A drug company abandoned a treatment for ‘bubble boy disease.' After a 5-year fight, this little girl is about to get it

CNN

A little girl from California, who has a weakened immune system, will be treated for "bubble boy" disease this spring thanks to the perseverance of parents, pediatricians, veteran journalists and even a few episodes 'Grey's Anatomy'.

Seersha, five-years-old Seersha has the same rare illness as the boy in the plastic bubble in the 1976 John Travolta film. She is afraid that a germ, even a cold, could kill her. So she avoids anyone who is not in her immediate family.

The drug she has been waiting for showed near-perfect results during a clinical study, but the company that owned the license for it abandoned it after deciding not to seek approval from the US Food and Drug Administration.

Brooks, acting director of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences' National Institute of Health. Brooks, the acting director of Rare Diseases Research Innovation for the National Center for Advancing Translational Sciences of the National Institute of Health. You have an effective treatment like (this) but people cannot get access to.

Seersha will receive the treatment next month. She will be the only child in America to receive the treatment in the last five years. The first child was treated earlier this month.

Treatment is available for a rare type of severe immunodeficiency known as ADA-SCID. In the US, only eight babies are born each year with this condition. According to Dr. Donald Kohn of UCLA, who has worked on this treatment for almost 40 years, there are currently 26 children on the waiting lists in the US and Canada.

This treatment is a form of gene therapy. Doctors will give Seersha an intact copy of the defective genetic material that caused Seersha to have a disabled immune system.

Gene therapies are a great way to treat a wide range of diseases. However, they can be very expensive and the pharmaceutical companies cannot guarantee that they will make a profit, as health insurance companies don't always agree to pay for these multi-million dollar prices.

Dr. Peter Marks of the US Food and Drug Administration Center for Biologics Evaluation and Research said, "It is not lost on us that there are some clouds in the horizon for gene therapy." He made this statement at a California biotech conference held in October. We want to do everything we can to make things move forward.

Orchard Therapeutics Limited used to call the gene therapy Seersha was waiting for OTL-101. Orchard launched OTL-101 in 2016 as its "lead candidate." Four years later, it announced that the company would "reduce investment" in the therapy in order to prioritize more common conditions.

Shayla Sulack said that OTL-101 had been developed with the help of millions of dollars from state and federal governments.

She added, "We were always saying, 'it will happen. It's going happen.'" After Orchard chose not to continue with the therapy, "a bunch of us moms who have SCID were like, Excuse me?" '

A spokesperson for Orchard wrote in a CNN statement that "after encountering challenges with the commercial manufacture of this therapy, we took the difficult decision to limit further investment [in the SCID genetherapy]." The spokesperson spoke under the condition of anonymity.

The mother's "oh, crap" moment

Shayla Sulack IV and Stephen Sulack IV were sweethearts in high school at Tehachapi High School located about 100 miles north-east of Los Angeles. They married in 2010 at the Little White Wedding Chapel, Las Vegas. She was 18 years old and he 19 years old.

Stephen served in the Army and the couple lived at various bases for several years. Skylar, their daughter was born in 2012, and Stephen V in 2014.

In 2017, Stephen was assigned to Schofield Barracks on Oahu as a Black Hawk helicopter Pilot. Seersha was then born two weeks later at Tripler Army Medical Center, Honolulu.

Seersha weighed 6 pounds, 10 ounces and appeared to be in perfect health. Her parents took her out on family trips, taking her to Dole Plantation, Waikiki Beach and other places when she was just five days old.

The family was strolling through the shops by the beach and decided to stop into the Tesla dealership for a little fun. Shayla received a call while sitting in the showroom of a car.

A geneticist was working at Tripler. He told Shayla a routine blood-test, a prick of a newborn heel, done in almost every state, revealed Seersha had only five T cells, which are a type white blood cell vital to fighting infections. The normal T cell level for newborns is around 3,000.

Seersha could die from any infection, however small. The geneticist told her to return to Tripler Hospital immediately.

The geneticist told her to return to Tripler Hospital immediately.

Shayla's first reaction is: "Oh, crap."

Seersha’s older brother and sister were also rubbing all over their baby.

