Avalo Therapeutics (Nasdaq: AVTX) reported that abdakibart (AVTX-009), its anti-IL-1β monoclonal antibody, met the primary endpoint in the Phase II LOTUS trial in moderate-to-severe hidradenitis suppurativa, with HiSCR75 response rates of 42.2% and 42.9% at the 150 mg and 300 mg doses respectively, compared to 25.6% on placebo — results the company said support advancing into a registrational Phase III program.
The LOTUS trial (NCT06603077) is a randomized, double-blind, placebo-controlled, parallel-group Phase II study that enrolled 253 adults with moderate-to-severe hidradenitis suppurativa across two abdakibart dose regimens and placebo in a 1:1:1 ratio over a 16-week treatment period.
Both doses of abdakibart met the primary endpoint of HiSCR75 at Week 16, with p-values of 0.018 and 0.015 for the 150 mg and 300 mg arms respectively, and a combined p-value of 0.004. Abdakibart also demonstrated statistically significant benefit on key secondary endpoints including HiSCR50, change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4), and change in draining tunnel count. Notably, HiSCR75 response rates were consistent regardless of prior biologic exposure. The safety profile was characterized by treatment-emergent adverse events at rates similar to placebo, with headache and nausea the most commonly reported events; no neutropenia, serious infections, or opportunistic infections were observed across the 16-week period.
Context and competitive positioning
Abdakibart is a humanized IgG4 monoclonal antibody that neutralizes IL-1β, a pro-inflammatory cytokine that drives activation of downstream mediators including IL-6, TNF-α, and IL-17. The IL-1β pathway is mechanistically distinct from the targets of the three currently approved biologics for moderate-to-severe HS: AbbVie's Humira (adalimumab), which inhibits TNF-α; Novartis's Cosentyx (secukinumab), which blocks IL-17A; and UCB's Bimzelx (bimekizumab), which inhibits both IL-17A and IL-17F. If abdakibart advances through Phase III, it would enter a field where adalimumab has held first-mover status since its FDA approval for HS in 2015, secukinumab gained approval in October 2023, and bimekizumab followed in November 2024.
The LOTUS HiSCR75 rates of approximately 42% across both arms sit above the placebo rate of 25.6% by roughly 16–17 percentage points. Avalo has characterized these as the highest absolute HiSCR75 improvements observed in a trial of this size or larger, though cross-trial comparisons are limited given differences in patient populations, prior treatment history, and study designs across the HS biologic landscape. The company has also highlighted a potential monthly dosing option — the 300 mg every-four-weeks regimen — as a patient-friendly differentiator.
The consistency of response in patients with and without prior biologic exposure is a clinically relevant observation, given that a meaningful proportion of HS patients cycle through available therapies without achieving durable control. Whether that consistency holds in a larger, more heterogeneous Phase III population remains to be established.
The rationale for IL-1β inhibition in HS rests on the cytokine's role as an upstream regulator of the inflammatory cascade implicated in the disease. By neutralizing IL-1β directly, abdakibart targets a node that sits proximal to the IL-17 and TNF-α pathways already validated in HS, potentially offering a complementary or alternative mechanism for patients who do not respond adequately to existing biologics.