Acelyrin Inc announces proof-of-concept data in trial of lonigutamab in thyroid eye disease

Acelyrin Inc announced positive proof-of-concept data from its ongoing Phase 1/2 trial (NCT05683496) of lonigutamab in thyroid eye disease (TED). According to the company, lonigutamab demonstrated rapid improvements in proptosis and clinical activity score (CAS) at the first measurement (3 weeks after the first dose).¹

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

The ongoing trial is a double-masked, placebo-controlled, multicenter trial in 3 cohorts of patients with active TED. Cohort 1 is placebo-controlled testing lonigutamab 40mg every 3 weeks through 6 weeks, with 6 patients receiving lonigutamab and 2 receiving placebo. Cohort 2 is open-label testing a 50mg loading dose followed by 25mg every week with data available from 6 patients at 6 weeks. Cohort 3 is testing every 4 weeks dosing. A total of 38 patients have been enrolled in the trial.²

In cohort 1, of the patients treated with lonigutamab, 50% saw a proptosis response of ≥ 2 millimeter reduction in proptosis from baseline, all saw a ≥ 2 point reduction in CAS, and 25% saw > 1 Bahn-Gorman improvement.¹

While in cohort 2, 67% saw a proptosis response of ≥ 2 millimeter reduction in proptosis from baseline, 83% saw a ≥ 2 point reduction in CAS, and 40% saw > 1 Bahn-Gorman improvement.¹

“It is important to note that this is preliminary data in a small group, however the positive results are highly promising. Given the growing body of evidence that suggests thyroid eye disease may have long-term sequelae, the convenience of a subcutaneous administered medication with a potentially favorable side effect profile becomes critical,” said Shoaib Ugradar, MD, Department of Orbital and Oculoplastic Surgery, private practice, Beverly Hills, California in the press release.¹

Shao-Lee Lin, MD, PhD, founder and CEO of Acelyrin, discussed the results in a press release from the company.¹

“The data support our hypothesis that lonigutamab has the potential to optimize benefit-risk by enabling longer-term subcutaneous dosing to increase depth and durability of clinical response while attempting to limit safety liabilities by avoiding the high maximal concentrations resulting from IV administration, while maintaining optimal therapeutic levels,” said Lin. “Tackling thyroid eye disease has special meaning for our team, and we are thankful to the patients and investigators who have partnered with us. We are delighted to have achieved proof of concept for lonigutamab in TED and intend to advance clinical development with the potential to move patients toward resolution of their disease.”

According to the company, no reports of hyperglycemia, hearing impairment and no serious adverse events have been reported. With proof of concept achieved in cohort 1, a phase 2b/3 trial is planned to be initiated in the second half of 2024.

References:

1. ACELYRIN, INC. Announces Positive Phase 1/2 Proof-Of-Concept Data For Lonigutamab, First Subcutaneous Anti-IGF-1R To Demonstrate Clinical Responses In Thyroid Eye Disease. Press release; March 20, 2024. Accessed March 21, 2024. https://investors.acelyrin.com/news-releases/news-release-details/acelyrin-inc-announces-positive-phase-12-proof-concept-data

2. Efficacy and Safety of Lonigutamab in Subjects With Thyroid Eye Disease (TED). ClinicalTrials.gov. Updated February 9, 2024. Accessed March 21, 2024. https://clinicaltrials.gov/study/NCT05683496?tab=table