Originally Published: 27 APR 23 08:28 ET

Updated: 27 APR 23 17:01 ET

By Elizabeth Cohen and Lauren Mascarenhas, CNN

(CNN) -- Later this spring, a little girl in California who essentially has no immune system will receive a lifesaving treatment for "bubble boy disease" thanks to the persistence of a dogged group of parents, a pediatrician, a veteran newsman and a few episodes of "Grey's Anatomy."

Five-year-old Seersha Sulack has the same rare disease portrayed in the 1976 John Travolta movie, "The Boy in the Plastic Bubble." A germ -- even a common cold -- could kill her, and so she stays away from anyone outside her immediate family.

The treatment she's been waiting for had stunning, near-perfect results in a clinical trial, but it's been sitting on the shelf for years in the US because the pharmaceutical company that once owned the license abandoned it when it decided not to not to pursue approval from the US Food and Drug Administration.

"It's a pretty tough situation," said Dr. P.J. Brooks, acting director of the Division of Rare Diseases Research Innovation at the National Institute of Health's National Center for Advancing Translational Sciences. "You have an effective therapy like (this one) and people can't get access to it."

Seersha is expected to get the treatment next month. She'll become only the second child in the US in the past five years to receive it; the first child received it earlier this month.

The treatment is for a particular type of severe combined immunodeficiency called ADA-SCID that's extremely rare -- in the US, eight babies a year are born with it. Currently, 26 children in the US and Canada are on the waiting list to get the therapy, according to Dr. Donald Kohn, a UCLA scientist who has been working on the treatment for nearly 40 years.

The treatment is a type of gene therapy: Doctors will give Seersha a normal copy of the defective gene that disabled Seersha's immune system.

Gene therapies hold great hope for all sorts of diseases, but they're very expensive to develop, and pharmaceutical companies can't be sure that they'll make a profit because health insurance companies haven't always agreed to pay the multi-million dollar price tags.

"It has not escaped our attention at FDA that there have been some clouds on the horizon in gene therapy," Dr. Peter Marks, head of the US Food and Drug Administration's Center for Biologics Evaluation and Research, said at a biotech conference in California in October. "We really want to try to see what we can do to move things forward."

The gene therapy Seersha's been waiting for was once called OTL-101, for Orchard Therapeutics Limited. Orchard launched in 2016 with OTL-101 as its "lead candidate," but four years later, the company announced it would "reduce investment" in the therapy and prioritize treatments for more common conditions.

"A lot of us were upset and angry," said Seersha's mother, Shayla Sulack, noting that OTL-101 was developed with millions of dollars in state and federal government aid.

"We were always, 'it's going to happen, it's going to happen,' " she added. Then, after Orchard decided not to pursue the therapy, "a bunch of us SCID moms were like, 'Excuse me?' "

In a statement to CNN, an Orchard spokesperson wrote that "after encountering technical challenges related to the commercial-grade manufacture of this particular therapy, we made the very difficult decision to limit additional investment in [the SCID gene therapy]." The spokesperson spoke on the condition of anonymity.

A mother's 'oh, crap' moment

Shayla and her husband, Stephen Sulack IV, were high school sweethearts at Tehachapi High School, about 100 miles north of Los Angeles. In 2010, when she was 18 and he was 19, they married at the Little White Wedding Chapel in Las Vegas.

Stephen was in the Army, and over the next few years, the young couple moved to various military bases. Their daughter Skylar was born in 2012 and son Stephen V in 2014.

In 2017, the family moved to Hawaii for Stephen's new post as a Black Hawk helicopter pilot at Schofield Barracks in Oahu. Two weeks later, Seersha was born at Tripler Army Medical Center in Honolulu.

Weighing 6 pounds and 10 ounces, Seersha appeared perfectly healthy, and her parents took her on family outings, going to Dole Plantation and Waikiki Beach when she was five days old.

Strolling around the shops near the beach that day, the family went into a Tesla dealership just for fun. While sitting in a showroom car, Shayla got a phone call from a number she didn't recognize.

It was a geneticist at Tripler. He told Shayla that a routine blood test, a prick on a newborn's heel done in nearly every state, showed Seersha's level of T cells -- a type of white blood cell crucial to fighting off infections -- was just five. Normal T cell levels for newborns are around 3,000.

