Acelyrin unveils phase 3 program design for lonigutamab in thyroid eye disease

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Acelyrin announced additional data from its phase 2 clinical trial as well as the design for its phase 3 LONGITUDE program of lonigutamab in thyroid eye disease (TED) patients.

Lonigutamab is a subcutaneously (SC) delivered humanized IgG1 monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R). Furthermore, the characteristics of lonigutamab that enable subcutaneous delivery also enable the potential for longer-term dosing and allow the potential to minimize exposures relative to IV therapy which the company believes will “improve depth and durability of clinical response.”¹

New data from the phase 2 clinical trial of lonigutamab included clinically meaningful and competitive improvements across all manifestations of TED, including proptosis, Clinical Activity Score (CAS) and diplopia, as well as the Graves Ophthalmopathy-Quality of Life (GO-QoL) tool. The data showed a significant proptosis response rate with a 50 mg loading and 25 mg weekly (QW) subcutaneous dose of lonigutamab.¹

Additionally, no cases of hearing impairment as measured by audiogram, hyperglycemia or menstrual disorders in TED patients were reported at any dose level.

In addition to the phase 2 data, Acelyrin also released the design of its phase 3 LONGITUDE program of lonigutamab, which will consist of the LONGITUDE-1 and LONGITUDE-2 trials.¹ Both will be conducted across approximately 350 patients in 2 global double-masked, placebo-controlled trials to evaluate the safety and efficacy of a subcutaneously delivered 100 mg loading dose of lonigutamab followed by 50 mg every 2 weeks. Patients will be randomized 2:1 to either lonigutamab or placebo during the first 24 weeks. The primary endpoint in both trials will be proptosis response rate at 24 weeks. Additionally, all patients will receive lonigutamab after the 24-week mark through to 52 weeks, which the company states is designed to potentially enable longer-term treatment.

LONGITUDE-1 will enroll a minimum of 81 patients with active TED, while LONGITUDE-2 will have no minimum enrollment number and look at patients with both active and chronic TED.

Shep Mpofu, MD, chief medical officer at Acelyrin commented on the trials in a press release from the company¹ stating, “We look forward to working closely with clinicians around the world to rapidly initiate and enroll the Phase 3 LONGITUDE program starting in Q1 2025 for the benefit of TED patients. Our Phase 3 study is designed to address the significant unmet needs of patients, and we believe lonigutamab has the potential to be a more effective, safer and more convenient alternative to the current standard of care.”

Initiation of the Phase 3 program is expected this quarter and topline data are expected in the second half of 2026.

References:

1. Acelyrin Inc. Announces Additional Phase 2 Data and Phase 3 Program Design for Lonigutamab in Thyroid Eye Disease. Press Release. Published January 6, 2025. Accessed January 7, 2025. https://investors.acelyrin.com/news-releases/news-release-details/acelyrin-inc-announces-additional-phase-2-data-and-phase-3