Acelyrin Inc. (NASDAQ: SLRN) has announced updated data from its Phase 1/2 study of lonigutamab (loni) for the treatment of thyroid eye disease (TED), revealing key insights into optimal dosing strategies. The findings have influenced the design of the upcoming Phase 3 program, slated to commence in the first quarter of 2025.
Lonigutamab Phase 1/2 Study Update
The updated data indicated that a dosing regimen of 50 mg administered every four weeks (Q4W) was subtherapeutic, prompting a revised approach for the Phase 3 trial. Acelyrin's analysis pinpointed an ideal minimum concentration (Cmin) of 3 ug/ml as necessary for consistent and maximized efficacy. This level was achieved with a 50 mg loading dose followed by 25 mg weekly (QW), resulting in a Cmin of 3.6 ug/ml. In contrast, the 50 mg Q4W regimen only reached a Cmin of 0.1 ug/ml, leading to a loss of proptosis response after Week 6.
Phase 3 Dosing Strategy
Based on pharmacokinetic (PK) data, Acelyrin has chosen a 100 mg loading dose followed by 50 mg every two weeks (Q2W) for the Phase 3 program. The company's analysis indicated that the PK data with the 100 mg loading dose plus 50 mg Q2W regimen was comparable to the 50 mg loading dose plus 25 mg QW regimen, suggesting that it could achieve receptor saturation and therapeutic concentration within days.
Efficacy Comparison
Data from the Phase 1/2 study showed that the 50 mg loading dose plus 25 mg QW regimen yielded a proptosis response of 63% and a Clinical Activity Score (CAS) of 0/1 in 38% of participants. The 50 mg Q4W dose, however, demonstrated a proptosis response of just 25% and a CAS 0/1 of 50%.
Analyst Perspective
H.C. Wainwright analyst adjusted the price target on shares of Acelyrin Inc to $6.00 from the previous $8.00 but maintained a Neutral rating on the company's shares. Bodnar posited that some investors might be disappointed by the less frequent dosing regimen chosen for Phase 3. Loni's subcutaneous dosing method, with the potential for long-term treatment up to 52 weeks, stands in contrast to competitor regimens, which are administered via fixed intravenous (IV) schedules over 12 and 24 week periods.
Financial Health
InvestingPro data shows the company maintains a strong liquidity position with a current ratio of 7.15 and more cash than debt on its balance sheet, though it's currently unprofitable with negative earnings of $2.68 per share.
