Clinical trials okayed for children with ‘bubble boy’ disease

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 therapy originated at UCLA with the help of more than $40 million from the California stem cell agency.

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.

(Capitol Weekly was 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 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. The three are expected to be enrolled in the trial next month, Steve Peckman, deputy director of the UCLA Broad Stem Cell Research Center, told Capitol Weekly today. Transplants are scheduled for March.

Today, the California Institute for Regenerative Medicine is the largest such state-funded effort in the nation.

Through CIRM, the state is providing $5.8 million for the resumption of the trial. The agency is likely to provide more through 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.

The abandonment raised ethical and policy questions about how CIRM can avoid a recurrence. It is not the first such case.

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,”  Francoise Baylis, a bioethicist at Dalhousie University in Canada, wrote 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.”
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Editor’s Note: David Jensen is a retired newsman who has been writing about the California stem cell agency since 2005 on his newsletter, The California Stem Cell Report. More articles concerning the issues involved in the Orchard case can be found on the newsletter’s website.