Sling shoots at thyroid eye disease with its oral therapy

Thyroid eye disease (TED) therapy Tepezza – the top asset in Amgen's $26 billion takeover of Horizon in 2023 – could be facing competition from an easier-to-dose alternative from Sling Therapeutics.

The Michigan, US, biotech has announced topline data from a phase 2b/3 trial of linsitinib – claimed to be the first oral therapy to pass that milestone – and is planning to start a confirmatory phase 3 trial in the coming months that could support regulatory filings.

TED is a rare autoimmune disorder in which the muscles and fatty tissues behind the eye become inflamed, causing the eyes to be pushed forward and bulge outwards in a condition known as proptosis that, if severe, can become disfiguring and disabling.

Linsitinib is a small-molecule inhibitor of IGF-1R, taken twice daily. In the phase 2b/3 LIDS trial, more patients treated with a 150mg dose of the drug achieved a 2mm or better reduction in proptosis after 24 weeks compared to placebo, which was a statistically significant difference.

A lower, 75mg twice-daily dose did not outperform placebo, according to the company, but with both doses there was a "favourable safety profile", including for adverse events that are associated with IGF-1R-acting drugs, including hearing impairment, high blood sugar levels, and menstrual cycle changes.

Tepezza (teprotumumab) became the first FDA-approved treatment for TED in 2020 and is still the only drug for the disorder, which otherwise needs to be treated with surgery. It is already a blockbuster, with sales reaching more than $1.3 billion in the first nine months of 2024.

The drug is currently given once every three weeks for a total of eight infusions, so an oral alternative could be an attractive proposition for patients and healthcare systems if it reaches the market.

Amgen isn't resting on its laurels, though, particularly with other potential rivals circling, such as Viridian Therapeutics and its anti-IGF-1R antibody veligrotug that needs five infusions and has cleared a phase 3 trial.

It is developing a new formulation of Tepezza that could be dosed subcutaneously every two weeks, doing away with the need for visits to an infusion clinic, although, Viridian is also working on an injectable antibody that it believes could be given every four to eight weeks.

"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 Raymond Douglas, a professor at Cedars-Sinai Medical Center, who also serves as Sling's chief scientific officer.

"As a practising physician, it makes sense to start a new patient's treatment journey with an oral therapy that shows an early response that increases over time," he added.

Photo by Elsa Olofsson on Unsplash