Megan Selser has been savoring the antics of her toddler son, who laughs as he leaps from a household ottoman each night before bed and points to Minion characters on TV while shouting, “Eyeballs!”
She has also been anxiously awaiting the Food and Drug Administration’s decision on a promising gene therapy for children like her son, who has Hunter syndrome. The disease floods children with cell fragments that their brains and bodies can’t break down, robbing them of the ability to walk and talk by age 8.
The agency rejected the therapy last month, one in a series of denials over the last eight months that have dashed the hopes of desperate families. Though Ms. Selser’s son wasn’t a candidate for this particular gene therapy, she has been worried about other options awaiting an F.D.A. decision.
She fears that her son’s first steps and words will soon be followed by his last.
“I don’t want to see anything that makes my son disappear, slip away,” she said.
In the Trump administration, the F.D.A.’s drug review process has undergone a considerable shift, brought into stark relief in recent weeks by the agency’s refusal to consider Moderna’s flu vaccine, and then its reversal of that decision.
Many attributed the initial Moderna action to the anti-vaccine leanings of Health Secretary Robert F. Kennedy Jr. and his opposition to mRNA technology, which the company successfully used in Covid vaccines and was testing in the flu shot.
But the agency has increasingly issued drug rejections or refusals — about 20 in the last eight months — that underscore a break from decades of general stability in the F.D.A.’s top ranks across several presidential administrations. It has advised companies to launch costly and complex studies that could add years to finding treatments for rare diseases with no cure.
The F.D.A.’s recent decisions have generated concerns in Congress and at the White House.
Emily Hilliard, a spokeswoman for the Department of Health and Human Services, defended the agency’s actions. “The American people voted for an F.D.A. that works for them, not the industry, and the agency is delivering by refusing to rubber-stamp approvals,” she said.
Though the F.D.A.’s current approach partly reflects growing skepticism aimed at pharmaceutical companies, it has also taken hold with little public dialogue or debate.
Dr. Marty Makary, the agency’s commissioner, often sends mixed messages in TV appearances and interviews, promising speedy drug reviews and fewer clinical trials at the same time that the agency is rejecting new treatments for rare diseases.
“I bring a sense of urgency and a sense of ‘We’ve got to do something about this community’ to my role at the agency,” Dr. Makary said on CNBC last week. “We say, ‘If this is safe and looks like it works for an ultrarare disease, we’re going to go ahead and greenlight that therapy.’ ”
Still, he defends the spate of denials issued under the leadership of Dr. Vinay Prasad, his chief science and medical officer, who often overruled agency scientists last year. Dr. Prasad rose to prominence as an academic known for picking apart medical studies. Before his appointment, he castigated the F.D.A. for what he called “revolving-door politics,” saying that scientists were approving marginal drugs to curry favor with potential future employers in the industry.
“I constantly see medicine that’s completely Hail Mary batshit crazy medicine,” Dr. Prasad said in a podcast released in January 2025, several months before he joined the F.D.A. He added, “I guess my concern is: How can we live in a world where society is taxed to pay for these unproven things?”
Before joining the F.D.A., some of Dr. Prasad’s harshest critiques targeted a gene therapy by the company Sarepta, which agency officials approved over the objections of staff scientists who said it was ineffective. The treatment, for boys with Duchenne muscular dystrophy, proved deadly for two teenagers. After the second death last year, Dr. Prasad demanded that the company stop using it to treat older children.
The F.D.A. estimates that about 30 million people, nearly one in 10 in the United States, has a rare disease. So the agency’s decisions have hit companies developing drugs for rare diseases in a particularly hard way, and rare-disease treatments make up a large share of drugs seeking approval.
Frustrated by the F.D.A., advocates for rare-disease treatments flooded the Capitol last month. Lawmakers held a hearing on the topic. Though no one from the agency testified, Dr. Makary defended Dr. Prasad on television that day, calling him a “genius” and claiming that he was being targeted unfairly.
The F.D.A. has unveiled a series of new initiatives, including one to expedite approval of individual gene therapies like the high-profile treatment for Baby KJ that was tailor-made to treat his rare disease.
But those announcements have not slowed the drug rejections, which are startling companies that worked for years with the agency to define the criteria for approvals.
“The F.D.A. actions are not backing up the positive rhetoric about accelerating development of cell and gene therapies,” said Stephen Majors, vice president of communications for the Alliance for Regenerative Medicine, a trade group. “And over the past few months, surprising regulatory U-turns on promising medicines for rare diseases are frustrating patients and confusing the companies trying to bring them to the market.”
He called for the agency to hold more public meetings of advisory committees on proposed drugs “to transparently review the evidence.”
