Acelyrin Unveils Phase 3 Program Design for Lonigutamab in Thyroid Eye Disease

Acelyrin has announced new data from its Phase 2 clinical trial of lonigutamab and revealed the design for its Phase 3 LONGITUDE program for patients with thyroid eye disease (TED). This innovative program aims to address significant unmet needs in TED management through a subcutaneously delivered treatment with promising results.

About Lonigutamab

Lonigutamab is a humanized IgG1 monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R). Its design enables subcutaneous (SC) delivery, allowing for longer-term dosing and potentially minimizing exposures compared to IV therapies. This delivery method is expected to enhance the depth and durability of clinical response.

Phase 2 Clinical Trial Results

The Phase 2 trial demonstrated significant and clinically meaningful improvements across various TED manifestations, including:

       • Proptosis

       • Clinical Activity Score (CAS)

       • Diplopia

       • Graves’ Ophthalmopathy-Quality of Life (GO-QoL) tool

Key findings include:

       • A significant proptosis response rate was achieved with a 50 mg loading dose followed by a 25 mg weekly subcutaneous dose of lonigutamab.

       • No reports of hearing impairment, hyperglycemia, or menstrual disorders at any dose level.

Phase 3 LONGITUDE Program Design

The Phase 3 LONGITUDE program consists of two global, double-masked, placebo-controlled trials, LONGITUDE-1 and LONGITUDE-2, which will collectively include approximately 350 patients.

Key Details of the Program:

       1. Dosing Protocol:

               • Patients will receive a 100 mg loading dose of lonigutamab followed by 50 mg every two weeks.

       2. Study Structure:

               • Randomization: Patients will be randomized 2:1 to receive either lonigutamab or placebo for the first 24 weeks.

               • Open-Label Extension: All patients will transition to lonigutamab treatment after 24 weeks, continuing through 52 weeks.

       3. Primary Endpoint:

              • Proptosis response rate at 24 weeks.

       4. Enrollment Criteria:

              • LONGITUDE-1: Minimum of 81 patients with active TED.

              • LONGITUDE-2: Includes both active and chronic TED patients, with no minimum enrollment.

Timeline

       • The Phase 3 LONGITUDE program is set to begin Q1 2025, with topline results expected in the second half of 2026.

Expert Commentary

Dr. Shep Mpofu, Chief Medical Officer at Acelyrin, stated:

“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.”

Conclusion

With its innovative design and promising Phase 2 results, lonigutamab has the potential to transform TED treatment by offering a safer and more convenient alternative to existing therapies. The Phase 3 LONGITUDE program is an exciting step forward in addressing the needs of both active and chronic TED patients.