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(Reuters Health) - The experimental orphan drug teprotumumab significantly reduces the eye bulging associated with Graves’ disease, according to results of a small trial.
Among the 88 participants with moderate-to-severe disease who were given intravenous infusions of either teprotumumab or a dummy drug every three weeks for eight treatments, 43 percent who got the real drug had a reduction of at least 2 millimeters in eye protrusion by the sixth week compared to 4 percent in the placebo group.
"In virtually all the responders, the changes are frequently what anyone would call dramatic," said lead study author Dr. Terry Smith of the University of Michigan Medical School in Ann Arbor.
The eyes don’t have that bulging appearance, he said, and many of them return to the degree of bulging they had before they got the disease.
“That's something that we almost never see in someone who's manifested the degree of disease one needed to have in order to get into the study," Smith said.
The marked reduction in bulging is similar to that reported after decompression surgery, Smith and his colleagues write in the New England Journal of medicine.
Graves’ disease is the most common cause of overactive thyroid in the United States, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). It is an autoimmune disorder, in which the immune system attacks the thyroid gland.
Certain immune-system signaling molecules also target other tissues in the body, including in the eyes, which causes their bulging appearance, sometimes known as Graves’ eyes. About 30 percent of people with Graves’ disease develop mildly bulging eyes, and 2 to 5 percent develop severe bulge. This eye condition usually lasts one to two years and often improves on its own, according to NIDDK.
Teprotumumab blocks one of these immune signaling molecules, so researchers wanted to see what effect it might have on the eyes of Graves’ patients with moderate to severe bulge.
The study "included some of the worst cases imaginable and we're now wondering whether the drug might find expanded utility in much-less-severe disease," Smith told Reuters Health in a telephone interview.
By week 24, the response rate was 69 percent with the drug and 20 percent with placebo. Among those who completed therapy, the rates were 79 percent and 22 percent, respectively.
More people who received the drug had sizeable reductions in disease activity and reductions of 3 mm or more in eye bulge compared to the placebo group, the researchers note.
However, while only 10 percent of patients who received the drug had double vision before the study, that rose to 50 percent by 24 weeks.
High blood sugar was also a key side effect in participants who already had diabetes, the study team notes, but adjusting diabetes medications solved that problem.
The typical treatment for Graves’ eyes is glucocorticoids, which are not always effective and also have side effects, the study team notes.
The drug, also known as RV001 or R1507, has been developed by Genmab and Roche. River Vision Development Corporation licensed the drug from Roche. On Monday, Horizon Pharma announced that it was acquiring River Vision, which paid for the new study.
Smith said FDA approval could come sometime in 2018. Enrollment in a follow-up trial is expected to begin within six weeks.
The duration of response to the autoimmune inflammatory disease, along with the quick response to initial therapy, suggests fewer infusions may be just as effective, "but future studies will sort that out," Smith said.
The researchers also cautioned that the study only included volunteers with active disease of recent onset so "the potential of teprotumumab in benefiting patients with milder, less active, or stable disease was not assessed."
SOURCE: bit.ly/2qSTjSn New England Journal of Medicine, online May 3, 2017.