Las Vegas Review-Journal

Pioneering gene therapy freed her of sickle cell. Is a cure at hand?

- By Gina Kolata

MESA, Ariz. — Helen Obando, 18 and soon to be a high school senior, nibbled french fries at a cafe and chatted about her future. Dressed in a halter top and shorts, her toenails painted turquoise,

she described her plans to enroll at a community college, teach hip-hop dance and become a trauma nurse someday.

For most of her life, such modest dreams would have been unattainab­le. Helen was born with sickle cell disease. Since babyhood, she had experience­d episodes of searing pain, hospitaliz­ation and organ damage, and would have been expected to die in her 40s.

But in 2019 she became the first American teenager with sickle cell to be declared free of the disease six months after undergoing an experiment­al gene therapy meant to cure her. Her symptoms have vanished. She assures teenagers she met at a camp for children with sickle cell: “One day they can have what I had.”

Such therapies are years off unless the federal government finds a way to speed progress.

This is a time of great promise for Americans with the disease, who are mostly Black. In recent years, clinical trials of three gene therapies for sickle cell have produced astonishin­g results for a few dozen lucky participan­ts like Helen, raising hopes that a cure could be at hand for some, if not many, of the 100,000 people in the United States who have the disease. And in the midst of a pandemic that has laid bare profound racial inequities in health care, President Joe Biden has pledged to combat them.

But the hope is shadowed by a legacy of underinves­tment in treatments for sickle cell compared with diseases that most

ly afflict white people, researcher­s have shown. Only four medication­s have been approved for the disease — and even they are often not used.

As inspiring as the early gene therapy results have been, the pace of progress has been slowed by the same factor that could greatly limit the treatments’ wide availabili­ty if and when they come to market: their sheer expense, with an expected price tag of $1 million to $2 million per patient.

Dr. Francis Collins, director of the National Institutes of Health and a geneticist who has long pushed for more research into sickle cell, an inherited disease, said in an interview that he had been in “high-level talks” with officials at the Centers for Medicaid and Medicare Services for two years about covering the cost of experiment­al sickle cell therapies for patients in clinical trials, which would greatly speed the process. He noted that the price of a potentiall­y curative one-time treatment would be significan­tly less than the lifetime cost of caring for people with the disease.

The federal government has paid such costs before for bone-marrow transplant­s for sickle cell, for example, and amyloid positron emission tomography (PET) brain scans for Alzheimer’s disease. But, Collins said, the progress of his talks with health officials slowed with the change of presidenti­al administra­tions; the appointmen­t of a new director for the Centers for Medicaid and Medicare Services, Dr. Chiquita Brooks-lasure, only in May; and the overwhelmi­ng focus on the pandemic. Collins said he would meet with Brooks-lasure and her team in October to discuss his proposal.

“This is an opportunit­y to save lives and save suffering,” Collins said.

“A lot of other diseases have gotten way more attention,” he said, a situation he attributed in large part to systemic racism. With the excitement over gene therapy, Collins added, “we might make up for decades of neglect.”

The clinical trials, run by Bluebird Bio, Boston Children’s Hospital and Vertex Therapeuti­cs, have changed the lives of the lucky patients like Helen who got them. Almost all the few dozen patients in the trials who passed the six-month marker since their treatments ended have had stunning results like hers.

“It’s an exciting time for sickle cell,” said Dr. Erica Esrick, a hematologi­st at Boston Children’s Hospital who led the clinical trail in which Helen participat­ed. “We’re enthusiast­ic. We’re optimistic.”

Researcher­s will follow these patients for 15 years to see if there are long-term complicati­ons, or if they remain free of sickle cell and can be considered truly cured.

One concern is that altering genes to rid them of sickle cell could introduce mutations that cause cancer. Bluebird Bio, one of the companies testing a gene therapy for sickle cell — not Helen’s — recently paused its clinical trial after two patients developed cancer to study whether their illnesses were caused by the treatment. But further investigat­ion exonerated the gene therapy, and the Food and Drug Administra­tion allowed the studies to resume.

If and when a gene therapy is approved for sickle cell, it is not clear how many people would be able to get it. Nor is it clear who would pay for it.

The NIH has formed two independen­t committees to study how much money could be saved over a lifetime of treatment for sickle cell if people with the disease could be cured with a costly gene therapy.

Dr. Scott Ramsey, a health economist and internist at the Fred Hutchinson Cancer Center, who leads one of the committees, said data from private insurers indicated that the lifetime cost for a person with sickle cell was $2.7 million.

“I’m not aware of another chronic disease that even comes close” to costing that much, he said.

He said he only recently received data for patients whose care was paid for through Medicaid and Medicare. His group is now analyzing it.

The ultimate goal is to find a simple, cheap way to cure sickle cell with a gene therapy that could be injected like a vaccine and used in developing countries with weak health care systems where complex, costly gene therapies would generally be unaffordab­le or impractica­l.

To reach that goal, the NIH is working with the Gates Foundation, along with researcher­s, several small biotechs and the drug company Novartis, which has experience bringing drugs to market. But it may be a decade before the first people get injections, said Dr. J. Mike Mccune, who leads the project for the foundation.

People with the disease want help now — and those who have gotten the gene therapies and their loved ones attest to the power of the treatments.

“Now she can have a life,” said Helen’s mother, Sheila Cintron. “She never did before.”

A chance for a cure

Like every sickle cell patient, Helen had a mutation in a gene that turned her

red blood cells into rigid crescents instead of soft disks. Those misshapen cells got trapped in her blood vessels, injuring them, causing severe pain and leading to lasting damage to tissues and organs.

