A laugh in the front seat changed everything for Sierra Smith.
Weeks after her son Travis had surgery for a new gene therapy, Smith was driving with him asleep in the back when she laughed loudly. Travis jolted, reacting to a sound for the first time.
For Smith and Travis, who was born deaf, the therapy has been life-changing. The surgically delivered drug, developed by Regeneron and called Otarmeni, recently received accelerated approval from the U.S. Food and Drug Administration to treat a rare genetic hearing loss condition.
Otarmeni is the first gene therapy approved under the FDA’s National Priority Voucher program. Regeneron has made the treatment free in the United States. Pricing for the rest of the world has not yet been set.
“We just thought it was the right thing to do here,” said Christos Kyratsous, Regeneron’s senior vice president, genetic medicines, internal and research. “We thought it was a nice demonstration about the power of science.”
Smith called that access for other families “a miracle.”
Travis, now 2 and a half, had the surgery when he was 18 months old. Since then, hearing tests have shown progress, but Smith said she did not need the test results to know it worked.
“He was such a mute baby, very serious,” Smith said. “Now he babbles, uses different pitches.”
She said he has started to socialize with other kids at library story hour and bops along to music now. “He loves Bruno Mars.”
Language acquisition is still “a bit of a way off,” Smith said, but Travis is making the right sounds and gets speech therapy three times a week. “I know it’s coming.”
Researchers said the results for children who can benefit from the therapy have been clear and dramatic.
“What we saw in clinical studies was that in a few weeks, children started to hear; within a few months, they could hear whispers,” said Jonathon Whitton, head of the auditory global program for Regeneron. “These are kids that before the surgery, wouldn’t hear a gas-powered lawnmower if they were standing next to it.”
Otarmeni is considered an orphan drug because it affects so few people that creating and manufacturing it usually is not a priority. The specific OTOF-related hearing loss it treats is believed to affect about 50 newborns a year in the United States.
In that genetic disorder, a person lacks a functional otoferlin protein, which is critical for communication between the sensory cells of the inner ear and the auditory nerve.
About 1 in 500 children are born with hearing loss in the United States, Whitton said.
Travis was born six weeks early and failed the newborn hearing test in the NICU. Because he had several birth complications, his hearing loss was first categorized as auditory neuropathy. Smith said she pushed for genetic testing, which showed he was a “perfect candidate” for Otarmeni.
When she first learned Travis could benefit from the experimental treatment, Smith said she worried about how to pay for it.
“I was ready to sell anything, take out a million loans if my child could hear me say ‘I love you,’ ” Smith said.
Then Travis’s surgeon told her it was part of a clinical trial, so it was free. Travis’s surgery was performed by Dr. Lawrence Lustig, chair of the Department of Otolaryngology – Head and Neck Surgery at the Columbia University College of Physicians and Surgeons and otolaryngologist-in-chief at NewYork-Presbyterian Hospital/Columbia University Medical Center.
Smith said the relief brought her father to tears.
Whitton said the treatment idea is simple in concept: “Put the thing in that’s missing.”
Otarmeni is an in vivo therapy, meaning it goes into the body’s cells. The gene therapy is placed surgically in the inner ear, similar to how and where a cochlear implant is placed. Instead of attaching a device, the treatment introduces the missing protein.
“We can create code for making the protein they need,” Whitton said.
He said that code has to get into a certain kind of cell in the inner ear. Regeneron identified the code that tells a cell to turn on protein-making abilities, then worked out a shell to package the code and get it to the right cell type.
“This is truly precision medicine,” Whitton said.
To get the instructions into the cell, he said, “you need an escort.”
Whitton said the code-carrying packages are attached to a common adenovirus that helps them get into the right cell. “Most people already have antibodies to the virus,” he said. “It’s not a virus that gets you sick.”
The protein shell is then injected into the right spot in the inner ear. “When the shell bumps up to the right cell type,” Whitton said, “it opens up and the protein directions are delivered.”
Kyratsous said other gene therapies need other delivery methods. “For many of these genetic medicines you have the payload you want to deliver into the cell, and then you choose the chauffer to get it into the cell.”
Whitton and Kyratsous said Regeneron is also using genetic medicines in work on other conditions, including a Parkinson’s disease program focused on getting new medicines to the brain and a treatment for fatty liver disease that would deliver genetic instructions by IV through the liver.
“The similarity is in the way the medicine is working,” Kyratsous said.
Whitton said the difference is that Otarmeni gives directions to create a missing protein, while some other treatments would turn down production of certain proteins.
“The packages you deliver to the body, some create proteins, some silence proteins,” Whitton said.
Smith said it was scary to let her son be a medical pioneer and to let a doctor operate on his head, but she is proud of his part in developing therapies for other children.
“Every surgery has to be done for the first time,” she said. “He’s helping other kids and he doesn’t even know it yet.”
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