This meant any infection, no matter how small, could kill Seersha. The geneticist said to bring her back to the hospital at Tripler immediately.

Shayla says her first reaction was: "Oh, crap."

Not only had they been going everywhere with their new baby, but Seersha's big brother and sister had been affectionately pawing all over her.

Shayla and Stephen left the Tesla dealership and made the 20-minute drive to the hospital while Shayla's parents took the older two children home in their car.

At Tripler, doctors explained more about SCID, and a psychologist was on hand to help the Sulacks deal with the shocking news.

Only about one baby a year is born with the SCID in Hawaii, according to Sylvia Mann, genetics coordinator at the state's department of health.

The next day, Shayla and Seersha were on a military medical transport flight to Los Angeles. Seersha was in an incubator in the front of the plane, and the other patients were kept in the back to decrease the chances they could get her sick.

An ambulance drove Shayla and Seersha to UCLA Mattel Children's Hospital, one of 47 medical centers in the US and Canada that specialize in SCID as members of the Primary Immune Deficiency Treatment Consortium funded by the National Institutes of Health.

Once there, doctors laid out the options for saving Seersha's life.

Options for Seersha

It turned out none of them were very good.

ADA-SCID is treated with regular injections to replace a missing enzyme that helps with immune function. They help a great deal, but they don't give the child a full immune system, and their effectiveness can wane over time.

The UCLA doctors laid out two longer-term options. Seersha could receive a stem cell transplant, which is lifesaving and the standard treatment for SCID. Doctors would test her mother, father, brother, and sister and determine the best genetic match, and then would extract cells that specialize in forming blood cells and give them to Seersha.

Testing showed that any of her family members could donate to her, but none of them was a particularly good match. This was bad news for two reasons: One, the transplant likely wouldn't be as effective. Two, Seersha would be more likely to suffer complications.

Those complications could be very serious. In preparation for the transplant, Seersha would need high doses of chemotherapy, which would leave her vulnerable to infection in the short term and at increased risk for cancer and infertility in the long-term. After the transplant, the donor's cells might attack Seersha's organs and tissues, which is treatable but could make her very sick.

The doctors laid out another option: gene therapy. They would take Seersha's blood cells, treat them to give her a normal copy of her defective gene, and then give the cells back to her. Essentially, Seersha would be giving herself a transplant, which has two advantages: She could get much lower doses of chemotherapy, and her body wouldn't perceive the new cells as a foreign attack.

This sounded familiar to Shayla. She realized she'd seen episodes of "Grey's Anatomy" where a character with SCID received gene therapy.

She brought it up to Kohn, the UCLA gene therapy researcher. He told her that not only had he seen the episodes, but he'd given "Grey's Anatomy" staffers a tour of his lab and answered their questions while they were preparing the story arc, which aired in 2014. He still had the "Grey's Anatomy" mug and note pads they gave him as a thank you.

Kohn explained to Shayla that doctors in the US and UK had done a clinical trial with dozens of children with this gene therapy and the results had been very good, but Seersha couldn't participate since the trial had enrolled its last patient. The treatment wasn't on the market -- Orchard had yet to apply for FDA approval -- so she couldn't get it that way, either.

The only thing they could do was wait for FDA approval, and there was a bit of good news there: Just a few months before Seersha was born, the agency granted Orchard a rare pediatric disease designation, which would give the treatment priority review by the FDA. Kohn says he believed the therapy would be available to Seersha and other children in two to three years, so in 2019 or 2020.

The Sulacks weighed their options: Have a transplant with a match that was less than ideal -- far less -- or wait for gene therapy to become available.

They chose gene therapy.

Anxious families await word on treatment

After spending nearly eight weeks at Mattel in the fall of 2017, Seersha was discharged from the hospital. Stephen put in for a transfer from Hawaii to Fort Irwin in San Bernardino, California, so they could live closer to UCLA and to family.

For her first year of life, Seersha hardly ever left her bedroom, which her parents filled with toys to entertain her. She had contact with only her parents and Shayla's parents -- not even her siblings -- and the adults changed into clean clothes before coming near her.

