US-based Acelyrin reported positive Phase II data for its monoclonal antibody lonigutamab in thyroid eye disease (TED), but was met by as bleak response by the biotech markets.
The results failed to impress investors, leading to an 18% drop in after-hours trading following the 6 January announcement. The stock price plunge continued through the day on 7 January, eventually closing more than 36% lower than the previous day.
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The company highlighted “clinically meaningful” improvements in symptoms, including reductions in eyeball bulging (proptosis), clinical activity score (CAS) and double vision. In the Phase I/II trial (NCT05683496), seven out of eight patients given a 50 mg loading dose followed by 25 mg weekly administration showed improvement in proptosis within 12 weeks, according to the 6 January company presentation.
Acelyrin also emphasised that lonigutamab could be safer than Amgen’s Tepezza (teprotumumab) – currently the only US Food and Drug Administration (FDA)-approved TED treatment – due to potentially lower risks of hearing impairment, menstrual disorders, and hyperglycaemia. The FDA added hearing loss to the drug’s warning label in 2023 after several lawsuits over the complications involving hearing impairment/loss from Tepezza injections were filed that claimed the side effects were not adequately disclosed on the initial warning labels for the drug.
Along with the results, Acelyrin announced plans to initiate two Phase III studies, LONGITUDE-1 and LONGITUDE-2, this quarter, enrolling around 350 patients. The trials will evaluate a higher loading dose of 100 mg followed by a maintenance dose of 50 mg every two weeks, with proptosis response rates at 24 weeks as the primary endpoint. This change in dosing regimen from Phase II to Phase III may be one of the reasons behind the dampened enthusiasm with investors. Acelyrin said that topline results are expected in H2 2026.
In a previous update released in September, 50% of patients in a six-patient cohort achieved a proptosis response, indicated by a more than or equal to 2mm reduction in protopsis, within three weeks after a single 40 mg SC injection of lonigutamab. Additionally, 67% of a second six-patient cohort who received a 50mg loading dose followed by 25mg weekly doses achieved a similar response within four weeks. In comparison, 71% and 83% of patients in two studies that enrolled a total of 170 patients treated with Tepezza achieved a reduction in protopsis of more than 2mm, as per the FDA release on the drug’s approval.
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By GlobalDataTED is a rare autoimmune condition that causes inflammation and tissue expansion behind the eyes, leading to proptosis and diplopia. Lonigutamab is being positioned as a competitor to Tepezza, as its subcutaneous administration is more convenient than Tepezza’s infusion-based delivery. Tepezza is forecast to generate $2.9bn in 2030, whereas lonigutamab is set to generate $624m in the same year, if it secures approval, according to GlobalData.
GlobalData is the parent company of Pharmaceutical Technology.
The focus on lonigutamab follows a strategic pivot in August 2024, when Acelyrin discontinued new investments in its former lead asset, izokibep, despite positive Phase III data in hidradenitis suppurativa (HS). This shift included a 33% workforce reduction, impacting 40 employees. Acelyrin officially bid goodbye to the drug in December 2024 after a Phase IIb/III study (NCT05384249) with the drug failed to hit the primary and secondary endpoints in inflammatory eye disease uveitis.
