Top-line data demonstrate efficacy, safety of teprotumumab for thyroid eye disease
Most adults with thyroid eye disease who experienced meaningful improvement in proptosis after 21 weeks of teprotumumab treatment maintained proptosis response at week 72 without additional treatment, according to top-line data.
Data from the OPTIC 48-week off-treatment follow-up period demonstrated that 56% of participants who received teprotumumab-trbw (Tepezza, Horizon Therapeutics) and were proptosis responders at week 24 in the OPTIC trial maintained their proptosis response at week 72 without receiving additional thyroid eye disease treatment. In a second study, OPTIC-X, 89% of participants who received placebo during the OPTIC trial and then received teprotumumab — and therefore had a longer disease duration — similarly achieved the OPTIC primary endpoint of a 2 mm or more reduction in proptosis at week 24, with an average reduction of –3.5 mm.
“These data can give patients comfort in knowing that even if they have had thyroid eye disease for a longer period of time, Tepezza may still be effective,” Raymond Douglas, MD, PhD, director of the orbital and thyroid eye disease program at Cedars-Sinai Medical Center and the trial’s co-principal investigator, told Healio. “It is also incredibly reassuring to know that patients can safely be retreated with Tepezza, if needed, and that there can even be durability moving forward.”
As Healio previously reported, adults with thyroid eye disease assigned teprotumumab during OPTIC were significantly more likely to experience a meaningful improvement in proptosis after 21 weeks of treatment compared with those who received placebo. The findings, published in The New England Journal of Medicine, showed that at 24 weeks, more people in the teprotumumab group experienced a reduction in proptosis vs. placebo (83% vs. 10%; P < .001), with a number needed to treat of 1.36. Among adults assigned teprotumumab, researchers observed a greater overall response vs. placebo (78% vs. 7%), as well as more treated adults with a clinical activity score of 0 or 1 (59% vs. 21%), a greater mean change in proptosis (mean, –2.82 mm vs. –0.54 mm), greater diplopia response (68% vs. 29%) and greater mean change in overall quality of life score (mean, 13.79 points vs. 4.43 points; P .001 for all).
At week 24 of OPTIC, proptosis responders entered into a 48-week off-treatment follow-up period, without receiving additional thyroid eye disease treatment.
OPTIC-X evaluated the safety and efficacy of teprotumumab in OPTIC participants who were either proptosis nonresponders at week 24 or were proptosis responders at week 24 but relapsed during the 48-week off-treatment follow-up period. Nonresponders were defined as patients who did not achieve at least a 2-mm proptosis improvement from baseline at week 24 of OPTIC. Relapse was defined as participants who lost at least 2 mm of their week 24 proptosis improvement during the 48-week off-treatment follow-up period — even if their proptosis was still substantially better than at baseline during OPTIC — or who experienced a substantial increase in the number of inflammatory signs or symptoms without worsening proptosis.
For relapsed patients who were retreated with an additional course of teprotumumab, more than 60% experienced a 2 mm or more proptosis improvement from OPTIC-X baseline at week 24, according to the release.
Only five patients had not achieved a proptosis response after completing a full course of teprotumumab in OPTIC; of those, two achieved a 2 mm or more proptosis reduction during OPTIC-X after an additional course of teprotumumab, according to the release. There were no new safety concerns observed during OPTIC-X or the OPTIC off-treatment follow-up period.
“Data from OPTIC-X provide evidence supporting the potential for Tepezza to meaningfully reduce proptosis in patients who have had thyroid eye disease for a longer period of time than what was originally studied in the phase 2 and phase 3 clinical trials,” Elizabeth H.Z. Thompson, PhD, group vice president, development and external search, research and development, Horizon Therapeutics, said in the release. “It is also promising to see that there are patients who may benefit from additional therapy with Tepezza, and the data suggest that they can experience these improvements without added safety concerns. We look forward to continuing our development program and further understanding the efficacy and safety of Tepezza among patients who are at various stages of their thyroid eye disease journey, from early diagnosis to chronic patients.”
The FDA approved teprotumumab in January for the treatment of adults with thyroid eye disease, marking the first drug approved for the condition. Teprotumumab, an insulin-like growth factor I receptor inhibitor, is a fully human monoclonal antibody developed to address a substantial unmet need for patients with thyroid eye disease. The drug blocks the inflammatory/autoimmune pathophysiology that underlies thyroid eye disease.
Horizon said detailed data from the OPTIC off-treatment follow-up period and OPTIC-X will be presented at a future medical congress.