Phase 3 Study Shows Teprotumumab Significantly Reduced Double Vision for People with Active Thyroid Eye Disease

Horizon Therapeutics announced new data from the phase 3 OPTIC confirmatory clinical trial showing that teprotumumab provided significant benefit on several effects of active thyroid eye disease (TED) compared with placebo, including diplopia (double vision), quality of life (QoL) and clinical activity score (CAS). These data were presented during the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) 50th Anniversary 2019 Fall Scientific Symposium, and build upon data presented earlier this year that demonstrated the significant benefit of teprotumumab on proptosis (bulging eyes), according to a company news release. 

Teprotumumab is an investigational medicine for the treatment of active TED and is currently under review by the FDA. The teprotumumab Biologics License Application (BLA) was recently granted Priority Review by the FDA and if approved, teprotumumab would be the first FDA-approved medicine for the treatment of active TED. The Prescription Drug User Fee Act (PDUFA) goal date is March 8, 2020.

“Thyroid eye disease commonly causes a variety of vision impairments, with double vision reported in about half of all people living with the disease, and almost 70 percent of patients enrolled in the OPTIC study,” Raymond Douglas, MD, PhD, of Cedars Sinai Medical Center and lead investigator of the OPTIC study, said in the news release. “People suffering from double vision often lose the ability to perform daily tasks, like reading and driving, impacting their ability to work and causing depression. The results of this study are very encouraging, showing that 68 percent of patients had an improvement of at least one grade in double vision, and also improved on other measures including quality of life and CAS score.”

Previously presented primary endpoint data from OPTIC (Treatment of Graves’ Orbitopathy (Thyroid Eye Disease to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study) showed that significantly more patients treated with teprotumumab had a meaningful improvement in proptosis, the primary study endpoint, as compared with placebo (82.9% of teprotumumab patients compared to 9.5% of placebo patients; P˂0.001).

The following new data on three secondary endpoints were presented at ASOPRS:

• Diplopia: At Week 24, 68% of patients receiving teprotumumab had an improvement from baseline of at least one grade in diplopia, compared to 29% of patients receiving placebo (P=0.001). This endpoint measured the percentage of patients who reported at least some diplopia at baseline in the study eye and who had a reduction of ≥ 1 grade with no corresponding deterioration (≥ 1 grade worsening) in the fellow eye at Week 24.
• Quality of Life: Patients receiving teprotumumab had a mean change of 13.79 on the Graves’ Ophthalmopathy Quality of Life (GO-QoL) scale compared with a change of 4.43 for patients receiving placebo (p<0.001). These scores indicate a statistical and clinically meaningful improvement over placebo in these QoL measures. The GO-QoL scale consists of two subscales to evaluate the quality of life of TED (Graves’ Ophthalmology) patients, including impacts on visual function and self-assessment of appearance. A change of 6 points is considered clinically significant.¹
• CAS Score: At Week 24, more patients achieved a CAS value of 0 or 1 with teprotumumab treatment (59% vs 21% of placebo participants) (P<0.001). CAS is a scale used to assess the disease activity of TED, and measures the degree of inflammation, including pain, swelling and redness. The CAS scale ranges from 0 to 7, with a score of 0 representing no swelling or activity.²
• Significant improvement in other secondary endpoints, including average change in proptosis and overall response rate over the 24-week treatment period, were presented during the 2019 American Association of Clinical Endocrinologists (AACE) Annual Scientific & Clinical Congress.

As previously reported, teprotumumab was generally well tolerated; the majority of adverse events were mild or moderate, manageable and resolved during or after treatment. The earlier phase 2 study results were published in The New England Journal of Medicine in May 2017.

“The phase 3 data further illustrate the potential for teprotumumab to benefit the most prominent and challenging characteristics of active thyroid eye disease, most notably the vision impairment and subsequent detrimental effect on daily life,” Shao-Lee Lin, MD, PhD, executive vice president, head of research and development and chief scientific officer, Horizon, said in the news release. “With the findings of our phase 3 clinical trial demonstrating benefit across all of the ranked endpoints studied, we are one step closer to addressing the unmet need in the TED community for an FDA-approved medicine.”