Clinical Trial Data Supports Teprotumumab for Treating Thyroid Eye Disease

Data presented at the 2019 American College of Rheumatology annual meeting in Atlanta, GA is painting a clearer picture for physicians on the effects of teprotumumab for the treatment of thyroid eye disease.

With a PDUFA data in March 2020 looming, pooled data from phase 2 and phase 3 trials presented at demonstrated teprotumumab’s ability to reduce proptosis and improve quality of life in more than 150 patients with active thyroid eye disease compared to placebo.

The phase 2 and phase 3 teprotumumab trials were 24-week randomized, double-masked, placebo-controlled trials that included adults between the ages of 18 and 80 years old. Patients included in the study received 8 intravenous infusions every three weeks for 21 weeks. Investigators noted the first injection was 10 mg/kg followed by 20mg/kg for the remaining seven infusions.

For inclusion, patients needed to be less than 9 months since active thyroid eye disease onset with no prior treatment and a clinical activity score of 4 or more. Additionally, steroid use needed to be limited to low doses with no use at least 4 weeks prior to study entry.

Pooled analyses revealed 77.4 of patients receiving teprotumumab experienced a reduction of 2 mm or greater in proptosis compared to 14.9% of patients receiving placebo (P<0.001). Reduction in average change from baseline in proptosis was -2.63 mm among patients receiving teprotumumab and -0.31 in the placebo group (P<0.001).

Investigators also noted 69.7% of patients receiving teprotumumab experienced improvements in diplopia of 1 or more grades compared to 30.5% of the placebo group (P<0.001) in those with baseline diplopia. In regard to quality of life, teprotumumab patients experienced greater average change from baseline through week 24 in quality of life scores (overall 15.55 vs 5.92, P<0.001)—this included scores in visual functioning (16.81 vs 6.10, P<0.001) and appearance (13.51 vs 5.78, P=0.002).

With no FDA-approved treatments for thyroid eye disease available to patients and the Biologics License Application for teprotumumab having received Priority Review, many clinicians and patients are awaiting news of the therapy’s potential approval in March 2020.

For more on what the approval of teprotumumab would impact patients and care providers, MD Magazine® sat down with lead investigator of the phase 2 and phase 3 trials Raymond Douglas, MD, PhD, professor of ophthalmology and director of the Orbit and Thyroid Eye Disease Center at Cedars-Sinai, for his perspective.

MD Mag: What would the approval of teprotumumab mean for patients with thyroid eye disease?

Douglas: Currently, there are no FDA approved therapies for this disease. So, now patients are left either to watch and wait over the course of this disease development as they see their disease and their eye-bulging, and their double vision, and their redness, and their pain grow day by day. And we either have to treat them with high dose steroids or watching weight. This can be a course over many years, often over 5 years until we can then do surgery to try to improve that proptosis or the double vision. Even those treatments are far from successful for most patients.

So, this treatment really offers an entirely new way of thinking about this disease for patients and options for treatment, and that they can undergo a course of medical therapy and in reverse all the aspects of thyroid eye disease including the bulging of the eyes, but also all the periorbital changes—the eyelid retraction, in addition to the double vision, and improvement with their quality of life. So it really is a profound game-changer in their life and how they can go out into the public and how they can function.

MD Mag: What were the quality of life changes seen during teprotumumab trials?

Douglas: In both these trials, I treated the most patients in the US and it was really astonishing what improvements these patients would have. Many of my patients had to take time off from work, couldn't drive their kids to school, were in constant pain, just couldn't visually function—and even after a short period of treatment, which eventually got better and better during the course of the trial, these patients had a remarkable improvement of their quality of life.

That is not just from the external signs and appearance, which was remarkable in and of itself, but really the improvement of how they could function. Many of the patients who had taken time off from work we're able to regain their employment.

In fact, one of my patients had to take time off and owned his own business. He just no longer could function because of the double vision and the constant pain and it actually probably saved his business because he was able to go back and function and continue to work while having treatment and pursuing and being part of the clinical trial. He was extraordinarily grateful because not only did it affect his health, it meant that he no longer lost his business and could continue to function.

So, as I've said before in some other scenarios and talking to other physicians, I've never received so many hugs and hugs of gratitude as I had for this treatment, as being a surgeon for so many years.