Horizon Therapeutics announces positive topline data from teprotumumab-trbw Phase 4 clinical trial in patients with chronic/clinical activity score TED

Horizon Therapeutics plc announced positive and statistically significant topline results from its randomized, double-masked, placebo-controlled Phase 4 clinical trial (NCT04583735) evaluating teprotumumab-trbw (Tepezza) for the treatment of adults with chronic TED and low CAS, which is a measure of disease activity.

According to the company, teprotumumab-trbw is the first and only medicine approved by the FDA for the treatment of thyroid eye disease (TED) – a serious, progressive and potentially vision-threatening rare autoimmune disease.

The totality of clinical trial data continues to strongly support the efficacy of teprotumumab-trbw across a broad spectrum of TED patients regardless of disease activity or duration, with a well-established safety profile. Teprotumumab-trbw is the first and only medicine approved by the FDA for the treatment of TED – a serious, progressive, debilitating and potentially vision-threatening rare autoimmune disease.1

According to a news release from the company, the Phase 4 trial evaluated patients with an initial diagnosis of TED between two to 10 years (mean duration of 5.2 years; SD 1.77) and low levels of disease activity (mean CAS of 0.4; SD 0.49), whereas the prior pivotal trials (Phase 2 and 3) that formed the basis of the original FDA approval of teprotumumab-trbw evaluated patients with disease duration of nine months or less and higher levels of disease activity.

“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 three years of real-world use of TEPEZZA,” Elizabeth H.Z. Thompson, PhD, executive vice president, research and development, Horizon, said in the news release. “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.”

Topline Data Overview

At Week 24, topline data per the pre-specified primary analysis method (intent-to-treat) demonstrated that the primary endpoint was met, and patients treated with teprotumumab-trbw achieved a statistically significant reduction in proptosis from baseline compared to those receiving placebo. In addition, in the pre-specified per-protocol analysis, the differences between patients treated with teprotumumab-trbw and patients treated with placebo increased.

No new safety signals were observed.

According to the company, it plans to present these data at a future medical congress and publish them in a peer-reviewed medical journal to help educate key stakeholders, including physicians, patients and payors.

“Given this new and positive clinical evidence in patients with long-duration Thyroid Eye Disease and low CAS, it is important for physicians to thoroughly assess all of their Thyroid Eye Disease patients to determine whether Tepezza might be an option,” said Raymond Douglas, MD, PhD, the trial’s principal investigator and director of the Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center in Los Angeles. “It is important to specifically ask patients if their symptoms are interfering with their ability to work, socialize and go about daily activities. These conversations can help physicians uncover the true burden of the disease and need for treatment, regardless of how much inflammation they have behind the eye or how long they have been living with the disease.”

Trial Design

This randomized, double-masked, placebo-controlled, parallel-group, multicenter trial evaluated the efficacy, safety, and tolerability of teprotumumab-trbw (n=42) compared to placebo (n=20) in adults with chronic TED (two to 10 years duration prior to the study) and low CAS. The primary efficacy objective was to measure the effect of teprotumumab-trbw versus placebo in the change of proptosis measurements in the study eye from baseline at Week 24. All study participants were required to have an initial diagnosis of TED two to 10 years prior to screening, and a CAS of ≤1 in both eyes for at least one year prior to screening or all of the following one year prior to screening: no progression in proptosis, no progression in diplopia and no new inflammatory TED symptoms. Participants could not have had prior orbital irradiation, orbital decompression surgery or strabismus surgery. The mean duration of disease for teprotumumab-trbw and placebo patients was 5.1 years (SD 1.88) and 5.4 years (SD 1.61), respectively. The mean CAS for teprotumumab-trbw and placebo patients was 0.3 (SD 0.47) and 0.5 (SD 0.51), respectively.