Amgen scores with new thyroid eye disease formulation

Amgen's Tepezza became the first drug approved by the FDA for thyroid eye disease (TED) in 2020, and the company is now looking to extend its role with a new, more patient-friendly formulation.

The original intravenous version of IGF-1 inhibitor Tepezza (teprotumumab) is still the only therapy for TED, and made sales of $1.9 billion last year, however, its growth has stalled due to supply issues and difficulties in building the patient base. The new subcutaneous version of the drug could help extend the franchise's reach, with a two-weekly injection, rather than intravenous infusions three weeks apart.

A phase 3 trial of subcutaneous Tepezza has revealed that delivery using a wearable on-body injector achieved comparable efficacy to the current intravenous formulation, said Amgen in a statement.

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, with accompanying visual disturbances like double vision as well as pain, redness, and swelling.

The TEPEZZA OBI trial in patients with moderate-to-severe TED showed a 77% proptosis response rate after 24 weeks, compared to 20% for the placebo group, which Amgen's head of R&D, Jay Bradner, said was indicative of "IV-level efficacy." A response was defined as a 2 mm or greater reduction in proptosis from baseline.

The average reduction achieved with Tepezza OBI was nearly 3.2 mm, compared to a 0.8 mm reduction in the control group.

Subcutaneous delivery had a side-effect profile similar to IV Tepezza, with mild-to-moderate injection site reactions in some patients that, according to Amgen, did not lead to any interruptions in treatment or discontinuations.

The new delivery route could help expand the market for Tepezza to include people unprepared to go through regular IV infusions or who struggle to access infusion clinics, and help Amgen defend the brand as rivals approach the market.

Potential competitors include a pair of IGF-1 inhibitors from Viridian Therapeutics. Lead candidate veligrotug has been filed for approval with an IV dosing regimen similar to Tepezza, with a verdict from the FDA due by 30th June.

Meanwhile, Viridian is also developing elegrobart, which can be given subcutaneously by autoinjector every four or eight weeks, and is in late-stage clinical testing with a US filing expected early in 2027.

Another potential rival, Immunovant's injectable FcRn blocker batoclimab, failed a phase 3 trial in TED earlier this month, while Sling Therapeutics is working on a small-molecule IGF-1 inhibitor, linsitinib, which has generated promising results in mid-stage testing and is being advanced into phase 3.