The THRIVE data demonstrated clear separation of the veligrotug and placebo curves across all timepoints in the study. For patients treated with veligrotug, PRR at each measured time point was: 53%, 64%, 64%, 72%, and 70% (at weeks 3, 6, 9, 12, and 15, respectively). PRR for patients receiving placebo ranged from 5-13% across the time points. Patients receiving veligrotug had a mean change in proptosis from baseline of -1.82, -2.39, -2.66, -2.76, and -2.89 mm (at weeks 3, 6, 9, 12, and 15, respectively). Mean change in proptosis for patients receiving placebo was -0.48 mm to -0.72 mm across time points.
Diplopia and Clinical Activity Score: All secondary endpoints were highly statistically significant (p < 0.0001), including complete resolution of diplopia in 54% of patients (placebo-adjusted rate of 42%) and reduction of Clinical Activity Score to 0 or 1 in 64% of patients (placebo-adjusted reduction of 46%) treated with veligrotug. The diplopia response rate and mean reduction in CAS in patients receiving veligrotug was 63% and 3.4 points, respectively, compared with 20% and 1.7 points, respectively in patients receiving placebo (43% and 1.7 points, respectively, placebo-adjusted) (p < 0.0001).
Patients receiving veligrotug had diplopia complete resolution at a rate of 26%, 32%, 35%, 44%, and 54% (at weeks 3, 6, 9, 12, and 15, respectively) and had a CAS score of 0 or 1 at a rate of 30%, 46%, 53%, 64%, and 64% (at weeks 3, 6, 9, 12, and 15, respectively). Patients receiving placebo had diplopia complete resolution at rates ranging from 4-12% across time points, and a CAS score of 0 or 1 at rates ranging from 7-25% across time points.
Overall Responder Rate: The overall responder rate, defined as achieving a proptosis response and a ≥2-point reduction in CAS from baseline without worsening in the fellow eye in either proptosis (2 mm increase) or CAS (2 point increase), was 67% of patients receiving veligrotug, compared with 5% of patients receiving placebo (62% placebo-adjusted) (p < 0.0001).
Tolerability: Veligrotug was generally well-tolerated with no treatment-related serious adverse events (“AEs”), and a 5.5% placebo-adjusted rate of hearing impairment adverse events. None of these hearing events led to dose interruptions or discontinuations and all patients with hearing impairment AEs completed their full course of treatment. Overall, 96% of veligrotug-treated patients completed all doses with a low treatment discontinuation rate of 4% in the treatment arm.
The AEs occurring at greater than or equal to 10% frequency in either arm were (veligrotug vs. placebo): muscle spasms (43% vs. 5%), headache (21% vs. 13%), infusion related reactions (17% vs. 3%), hearing impairment (16% vs. 11%), hyperglycemia (15% vs. 5%), fatigue (13% vs. 16%), nausea (13% vs. 8%), ear discomfort (12% vs. 3%), diarrhea (11% vs. 3%), alopecia (8% vs. 11%), and menstrual disorders (24% vs. 8%, of menstruating women in the trial).
THRIVE Study Measurement Tools: The THRIVE data also demonstrated consistency between Hertel exophthalmometry and MRI / CT, supporting the reliability of both tools for the measurement of proptosis. The data also provide additional support for the clinical activity of veligrotug. PRR as measured by exophthalmometry at week 15 was 70% versus 5% (for patients receiving veligrotug and placebo, respectively), compared with PRR as measured by MRI/CT at week 15, which was 69% versus 9% (for patients receiving veligrotug and placebo, respectively). Proptosis mean change from baseline at week 15 was -2.89 mm versus -0.48 (for patients receiving veligrotug and placebo, respectively) as measured by exophthalmometry and -2.91 versus -0.58 mm (for patients receiving veligrotug and placebo, respectively) as measured by imaging (MRI/CT).
Next Steps for Veligrotug
A second phase 3 clinical trial of veligrotug, THRIVE-2, in patients with chronic TED is ongoing. We completed enrollment of THRIVE-2 in July 2024, and topline data readout is on track for year-end 2024. We anticipate submitting a BLA for veligrotug in the second half of 2025, as planned.