Sling Therapeutics’ oral challenger to Amgen’s intravenous Tepezza has hit the mark in a phase 2b/3 thyroid eye disease (TED) trial, teeing the biotech up to run a confirmatory study of its ex-Astellas asset. But a cross-trial comparison suggests Amgen’s blockbuster may have the advantage on the efficacy front.
Astellas studied the small-molecule IGF-1R inhibitor linsitinib as a cancer treatment. However, with the anti-IGF-1R antibody Tepezza showing the benefits of targeting the receptor in TED, Sling spied a chance to use linsitinib in the eye disease. The biotech launched with $35 million to run a phase 2b trial in TED, a complication of Graves’ disease that causes the eyes to bulge, in 2022.
About 18 months later, Sling has evidence linsitinib works in TED. Investigators randomized 90 patients to receive one of two doses of linsitinib or placebo. After 24 weeks, 52% of people on the high dose had a big enough reduction in eye bulging to meet the response criteria.
The response rate was significantly higher than in the placebo group, causing the high dose to achieve the primary endpoint. Sling made no mention of the performance of the low dose. The biotech is now preparing to start a confirmatory phase 3 trial this year.
Horizon Therapeutics, which brought Tepezza to market before selling up to Amgen, reported a higher response rate in its phase 3 program. After eight infusions across 24 weeks, the response rates in the two Tepezza trials were (PDF) 71% and 83%. Cross-trial comparisons can be misleading, but the available data suggest Sling may need to focus on areas other than efficacy to compete.
Convenience is one area Sling may have an edge over the incumbent. Tepezza patients receive 60- to 90-minute infusions every three weeks. Linsitinib is taken orally twice a day. Amgen began a phase 3 trial of a subcutaneous formulation of Tepezza last year, positioning it to potentially free patients from lengthy infusions in the future.
Safety and tolerability is another potential battleground. In Tepezza’s phase 3 program, 10% of patients on the drug developed hearing impairment, a catch-all term for conditions such as deafness and tinnitus. Sling said no drug-related hearing impairment was reported in its trial, although there was one unrelated report, and the placebo-adjusted tinnitus rate was 0%. Hyperglycemia was rarer than for Tepezza, too.
Sling saw elevated liver enzymes, but they resolved quickly and caused no signs of drug-induced injury, leading the biotech to conclude linsitinib was well tolerated. The planned phase 3 trial will shed more light on the molecule’s safety and efficacy profile and potentially position Sling to challenge Amgen for the TED market.