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LOS ANGELES – An experimental human monoclonal antibody has dramatically reduced the most debilitating symptoms of Graves' orbitopathy, including proptosis and double vision, giving patients new hope that a cure for the disease the thyroid could be on hand, according to a speaker at the AACE Scientific and Clinical Congress annually.
Raymond Douglas
According to the new Phase 3 data from the OPTIC study presented here, adults with active Graves' orbitopathy treated with teprotumumab (Horizon Pharma) for 21 weeks had an average reduction of 2.82 mm in proptosis at 24 weeks, against an average of 0.54 mm for those badigned. placebo, with intergroup differences in proptosis reduction observed at all times of the study, as a function of Raymond Douglas, MD, PhD, Director of the Orbital and Thyroid Disease Program at the Cedars-Sinai Medical Center. Other symptoms badociated with the disease, including inflammation, pain, swelling and redness, were also reduced for patients to whom teprotumumab was badigned compared to placebo, he said. Proptosis is the leading cause of morbidity in thyroid eye disease; there is currently no treatment approved by the FDA.
"I often talk about thyroid eye disease, it's something you look at and wait for," Douglas said Endocrine today. "You have an active phase and an inactive phase, but in reality, you are watching these people with a permanent debilitating disease and you can not do anything about it. This is the first time, and the first hope, that there will be an indication for a drug that will change all that paradigm. "
Thyroid disease is most commonly badociated with Graves hypothyroidism, but may also be badociated with Hashimoto's thyroiditis, Douglas said in his presentation. In the 18 months following the diagnosis of Graves' disease, approximately 80% of patients will develop thyroid disease, usually resulting in a range of symptoms, including proptosis, eyelid retraction, strabismus, compressive optic neuropathy, and a poor quality of life overall. .
"This gives us a huge opportunity as a window to work together, as oculoplastic surgeons and as endocrinologists, to identify these patients and possibly refer them to early treatment," Douglas said.
Study the design
Douglas, a co-principal investigator of the OPTIC trial, and colleagues badyzed data from 83 patients with active Graves orbitopathy randomly badigned to an IV infusion of teprotumumab. a targeted insulin-like growth factor I receptor inhibitor (n = 41, mean age, 52 years, 70.7% women, 85.4% white) or placebo (n = 42 years), mean age 49 years; 73.8% women; 88.1% white) every 3 weeks for 21 weeks. The median time since the diagnosis of Graves' disease was 1.04 years for the teprotumumab group and 0.9 years for the placebo group; 78% and 81%, respectively, were non-smokers in each group. The primary endpoint was a reduction of 2 mm or more of proptosis in the study eye, without deterioration of the eye of the same eye, at week 24.
"The primary endpoint is essential because this study differs from the ones you've heard about," Douglas said. "The main evaluation criterion is actually proptosis. In reality, it modifies the disease. "
As Endocrine today Previously reported in March, preliminary results showed that 82.9% of patients who were given teprotumumab and 9.5% of patients who received placebo responded to proptosis at week 24 (P < .001). In the new data presented, Douglas indicated that there was a difference between groups with respect to the reduction of proptosis compared to baseline values at week 6 (mean, -2 mm vs. -0 , 38 mm), at week 12 (average, -2.7 mm versus -0.64 mm). week 18 (mean, -3.26 mm vs. -0.59 mm) and week 24 (mean, -3.32 mm vs. -0.53 mm).
Patients treated with teprotumumab had an overall response rate of 78%, compared to 7.1% in the placebo group at week 24 (P < Douglas, said, with an overall response rate higher than that observed for teprotumumab at all times of the study.
According to Douglas, one of the most interesting findings is that the observed effect was stronger in patients with more serious illness.
"This drug marks a decisive dividing line in the way we will progress in treating this disease in the future," Douglas said in an interview.
Demonstrated security
The safety profile of teprotumumab in the Phase 3 study was similar to that observed in the Phase 2 trial, Douglas said. Muscle spasms were the most commonly reported adverse event (31.7%), followed by potential infusion-related reactions (14.6%), diarrhea (9.8%), and dystrophy disorders. Hearing (9.8%), all considered mild to moderate.
"This pivotal phase 3 placebo-controlled study demonstrates a significant reduction in proptosis, confirming the results of phase 2 almost as a mirror," Douglas said. "Targeting the IGF-I receptor is essential for the treatment of thyroid and eye disease. This seems to be a very effective medicine for reducing proptosis and probably improving dual vision and quality of life. "
Douglas said the therapy, if approved, could potentially replace surgery for many patients, including those with more advanced disease.
"All surgeries for thyroid diseases are not equivalent," Douglas said. "The more you do surgery, the more you take chances to cause double vision. These patients often undergo five to seven surgeries to improve this condition. If you could reduce that to zero or a couple in a lot of these patients, it would be revolutionary. We will have to see how that goes.
Tprotumumab has received advanced treatment, an orphan drug and FDA-accelerated designations. Horizon plans to submit a biologics license application to the FDA in mid-2019, according to a press release from the company. – by Regina Schaffer
Reference:
Douglas RS. Last minute oral session. Presented at: AACE Annual Scientific and Clinical Meeting; April 24 to 28, 2019; Los Angeles.
Disclosure: Douglas says he's a consultant for Horizon Pharma.
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