Acelyrin announces new lonigutamab data and plans

“Lonigutamab, with its unique mechanism of action, is the first subcutaneous anti-IGF-1R to have demonstrated robust efficacy in TED patients comparable to the IV administered standard of care. We are further encouraged by its potential for a best-in-class safety profile with no reported cases of hearing impairment, hyperglycemia or menstrual disorders to date,” said Mina Kim, Chief Executive Officer of Acelyrin. “Our innovative dose exploration work in TED patients gives us confidence our Phase III dose has the potential to optimize patient benefit and risk and transform the TED treatment paradigm. Our registrational program is designed for real-world patients and focused on addressing the significant unmet needs in TED.”

Additional Phase II data - In the newly announced data from the ongoing Phase II trial in TED, lonigutamab demonstrated:

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:

i) Significant proptosis response rate shown with a 50 mg loading and 25 mg weekly (QW) subcutaneous dose of lonigutamab

ii) Efficacy achieved with lower levels of exposure than seen with IV-administered anti-IGF-1R agents

iii) No cases of hearing impairment as measured by audiogram, hyperglycemia or menstrual disorders in TED patients reported to date at any dose level

iv) 100 mg loading dose achieves target therapeutic concentration within days

Phase III LONGITUDE Program - Acelyrin announced the design for its Phase III LONGITUDE program, which is informed by significant dose ranging evaluation of subcutaneous lonigutamab in TED patients. Initiation of the Phase III program is expected this quarter and topline data are expected in the second half of 2026.

LONGITUDE-1 and 2 will be conducted across ~350 patients in two 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 two weeks. Patients will be randomized 2:1 to either lonigutamab or placebo arms during the first 24 weeks, and the primary endpoint in both trials will be proptosis response rate at 24 weeks. All patients will receive lonigutamab after 24 weeks through to 52 weeks of treatment, which is designed to potentially enable longer-term treatment.

Both LONGITUDE-1 and LONGITUDE-2 will evaluate “active” TED patients and “chronic” TED patients, with LONGITUDE-1 enrolling a minimum of 81 active patients. The primary endpoint for LONGITUDE-1 will be proptosis response rate at 24 weeks for active patients, with a secondary endpoint of proptosis response rate at 24 weeks for all enrolled patients. LONGITUDE-2 will recruit both active and chronic TED patients and have no minimum number of required active patients. The primary endpoint for LONGITUDE-2 will be proptosis response rate at 24 weeks for all patients. Secondary endpoints for both trials include CAS, diplopia response and GO-QoL at 24 weeks.  

As previously announced, Acelyrin held an End of Phase II (EOP2) meeting with the FDA in Q3 2024 and gained alignment on the proposed LONGITUDE-1 and LONGITUDE-2 Phase III trial designs.

Shep Mpofu, M.D., Chief Medical Officer at Acelyrin, added, “We are excited about the data generated in our Phase I/II trial and the potential for lonigutamab to change the treatment paradigm for TED patients. We look forward to working closely with clinicians around the world to rapidly initiate and enroll the Phase III LONGITUDE program starting in Q1 2025 for the benefit of TED patients. Our Phase III 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.”