Viridian’s Veligrotug Poses Formidable Challenge For Amgen’s Tepezza In TED

The Waltham, MA-based biotech announced 10 September results from the Phase III THRIVE trial, which showed the drug met all of the primary and secondary endpoints, including the proptosis responder rate (PRR) at week 15, placebo-adjusted PRR and resolution of diplopia. The company additionally said the Phase III THRIVE-2 study in chronic TED is fully enrolled, with a topline data readout on track for the end of this year and a biologics license application for veligrotug planned for the second half of 2025.

The results place veligrotug, formerly VRDN-001, in a position to challenge the current standard of care, Amgen, Inc.’s Tepezza (teprotumumab-trbw), which the US Food & Drug Administration approved for TED in 2020. Both drugs are antibodies that target the insulin-like growth factor-1 receptor (IGF-1R). Amgen reported sales of Tepezza of $479m in the second quarter. (Also see "Amgen Gets Into Position For MariTide Development" - Scrip, 6 Aug, 2024.)

Viridian is additionally developing a subcutaneous IGF-1R antibody with the same binding domain as veligrotug; two Phase III trials of VRDN-003 started last month.

“With the approval of [Tepezza] in 2020, TED patients had a targeted therapy available to them for the first time,” Viridian CEO Steve Mahoney told a 10 September call with analysts, noting that patients before then were dependent on steroids and invasive surgery. “However, [Tepezza’s] high treatment burden of eight intravenous infusions given almost over six months, every three weeks can present a significant barrier to patients to start therapy.”

Results Seen As Best-In-Class

Patients in THRIVE received five doses of veligrotug or placebo every three weeks for a total treatment period of 12 weeks, with PRR measured at week 15.

At week 15, the PRR – defined as the percentage of patients with at least a 2mm reduction in proptosis, or abnormal protrusion or displacement of the eye, from baseline without worsening in the other eye – in THRIVE was 70% among patients receiving veligrotug, compared with 5% of those in the placebo arm (p<0.0001). The mean reduction in proptosis was 2.9mm in the treatment arm versus 0.5mm in the placebo arm (p<0.0001). Complete resolution of diplopia, or double vision, occurred in 54% of patients in the veligrotug arm, compared with 12% of those in the placebo arm (p<0.0001), while 63% of patients in the treatment arm had a diplopia response, compared with 20% of those in the placebo arm (p<0.0001).

In addition, the drug was considered generally well-tolerated, with mostly mild adverse events and a 4% discontinuation rate in the veligrotug arm, with 96% of patients completing all five doses. Moreover, there was a low rate of hearing impairment events at 16% in the veligrotug arm and 10.5% in the placebo arm.

“The potential for hearing impairment is a known side effect of the IGF-1R class, and we were pleased to observe [just] a 5.5% placebo-adjusted rate of hearing impairment,” Mahoney said, noting that none of the hearing-impairment effects led to dose interruptions or discontinuations. He said that the results for veligrotug provide “strong support” for VRDN-003, adding that it only differs from veligrotug in its half-life extension technology.

Analysts likewise said they saw positive readthrough to VRDN-003 from the THRIVE results, generally seeing the efficacy as within range of Tepezza’s.

BTIG analyst Julian Harrison said in a 10 September note that veligrotug looks “best-in-class” in terms of diplopia resolution and hearing-impairment adverse events, “persuasively demonstrating that veligrotug achieves comparable-to-better efficacy and safety with a less burdensome infusion regime (5 vs. 8).” Harrison also pointed to veligrotug’s 70% shorter infusion time and around two-thirds less drug exposure, which he said “could solidify veligrotug as the preferred I.V. option for TED when it becomes commercially available.”

 With an apparent lack of any publicly announced late-stage development efforts for a subcutaneous, autoinjector IGF-1R option, he said, “we expect Viridian to corner most of the TED market later this decade with the best-in-category SC Tx option” assuming that competitive positioning remains unchanged.

In a same-day note, H.C. Wainwright analyst Douglas Tsao likewise said the drug demonstrated “best-in-class” potential and “looks poised to take share in the TED market,” attributing that also to the shorter treatment course and the shorter infusion time of 30 minutes versus 60-90 minutes for Tepezza. That, he said, “makes it much more patient-friendly and certainly preferred for infusion centers looking to improve through-put.” Wells Fargo analyst Derek Archila and Jefferies analyst Michael Yee both said the results de-risk the program overall as well as the VRDN-003 program.

Archila added that the hearing-impairment rate also looked better than Tepezza’s. Although Tepezza’s was 10%, the rate in the placebo arm was 0%, meaning that the placebo-adjusted hearing-impairment rate is lower for veligrotug. Evercore ISI analyst Gavin Clark-Gartner said in a same-day note that “the hearing events came in even better than our bull case,” while efficacy “was in the ballpark of matching Tepezza.”