Avalo Therapeutics hits Phase 2 primary endpoint in HS trial

Avalo Therapeutics has reported positive topline results from its Phase 2 LOTUS trial of abdakibart (AVTX-009) in adults with moderate to severe hidradenitis suppurativa (HS), saying the study met its primary endpoint at both doses examined and that the company intends to advance directly into a registrational Phase 3 programme.

The randomised, double-blind, placebo-controlled trial enrolled 253 adults and assessed two dose regimens — 150 mg every two weeks and 300 mg every four weeks — against placebo over 16 weeks. The primary endpoint, the proportion of patients achieving HiSCR75 (a 75% reduction in abscess and inflammatory nodule count), was met at both doses: 42.2% in the 150 mg arm (p=0.018) and 42.9% in the 300 mg arm (p=0.015), against a placebo response rate of 25.6%. Avalo says these represent the highest absolute HiSCR75 rates observed in any HS trial of comparable or greater size.

Trial data and mechanism

Key secondary endpoints — HiSCR50, change in the International HS Severity Score (IHS4), and change in draining tunnel count — also achieved statistical significance. Numerically favourable trends were observed across remaining secondary measures. Notably, HiSCR75 response rates were consistent regardless of whether patients had previously received biologic therapy, a subgroup that typically presents a more challenging treatment context.

Abdakibart is a humanised IgG4 monoclonal antibody that neutralises interleukin-1β (IL-1β), a pro-inflammatory cytokine implicated in the pathogenesis of HS and a range of other autoimmune disorders. The safety profile in LOTUS was described as favourable: treatment-emergent adverse events were distributed similarly across active and placebo arms, with headache and nausea the most commonly reported. There were no signals of neutropenia, serious infection, or opportunistic infection across the 16-week period.

Garry Neil, chief executive of Avalo, said the results "powerfully validate the clinical promise of IL-1β inhibition for hidradenitis suppurativa" and described the dataset as de-risking for the Phase 3 transition. The company is designing a monthly dosing regimen it positions as patient-friendly relative to current standard of care.

Market context and competitive landscape

HS is a chronic inflammatory skin disease estimated to affect between 0.7% and 2–4% of the US population, with onset typically in late adolescence or early adulthood. Despite its prevalence, the approved treatment landscape has historically been sparse. Secukinumab (Novartis, approved 2023) and adalimumab (AbbVie, approved 2015) are the only biologics with US regulatory approval in the indication; bimekizumab (UCB) received approval from the FDA in 2024, expanding the IL-17 franchise in HS.

Abdakibart's IL-1β mechanism is distinct from the IL-17 and TNF-α pathways targeted by those approved agents, and from the IL-1α/β inhibitor approach being explored by a small number of other clinical-stage programmes. If the Phase 3 data hold, Avalo would be positioned as the first IL-1β-selective antibody to reach the HS market — though cross-trial comparisons with existing therapies remain unreliable in the absence of head-to-head studies, as the company itself acknowledges in its forward-looking statement boilerplate.

The HS market has attracted increasing interest from mid-size and large-cap dermatology franchises, and a successful Phase 3 readout would likely elevate Avalo's profile as a licensing or acquisition target. Full LOTUS data are expected to be presented at an upcoming medical congress; investors will look for granular subgroup data, longer-term durability signals, and Phase 3 design details before assigning firm probability-of-success estimates to the programme.