On May 26, Tracy Atteberry checked in to the hospital at the National Institutes of Health in Bethesda, Md. The 57-year-old has an ultrarare inherited disease that hobbles his immune system so that the most innocuous of germs could kill him. Now he was going to receive a potential cure in the form of a gene editing treatment that had never before been tried in patients.
But, in a tale that gene therapy experts say is too common, Mr. Atteberry and one other patient, a Canadian teenager, may be the only ones ever to get this treatment. As has happened over and over when gene therapies are developed, the company that made it, Prime Medicine, is no longer offering it.
The problem is economics. The science is there to cure Mr. Atteberry’s condition, a subtype of chronic granulomatous disease, or CGD. But it costs so much to develop a treatment and get it approved that even when a company decides to start along this path, it often abandons the effort.
In part, that is because there are so few patients. Only about 200 people in the United States share Mr. Atteberry’s genetic condition, according to Prime Medicine’s chief medical officer, Dr. Mohammed Asmal. But only about 50 of them might be eligible for gene editing, Dr. Asmal said.
He added that the company — before it ran out of money for the study — planned to treat six to 12 patients at a cost of $20 to $30 million.
As gene therapies are developed, then discarded, the result is dashed hopes for many of the 400 million people in the world with rare genetic diseases.
“It’s frustrating to see promising therapies stall after successful preclinical studies,” said Joseph Hacia, who studies innovative genetic treatments at the Keck School of Medicine of the University of Southern California. He was not involved in the Prime trial.
He called such outcomes “gut wrenching” and added that “it keeps me up at night.”
Dr. Asmal says the only way the company can provide the treatment to others is if the Food and Drug Administration decides to grant approval on the basis of results with just two patients after just a few months of observation.
“It’s a Hail Mary move,” Dr. Harry L. Malech, Mr. Atteberry’s doctor at the N.I.H. and chief of genetic immunotherapy, said of Prime’s hope for approval.
In other gene therapy trials for ultrarare diseases, companies submitted data for many more patients and followed them for much longer. For example, approval of a gene therapy for spinal muscular atrophy came after two clinical trials, one involving 21 patients and the other involving 15. In both studies patients were followed for more than 6 months. Another, for inherited retinal dystrophy, involved 29 patients followed for one year.
But Dr. Asmal and others are clinging to hope that some of these treatments might get approved. Dr. Martin Makary, head of the Food and Drug Administration, has suggested the agency might make approvals easier when they are for treatments for ultra rare diseases.
Mr. Atteberry, a software developer in Lincoln, Neb., knows how lucky he is to get a chance to be cured. Life with CGD, which destroys the immune system’s ability to fight everyday bacteria and fungi, has meant “there always will be another life-threatening infection,” he said.
It also meant taking numerous pills every day for prophylaxis and adhering to “a raft of restrictions,” which include staying away from soil and never raking leaves.
Mr. Atteberry couldn’t own house plants or put up a live Christmas tree. He has lived with frequent hospitalizations for pneumonia and infections that scarred his liver. And he knows his time is limited. He’d outlived the average life expectancy of people with CGD: 40.
Development of the experimental treatment he received was initiated by Prime Medicine.
It involves a new type of gene editing that can perform the equivalent of a find-and-replace command on DNA. The treatment can turn a gene like his, with two missing DNA letters, into a normal one. And it seems to have fixed the genetic defect in both Mr. Atteberry and the teenage patient. During follow-ups with doctors in September, both patients had normal levels of an enzyme that the mutated gene had failed to produce.
Now that cure is being dangled in front of other patents, according to David R. Liu, a Harvard researcher whose lab invented the gene edit used by Prime Medicine. No one else can have it.
“I want to get this science out to people,” said Dr. Liu, a co-founder of Prime Medicine who has no operational role in the company. “It’s the whole purpose of my life."
Dr. Asma says Prime Medicine has not given up. He has been talking to the F.D.A. about ways to get the treatment approved.
“We are leaning into the moment,” Dr. Asmal said, “and trying to give it a shot.”
Other experimental therapies are developed after families of patients, full of bravado and optimism, form foundations and raise money to pay for the development of gene therapies.
That is what Terry Pirovolakis of Toronto did.
His son Michael has spastic paraplegia 50, or SPG50. It comes with a grim prognosis.
