Totality of data observed with subcutaneous lonigutamab in Thyroid Eye Disease (TED) patients demonstrate potential for efficacy in line with standard of care and a more favorable safety profile
Conducted positive end of Phase 2 FDA meeting; Phase 3 program expected to be initiated in Q1 2025
Topline Phase 3 data expected in second half of 2026; cash runway expected through mid-2027.
ACELYRIN, INC. announced additional phase 2 data and the phase 3 program design for lonigutamab in Thyroid Eye Disease (TED).
“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, CEO of ACELYRIN. “Our innovative dose exploration work in TED patients gives us confidence our Phase 3 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 2 data
In the newly announced data from the ongoing phase 2 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:
- Significant proptosis response rate shown with a 50 mg loading and 25 mg weekly (QW) subcutaneous dose of lonigutamab
- Efficacy achieved with lower levels of exposure than seen with IV-administered anti-IGF-1R agents
- No cases of hearing impairment as measured by audiogram, hyperglycemia or menstrual disorders in TED patients reported to date at any dose level
- 100 mg loading dose achieves target therapeutic concentration within days
Phase 3 LONGITUDE program
ACELYRIN today also announced the design for its phase 3 LONGITUDE program, which is informed by significant dose ranging evaluation of subcutaneous lonigutamab in TED patients. Initiation of the phase 3 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 2 (EOP2) meeting with the United States Food and Drug Administration (FDA) in Q3 2024 and gained alignment on the proposed LONGITUDE-1 and LONGITUDE-2 Phase 3 trial designs.
Shep Mpofu, MD, chief medical officer at ACELYRIN, added, “We are excited about the data generated in our Phase 1/2 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 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.”
About Lonigutamab
Lonigutamab is a humanized IgG1 monoclonal antibody targeting the insulin-like growth factor 1 (IGF-1) receptor and is delivered subcutaneously. Relative to standard of care, lonigutamab binds to a distinct epitope, which results in internalization of the receptor within minutes. The characteristics of lonigutamab that enable subcutaneous delivery also enable the potential for longer-term, convenient dosing, which can potentially improve depth and durability of clinical response.