Amgen releases positive topline results from phase 3 trial of teprotumumab-trbw (TEPEZZA)

Amgen announced positive topline results from the phase 3 study of subcutaneous injection of TEPEZZA (teprotumumab-trbw) for moderate-to-severe thyroid eye disease (TED).

The key takeaways are:

• the study met the primary and key secondary endpoints
• 77% of patients achieved highly statistically significant proptosis response and
• the study showed clinically meaningful reduction in proptosis, greater than 3 mm

TEPEZZA, the first and only approved treatment for TED, when injected subcutaneously, was found to have efficacy that is comparable to intravenous treatment, including a 77% proptosis response and a reduction in eye bulging that exceeded 3 mm over 24 weeks, according to the press release.

TEPEZZA is injected subcutaneously by an on-body injector (OBI). and provides comparable efficacy to, and builds upon the success of, intravenous TEPEZZA, the press release states.

Phase 3 TEPEZZA trial

The phase 3 study was a randomized, double-masked, placebo-controlled, parallel-group, multicenter trial that evaluated the efficacy and safety of subcutaneous TEPEZZA vs. placebo in patients with active TED. The primary endpoint was the proptosis responder rate (percentage of participants with a 2-mm or greater reduction from baseline in proptosis in the study eye without deterioration, defined as a 2-mm or greater increase in proptosis in the fellow eye at week 24.

The patients were treated with either TEPEZZA or a placebo via an on-body injector every 2 weeks for a total of 12 injections. All patients had moderate-to-severe TED diagnosed within 15 months and proptosis of 3 mm or more from baseline (before TED was diagnosed). Participants with baseline hearing impairment were included in the study.

The company reported, “The phase 3 TEPEZZA OBI trial met its primary endpoint in moderate-to-severe active TED, showing a statistically significant and clinically meaningful 77% proptosis response rate during the 24-week placebo-controlled period (76.7% TEPEZZA OBI vs. 19.6% placebo [p<0.0001]). Importantly, the mean proptosis reduction, a key secondary endpoint, was -3.17 mm at week 24 (-3.17 mm TEPEZZA OBI vs. -0.80 mm placebo; p<0.0001).”

The study also found significant and clinically meaningful improvements in the secondary endpoints: ie, the overall responder rate, the percentage of patients achieving a Clinical Activity Score of 0 or 1, the change in diplopia as ordinal response categories, the diplopia response rate, the complete diplopia responder rate, and the mean change from baseline in week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) appearance subscale. Regarding the last, the change was not significant, but data showed a numerical trend favoring TEPEZZA OBI in the mean change in baseline at week 24 in the GO-QoL visual functioning subscale.

The treatment’s safety results were generally consistent with the known safety profile of TEPEZZA IV. Specifically, mild-to-moderate reactions at the injection site were seen with subcutaneous administration in some patients, which did not result in treatment interruption or discontinuation. The most common adverse events (≥10%) were muscle spasms, tinnitus, weight decrease, ear discomfort, nausea, and diarrhea, according to the press release.

Madhura A. Tamhankar, MD, professor of ophthalmology and neurology at the Scheie Eye Institute, University of Pennsylvania, Philadelphia, commented, "TED can be a profoundly debilitating condition, affecting not only vision but also daily functioning with symptoms like double vision and eye bulging. Expanding administration options through subcutaneous delivery opens the possibility of a more accessible experience for patients with TED and is critical to serving diverse patient needs. The potential to achieve comparable efficacy to IV makes this advancement compelling."

Post-marketing requirement study

Another Phase 3b/4 trial was carried out and completed based on an FDA post-marketing requirement for TEPEZZA IV. The study evaluated the drug’s safety and tolerability associated with four, eight, and 16 infusions of TEPEZZA IV and assessed the need for retreatment. The observed risk profile was consistent with the known profile of TEPEZZA IV. The post-marketing data will be submitted to regulatory authorities and presented at an upcoming medical congress, the company announced.
TEPEZZA IV was approved in 2020 to treat TED regardless of the disease activity or duration.