Acelyrin, Inc. (Nasdaq: SLRN) has announced positive topline results from its Phase 3 trial evaluating izokibep in patients with moderate-to-severe hidradenitis suppurativa (HS). The trial met its primary endpoint, demonstrating a statistically significant Hidradenitis Suppurativa Clinical Response (HiSCR) 75 at 12 weeks. Simultaneously, the company revealed a strategic shift, prioritizing the development of lonigutamab for thyroid eye disease (TED).
The global Phase 3 trial of izokibep in HS showed that 33% of patients receiving izokibep 160mg weekly achieved HiSCR75, compared to 21% receiving placebo (p-value=0.0294). Higher order endpoints also demonstrated statistically significant results, with 25% of patients achieving HiSCR90 compared to 9% on placebo (p-value=0.0009), and 22% achieving HiSCR100 compared to 8% on placebo (p-value=0.001).
Continued Efficacy and Safety of Izokibep
Acelyrin has continued dosing patients in a placebo-controlled manner through week 16. Preliminary data from two-thirds of patients at week 16 demonstrate continued deepening of HiSCR responses over time. No new safety signals for izokibep were observed. The most common adverse events were mild-to-moderate injection site reactions, headache, nasopharyngitis, fatigue, and diarrhea. Notably, there were no cases of candida infection, liver toxicity, or suicidal ideation/behavior in the izokibep treatment arm.
Strategic Shift to Lonigutamab
Despite the positive data for izokibep in HS and psoriatic arthritis (PsA), Acelyrin is prioritizing the development of lonigutamab, a humanized IgG1 monoclonal antibody targeting the IGF-1 receptor, for TED. The company has completed the Phase 1 proof-of-concept portion of the ongoing lonigutamab trial, and the dose-ranging Phase 2 portion in TED patients is continuing. Acelyrin plans to move directly into a Phase 3 program in Q1 2025.
"While today’s positive HS data and previously announced psoriatic arthritis (PsA) data support a path to approval for izokibep, we have determined that a program of this breadth and size is best brought to market by a larger organization with the resources and existing footprint in these indications," said Mina Kim, Chief Executive Officer of ACELYRIN.
Financial Outlook and Corporate Reorganization
Acelyrin's strategic shift includes an approximately 33% reduction in its workforce. The company expects these combined efforts will extend its cash runway to mid-2027. Cash, cash equivalents, and short-term marketable securities totaled $635.2 million at June 30, 2024. These resources are expected to fund the ongoing Phase 2 trial and two planned registrational Phase 3 trials for lonigutamab in TED, the ongoing izokibep Phase 3 trial in uveitis, and the completion of the ongoing izokibep HS and PsA trials.
About Lonigutamab
Lonigutamab is designed for subcutaneous delivery and binds to a distinct epitope on the IGF-1 receptor, resulting in rapid internalization of the receptor. Preclinical data suggest it is 75-fold more potent than the standard of care. The characteristics of lonigutamab enable the potential for longer-term, convenient dosing, which can potentially improve the depth and durability of clinical response.
