Horizon Therapeutics Reports Positive Topline Data from Phase 4 Tepezza Study

Rare Daily Staff

Horizon Therapeutics reported positive and statistically significant topline results from its randomized, double-masked, placebo-controlled phase 4 clinical trial of its therapy Tepezza for the treatment of adults with chronic thyroid eye disease and low measure of disease activity.

The company said the trial data continues to support the efficacy of Tepezza across a broad spectrum of thyroid eye disease patients regardless of disease activity or duration, with a well-established safety profile.

Thyroid eye disease (TED) is a serious, progressive, debilitating and potentially vision-threatening rare autoimmune disease. TED often occurs in people living with Graves’ disease, but it is a distinct disease that is caused by autoantibodies activating an IGF-1R-mediated signaling complex on cells within the retro-orbital space. This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness. Signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis (bulging eyes); pressure and/or pain behind the eyes; and diplopia.

Tepezza is the first and only medicine approved by the U.S. Food and Drug Administration for the treatment of TED – a serious, progressive, debilitating and potentially vision-threatening rare autoimmune disease. It is a fully human monoclonal antibody and a targeted inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) that is administered to patients once every three weeks for a total of eight infusions.

The phase 4 trial evaluated patients with an initial diagnosis of TED between two to 10 years and low levels of disease activity. The prior pivotal trials that formed the basis of the original FDA approval of Tepezza evaluated patients with disease duration of nine months or less and higher levels of disease activity.

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 Tepezza 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 Tepezza and patients treated with placebo increased.

No new safety signals were observed.

The company 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, the trial’s principal investigator and director of the Orbital and Thyroid Eye Disease Program at 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.”

Photo: Raymond Douglas, the trial’s principal investigator and director of the Orbital and Thyroid Eye Disease Program at Cedars-Sinai Medical Center in Los Angeles