Acelyrin, a US-based biopharmaceutical company, recently announced positive Phase II trial results for lonigutamab, its monoclonal antibody treatment for thyroid eye disease (TED). However, the news was met with a significant drop in the company’s stock price, indicating investor skepticism despite the promising clinical data.
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Acelyrin’s presentation highlighted “clinically meaningful” improvements in TED symptoms, including reduced proptosis (eyeball bulging), decreased clinical activity score (CAS), and improved double vision. In the Phase I/II trial (NCT05683496), seven out of eight patients receiving a 50 mg loading dose followed by weekly 25 mg doses experienced proptosis improvement within 12 weeks.
Potential Advantages and Upcoming Phase III Trials
A key selling point for lonigutamab is its potential safety advantages over Tepezza (teprotumumab), the current standard of care for TED. Acelyrin suggests lonigutamab may carry lower risks of hearing impairment, menstrual disorders, and hyperglycemia, side effects associated with Tepezza. The FDA added a hearing loss warning to Tepezza’s label in 2023 following lawsuits alleging inadequate disclosure of hearing-related complications.
Despite the positive Phase II data, Acelyrin announced a revised dosing regimen for its upcoming Phase III trials, LONGITUDE-1 and LONGITUDE-2. These trials, enrolling approximately 350 patients, will utilize a 100 mg loading dose followed by 50 mg every two weeks, with proptosis response at 24 weeks as the primary endpoint. This change in dosing strategy, along with the extended timeline for topline results (expected in H2 2026), may contribute to investor concerns.
Previous Data and Market Landscape
Earlier data released in September 2024 showed promising proptosis reduction in patients receiving different lonigutamab dosing regimens. While these results were encouraging, they fell slightly short of the response rates observed in Tepezza trials. Tepezza, with projected 2030 sales of $2.9 billion, dominates the TED market. GlobalData forecasts lonigutamab could reach $624 million in sales by 2030 if approved.
TED, a rare autoimmune disorder causing inflammation and tissue expansion behind the eyes, leads to proptosis and diplopia (double vision). Lonigutamab’s subcutaneous administration offers a more convenient alternative to Tepezza’s intravenous infusions.
Acelyrin’s Strategic Shift
The focus on lonigutamab follows Acelyrin’s strategic decision in August 2024 to discontinue investment in izokibep, its previous lead asset for hidradenitis suppurativa (HS), despite positive Phase III data. This shift included a 33% workforce reduction. Acelyrin ultimately abandoned izokibep in December 2024 after a failed Phase IIb/III trial in uveitis, an inflammatory eye disease.
The market’s reaction underscores the challenges faced by biotech companies in navigating the complexities of drug development and investor expectations. While Phase II data provides crucial insights into efficacy and safety, the ultimate success of lonigutamab hinges on the outcome of the pivotal Phase III trials and subsequent regulatory approval.
