People with a rare eye disease may soon get an alternative to surgery. All 12 members of an FDA advisory committee voted to recommend the approval of teprotumumab, a drug Horizon Therapeutics picked up in its buyout of River Vision two years ago.
Horizon is seeking approval for teprotumumab, an inhibitor of the insulin-like growth factor type 1 receptor, in thyroid eye disease (TED), a rare, autoimmune disorder that can lead to blurred or double vision. Patients typically seek treatment when they notice their eyes bulging in photos or that their eyes and eyelids constantly seem to be red and swollen, Raymond Douglas, M.D., Ph.D., one of the leaders of teprotumumab’s phase 3 study, said in a previous interview.
If approved, teprotumumab would be the first treatment for TED that changes the course of the disease rather than just addressing symptoms. Today, patients take steroids to keep swelling at bay or undergo bone-shaving surgery that returns the eyeball to a normal position in the eye socket.
In documents released ahead of the meeting, FDA staff highlighted some potential speed bumps for teprotumumab, including the small number of patients who have been treated with the drug in clinical trials. Its application is based on a phase 2 study and a phase 3 trial that tested teprotumumab against placebo in 170 patients.
“Less than 90 subjects treated with infusions of teprotumumab have been enrolled in controlled clinical trials. This is a considerably smaller database than the common safety database of greater than 300 patients treated with a course of therapy,” the documents read.
The documents identified a number of side effects suffered by some patients, including muscle spasms, loss of hearing, diarrhea and irritable bowel syndrome. They also zeroed in on hyperglycemia; because teprotumumab blocks the insulin-like growth factor type 1 receptor, it could interfere with how the body manages glucose levels, especially in people with diabetes.
“Some patients receiving teprotumumab required additional amounts of insulin to maintain glycemic control,” the FDA staff wrote.
But the panelists agreed that although the data set was small, the benefits of teprotumumab outweigh the risks and side effects.
“Despite the conversations about the numbers, I think it has huge promise to change the course of disease for all these patients," said David Yoo, M.D., an associate professor of ophthalmology and director of ophthalmic plastic, reconstructive and orbital surgery at Loyola University Medical Center.
“It was an easy vote—easier than they usually are,” said Erica Brittain, Ph.D., a mathematical statistician and deputy branch chief at the National Institutes of Health’s National Institutes of Allergy and Infectious Diseases. “I am concerned about the small database, the safety database. Some issues were identified and there may be some that were not identified, so it is a concern. But it is clear the risk/benefit is favorable for a clear majority of patients.”
She, like other panelists, emphasized the need for post-approval studies, including those to better understand the loss of hearing in some patients.
“As a statistician, I would generally require for larger studies to be done, but I think this was very convincing … Other studies can be done to monitor other side effects post-approval,” said Tonya King, Ph.D., a professor of biostatistics at Penn State’s college of medicine.
James Chodosh, M.D., associate director of the Cornea and Refractive Surgery Service at Massachusetts Eye and Ear, said the “vast majority” of the side effects seen so far have been “very manageable.”
One of those side effects was alopecia, or sudden hair loss, which the panel added to the docket after the briefing documents were published.
Multiple panelists agreed “it is safe to say we’d rather be bald than be blind” but that alopecia should be listed on the label as a potential side effect.
And Yoo reminded the panel that current treatments, which only address symptoms, have side effects, too: “When we do surgery, patients can get re-inflamed. When patients go on high-dose steroids, they can get psychotic from those as well. I have patients terrified of going back on steroids. Yes, [teprotumumab’s] disease-modifying benefits outweigh its risks,” he said.
The FDA is expected to make a decision by March 8.