Horizon Pharma announced recently the results of its phase 3 confirmatory drug trial evaluating teprotumumab, a fully human monoclonal antibody and targeted inhibitor of the insulin-like growth factor 1 receptor IGF-1R, for the treatment of active, inflammatory thyroid eye disease (TED). The results show that approximately 83% of the TED patients treated with this new medication achieved a 2 mm or more reduction in proptosis (the primary endpoint of the study), which was statistically significant (P < .001). All secondary endpoints were met statistically as well, including reduction of the clinical activity score (CAS), change in diplopia and improved quality of life scores. Less than 10% of patients in the placebo arm showed improvement.
Until now, treatment of TED often consisted of symptomatic management and in some cases temporizing steroids and orbital radiation. In general, treating physicians would wait until the inflammatory phase of the disease had subsided and the patient was stable before proceeding with surgical management that often meant several surgeries spread out over 1 to 3 years with significant time off from work and life.
I participated in the phase 2 and phase 3 trials of this medication and was impressed by patients who showed a reduction in proptosis and CAS score early in the phase 2 trial. It was as though the inflammatory component was turned off with a light switch. I have been treating TED for more than 35 years now and had never experienced this type of rapid reversal of signs and symptoms. These results were published in the New England Journal of Medicine in 2017.
I believe this is exciting news for patients with the disfiguring, disabling and sometimes blinding disease of TED. The company plans to submit a biologics license application with the FDA in mid-2019. Teprotumumab has received breakthrough therapy, orphan drug and fast track designations from the FDA, so we are hopeful that it will be available for patients in the relatively near future.
Given my experience, I suspect that treating physicians will want to give patients the option to receive this medication shortly after the diagnosis is confirmed before the inflammation has a chance to cause so many troubling symptoms and physical changes. The medication needs to be given IV, and we have used infusion centers for this up to this time.
It appears likely that we will witness “a new dawn” in the medical treatment of TED, with the first drug that can specifically treat the underlying cause of this ailment and reduce signs and symptoms of the disease and likely keep it from getting worse. It has been exciting to be a part of this research, and I expect that the treatment results will be gratifying going forward.
Smith TJ, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1614949.
Roger A. Dailey, MD, FACS
Lester T. Jones Endowed Chair, Division of Oculofacial Plastic Surgery Center and Thyroid Eye Disease Center
Chief, Casey Aesthetic Facial Plastic Surgery Center and Thyroid Eye Disease Center
Disclosures: Dailey reports he receives industry research support from Horizon Pharma to complete phase 2 and phase 3 clinical trials at Oregon Health and Science University.