Sling Therapeutics Challenges Tepezza in Thyroid Eye Disease Treatment

Sling Therapeutics has achieved a milestone in the development of its oral treatment for thyroid eye disease (TED), linsitinib. In a recent phase 2b/3 clinical trial, the investigational drug demonstrated promising results, prompting the biotech company to move forward with a confirmatory phase 3 study.
This development places Sling in potential competition with Amgen’s Tepezza, an established intravenous therapy for TED. However, cross-trial comparisons highlight some challenges for Sling in matching Tepezza’s efficacy.
Linsitinib’s journey began as an asset from Astellas, where it was initially developed as a small-molecule IGF-1R inhibitor for cancer treatment. Recognizing the therapeutic potential of IGF-1R inhibition in TED, Sling repurposed linsitinib for this indication. With $35 million in funding, the company launched its phase 2b trial in 2022 to address TED, a condition associated with Graves’ disease that leads to eye bulging and other complications.

The trial enrolled 90 patients who were randomized to receive either a high dose or low dose of linsitinib or a placebo. Results after 24 weeks revealed that 52% of participants on the high dose experienced a clinically significant reduction in eye bulging, meeting the primary endpoint. This response rate was significantly higher than that observed in the placebo group, providing evidence of linsitinib’s efficacy. However, Sling did not provide details on the outcomes for the low-dose group.
In contrast, Tepezza’s phase 3 trials reported higher response rates of 71% and 83% after eight intravenous infusions over 24 weeks. While cross-trial comparisons can be problematic due to differences in study design and patient populations, these figures suggest that Sling may face an uphill battle in demonstrating comparable efficacy. As a result, Sling’s strategy may need to emphasize factors beyond efficacy to carve out its place in the TED treatment landscape.
One such factor is convenience. Tepezza’s administration requires 60- to 90-minute infusions every three weeks, which can be burdensome for patients. In contrast, linsitinib’s oral formulation, taken twice daily, offers a more convenient alternative. Recognizing the importance of ease of use, Amgen has initiated a phase 3 trial for a subcutaneous version of Tepezza, aiming to address this limitation and maintain its competitive edge.

Safety and tolerability represent another critical consideration. In Tepezza’s clinical program, 10% of patients experienced hearing-related side effects, such as tinnitus or hearing loss. Sling’s trial reported no drug-related hearing impairments, with only one unrelated case of tinnitus and a 0% placebo-adjusted tinnitus rate. Hyperglycemia, another side effect observed with Tepezza, appeared less common with linsitinib. Elevated liver enzymes were noted in Sling’s trial but resolved without evidence of significant liver injury, leading the company to conclude that linsitinib was well tolerated overall.
As Sling Therapeutics prepares for its phase 3 trial, the study will be pivotal in further elucidating linsitinib’s safety and efficacy profile. While challenges remain, particularly in matching Tepezza’s demonstrated efficacy, Sling’s oral delivery and favorable tolerability profile may position it as a viable alternative in the TED treatment market. The ongoing developments in this space will ultimately determine how the two therapies compare and whether Sling’s approach can reshape treatment options for patients with TED.