The study met its primary endpoint, showing more patients treated with teprotumumab compared with placebo had a meaningful improvement in proptosis, or bulging of the eye: 82.9 percent of teprotumumab patients compared to 9.5 percent of placebo patients achieved the primary endpoint of a 2 mm or more reduction in proptosis (p<0.001). Proptosis is the main cause of morbidity in TED. All secondary endpoints were also met and the safety profile was consistent with the Phase 2 study of teprotumumab in TED.
Horizon expects to submit a Biologics License Application to the U.S. Food and Drug Administration (FDA) in mid-2019. Teprotumumab has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA. Detailed Phase 3 data will be submitted for publication in a peer-reviewed journal and presented at a medical congress later this year.
“The dramatic results of the teprotumumab Phase 3 confirmatory trial, in addition to positive Phase 2 data, form a highly convincing body of clinical evidence supporting teprotumumab for the treatment of active thyroid eye disease,” said Timothy P. Walbert, chairman, president and chief executive officer, Horizon Pharma plc. “This is a key milestone as we evolve into a research-focused company developing innovative new medicines to address challenging diseases with very few effective options. We are one step closer to delivering the first FDA-approved treatment to people living with active thyroid eye disease, and we are grateful to the patients, physicians and investigational sites who have partnered with Horizon to make the teprotumumab research and development program possible.”
“In the study, patients treated with teprotumumab had an unprecedented reduction in proptosis, which is currently only treatable via surgery after the active disease has ended,” said Raymond Douglas, M.D., Ph.D., the study’s co-principal investigator and director of the orbital and thyroid eye disease program, Cedars-Sinai Medical Center. “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.”
Highlights from 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):
- Designed to investigate the efficacy, tolerability and safety of teprotumumab in patients with active TED.
- Eighty-three patients were assigned to receive teprotumumab or placebo in eight intravenous infusions (10mg/kg for their first infusion followed by 20mg/kg for the remaining seven infusions) every three weeks for 21 weeks.
- The primary endpoint was a responder rate of ≥ 2 mm reduction of proptosis in the study eye (without deterioration in the fellow eye) at Week 24.
- 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).
All secondary endpoints were also met (p≤0.001), which include the effect of teprotumumab vs. placebo on:
- Overall responder rate at Week 24 (primary endpoint in the Phase 2 study): Percent of participants with ≥2 point reduction in Clinical Activity Score (CAS) and ≥2 mm reduction in proptosis from baseline, provided there is no corresponding deterioration (≥2-point/mm increase) in CAS or proptosis in the fellow eye.
- 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 proptosis measurement from baseline to Week 24 in the study eye.
- Mean change in Graves’ Ophthalmopathy Quality of Life from baseline to Week 24.
- 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.
TED is a progressive, debilitating autoimmune disease with a limited window of active disease during which it can be treated without surgical intervention. While TED often occurs in people living with hyperthyroidism or Graves’ disease, it is a distinct disease that is caused by autoantigens activating an IGF-1R-mediated signaling complex on cells within the orbit. This leads to a cascade of negative effects, which cause long-term, irreversible damage. Active TED lasts for up to three years and is characterized by inflammation and tissue expansion behind the eye. As TED progresses, it causes serious damage – including proptosis (eye bulging), strabismus (misalignment of the eyes), and diplopia (double vision) – and in some cases can lead to blindness. Currently, patients must suffer through active TED until the disease becomes inactive – often left with permanent and sight-impairing consequences – before they can have complex and costly surgical procedures that may never fully restore vision or appearance. People living with TED often experience long-term functional, psychological and economic burdens, including inability to work and perform activities of daily living.
Source: Company Press Release