After that year, her weekly enzyme injections started to kick in, and Seersha could go into other rooms of the house and be near her immediate family. But still, her immune system wasn't very strong: Normal T cell levels for a child her age are about 2,390 and Seersha never got above 250.

Seersha started to leave the house, but avoided crowds and contact with people. She watches her brother and sister's baseball and softball games from a distance, sitting on the tailgate of the family's truck. If her parents and siblings ever start to feel sick, even just a sore throat or a sneeze, they have to keep their distance.

In January 2020, a few months after Seersha's second birthday, Orchard announced encouraging news: The company said in the first half of the year, it planned to to initiate the FDA approval process for the gene therapy and it anticipated it would take a year to complete the application.

The Sulacks were shocked when four months later, the company issued a news release saying it had a net loss of $50.6 million in the previous quarter and would "reduce investment" in its SCID gene therapy and prioritize research for other diseases.

The news release didn't say anything else about the SCID gene therapy. At this point, there were 14 families in the US and Canada like the Sulacks waiting to get it. They were filled with anxiety as they waited to see what would happen.

Was the company still planning to apply to the FDA to get approval? If so, would the timetable be slower than expected?

Or was the company abandoning its plans for SCID gene therapy altogether?

'Superhero meets Florence Nightingale'

Whenever Dr. Fyodor Urnov, a scientist at the Innovative Genomics Institute at the University of California, Berkeley, gives a presentation about ADA-SCID, he starts with a picture of Kohn next to a boy he treated in the clinical trial. Kohn has been working on this therapy for decades, Urnov explains to his audience, persevering through countless hurdles.

"His juxtaposition of accomplishment and goodness is unbelievably rare," said Urnov, a professor of molecular and cell biology at Berkeley, who has worked with Kohn for 20 years. "He's some sort of superhero meets Florence Nightingale."

Now 68, Kohn first started researching gene therapy for ADA-SCID when he was 31 and a fellow at the National Institutes of Health, working in the lab of Dr. Michael Blaese, a pioneer of gene therapy.

It was an exciting new field. In 1986, Kohn, Blaese and their colleagues published a study on the ADA-SCID treatment in the Proceedings of the National Academy of Sciences. More than 25 years later, in 2012, Kohn and his team started the clinical trial for their ADA-SCID therapy with children at UCLA, the NIH, and the Great Ormond Street Hospital in London.

By 2016, when Orchard launched, the clinical trial results looked promising, with 100% survival in 32 patients, according to a company news release at the time.

Four years later, when Orchard announced it would reduce investment in the gene therapy, Shayla Sulack called Kohn asking if Seersha would ever get the treatment.

"He said, 'this is my life's work,' basically, and there's no way I'm not going to get this back," Shayla remembers. "He said, 'this is mine, this is my thing and I'm not going to let it die.' "

Shayla said she had "full faith" that Kohn would keep to his word.

'A desperate call to save young lives'

Once Orchard abandoned the treatment, Kohn's mission became to get the license for the therapy back so he could start using it to treat Seersha and the other children.

It wasn't an ideal solution. The typical route for biotech development is to start in an academic lab, sell the discovery to a pharmaceutical company, get FDA approval and then get it on the market. For Orchard to return it back to the academic researchers was a backward move.

"I didn't expect it," Kohn told CNN. "It's like having a college kid move back home."

Kohn says in 2020, UCLA and University College London initiated discussions with Orchard. In the meantime, parents of children with SCID took matters into their own hands.

Parents in a support group called the SCID Angels for Life Foundation, asked to meet with Orchard President Dr. Bobby Gaspar. While the company did not make Gaspar available, the parents did have a Zoom call with other staffers, according to Heather Smith, president and founder of the parents' organization.

The parents requested that Orchard abide by the academic researchers' request and return the license to the universities.

But the company kept the license, and the treatment continued to sit on the shelf. In February, 2021, the parents of more than 20 children who were waiting for the gene therapy treatment, including the Sulacks, wrote a letter to Gaspar.

The families implored Gaspar "to treat this as a desperate call for help to save young lives" and urged him to "please consider addressing this issue."

