Horizon Therapeutics announced integrated, pooled efficacy data from the phase 2 and phase 3 clinical trials of teprotumumab for the treatment of active thyroid eye disease (TED) compared to placebo. The results support prior analyses of significant reductions in inflammation, proptosis (eye bulging) and diplopia (double vision), as well as improvements in quality of life (QoL), according to a company news release. These data were presented at the 89th Annual Meeting of the American Thyroid Association (ATA). This is the first presentation of the pooled analyses and builds on the individual positive results of the phase 2 and phase 3 clinical studies.
Teprotumumab is an investigational medicine and its safety and efficacy have not been established. The teprotumumab Biologics License Application (BLA) was 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.
“This is the largest placebo-controlled evaluation of active thyroid eye disease to date and an important step towards better understanding the devastating, vision-threatening effects of this disease,” George Kahaly, MD, PhD, of the Johannes Gutenberg University Medical Center in Mainz, Germany and lead study author, said in a company news release. “These data highlight the urgent need for targeted intervention strategies and illustrate the potential for teprotumumab to reduce the painful and disfiguring symptoms of thyroid eye disease, and importantly, to help improve quality of life.”
The pooled analysis of the phase 2 (NCT01868997) and phase 3 OPTIC (NCT03298867) studies presented during ATA represent the experience of 171 patients with recent onset of TED (less than 9 months) treated with teprotumumab or placebo every three weeks for a total of eight infusions.
Key study findings include the following:
- Proptosis: At Week 24, 77.4% of patients receiving teprotumumab experienced a ≥2 mm reduction in proptosis, compared to 14.9% of patients receiving placebo (P<0.001). The reduction in average change from baseline through Week 24 in proptosis was greater in patients who received teprotumumab (-2.63 mm) than in those who received placebo (-0.31 mm, p<0.001).
- Diplopia: The diplopia responder rate, which is defined as the percentage of patients whose diplopia improved 1 or more grades, was higher with teprotumumab (69.7%) versus placebo (30.5%; P<0.001) in those with baseline diplopia.
- Quality of Life: Patients treated with teprotumumab experienced improvements in average change from baseline through week 24 in QoL scores (overall 15.55 vs 5.92, p<0.001), including visual functioning (16.81 vs 6.10, p<0.001) and appearance (13.51 vs 5.78, p=0.002). The GO-QoL scale consists of two subscales to evaluate the quality of life of patients with TED (Graves’ Ophthalmology), including impacts on visual function and self-assessment of appearance. A change of 6 points is considered clinically significant.1
- Clinical Activity Score (CAS): At Week 24, nearly two-thirds of teprotumumab-treated patients (61.9%) had no or minimal inflammatory symptoms as measured by CAS (described as a CAS of 0 or 1) compared to 21.8% of placebo-treated patients (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 signs or symptoms of inflammation.2
- In addition, 73.8% of teprotumumab patients versus 13.8% of placebo patients had an overall response at Week 24 – defined as the percent of patients with ≥ 2-point reduction in CAS and ≥ 2 mm reduction in proptosis from baseline.
As previously reported, the majority of adverse events experienced with teprotumumab treatment were graded as mild to moderate and were managed in the trials, with few discontinuations. In the phase 2 clinical study, the only drug-related adverse event identified by the investigators was hyperglycemia. Other adverse events included nausea, diarrhea, muscle spasms, hearing impairment and inflammatory bowel disease in a patient with a recent diagnosis of ileitis and colitis. No deaths occurred during the trial. The safety profile of teprotumumab in the phase 3 clinical study was similar to that seen in the phase 2 study with no new safety observations.
“The combined integrated results of the phase 2 and phase 3 teprotumumab clinical trials demonstrate compelling data in a disease state that is currently lacking therapies for the painful symptoms, disfigurement and vision impairment that TED patients endure,” Shao-Lee Lin, MD, PhD, executive vice president, head of research and development and chief scientific officer, Horizon, said in the news release. “We are excited by the positive effects demonstrated in the areas that matter most to patients – proptosis, double vision and quality of life – and we are excited about the potential teprotumumab has to be the first FDA-approved treatment for thyroid eye disease.”