An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
Amgen Announces Positive Top-Line Phase 3 Results for TED Treatment
On April 6, Amgen announced positive topline results from a Phase 3 trial of TEPEZZA (teprotumumab-trbw) administered by subcutaneous injection via an on-body injector (OBI) in participants with moderate-to-severe active thyroid eye disease (TED). TEPEZZA OBI provides comparable efficacy to, and builds upon the success of, intravenous (IV) TEPEZZA, the first and only medicine approved for the treatment of TED, which has now treated more than 25,000 patients worldwide.
The Phase 3 TEPEZZA OBI trial met its primary endpoint in moderate-to-severe active TED, showing a statistically significant and clinically meaningful 77% proptosis response rate during the 24-week placebo-controlled period (76.7% TEPEZZA OBI vs. 19.6% placebo [p<0.0001]). Importantly, the mean proptosis reduction, a key secondary endpoint, was -3.17 mm at week 24 (-3.17 mm TEPEZZA OBI vs. -0.80 mm placebo; p<0.0001).
“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,” said Jay Bradner, MD, executive vice president of Research and Development at Amgen. “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.”
The trial also showed statistically significant and clinically meaningful improvements across the following additional secondary endpoints: overall responder rate; percentage of patients achieving a Clinical Activity Score (CAS) of 0 or 1; change in diplopia as ordinal response categories; diplopia response rate; complete diplopia responder rate; and mean change from baseline in week 24 in the Graves’ Ophthalmopathy Quality of Life (GO-QoL) appearance subscale. Although not statistically significant, there was a numerical trend favoring TEPEZZA OBI in the mean change in baseline at week 24 in the GO-QoL visual functioning subscale. Full results from the study will be presented at an upcoming medical congress.
The overall safety results were generally consistent with the known safety profile of TEPEZZA IV. Mild-to-moderate injection site reactions were observed with subcutaneous administration in some patients, which did not result in treatment interruption or discontinuation. The most common adverse events (≥10%) were muscle spasms, tinnitus, weight decrease, ear discomfort, nausea and diarrhea.
TED is a serious, progressive and potentially vision-threatening rare autoimmune disease that can cause proptosis (eye bulging), diplopia (double vision), eye pain, redness and swelling.3
“Thyroid eye disease can be a profoundly debilitating condition, affecting not only vision but also daily functioning with symptoms like double vision and eye bulging,” said Madhura A. Tamhankar, MD, professor of ophthalmology and neurology at the Scheie Eye Institute, University of Pennsylvania. “Expanding administration options through subcutaneous delivery opens the possibility of a more accessible experience for patients with thyroid eye disease and is critical to serving diverse patient needs. The potential to achieve comparable efficacy to IV makes this advancement compelling.”
Garetosmab Biologics License Application Accepted for FDA Priority Review for Treating FOP
In February, Regeneron Pharmaceuticals, Inc., announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for garetosmab for the treatment of adults with fibrodysplasia ossificans progressiva (FOP). Garetosmab is a monoclonal antibody that blocks Activin A, a protein that Regeneron scientists discovered to be critical in the development of heterotopic ossification (HO) lesions in people with FOP. The target action date for the FDA decision is August 2026.
FOP is a relentless, ultra-rare genetic disorder in which muscles, tendons, ligaments and other connective tissues are progressively infiltrated by abnormal bone formation, a process known as HO, which results in significant disfunction of these structures and skeletal deformity. HO of the jaw, spine, hip and rib cage can make it difficult to speak, eat, walk or breathe, leading to weight loss and escalating loss of mobility. Most people with FOP are wheelchair bound by 30 years old, and the median age of survival is approximately 56 years. Approximately 900 people are diagnosed with FOP worldwide, with many others thought to remain undiagnosed or misdiagnosed.
The BLA is supported by efficacy and safety data from the positive Phase 3 OPTIMA trial evaluating garetosmab in adults with FOP. Both garetosmab doses (3 mg/kg and 10 mg/kg) evaluated in the trial were highly efficacious in reducing the total number and volume of new HO lesions at 56 weeks, compared to placebo. Regarding the primary endpoint analysis of reduction in total number of new HO lesions compared to placebo (n=21), those receiving the 3 mg/kg dose (n=19) experienced a 94% reduction (1 lesion vs. 19 lesions; p=0.0274), while those receiving the 10 mg/kg dose (n=23) experienced a 90% reduction (2 lesions vs. 19 lesions; p=0.0260). A post-hoc analysis also found both doses of garetosmab demonstrated a greater than 99% reduction in mean total volume (cm3) of new HO lesions compared to placebo (3 mg/kg: 0.01 cm3 vs. 10.45 cm3; nominal p=0.0013; 10 mg/kg: 0.02 cm3 vs. 10.45 cm3; nominal p=.0005).
At 56 weeks, among all 63 people with FOP aged 18 years and older who participated in the OPTIMA trial, serious treatment-emergent adverse events occurred in 1 patient treated with 3 mg/kg garetosmab, 2 patients treated with 10 mg/kg garetosmab and 2 patients treated with placebo. The most common adverse reactions (incidence ≥30%) are epistaxis, increased hair growth, abscess and acne.
Priority Review is granted to regulatory applications seeking approval for therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions. The FDA previously granted Fast Track designation and Orphan Drug Designation for garetosmab for the prevention of HO in patients with FOP. Garetosmab has also been granted Orphan Designation in the European Union, and additional garetosmab regulatory submissions are planned in countries around the world.
The safety and efficacy of garetosmab, as well as its potential use for the treatment of FOP, are investigational and have not been fully evaluated or approved by any regulatory authority.
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