In January, Endocrine News reported on the possible upcoming availability of teprotumumab as a promising treatment for of thyroid eye disease (TED), a serious, progressive and vision-threatening rare autoimmune disease that is associated with proptosis (eye bulging), diplopia (double vision), blurred vision, pain, inflammation, and facial disfigurement. Up to 50% of patients with Graves’ disease will develop TED. However, TED is a distinct disease and can develop even in people who do not have Graves’.
Later that month, the FDA approved teprotumumab to treat TED, which means the drug could be available in the U.S. soon. Horizon Therapeutics is marketing the drug as TEPEZZA, a fully human monoclonal antibody (mAb) 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 came ahead of the Prescription Drug User Fee Act (PDUFA) goal date of March 8, 2020. The medicine received Priority Review, Orphan Drug, Fast Track, and Breakthrough Therapy designations from the FDA.
“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,” says Raymond Douglas, MD, PhD, director of the Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center and co-principal investigator of the TEPEZZA 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.”
The FDA approval of TEPEZZA is supported by a robust body of clinical evidence, including statistically significant, positive results from the Phase 2 clinical study, as well as 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 TEPEZZA (82.9%) had a meaningful improvement in proptosis (≥ 2 mm) as compared with placebo patients (9.5%) (p˂0.001) without deterioration in the fellow eye at week 24. Additional secondary endpoints were also met, including a change from baseline of at least one grade in diplopia (double vision) in 67.9% of patients receiving TEPEZZA compared to 28.6% of patients receiving placebo (p=0.001) at Week 24. 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 TEPEZZA (53%) compared with those treated with placebo (25%). The majority of adverse events experienced with TEPEZZA treatment were graded as mild to moderate and were manageable in the trials, with few discontinuations or therapy interruptions.
Horizon will conduct a post-marketing study to evaluate safety in a larger patient population as was discussed at the Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) FDA Advisory Committee meeting on December 13, 2019, where the committee voted unanimously (12-0) that TEPEZZA demonstrated a positive benefit risk profile. This study will also evaluate retreatment rates relative to how long patients receive the medicine.