California-backed cure for ‘bubble baby’ disease stalls — again

The “bubble babies” saga and a California-financed cure for their life-threatening affliction have hit another snag, more than two years after a British company abandoned the effort.

It is a story that involves more than $40 million from California’s stem cell agency, federal regulators, the University of California, the agonizingly slow pace of science and 20 children who have been denied care — not to mention a company called Orchard Therapeutics PLC.

Last February, it appeared that the trial could be revived and at least some of the children could begin treatments this month. But the latest word is that treatments are not likely to begin until November or December.

The rare disease in question is ADA-SCID, a genetic defect that cripples a baby’s immune system and makes them vulnerable to even minor infections and childhood diseases. Without treatment, most children die by the age of two. It has come to be known as the “bubble baby” disease because one child was encased in 1971 in a plastic bubble for 12 years to avoid infections.

Today, 51 years later, a successful stem cell/gene therapy treatment at UCLA has already cured some 50 patients. However, Orchard quietly abandoned the trial in May of 2020, preferring to turn to potential treatments that it thought would be more profitable. In the spring of 2021, the company rejected an appeal by the families of the children to allow them to be treated under what is often called compassionate use.

Orchard, which had purchased the rights to the treatment from the University of California, subsequently returned them to UCLA.

The California Stem Cell Report disclosed the situation in May of 2021 in a story that was first carried on Capitol Weekly. At the Los Angeles Times, columnist and author (“Big Science”) Michael Hiltzik advanced the story and quoted Stanford University bioethicist David Magnus as saying,

“There are good reasons for pausing or stopping a trial. However, a strictly business decision that has nothing to do with risks and benefits but is a company just saying, ‘We decided to move in a different direction, we’re putting our eggs in a different basket.’ …To me, ethically, that’s highly problematic.”

Orchard, which had purchased the rights to the treatment from the University of California, subsequently returned them to UCLA where scientist Donald Kohn developed it over a period of decades along with work by scientists in the United Kingdom.

The California Institute for Regenerative Medicine (CIRM) has contributed $40 million-plus to Kohn’s work, which has also received many millions from other sources. CIRM has $5.8 million left over from its grant to Orchard which it has turned over to Kohn, who is trying to renew the trial with the Food and Drug Administration (FDA).

However, the federal regulators have asked for more work from Kohn and his team, which will take months.

“The FDA asked for some improvements to the project. So that will make it more effective and safer for the kids, which we totally appreciate and are happy to do,” said Steve Peckman, deputy director, UCLA Broad Stem Cell Research Center, “but it’s going to take us some time to do the experiments and compile the data. So it looks like we won’t be initiating the clinical trial until November or December.”

The trial is one of 80 backed by CIRM. The trials are the final steps to winning approval of new therapies for general use.

In an interview with the California Stem Cell Report, Peckman said that Kohn is moving “away from bone marrow collection (from the children) to get the stem cells and go to mobilized peripheral blood. But to do that, we have to do some experiments and provide the data to FDA.”

He said that would mean more gene-modified stem cells to put back in the children and increased effectiveness plus avoiding the risks involved with bone marrow extraction.

The trial is one of 80 backed by CIRM. The trials are the final steps to winning approval of new therapies for general use.

Some concern exists within CIRM that it might fall prey again to a company that dumps successful or promising research that taxpayers have financed. Following the publication of an article on Sunday on the California Stem Cell Report about the new delay, the mother of one child waiting for the treatment expressed dismay about the long delay in the work.

It is not as “if our ADA-SCID children  have all the time in the world to continue with this condition, like as if it was easy for them to endure the pokes every week, the (intravenous injection) visits, the isolation, the don’t-touch-here-or-that….Every stop on the way it’s an agonizing wait that we can’t afford,” said Andrea Fernandez.

On Monday, the chair of the CIRM board’s Science Subcommittee, Larry Goldstein of UC San Diego, a stem cell researcher himself, told the agency’s board, “I’m very disappointed by the situation with Orchard where we’re developing what looks like a very effective therapy for kids with no immune system, but where the industry partner bailed for financial reasons, not for lack of effectiveness of the therapy,” Goldman said.

“The issue I’m raising is should we develop a policy or a plan for how to deal with situations where the industry partner drops what looks like an effective therapy for financial reasons?”

Other board members echoed Goldstein’s remarks, but CIRM has set no timetable for dealing with the matter.

Meanwhile, Orchard’s stock price has plummeted. It stood at 56 cents on June 28, down from an all-time high of $20.25 in 2019.
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Editor’s Note: Below is a sampling of earlier stories concerning the Orchard-UCLA-CIRM affair beginning with the very first article that was carried by Capitol Weekly.

Tangled tale: Research, profits and the ‘bubble baby’ syndrome

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

Bubble Baby Families Denied ‘Compassionate Use’ of Life-Saving Therapy

Orchard Therapeutics Exits the Bubble Baby Treatment Business; Decision Praised by Parents

California Stem Cell Agency Withholds $5.8 Million from Orchard in Bubble-Baby Flap

Jakob’s Dream: ‘Mud in My Teeth…Finally Be Free’
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David Jensen is a retired newsman and has been writing since 2005 about the California stem cell agency on his newsletter, the California Stem Cell Report.