The 'Best Christmas Gift:' Once Abandoned Clinical Trial for Bubble Babies Wins Regulator Go Ahead

Patients with life-threatening affliction begin enrollment next month in state-financed therapy

Dec 5, 2022

Andrea Fernandez and son Jakob, photo courtesy of the family

Editor’s note: An shorter version of this article appeared earlier Sunday on Capitol Weekly, the respected California state and political news and information service.

Nearly three years after a British firm abandoned a successful therapy for the life-threatening “bubble baby” disease, children will again be treated in a clinical trial backed with millions of dollars from the state of California.

“It’s the best Christmas gift ever,” said the mother of an afflicted child, Andrea Fernandez. “We are so, so happy and hopeful that Jakob would have an opportunity to be in the trial soon. It’s a possibility of a new life for him and other children.”

Fernandez’s family is among 20 families that were denied care by Orchard Therapeutics, PLC, in 2021 for their children who have the rare bubble baby disease. The affliction is scientifically known as ADA-SCID. The bubble baby term arose from an attempt in the 1980s to treat a child with the genetic disease by encasing him in a plastic bubble.

The affliction compromises children’s immune systems soon after birth, leaving them open to death from even minor infections. The disease occurs approximately once in every 500,000 births or about 76 cases annually in the United States.

Despite the success of its treatment, Orchard quietly shelved the therapy in the spring of 2020 in favor of pursuing potential treatments that it thought would generate more income.

(The California Stem Cell Report and Capitol Weekly were the first to disclose on May 11, 2021, the impact of Orchard’s decision to drop the therapy.)

The therapy originated at UCLA with the help of more than $40 million from the California stem cell agency. Donald Kohn, a professor of microbiology, immunology and molecular genetics at UCLA, produced the cure after decades of work, including the research supported by the state agency, officially known as the California Institute for Regenerative Medicine (CIRM).

Last week, UCLA notified three families at the top of the patient list that the Food and Drug Administration has approved a slightly altered version of the trial that was dropped by Orchard. Patient enrollment in the trial is expected to begin next month, said Steve Peckman, deputy director of the UCLA Broad Stem Cell Research Center. He told the California Stem Cell Report on Sunday that transplants are scheduled to begin in March. It’s a relatively slow process — one patient at a time, more or less — because of the still experimental nature of the treatment and its complexity.

Through CIRM, the state is providing $5.8 million for the resumption of the trial. The agency is likely to provide more via its ongoing clinical trial support program, which now includes 85 trials for a host of afflictions ranging from cancer to heart disease.

A California historical first, CIRM was created in 2004 through a ballot initiative that funded it with $3 billion in borrowed state money. When that ran out, CIRM was refinanced in 2020 with $5.5 billion more through another ballot measure, Proposition 14. Depending on CIRM’s spending rate, the cash will run out again in roughly 10 to 15 years or so. Today, the agency is the largest such state-funded effort in the nation.

The resumption of the trial is a landmark event in the long-running UCLA-CIRM-Orchard case and a leading example of the tangled financial, policy and ethical issues that surround what are called “one-and-done” treatments. They involve cell and gene therapies that cure afflictions previously considered incurable and avoid the prolonged costs of years of arduous, more conventional treatments.

However, few one-and-done treatments exist, and they are extraordinarily expensive. Just last month, CSL Behring announced it was pricing its gene therapy for a type of hemophilia at $3.5 million, which would make it the most expensive therapy in the world. Awareness of those costs has not filtered out to the general public.

Orchard had an exclusive license for the ADA-SCID therapy, which it did not relinquish until May 2021, which prevented the resumption of the trial by other parties. The abandonment has raised ethical and policy questions about how CIRM can avoid a recurrence. It is not the first such case. In 2011, Geron abandoned a $25 million spinal cord injury research award from CIRM for financial reasons, also seeking to pursue potentially more profitable endeavors.

Geron has since sold off its human stem cell research assets and today is a much different company. Orchard’s stock price closed last week at 46 cents per share, down from $10.28 when it formally announced the abandonment of the therapy.

Therapy abandonment scenarios force “us to consider what measures should be taken with respect to future trials funded in the private sector so that (patients) are not left stranded,” said Francoise Baylis, a bioethicist at Dalhousie University in Canada, shortly after Geron dumped its trial.

“Perhaps regulators and institutional review boards should critically examine whether a company has both the financial (and other) resources and the will to complete a trial under review before granting regulatory or ethics approval,” she continued.

“If there are doubts about this, then either the trial should not be approved, or there should be stringent disclosure requirements so that prospective research participants are aware of the possibility that research may stop mid-trial for financial reasons."

Here is a brief sampling of some of the Orchard stories carried on the California Stem Cell Report.

May 11, 2021

'Wicked' Problems, Orchard Therapeutics and Bubble Babies: A California Stem Cell Story

May 13, 2021

California Stem Cell Agency Pledges to Do "Everything" to Salvage Cure for Bubble Baby Disease

Orchard Therapeutics Says, However, It Will Continue to Deprioritize the Therapy and Has Already Saved $2.5 Million

May 21, 2021

Can a California 'March-In' Save Terminally Ill 'Bubble Babies?'

May 27, 2021

Three Bubble-Baby Families, Multimillion-Dollar Negotiations, California's Stem Cell Agency and Life and Death

Anxious Waiting, Constant Vigilance and Frustration

July 27, 2022