Veligrotug

A phase 3 trial of patients with thyroid eye disease has shown that subcutaneous injection of Tepezza by way of an on-body injector can provide comparable efficacy to its current route of administration, which includes eight infusions over 24 weeks. Since acquiring rare disease specialist Horizon Therapeutics in 2023 for $27.8 billion, Amgen has had difficulty boosting sales for the top product gained in the buyout, thyroid eye disease (TED) treatment Tepezza.But with a new, patient-friendly route of administration, the California biotech may have found a way to increase demand for Tepezza, which is the lone drug on the market for the inflammatory, bulging-eye condition.A phase 3 trial of patients with moderate-to-severe TED has shown that subcutaneous injection of Tepezza by way of an on-body injector (OBI) can provide comparable performance to its current route of administration, which includes eight intravenous (IV) infusions, three weeks apart, each lasting between 60 and 90 minutes.The trial met its primary endpoint, as Tepezza OBI demonstrated a statistically significant and clinically meaningful proptosis response rate of 77% compared to a 20% figure for those on placebo, according to a Monday press release from Amgen. Patients were considered responsive if they achieved a 2-mm or greater reduction from baseline in proptosis (eye protrusion) without deterioration after 24 weeks.As a key secondary endpoint, Tepezza OBI provided an average proptosis reduction of 3.17-mm at week 24, compared to an average reduction of 0.80-mm in the control arm.“These results extend and support the best-in-class efficacy of Tepezza for people living with thyroid eye disease, now with subcutaneous administration delivering IV-level efficacy,” Amgen’s R&D chief, Jay Bradner, said in the release. “With a well-understood mechanism and established impact in the clinic, we can evolve how the medicine is delivered to potentially reach even more patients through a more convenient subcutaneous option.”Amgen did not reveal its regulatory plan in its release. A spokesperson said that the company will submit the results to authorities but that it is “too early to comment on approval timing as that depends on a number of regulatory factors.” Horizon’s 2020 FDA approval for Tepezza IV was backed by results from a phase 3 trial, which showed an 83% response rate—again defined by a 2-mm proptosis reduction at 24 weeks—compared to a 10% reduction in the placebo arm.  In its second full year on the market in 2022, Tepezza’s sales peaked at $1.96 billion. Since then, sales have been stagnant. Last year, Amgen reported its sales at $1.90 billion.Competition may be coming for Tepezza. Massachusetts-based Viridian Therapeutics faces a June 30 FDA decision date for its TED candidate veligrotug, which is infused five times over a 12-week period.Last week, Viridian also scored a phase 3 win for its injected TED prospect elegrobart, but with results that did not impress investors. The study’s responder rate was 54% for the drug candidate compared to 18% for the placebo group. Elegrobart provided a 2.33-mm mean reduction at 24 weeks compared with 0.81-mm for placebo."We believe Viridian’s veligrotug and elegrobart have the potential to capture significant share in the TED market," William Blair analyst Lachlan Hanbury-Brown wrote in a note to investors. "We believe veligrotug offers a competitive profile relative to current standard-of-care Tepezza, and believe the more convenient dosing and diplopia benefits in chronic TED should translate into a meaningful commercial opportunity."Last year, Michigan-based Sling Therapeutics shared results from a phase 2b/3 TED trial of its oral challenger, former Astellas asset linsitinib, though the data suggested that the treatment doesn’t measure up to the efficacy of Tepezza, providing a 52% responder rate. Amgen added on Monday that it has completed a phase 3b/4 trial of Tepezza IV to fulfill an FDA post-marketing requirement. The trial’s mission was to assess the tolerability and efficacy of three treatment durations (four, eight and 16 infusions) and assess the need for retreatment.The company said that the observed risk profile was "consistent" with the known profile of the current administration regimen and that those results will be will submitted to regulators and presented at an upcoming medical conference.Editor's note: Commentary from William Blair analyst Lachlan Hanbury-Brown was added to this story after its initial publication.