Avalo Therapeutics, Inc. (Nasdaq: AVTX) has announced the dosing of the first patient in its Phase 2 LOTUS trial, designed to assess the efficacy and safety of AVTX-009 in adults with moderate to severe hidradenitis suppurativa (HS). This global study aims to enroll approximately 180 participants and is set to compare two dose regimens of AVTX-009 against a placebo, with topline data expected in 2026.
AVTX-009 is a humanized monoclonal antibody (IgG4) that selectively binds to interleukin-1β (IL-1β), neutralizing its activity. IL-1β is a central driver in the inflammatory process, and its inhibition could potentially alleviate the symptoms and progression of HS.
LOTUS Trial Design and Endpoints
The Phase 2 LOTUS trial is structured as a randomized, double-blind, placebo-controlled, parallel-group study. Participants are randomized in a 1:1:1 ratio to receive one of two doses of AVTX-009 or a placebo over a 16-week treatment period. The primary efficacy endpoint is the proportion of subjects achieving Hidradenitis Suppurativa Clinical Response (HiSCR75) at Week 16.
Secondary objectives include assessing the proportion of patients achieving HiSCR50 and HiSCR90, as well as changes from baseline in the International HS Severity Score System (IHS4), draining fistula count, abscess and inflammatory nodule (AN) count, and Patient’s Global Assessment of Skin Pain (PGA Skin Pain). The trial will also monitor the development of anti-drug antibodies, safety, and tolerability.
Hidradenitis Suppurativa: An Unmet Need
Hidradenitis suppurativa is a chronic inflammatory skin condition characterized by painful nodules, abscesses, and tunnels, primarily affecting areas such as the armpits, groin, and buttocks. The condition significantly impacts the quality of life for those affected. Estimates suggest that HS affects between 0.2% and 1.7% of the population worldwide. The exact cause of HS is not fully understood but is believed to involve a combination of genetic, hormonal, and environmental factors. Current treatment options are limited, highlighting the need for more effective therapies.
AVTX-009: Targeting IL-1β in HS
AVTX-009's mechanism of action targets IL-1β, a key cytokine involved in the inflammatory cascade underlying HS. By neutralizing IL-1β, AVTX-009 aims to reduce tissue damage, inflammation, and disease progression. This approach offers a potential new avenue for treating HS, addressing the unmet needs of patients suffering from this condition.
Management Commentary
"The Avalo team has efficiently executed to achieve this important milestone and we are excited to have this trial underway. Hidradenitis suppurativa is a disease that can significantly impact quality of life and there is a need for improved treatment options. We believe AVTX-009’s high potency could make it a best-in-class and best-in-indication treatment option for patients suffering from hidradenitis suppurativa,” said Dr. Garry Neil, Chief Executive Officer and Chairman of the Board. “We look forward to releasing topline results in 2026.”