Shayla, Stephen and the two older children left the Tesla dealership to drive the 20 minutes to the hospital. Shayla's mother drove the younger two children back home.

A psychologist helped the Sulacks cope with the shock of the news.

According to Sylvia Mann of the Hawaii Department of Health's Genetics Coordinator, only one baby is born in Hawaii each year with SCID.

Shayla, Seersha and I were flying to Los Angeles the next day on a military transport flight. Seersha was placed in an incubator at the front of plane and all other patients were seated in the rear to reduce the chance that they would get sick.

Shayla and Seersha were driven to UCLA Mattel Children's Hospital by ambulance. The hospital is one of 47 medical facilities in the US and Canada which specialize in SCID and are funded by the National Institutes of Health.

Seersha was taken to the hospital by doctors who explained all of her options.

Seersha: Options and Alternatives

They were all very bad.

ADA-SCID can be treated by regular injections that replace a missing immune enzyme. Although they are very effective, the immune system of a child is not fully developed.

UCLA doctors presented two options for the longer term. Seersha can receive a life-saving stem cell transplant. This is the standard treatment for SCID. Seersha's mother, father and siblings would be tested to determine the best genetic match. Then, cells that are specialized in producing blood cells would be extracted and given to Seersha.

The tests showed that she could receive a donation from any family member, but no one was a good match. The bad news was that the transplant would probably not be as successful. Seersha was more likely to experience complications.

These complications could be serious. Seersha will need to undergo high doses chemotherapy in preparation for her transplant. This could leave her susceptible to infection and increase the risk of cancer or infertility. Seersha could become very sick if the donor's cell attack her organs and tissue after the transplant.

They presented a second option: Gene therapy. The doctors would take Seersha’s blood cells and treat them so that she could have a normal copy her defective gene. They would then give the cells to her. Seersha is essentially giving herself a new transplant. This has two benefits: she could receive lower doses for chemotherapy and her body would not perceive the new cells to be a foreign threat.

Shayla recognized the sound. Shayla realized that she had seen episodes of " Grey's Anatomy" where a SCID character received gene therapy.

Kohn, a UCLA gene therapy researcher, was informed. He said that he had not only seen the episodes but also given the 'Grey's Anatomy' crew a tour of the lab and answered all their questions as they prepared the 2014 storyline. He still had the "Grey's Anatomy" mug and notepads they gave him as thanks.

Kohn told Shayla doctors had conducted a clinical study in the US and UK with dozens children using this gene therapy. The results were very positive, but Seersha was unable to participate as the trial had already enrolled its final patient. Orchard hadn't yet applied for FDA approval, so the treatment was not available.

They could only wait for FDA approval. There was some good news: just a few weeks before Seersha's birth, Orchard was granted a rare pediatric diseases designation by the FDA, giving the treatment priority review. Kohn said he thought the treatment would be available for Seersha and any other children within two to three year, or in 2019 or 2020.

The Sulacks considered their options. They could either have a transplant that was far from ideal, or they could wait until gene therapy became available.

They chose the gene therapy.

Families anxiously await treatment news

Seersha was released from hospital after spending almost eight weeks in Mattel's fall 2017 facility. Stephen applied for a move from Hawaii to Fort Irwin, San Bernardino in California so that they could be closer to UCLA and their family.

Seersha's parents filled her room with toys and kept her entertained for her entire first year. Seersha only had contact with her parents, Shayla's family and Shayla. She did not have any other siblings.

Seersha was able to move into other rooms in the house, where she could be close to her family. Seersha's immune system was still weak: the normal T-cell levels for children her age is 2,390, and Seersha didn't get above 250.

Seersha left the house but avoided people and crowds. Sitting on the rear of her family's truck, she watches from afar as her siblings play baseball and softball. She must keep her distance from her family if they ever feel sick - even a sore neck or a cold.

Orchard, which announced the news in January 2020, just a few weeks after Seersha celebrated her second birthday, said that it had plans to begin the FDA approval for the gene therapy during the first half year. It also predicted it would take an entire year to complete its application.

Four months later, they were stunned when the company released a press release stating that it had suffered a loss of $50.6 in the prior quarter and was'reducing investment' in SCID gene therapy. They also stated that the company would prioritize research on other diseases and'reduce its investment'.

