By SPC News Staff

The FDA approved teprotumumab-trbw (Tepezza, Horizon Therapeutics) for the treatment of adults with thyroid eye disease (TED), a rare condition of which the muscles and fatty tissues behind the eye become inflamed, causing proptosis. 

Teprotumumab-trbw 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 FDA approval of Tepezza is momentous for the TED community and has the potential to change the treatment paradigm for TED—providing new hope for people who are living with this horrible, vision-threatening disease,” said Raymond Douglas, MD, PhD, the director of the Orbital and Thyroid Eye Disease Program at Cedars-Sinai Medical Center, in Los Angeles, and a co-principal investigator of the teprotumumab-trbw phase 3 confirmatory clinical trial. “Today’s news brings forward a medicine for patients that targets the underlying biology of the disease and has been shown to significantly improve eye bulging and double vision, which are the most debilitating aspects of the disease.”

Teprotumumab-trbw was approved based on the results of two studies (Study 1 and 2) consisting of a total of 170 patients with active TED who were randomized to receive either teprotumumab-trbw or placebo. Of the patients who were administered teprotumumab-trbw, 71% in Study 1 and 83% in Study 2 demonstrated a greater than 2-mm reduction in proptosis compared with 20% and 10% of those who received placebo, respectively.

The two studies were a phase 2 clinical study and the phase 3 confirmatory clinical study OPTIC (Treatment of Graves’ Orbitopathy [Thyroid Eye Disease] to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study). The OPTIC study found that significantly more patients treated with teprotumumab-trbw (82.9%) had a meaningful improvement in proptosis (≥2 mm) compared with placebo patients (9.5%) without deterioration in the fellow eye at week 24 (P?0.001). 

Additional secondary end points were also met, including a change from baseline of at least one grade in diplopia (double vision) in 67.9% of patients receiving teprotumumab-trbw compared with 28.6% of patients receiving placebo at Week 24 (P=0.001). In a related analysis of the Phase 2 and Phase 3 clinical studies, there were more patients with complete resolution of diplopia among those treated with teprotumumab-trbw (53%) compared with those treated with placebo (25%). Most adverse events experienced with teprotumumab-trbw treatment were graded as mild to moderate and were manageable in the trials, with few discontinuations or therapy interruptions.

The most common adverse reactions observed in patients treated with teprotumumab-trbw are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing loss, dry skin, dysgeusia and headache. Teprotumumab-trbw should not be used if pregnant, and women of childbearing potential should have their pregnancy status verified before beginning treatment and should be counseled on pregnancy prevention during treatment and for six months after the last dose of teprotumumab-trbw.

TED is a serious, progressive and vision-threatening rare autoimmune disease. Although TED often occurs in people living with hyperthyroidism or Graves disease, 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. As TED progresses, it causes serious damage—including proptosis, strabismus and diplopia—and in some cases can lead to blindness. Historically, patients have had to live with TED until the inflammation subsides, after which they are often left with permanent and vision-impairing consequences.

“Currently, there are very limited treatment options for this potentially debilitating disease. This treatment has the potential to alter the course of the disease, potentially sparing patients from needing multiple invasive surgeries by providing an alternative, nonsurgical treatment option,” said Wiley Chambers, MD, the deputy director of the Division of Transplant and Ophthalmology Products in the FDA’s Center for Drug Evaluation and Research. “Additionally, thyroid eye disease is a rare disease that impacts a small percentage of the population, and for a variety of reasons, treatments for rare diseases are often unavailable. This approval represents important progress in the approval of effective treatments for rare diseases, such as thyroid eye disease.”

Horizon will conduct a postmarketing study to evaluate safety in a larger patient population, as was discussed at the FDA Dermatologic and Ophthalmic Drugs Advisory Committee meeting on Dec. 13, 2019, where the committee voted unanimously (12-0) that teprotumumab-trbw demonstrated a positive benefit–risk profile. This study will also evaluate re-treatment rates relative to how long patients receive the medicine.

The FDA granted this application priority review, as well as fast track, breakthrough therapy and orphan drug designations. The drug was approved ahead of the Prescription Drug User Fee Act goal of March 8.

Teprotumumab-trbw is expected to be available in the coming weeks, according to the company. To speak with a nurse advocate about TED, patients can call (833) 483-7399.