Development

Amgen's subcutaneous Tepezza meets primary endpoint in Phase III thyroid eye disease trial

Edited by Robert McTiernan··3 min read

Amgen (NASDAQ: AMGN) reported that a Phase III trial of subcutaneous teprotumumab-trbw (Tepezza) delivered via an on-body injector met its primary endpoint in moderate-to-severe active thyroid eye disease, with 76.7% of patients achieving a proptosis response at week 24 versus 19.6% on placebo — a result that positions the reformulation as a potential administration alternative to the already-approved intravenous version.

Trial specifics

The Phase III TEPEZZA OBI trial is a randomized, double-masked, placebo-controlled, multicenter study enrolling adults with moderate-to-severe active thyroid eye disease, delivering teprotumumab or placebo via on-body injector every 2 weeks for 12 injections over 24 weeks.

At week 24, the proptosis responder rate — defined as a ≥2 mm reduction in the study eye without ≥2 mm deterioration in the fellow eye — was 76.7% for the subcutaneous arm versus 19.6% for placebo (p<0.0001). The key secondary endpoint, mean proptosis reduction, was −3.17 mm versus −0.80 mm for placebo (p<0.0001). Additional secondary endpoints, including diplopia response rate, Clinical Activity Score of 0 or 1, and the Graves' Ophthalmopathy Quality of Life appearance subscale, also met statistical significance. The GO-QoL visual functioning subscale showed a numerical trend favoring treatment but did not reach statistical significance.

The safety profile was consistent with that of intravenous Tepezza. Mild-to-moderate injection site reactions occurred in some patients but did not lead to treatment interruption or discontinuation. The most common adverse events occurring in ≥10% of patients were muscle spasms, tinnitus, weight decrease, ear discomfort, nausea, and diarrhea — a pattern familiar from the IV formulation's established label.

The development context

Teprotumumab is a fully human monoclonal antibody that blocks insulin-like growth factor-1 receptor (IGF-1R) signaling on orbital fibroblasts, the pathway through which autoantibodies drive the inflammation, glycosaminoglycan deposition, and proptosis characteristic of thyroid eye disease. The IV formulation received FDA approval in 2020 as the first and only approved medicine for TED and has since been used in more than 25,000 patients. The subcutaneous program does not alter the molecule or its target; it repackages the same active ingredient into a format that could, if approved, eliminate the requirement for infusion center visits.

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That distinction matters commercially. The IV regimen involves eight infusions over 24 weeks, with infusion times of about 90 minutes for the first two doses and as little as 60 minutes thereafter if tolerated. For a condition that already imposes substantial functional burden — proptosis, diplopia, and periorbital pain can significantly limit daily activity — the added logistical demand of repeated infusion visits is a recognized friction point. A subcutaneous option delivered via an on-body injector could extend access to patients in geographies without infusion infrastructure and reduce the overall treatment burden, though whether payers and prescribers will view the convenience premium as justifying any additional cost differential remains to be seen.

The competitive context for this data is worth examining. Immunovant's batoclimab, an FcRn inhibitor that reduces pathogenic IgG antibodies rather than directly targeting IGF-1R, failed to meet the primary proptosis endpoint in two Phase III trials in TED. Sling Therapeutics' linsitinib, an oral small-molecule inhibitor of IGF-1R and the insulin receptor, has reported positive topline results from its Phase II/III LIDS study. Cross-trial comparisons are limited by differences in patient populations, endpoint definitions, and trial designs, but the landscape suggests that direct IGF-1R blockade via teprotumumab retains the most mature efficacy dataset in this indication, and the subcutaneous program extends that dataset without introducing mechanistic uncertainty.

Amgen noted separately that a Phase IIIb/IV post-marketing requirement study of intravenous Tepezza — evaluating three treatment durations of 4, 8, and 16 infusions and the need for retreatment — has been completed. That study was descriptive in nature, and its safety observations were consistent with the known IV profile. Data from both studies will be submitted to regulatory authorities and presented at an upcoming medical congress; no regulatory submission timeline for the subcutaneous formulation was disclosed in the topline release.

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