Tepezza Improves Proptosis in Patients With Chronic Thyroid Eye Disease

Tepezza^® (teprotumumab-trbw) significantly reduced proptosis in adults with chronic thyroid eye disease (TED) and chronic/low clinical activity score (CAS), according to data from a phase 4 trial.

The randomized, double-masked, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04583735) evaluated the efficacy and safety of Tepezza in 62 adults who were diagnosed with TED 2 to 10 years prior to screening and had low levels of disease activity (CAS of ≤1 in both eyes for at least 1 year prior to screening or all of the following 1 year prior to screening: no progression in proptosis, no progression in diplopia and no new inflammatory TED symptoms). The original approval of Tepezza was based on study data that included patients with disease duration of 9 months or less and higher levels of disease activity.

Among the study participants in the phase 4 trial, the mean duration of TED was 5.2 years and mean CAS was 0.4. Patients were randomly assigned 2:1 to receive either Tepezza 10mg/kg for the first intravenous (IV) infusion followed by 20mg/kg every 3 weeks for 7 additional infusions or placebo. The primary endpoint was the change from baseline to week 24 in proptosis in the study eye.

Results showed that treatment with Tepezza met the primary endpoint demonstrating the following reductions in proptosis at week 24 compared with placebo, respectively:

• Reduction in proptosis (intent-to-treat): 2.41mm vs 0.92mm (P =.0004)
• Reduction in proptosis (per protocol): 2.44mm vs 0.69mm (P =.0006)

At week 24, the proportion of proptosis responders (defined as the percentage of patients with 2mm or greater reduction in proptosis in the study eye from baseline; key secondary endpoint) was 62% vs 25% (P =.0134) in the intent-to-treat population and 63% vs 7% (P =.0008) in the per protocol population. No new safety signals were observed during the trial.

“We are thrilled with the topline results, which reinforce that Tepezza significantly reduces proptosis in people living with thyroid eye disease, regardless of their disease activity or duration, and underscores what we learned from our initial trials and what we have seen through more than 3 years of real-world use of Tepezza,” said Elizabeth H.Z. Thompson, PhD, executive vice president, research and development, Horizon. “With Tepezza, physicians have a medicine that can be used in a broad range of thyroid eye disease patients, including those with long-duration disease of more than 5 years on average in this trial, which is important because we know the negative impact of the disease can be significant across all types of thyroid eye disease patients. We look forward to discussing these data with the FDA to determine our next steps.”