“Paralysis from age 10, quadriplegic by age 20, microcephaly, seizures, never walk, never talk,” Mr. Pirovolakis said.
The diagnosis, when he heard it, shattered him.
“I went home in a fog,” he said, “crying in the corner of the street.”
Then he rallied. He started a charity and, in four years, raised $4.5 million to cover the costs of a gene therapy developed by Steven Gray at the University of Texas Southwestern in Dallas.
In three years, Dr. Gray developed a treatment using a disabled virus to insert a good gene into patients’ cells to function in place of the nonworking gene.
Mr. Pirovolakis’s charity then paid two companies to develop the treatment — one to do toxicology tests and the other to manufacture it. And the charity arranged for Children’s Medical Center Dallas to be a treatment center.
Michael got the gene therapy. His cognition improved, but so much damage had already been done that he was not cured, his father said.
Mr. Pirovolakis tried to give away the gene therapy. But no biotechnology company wanted it. There were too few SPG50 patients in the world — only 100 children, Mr. Pirovolakis said.
He started his own company, Elpida Therapeutics, hoping to develop gene therapies for his son’s disease and for several other ultrarare illnesses. But he needed more money to get the treatments tested sufficiently for the F.D.A.’s approval.
“All the funding dried up. We were almost done.” But, he added, “I never give up.”
Academic researchers have similar problems.
Dr. Donald B. Kohn of the University of California, Los Angeles, has spent 40 years trying to bring gene therapy to people with adenosine deaminase deficiency severe combined immunodeficiency disease. The inherited disease, known also as ADA-SCID, hinders patients’ immune systems.
Dr. Kohn and his colleagues developed a specific gene therapy for ADA-SCID. The treatment has been tried and tested, and a forthcoming paper in the New England Journal of Medicine shows that the gene therapy worked, Dr. Kohn said.
After a biotechnology company said it could not find a “path forward” for the drug, Dr. Kohn and his colleagues started a public benefit company called Rarity. “A public benefit company can make a profit, but the main driver is to make the drug available,” Dr. Kohn said. But Rarity, too, needs investors.
Dr. Kohn says he keeps getting calls from parents asking when their child can get the gene therapy. He’s keeping their names on a list, hoping that the day will come when he can tell them they can come in.
Maria Thianthong, of Los Angeles, said her daughter got on the list as a newborn.
She’s now 3 years old and still waiting, Ms. Thianthong said.
A spokesman for the Department of Health and Human Services did not describe any current changes in the F.D.A.’s approach to approving gene therapies for rare disease when asked for comment. But some patients have been cheered by the remarks of Dr. Makary, the F.D.A. commissioner, who has indicated openness to the agency’s being more flexible.
At a round table meeting in June, where he heard about the issue from scientists and patient advocates, he said, “We can learn from individual cases. That is the approach we need to take with cell and gene therapy.”
One idea he has suggested is to grant conditional approval for gene therapies when patients have ultrarare diseases. The approval could follow studies with just a few patients, but would also require safety and efficacy monitoring for patients after they get a treatment.
But such an approval leaves open the question of whether insurers would pay for what are likely to be very expensive treatments.
Economists say the issue should not be the high price of the drugs so much as how society views them.
“Therapies that treat the rarest of rare diseases have a high social value,” said Dr. Anupam B. Jena, a health care economist at Harvard Medical School. “Treatment for a disease may be valuable to you even if you never use it. Just like insurance.”
Craig Garthwaite, an economist at Northwestern University’s Kellogg School of Management, has the same view. Rare diseases, he said, “represent a genetic lottery that people have lost.” The price for the treatments might be “eye watering,” he said, but the overall cost, because there are so few patients with each condition, would not overwhelm the insurance system.
But with so few patients, it can be almost impossible to know if a drug truly works, these economists said. And maybe that is something that just cannot be answered the way regulators expect, they added.
“If there is a technology with very limited data, we should be willing to try it if patients understand the risks and benefits,” Dr. Jena said.
For CGD patients who cannot receive the gene editing treatment, a change of approach cannot come soon enough.
Laura Owens, 48, of Rincon, Ga., has had a raft of life-threatening infections and tissue damage caused by the disease. When she heard about the Prime Medicine gene editing study, she was excited.
“Then I found out it was canceled,” she said.
“I wish the F.D.A. would listen to the doctors,” she said. “Can you not help us?”