Avalo Therapeutics has fully enrolled its Phase 2 LOTUS study of AVTX-009 in hidradenitis suppurativa, randomizing roughly 250 adults 1:1:1 to two dosing regimens versus placebo for 16 weeks, with HiSCR75 at Week 16 as the primary endpoint. Secondary measures include HiSCR50 and HiSCR90, IHS4, draining fistula count, abscess and inflammatory nodule count, and a 30% reduction threshold on patient-reported skin pain.
The core development is speed and scale: Avalo exceeded its original 222-patient target and closed enrollment ahead of topline data expected mid-2026. The program tests high-affinity IL-1β inhibition in a moderate-to-severe HS population using a higher bar for response than many historical programs. With two active arms, the company is positioned to examine exposure–response and dose selection efficiently ahead of any registrational design.
Strategically, the choice of HiSCR75 as the primary endpoint signals an intent to compete against a rising standard set by recent biologic entrants while avoiding the optics of incremental improvement over HiSCR50. That carries risk. Raising the bar could sharpen differentiation if the signal is strong, but it also narrows the margin for error in a heterogeneous disease where tunnels, draining fistulas, and pain can confound lesion-count metrics. Leaning into IL-1β is a thematic swing at upstream inflammation in HS; it positions Avalo outside the dominant IL-17/TNF lanes, but the class’s track record in HS remains less defined, making this as much a mechanism bet as a competitive positioning play.
For sites and CROs, the enrollment overage suggests robust investigator engagement and patient availability despite a crowded HS trial landscape. That matters operationally: HS patients are increasingly pretreated with biologics, and screening failure rates can climb as endpoints get stricter. The inclusion of fistula counts and pain reduction alongside HiSCR creates a more comprehensive data package but also increases operational complexity, with reliance on standardized lesion assessments and consistent ePRO capture. Vendors supporting eCOA and centralized training will carry more weight in ensuring endpoint fidelity, especially across community and academic dermatology networks.
Regulators and payers will watch where the efficacy floor lands. A convincing HiSCR75 signal paired with clinically meaningful pain reduction and improvements in IHS4 could support a differentiated profile; an equivocal primary with stronger HiSCR50 or pain outcomes would revive familiar debates on endpoint selection in HS. Prior biologic exposure, Hurley stage distribution, and tunneling prevalence will be key effect modifiers. If Avalo can show balanced benefit across these strata, it would align with regulators’ widening emphasis on subgroup robustness and real-world applicability.
The next inflection comes with dose separation, safety, and durability beyond Week 16. Infection signals and immunogenicity will be scrutinized, given the cytokine target and chronic dosing realities in HS. If the dataset yields a clear dose, Avalo will face a pivotal trial design choice: continue against placebo with rescue or move to an active-controlled setting to position for payer negotiations. Comparator selection, regional footprint, and endpoint hierarchy will determine cycle time and commercial leverage. Watch for early indications of durability extensions, biomarker or responder-enrichment strategies, and any moves to lock in global site networks before the next wave of HS trials tightens patient supply.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
