biomarkers are needed as the HS toolbox expands).