Sling's oral challenger to Tepezza shows promise in thyroid eye disease study

Sling Therapeutics on Tuesday reported positive Phase IIb/III data for linsitinib in thyroid eye disease (TED), potentially setting the stage for the first oral alternative to Amgen's intravenous Tepezza (teprotumumab-trbw) in a market that analysts say remains significantly underpenetrated.

The LIDS trial randomised 90 patients to receive either one of two doses of linsitinib (75 mg or 150 mg) twice daily or placebo for 24 weeks.

The oral small molecule achieved its primary endpoint with a 52% proptosis responder rate at the 150-mg twice-daily dose, though that falls below the 71-83% response rates seen in Tepezza's pivotal trials. The results come just months after Viridian Therapeutics reported that its own TED candidate veligrotug (VRDN-001) achieved a 70% response rate in Phase III. Veligrotug is an intravenously delivered anti-IGF-1 receptor antibody given as five infusions, compared with eight for Tepezza.

'Ample opportunity'

"The positive data from this trial establish the clinical significance of linsitinib and represent the first ever successful clinical trial of an oral small molecule for the treatment of TED," said Sling CEO Ryan Zeidan. "We believe linsitinib can be a potential new treatment option that could enable a broader number of physicians across multiple therapeutic disciplines to treat patients diagnosed with TED."

On the safety front, linsitinib showed no drug-related hearing impairments or tinnitus, a class effect of anti-IGF-1 receptor antibodies like Tepezza that has "caused some headwinds to overall use," Oppenheimer analysts wrote in a report last year.

While Tepezza "changed the game" in TED treatment, the analysts said its roughly $2 billion in annual sales "leaves ample opportunity" in what they estimate could be a $4.5-billion total addressable market.

Clean safety profile

Meanwhile, adverse events (AEs) in the LIDS trial were typically mild or moderate, with the most frequent being diarrhoea, headache and nausea, each occurring at rates of about 21%. Other common side effects included fatigue (17.2%), ALT increase (17.2%), hyperhidrosis (13.8%), AST increase (10.3%), and muscle spasms (10.3%).

Sling said liver enzyme levels also returned to normal quickly and were not linked to any increases in bilirubin, ALP, hepatic dysfunction, or other signs of drug-induced liver damage. One patient out of 29 (3%) experienced hyperglycaemia, and no QTc prolongation was detected in any participant, even with thorough monitoring throughout the study.

"Patients must currently choose between an invasive orbital surgery or eight infusions over 24 weeks, which can be inconvenient and time-consuming and pose serious potential risks," said Chief Scientific Officer Raymond Douglas, noting that drug-related side effects such as hearing impairments or significant hyperglycaemia "are the largest barriers for current medical treatments."

Phase III start this year

Sling, which launched in 2022 with a $35-million series A financing after in-licensing linsitinib from Astellas, plans to initiate a confirmatory Phase III trial later this year. The company is joining an increasingly competitive field that aside from Tepezza, which Amgen acquired through its $27.8-billion Horizon Therapeutics takeout in 2023, and veligrotug also includes Immunovant's IMVT-1401, a monoclonal antibody that targets FcRn.