The press release did not mention anything else about SCID gene therapy. As of this moment, 14 families from the US and Canada were waiting for the gene therapy. As they waited for the outcome, they were filled with anxiety.

Is the company planning to submit a request to FDA for approval? Would the timeline be slower than anticipated?

Is the company abandoning all plans for SCID gene therapies?

"Superhero meets Florence Nightingale"

When Dr. Fyodorurnov, a scientist from the Innovative Genomics Institute of the University of California at Berkeley, presents a talk about ADASCID, he begins with a photo of Kohn and a boy he had treated during the clinical trial. Urnov tells his audience that Kohn has worked on this therapy for many decades and persevered through numerous hurdles.

His juxtaposition of achievement and goodness is unbelievably unusual,' said Urnov. A professor of molecular biology and cell biology in Berkeley who has worked with Kohn over 20 years. He's like a superhero who meets Florence Nightingale.

Kohn, now 68 years old, first began researching gene therapy to treat ADA-SCID at age 31 as a fellow in Dr. Michael Blaese's lab, a pioneer of the gene therapy field.

This was a new and exciting field. Kohn, Blaese, and their colleagues published a report on the ADA treatment in the Proceedings of the National Academy of Sciences in 1986. In 2012, more than 25 years after the study was published, Kohn, Blaese, and their colleagues began a clinical trial of the ADA-SCID treatment with children from UCLA, NIH and Great Ormond Street Hospital, London.

Orchard's clinical trial results were promising in 2016, according to an announcement from the company. 32 patients had 100% survival, and the news release stated that.

Shayla Sulack, who had called Kohn four years earlier, asked if Seersha was ever going to get the treatment when Orchard announced that it would be reducing its investment in gene therapy.

Shayla recalls that he said "this is my work and I will not let it die." He said, "This is mine, my thing, and I won't let it die." '

Shayla expressed her 'full trust' in Kohn's word.

"A desperate appeal to save young lives"

Kohn was determined to get back the license to the therapy after Orchard stopped the treatment. This would allow him to start treating Seersha, and other children.

It wasn't the ideal solution. Biotech is typically developed in academic laboratories, then sold to pharmaceutical companies, FDA approved, and finally put on the market. Orchard's decision to give it back to academic researchers was a step backward.

Kohn said to CNN, 'I did not expect it.' It's like a college student moving back home.

Kohn said that in 2020, UCLA began discussions with Orchard. Parents of children with SCID have taken matters into their hands.

Parents from a group of parents called SCID Angels for Life Foundation asked to meet Orchard president Dr. Bobby Gaspar. The company didn't make Gaspar readily available to the parents, but they did get a Zoom call from other staff, according Heather Smith, President and founder of the parent organization.

Parents asked Orchard to return the licenses to universities in accordance with the request of academic researchers.

The company retained the license and the treatment remained on the shelf. Gaspar received a letter from the parents of over 20 children, including the Sulacks.

Families urged Gaspar to "please address this issue" and to treat it as a desperate plea for help in order to save lives.

Parents wrote: 'If Orchard takes bold action to save these babies/children from mortal danger, and wipes the tears of their parents' faces, you can rest assured that financial gains will follow in the correct order, ensuring significant gains for you too. "Putting patients first, and taking a positive approach will lead to a successful outcome for everyone." You will change lives now and for evermore.

The information and pictures about each child are provided by the family.

Smith stated that the parents had not heard from Gaspar in months.

David Jensen is a retired journalist and editor at the California Stem Cell Report. The parents spoke to him as well. Jensen published a piece about the families on May 11, 2021. This was followed by over a dozen more posts about Orchard. The Los Angeles Times published his report two weeks later.

Smith said, 'He kept the story moving and really lit a flame'. He kept it on Orchard's radar so that he knew we weren't going away quietly.

'An enormous stain'

The New England Journal of Medicine published the results of Orchard’s clinical trial on May 11, 2021. This was the same day that Jensen’s first article appeared. It showed that the gene therapy had been successful for 48 of 50 patients and there were far fewer side-effects than with conventional transplants. Two patients who did not respond to the gene therapy received successful conventional transplants.

The 48 children who were once in the slums are now living in a normal environment