"(If) Orchard strikes out boldly now to lift these babies/children out of mortal danger and wipe the tears off the faces of their distressed parents, you may rest assured that the financial bits will fall in the right order, assuring significant gains for you as well," the parents wrote. "Thus, putting patients first and choosing a positive course of action will only lead to a happy outcome all around. Not to mention the lives you will be changing now and forevermore."

Each family included pictures and information about their child.

Smith said the parents did not hear from Gaspar for months.

The parents also spoke with David Jensen, a retired newsman and editor of the California Stem Cell Report. On May 11, 2021, Jensen wrote a story about the families' plight, followed by more than a dozen other posts about Orchard. Two weeks later, the Los Angeles Times picked up on his reporting.

"He really lit a fire and kept the story going," Smith said. "He kept it on the radar, so Orchard knew we were not just going to away quietly."

'An enormous stain'

On May 11, 2021, the same day as Jensen's first story, the New England Journal of Medicine published results of Orchard's clinical trial, which showed the gene therapy was successful for 48 out of the 50 patients treated and with far fewer side effects than conventional transplants. The two patients for whom it didn't work went on to have successful conventional transplants from donors.

Those 48 children are now living normal lives, going to school and playing with friends, and they no longer need to take enzyme shots or other treatments to boost and protect their immune systems, Kohn said.

"The other patients we treated in the past -- we barely hear from them anymore, they're doing so well," he said, adding that doctors continue to monitor the children.

Urnov, the director of technology and translation at Berkeley's Innovative Genomics Institute, noted that the gene therapy "cured 48" of the 50 patients in the study.

"When you have an efficacy of five out of 50, it's a celebration. Ten out of 50, literally, you feel like you've accomplished the biggest thing you've ever done in your life."

Still, the treatment sat on the shelf.

"To have something this astonishingly curative languish because the marketplace isn't configured to deliver curative therapies for rare diseases -- it's just an enormous stain," Urnov said.

Two weeks after the study published, Gaspar, the Orchard president, wrote an email to Smith and two other mothers of children with SCID.

"Earlier this morning we informed UCLA and [University College London] of our intent to return the OTL-101 license to them," Gaspar wrote. "This was not an easy decision to make, especially given my long history with the OTL-101 program and relationship with the community, but I recognize and respect your strong preference to transition OTL-101 back to our academic collaborators at this time."

Gaspar attached a letter he'd written that day to members of the ADA-SCID community.

The letter noted that the company would continue to give UCLA and University College London "financial and material resources" including material to help make the treatment. When asked by CNN, the company spokesman declined to say how much money the company was giving the universities.

Orchard also noted difficulties they had making the therapy.

"Although the clinical data for investigational OTL-101 are very encouraging, we have encountered technical issues specific to the commercial-grade manufacturing processes for this particular therapy that must be addressed before we, or any other entity, could progress the program toward a regulatory submission," Gaspar wrote. "Without the ability to reliably manufacture OTL- 101 at a commercial standard there is no way to receive FDA approval for the gene therapy."

Some parents doubted whether manufacturing issues were the real reason Orchard had abandoned SCID gene therapy. They say the company's true motivation was profit -- that Orchard saw its revenues decreasing and chose not to pursue the ADA-SCID treatment so they could focus on therapies for more common diseases with likely more lucrative markets.

The parents noted that abandoning the ADA-SCID treatment saved Orchard money. Direct expenses associated with the ADA-SCID gene therapy treatment declined by $3.8 million, according to an Orchard filing with the US Securities and Exchange Commission for the third quarter of 2021. The company did not specify the time period for this decline.

"At the end, what they're saying is, 'we're not going to make money off this, so goodbye.' And we never got an apology," said Andrea Fernandez, whose 3-year-old son, Jakob Guziak, is on the waiting list to receive the ADA-SCID gene therapy. "It hurts."

The Orchard spokesperson declined to comment when asked whether the decision to abandon the therapy was impacted by the shift to pursue therapies for more common diseases.

In an email to CNN, the Orchard spokesperson said that "we worked to find a viable path forward for this program outside of Orchard but were unable to identify a new partner." The spokesperson also noted that the decision to limit additional investment in OTL-101 was "due, in part, to the availability of standard-of-care treatments."

Once the academic medical centers got the license to the gene therapy back in 2021, they had to get funding for a new trial and start the process of making the treatment again.