Sickled cells blocked her spleen, which had to be removed. She had three life-threatenin­g blockages of blood to the lungs. And her hip bones were permanentl­y damaged by the disease.

Until now, the only cure was to give patients a bone-marrow transplant, which involved destroying their marrow and replacing it with marrow from a donor so closely matched that the body would not reject it.

Helen’s older sister had this treatment and was cured. Her healthy younger brother was the donor, but he was not a match for Helen.

Helen’s gene therapy took advantage of a discovery made decades ago. During fetal life, the production of red cells is directed by a gene that shuts down shortly after birth. Then an adult version of the gene takes over to direct red cell production. But that gene, the adult globin gene, is the one that can carry a sickle cell mutation.

Gene therapy flipped the switch backward, turning on her perfectly functional fetal gene and shutting down her mutated adult gene.

Researcher­s at Boston Children’s Hospital have now treated nine of 10 patients in their clinical trial and recently received a $30 million grant from the NIH and the California Institute of Regenerati­ve Medicine to treat 25 more patients at 10 medical centers.

The results so far, involving Helen and five other patients who got the same therapy, including a 7-year-old boy, were recently published in The New England Journal of Medicine. All were free of the disease.

Another paper, published in the same journal, involved Vertex’s therapy that used the gene editing technique CRISPR to turn on the fetal hemoglobin gene and turn off the adult gene.

The treatment, of a 33-year-old woman with sickle cell, was a success. The company has now given its therapy to six more patients, all of whom have passed the three-month mark. Vertex says the treatment appears to have succeeded.

Bluebird Bio has a different strategy — using a disabled virus to deliver a copy of a functionin­g globin gene. The company reported that in its most recent study, 32 patients had been treated, 22 of whom were at least six months past their treatment and now had normal or near-normal hemoglobin levels and were free of the debilitati­ng effects of sickle cell.

At Boston Children’s, more than 100 people inquired about getting themselves or their children into the four-year-long clinical trial for 25 patients ages 13-40. Most will be disappoint­ed.

Lives transforme­d

Braxton Hubbard of Evanston, Ill., began his treatment with Bluebird’s therapy on July 6 at age 27 — the same age at which his older brother Brandon died of sickle cell. It began with intense chemothera­py that destroyed his immune system.

In January, his doctor, Alexis Thompson of Northweste­rn University, told him he no longer had sickle cell disease.

It is strange, Hubbard said, to think he has a future. “I am becoming more serious about life,” he said. “I didn’t think I would have a life.”

Helen, too, has been adjusting to life as a healthy person — an alteration her pediatric hematologi­st, Dr. Alexander Ngwube of Phoenix Children’s Hospital, has observed in sickle cell patients cured with bone-marrow transplant­s.

“Remember, with sickle cell disease they are hospitaliz­ed a lot,” he said. “There are so many restrictio­ns on their lives. They become depressed, and when they are a little older, they realize they have a life expectancy of 40 years. They start to think, ‘What is the point of doing anything?’ ”

When they are cured, he said, “it is almost like the world is theirs to play with.”

When Esrick gave Helen the good news a year ago, Helen lay silent on the exam table, not daring to talk.

Helen and her family have since moved from Massachuse­tts to Arizona. I’ve followed her progress for more than two years. A lifetime of stoicism had taught her to keep her emotions to herself. During a harrowing monthlong stay in the hospital for the gene therapy, she barely spoke to me. Even after it was over, she tapped her mother on the arm and pointed when she wanted an ice cream cone as we walked through the Faneuil Hall Marketplac­e in Boston.

Freed of illness, Helen has become far more outgoing. On summer weekends, she has ventured to an arcade and a water park, and gone tubing.

“I’ve been trying to make new friends,” she said, “and get out into the world.”

Her passion is dancing. “I always wanted to be a dance instructor,” she said. Lasting damage to her hip from sickle cell makes it hard for her to dance but, she said, she should be able to teach.

She said she didn’t look back on her old life, but her mother relishes her daughter’s good fortune. “I keep thinking, ‘We are so blessed,’ ” Cintron said.

 ?? ASH PONDERS / THE NEW YORK TIMES (2020) ?? An experiment­al gene therapy Helen Obando received last year successful­ly rid her of her sickle cell disease, eliminatin­g her intense suffering and transformi­ng her into a teenager like any other.
ASH PONDERS / THE NEW YORK TIMES (2020) An experiment­al gene therapy Helen Obando received last year successful­ly rid her of her sickle cell disease, eliminatin­g her intense suffering and transformi­ng her into a teenager like any other.
 ??  ??
 ?? PHOTOS BY HILARY SWIFT / THE NEW YORK TIMES ?? Above: Helen Obando is joined by her parents, Bryon Obando, left, and Sheila Cintron, center, and Dr. Erica Esrick on Dec. 16, 2020, at the Dana-farber Boston Children’s Cancer and Blood Disorders Center in Boston. Below: Helen sits with her parents the previous day.
PHOTOS BY HILARY SWIFT / THE NEW YORK TIMES Above: Helen Obando is joined by her parents, Bryon Obando, left, and Sheila Cintron, center, and Dr. Erica Esrick on Dec. 16, 2020, at the Dana-farber Boston Children’s Cancer and Blood Disorders Center in Boston. Below: Helen sits with her parents the previous day.

Newspapers in English

Newspapers from United States