Amgen's Subcutaneous Tepezza Meets Primary Goal in Phase 3 Thyroid Eye Disease Trial

Amgen said on April 6 that a Phase 3 trial of Tepezza (teprotumumab-trbw) given by subcutaneous injection through an on-body injector met its primary endpoint in adults with moderate-to-severe active thyroid eye disease, according to the company's announcement.

The figures are company-reported topline results. They have not been presented at a meeting or published in a journal; Amgen said full results will be presented at an upcoming medical congress.

Tepezza is currently given as an intravenous infusion. Amgen said the IV form was approved in 2020 and described it as the first and only medicine approved for thyroid eye disease, a rare autoimmune condition that the company said can cause eye bulging (proptosis), double vision (diplopia), eye pain, redness and swelling.

The trial results

The randomized, double-masked, placebo-controlled trial gave participants Tepezza or placebo through the on-body injector every two weeks, for a total of 12 injections over a 24-week placebo-controlled period. Participants had to have been diagnosed with moderate-to-severe active disease within 15 months and to have proptosis of at least 3 mm from baseline, among other criteria. People with existing hearing impairment were allowed to enroll, the company said.

The primary endpoint was the proptosis responder rate at week 24, defined as a reduction of at least 2 mm in the study eye without a worsening of 2 mm or more in the other eye. The rate was 76.7% with Tepezza and 19.6% with placebo (p<0.0001), Amgen said. Mean proptosis reduction, a key secondary endpoint, was 3.17 mm with the drug and 0.80 mm with placebo (p<0.0001).

The company reported statistically significant improvements on other secondary endpoints, including overall responder rate, the share of patients with a Clinical Activity Score of 0 or 1, several diplopia measures and the appearance subscale of the Graves' Ophthalmopathy Quality of Life questionnaire. A numerical trend on the questionnaire's visual functioning subscale did not reach statistical significance.

"These results extend and support the best-in-class efficacy of TEPEZZA for people living with Thyroid Eye Disease, now with subcutaneous administration delivering IV-level efficacy," said Jay Bradner, Amgen's executive vice president of research and development.

Safety

Amgen said overall safety results were generally consistent with the known profile of the intravenous product. Some patients had mild-to-moderate injection site reactions, which did not lead to treatment interruption or discontinuation. The most common adverse events, seen in at least 10% of participants, were muscle spasms, tinnitus, weight decrease, ear discomfort, nausea and diarrhea. The prescribing information for intravenous Tepezza carries warnings on infusion reactions, inflammatory bowel disease, high blood sugar and hearing impairment, including hearing loss that may be permanent in some cases.

Post-marketing study

Amgen also said it has completed a separate Phase 3b/4 trial of intravenous Tepezza that was run to meet an FDA post-marketing requirement. That descriptive study compared the safety and tolerability of four, eight and 16 infusions and looked at the need for retreatment. The company said the observed risk profile matched the known profile of the IV product and that the data will be submitted to regulators.

PharmaTimes reported the results on April 7, noting that the company described the injector version's efficacy as comparable to the intravenous formulation. Amgen has not said when it plans to file the subcutaneous version with the FDA.