The universities received the money from California Institute for Regenerative Medicine, a state agency, and the first child in the US received the treatment earlier this month. Seersha had her stem cells extracted a few weeks ago and is expected to get the treatment in May.

It couldn't come soon enough, her mother says. The power of her weekly enzyme injections has waned over the past few years, and her T cell levels have dropped dramatically.

There are more than two dozen children waiting to get the gene therapy treatment in the US and Canada, but there's only enough money to treat a few more children, somewhere between one and four, and UCLA is looking for more funding.

Urnov, the scientist at Berkeley, said he hopes they figure it out soon.

"We're talking about giving patients access to treatments that show the best efficacy profile in the entire 30-year history of our field," he said.

Seersha packs her unicorn suitcase

Testifying to a Senate subcommittee last week, FDA Commissioner Dr. Robert Califf acknowledged that gene therapy "is an area we've got to move along more quickly."

He told the Senate appropriations subcommittee that gene therapy will be "a big focus of attention," with the agency hiring 150 to 200 people to work on it.

The agency is holding two public meetings this week on gene therapy. In the announcement for one of them, the agency notes that "the rapid pace of innovation for cell and gene therapy products holds promise for transforming medicine."

Later this year, the FDA will launch a pilot project to "further accelerate the pace of development of therapeutics for very small populations with very high medical need," which will "build off of the agency's experience with accelerated vaccine development as part of Operation Warp Speed during the Covid-19 pandemic," FDA spokesperson Carly Kempler wrote to CNN.

At the California meeting last fall, Marks, the FDA official, said high-income countries could have a "convergence of regulatory approach" for gene therapies for rare diseases. The theory is that if several countries have similar regulations, it would create a larger and more accessible market for pharmaceutical companies.

Dana Goldman, dean and co-director of the Schaeffer Center for Health Policy & Economics at the University of Southern California, has another idea to make gene therapy more financially viable.

Insurance companies have sometimes balked at paying for gene therapy, which is typically given in one treatment. Goldman proposes that insurers be allowed to pay for it over time rather than in one lump sum.

"We've solved the high cost of buying a home with home mortgages, not by policies that lower home prices. We should do something similar for drugs, particularly those that cure diseases, which are likely to have up-front costs in the hundreds or thousands, if not millions, of dollars," Goldman and his co-author Anupam Jena wrote in Stat in 2017.

In an email to CNN, David Allen, a spokesperson for America's Health Insurance Plans, an association of health coverage providers, said this and other approaches "are being explored," but that it "cannot be carte blanche for drug manufacturers to charge nearly-unlimited prices for their drugs, particularly for emerging therapies with limited evidence of long-term safety and efficacy." When asked if insurance companies have sometimes refused to pay for gene therapy, Allen wrote that insurance providers "have chief medical officers who lead clinical teams. These teams have expertise in reviewing the best available evidence pertaining to new and emerging treatments and making coverage decisions."

"As our society faces emerging treatments that are very high cost and potentially curative, stakeholders will need to explore innovative approaches to financing the treatments that are proven effective," he added.

While drug companies, insurance plans and regulators figure out the best way to get gene therapy to patients, Shayla and Stephen Sulack are just happy that finally, their daughter will be getting her treatment soon.

Shayla says Seersha understands that the treatment can help her, and last Christmas, she asked Santa for a unicorn suitcase to pack up her clothes and toys for her stay at the hospital.

"She's like, 'I'm ready. Let's do this. Let's go,' " Shayla said. "She's like, 'I want to play softball. I want to play baseball. I want to do jujitsu' [because now] she can't do any of those things."

If all goes as expected, once Seersha recovers from the gene therapy, she'll be able to stop taking the enzyme shots and getting infusions of immunoglobulin -- between the two, around seven needles every month.

As for Shayla, she says in some ways she's "terrified" for the upcoming treatment, since her daughter will have to get chemotherapy and spend weeks in the hospital, but she's also excited.

"She's missed so many things -- she wants to go to a Dodgers game, and Daddy has taken her brother and sister and she sat on the couch and watched it on TV and tried to see if she could see them," Shayla said. "I don't like the word 'normal', but I'm ready to have something normal for her."