Horizon Pharma announced positive topline results in a confirmatory phase 3 trial evaluating teprotumumab for active thyroid eye disease (TED). The key milestone brings the monoclonal antibody treatment closer to becoming the first approved treatment for this disease.
Originally developed as a cancer drug, teprotumumab works by inhibiting the insulin-like growth factor 1 (IGF-1R)-mediated signaling pathway in the orbital cells of patients with TED. The press release revealed that the treatment produced a “dramatic” reduction in proptosis compared with those who received a placebo. Currently, the only option is surgery once the active disease ends.
“If approved, teprotumumab would give physicians the first medicine shown to reduce proptosis during active thyroid eye disease, in addition to treating other painful symptoms,” said the study’s co-principal investigator, Raymond Douglas, MD, PhD.
The recent OPTIC trial enrolled 83 patients who received 8 intravenous infusions of teprotumumab or placebo every 3 weeks for up to 21 weeks. The first dose was 10 mg/kg, followed by 20 mg/kg for the remaining 7 infusions. By week 24, significantly more patients treated with teprotumumab achieved the primary endpoint—a 2-mm or more reduction in proptosis—without deterioration in the fellow eye compared with the placebo group (82.9% vs. 9.5%; P<0.001). Encouragingly, the trial also met all its secondary endpoints, such as the proportion of patients who achieved a 2-point or more improvement in clinical activity score and changes in Graves ophthalmopathy quality-of-life scores (all P≤0.001).
Teprotumumab’s safety profile in this trial was similar to what was previously observed in the phase 2 study. One patient in the treatment arm experienced an infusion reaction that led to discontinuation of the study drug, but the majority of treatment-related adverse events were deemed mild to moderate.
With breakthrough therapy, orphan drug and fast-track designations already in hand, Horizon plans to publish the findings and submit a biologics license application to the FDA later this year.
Read more about teprotumumab and other TED therapies on the horizon in this article from the February 2019 issue of EyeNet.