Former agency officials rejected their share of new drugs, upholding standards that caused drugmakers to abandon many therapies. But in interviews, they defended their overall record. By approving treatments that showed signs of helping dire conditions, the officials said, they encouraged biotech investments that could eventually result in breakthroughs.
Dr. Janet Woodcock, who worked at the F.D.A. for 37 years and retired as a top official in 2024, said the recent refusals had shocked both companies that invested hundreds of millions of dollars in new therapies and the patients who volunteered for studies.
“To then move the goal posts at the end cuts both of those parties down at the knees,” she said.
Ms. Selser has closely tracked therapies under development for her son’s disease, Hunter syndrome, a genetic defect that deprives children of an enzyme that breaks down sugar. Cellular waste builds up in the body and damages the brain and heart, reducing children around age 7 to a state that resembles dementia.
About 50 U.S. newborns, mostly boys, are diagnosed with the disease each year. Ms. Selser’s son, Ben, who is 2 and a half, receives a weekly infusion to manage the buildup in his body.
One gene therapy that Ms. Selser monitors is made by RegenXbio, a Maryland biotech company, which was seeking accelerated approval based on the drug’s ability to improve learning and motor skills. A year’s data showed an 82 percent reduction in heparin sulfate, a toxin that accumulates in spinal fluid, the company reported.
The F.D.A. denied authorization for RegenXbio’s therapy, according to the company. Ms. Hilliard of H.H.S. said RegenXbio “must identify a new, reliable biomarker or demonstrate that patients live longer and experience meaningful clinical improvement.”
Curran Simpson, the company’s chief executive, said the therapy took 10 years to develop and that the company would try to persuade the F.D.A. by providing more data.
“It’s like you have the rules to a game and you’ve won the game,” Ms. Selser said, adding, “Now, all of a sudden, the F.D.A. would change the rules.”
She is worried about other treatments in development, hoping that her son has a milder form of the syndrome and can benefit from an infusion aimed at the brain. It is up for F.D.A. approval next month.
Dr. Cara O’Neill, chief science officer for the Cure Sanfilippo Foundation, said her daughter was an early participant in a study 10 years ago for a gene therapy that was rejected last summer.
Last month, Ultragenyx Pharmaceutical, which makes the therapy, reported additional promising data from a small study of children given the gene therapy before the age of 2. The company is working toward agency approval.
“It’s painful to see these time windows tick on, the clock tick on, and children continue to be damaged when they don’t have to be,” Dr. O’Neill said.
Dr. Woodcock, the former F.D.A. official, said the most jarring decision in recent months was the agency’s decision not to review an application for a gene therapy to treat Huntington’s disease, a genetic condition that strikes in midlife and causes an early decline in mental and physical abilities.
As many as 40,000 people in the United States have symptomatic Huntington’s, for which there is no treatment. UniQure, a Massachusetts biotech company, reported in September that a small study of a dozen people given a gene therapy showed a slowing of the progression of symptoms by about 75 percent over three years.
In a news release, the company said that the F.D.A. told the company that it no longer agreed with the parameters of its study, which agency officials had OK’d in 2024. Matt Kapusta, the UniQure chief executive, called the reversal an unexpected and drastic change.
Ms. Hilliard, of H.H.S., said that agency scientists concluded the trial was not “adequate or well controlled,” F.D.A. nomenclature for an acceptable study. The company had compared people on the gene therapy with a control group described in a large data set gathered over years. UniQure reported Monday that the F.D.A. requested a new study.
Dr. Woodcock, a top drug regulator for decades, said that such reversals for a promising therapy send shock waves through the industry.
“The Huntington’s refusal I thought was truly evil,” she said. “I just feel so bad for those people.”
Amy Turner LaDow, 61, a retired software executive who lives in Northwest Indiana, has Huntington’s disease. Twenty-eight members of her family, living and dead, across four generations also have or had the disease.
Her nieces and nephews, many of whom are in college, form the largest group.
UniQure’s gene therapy would probably have been out of reach for many in her family, given that it would have involved costly brain surgery.
Still, she said, progress toward an approved treatment would have given them hope.
“It tells them there’s an opportunity for somebody to keep watching and paying attention and trying to make that solution better,” she said.
In January, Huntington patients and their allies marched to the F.D.A.’s Maryland headquarters to deliver a petition with more than 40,000 signatures asking the agency to honor its commitment and review the application.
“There’s bureaucracy involved, and it sometimes can move at a snail’s pace,” said Amy Gray, president of the Huntington’s Disease Society of America, “while Huntington’s disease continues to move forward, somewhat like a freight train.”
Christina Jewett covers the Food and Drug Administration, which means keeping a close eye on drugs, medical devices, food safety and tobacco policy.
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