A second phase 3 trial of Viridian Therapeutics’ anti-IGF-1R antibody has hit its primary endpoint as the company prepares to file for FDA approval next year and challenge Amgen for a blockbuster market.
Investigators randomized 204 thyroid eye disease (TED) patients to take Viridian’s elegrobart, either every four weeks or every eight weeks, or placebo. Elegrobart hits the same target as Tepezza, the drug Amgen acquired in its $27.8 billion takeover of Horizon Therapeutics. While Tepezza is given as eight infusions lasting 60 to 90 minutes every three weeks, elegrobart is self-administered as a subcutaneous injection.
In March, Viridian posted a phase 3 win for elegrobart in active TED, defined as patients who developed symptoms within 15 months of screening. Tuesday, the biotech followed up with another phase 3 win, this time in chronic TED patients who developed symptoms more than 15 months prior to screening.
The primary endpoint for the FDA looked at how many patients had at least a 2mm reduction from baseline in proptosis, the protrusion of the eyeball that characterizes TED. At Week 24, 50% of patients who received elegrobart every four weeks met the endpoint, compared to 15% of people on placebo. The eight-week elegrobart regimen achieved a 54% response rate.
Viridian used a different primary endpoint for the European Medicines Agency but achieved a similar result, with 47% of people in the four-week cohort meeting the criteria versus 15% of their counterparts on placebo. The eight-week elegrobart regimen achieved a 54% response rate on the European criteria. Mean proptosis change from baseline was statistically significant in both elegrobart arms versus placebo.
The biotech reported weaker data on secondary endpoints that looked at diplopia, the medical term for double vision. While the diplopia responder rate was significantly higher in the four-week cohort, 61%, than the placebo arm, 38%, the eight-week regimen fell short of the bar for statistical success. Neither elegrobart regimen achieved statistically significant better complete resolution of diplopia than placebo.
Horizon enrolled patients who developed TED within nine months of screening in the trials cited (PDF) on the Tepezza label, preventing a direct comparison to Viridian’s data. Amgen’s recent subcutaneous Tepezza trial targeted active TED. A phase 4 trial enrolled patients diagnosed with TED two to 10 years prior to screening, linking Tepezza and placebo to response rates of 62% and 25%, respectively, at Week 24.
While Amgen has limited data on Tepezza in chronic TED patients, the overall dataset suggests its drug may have an efficacy edge over elegrobart. Amgen’s incoming subcutaneous, on-body injector version of Tepezza potentially limits Viridian’s dosing edge, although TD Cowen analysts said in a note to investors about the active TED data that elegrobart may compete on convenience because it is given less often.
Viridian plans to file for FDA approval of elegrobart in the first quarter of next year. The filing is part of an attempt to challenge Amgen on two fronts, with Viridian also nearing approval of an intravenous TED drug. The FDA is set to rule on an application for approval of the intravenous treatment, veligrotug, by June 30.
Elegrobart and veligrotug will compete for a TED market that generated $1.9 billion for Amgen last year. TD Cowen analysts forecast Tepezza sales of $2.3 billion this year, rising to $2.5 billion by 2033, despite the arrival of competitors and the anticipated loss of the composition‑of‑matter patent in 2029.