New Data from Phase 3 Teprotumumab Trial Shows Reduction in Proptosis, or Eye Bulging, in Active Thyroid Eye Disease (TED)

Horizon Pharma announced that new data from the phase 3 confirmatory clinical trial (OPTIC) evaluating the investigational medicine teprotumumab for the treatment of active thyroid eye disease (TED) were presented as part of a late-breaking oral presentation at the 2019 American Association of Clinical Endocrinologists (AACE) Scientific and Clinical Congress in Los Angeles.

In addition to primary endpoint data previously announced on Feb. 28, 2019, the presentation includes new data from two secondary endpoints that show a dramatic reduction in proptosis (eye bulging) and a substantial improvement in overall response rate in patients treated with teprotumumab compared with placebo. These data demonstrate the potential for teprotumumab as a treatment for Active TED, which currently has no FDA approved treatments. Teprotumumab is an investigational medicine and its safety and efficacy have not been established.

“People living with Active TED who received teprotumumab in the study achieved key outcomes that are not addressed by current therapeutic approaches,” Raymond Douglas, MD, PhD, the study’s co-principal investigator and director of the orbital and thyroid eye disease program, Cedars-Sinai Medical Center, who presented the data at AACE, said in a company news release. “Currently, patients with Active TED suffer through life-altering symptoms and – once the active phase of disease ends – are often left with permanent damage. The results of this confirmatory study, together with the Phase 2 results, suggest that teprotumumab may help reduce proptosis and alleviate the inflammatory symptoms of Active TED, potentially avoiding the need for multiple complex surgeries.”

The primary endpoint of the phase 3 confirmatory trial, titled OPTIC (Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study), was the percentage of patients with a ≥ 2 mm reduction of proptosis from baseline in the study eye without deterioration of proptosis in the non-study eye at study week 24. Horizon previously reported that, in the intent-to-treat population, 34/41 (82.9%) patients receiving teprotumumab and 4/42 (9.5%) patients receiving placebo were proptosis responders at Week 24 (P˂0.001).

The following new data on two secondary endpoints was presented at AACE:

• Average change in proptosis throughout 24 weeks of treatment:
  • Throughout the 24 week treatment period, patients treated with teprotumumab had an average proptosis reduction of 2.82 mm compared with 0.54 mm for those who received placebo (P<0.001).
  • There was a significant difference in proptosis reduction from baseline between teprotumumab and placebo at all study time points: Week 6 (-2.00 mm vs. -0.38), Week 12 (-2.70 vs. -0.64), Week 18 (-3.26 vs. -0.59) and Week 24 (-3.32 vs. -0.53).
• Overall responder rate at Week 24, which includes proptosis reduction of ≥2 mm plus Clinical Activity Score (CAS) improvement of ≥2 points, was significantly better for patients treated with teprotumumab. CAS is a scale used to assess the disease activity of TED, and measures the degree of inflammation, including pain, swelling and redness.
  • Patients treated with teprotumumab had an overall responder rate of 78% compared with 7.1% in the placebo group at week 24 (P<0.001).
  • Overall response rate to teprotumumab was significantly better than placebo from baseline at all study time points: Week 6 (43.9% vs. 4.8%), Week 12 (63.4% vs. 11.9%), Week 18 (73.2% vs 11.9%) and Week 24 (78.0% vs. 7.1%).
• As previously reported, all secondary OPTIC trial endpoints were met (P≤0.001), which – in addition to the above – include the effect of teprotumumab vs. placebo on:
  • Percent of participants with a CAS value of 0 or 1 at Week 24 in the study eye.
  • Percent of patients with a change from baseline of at least one grade in diplopia (double vision).
  • Mean change in Graves’ Ophthalmopathy (GO) Quality of Life questionnaire from baseline to Week 24.

“After initially sharing primary endpoint results from the OPTIC trial, this is the first of several additional presentations that will explore and analyze secondary endpoints – all of which met statistical significance,” Shao-Lee Lin, MD, PhD, executive vice president, head of research and development and chief scientific officer, Horizon Pharma, said in the news release. “As Horizon continues its evolution into a research focused company, we strive to address some of the most challenging and overlooked rare diseases. We’ve met with and learned from the thyroid eye disease community – those living with the disease and the physicians who treat them – and these interactions have given us urgency to bring forward an effective option where none currently exist.”

As previously reported, the safety profile of teprotumumab in OPTIC was similar to that seen in the phase 2 study with no new safety observations. The drop-out rate was low (<5%) and balanced across placebo and treatment arms. There were no deaths during the study and a total of three serious adverse events: in the placebo arm, one patient had a visual field defect and received orbital decompression surgery and discontinued study; in the teprotumumab arm, one patient had pneumothorax (considered not related to study drug) and another had an infusion reaction that led to discontinuation of study drug. The vast majority of treatment-emergent adverse events were mild to moderate in intensity and no other adverse events resulted in discontinuation.