Clinical trial into ‘bubble baby disease’ back on track

Twenty children seeking treatment for a rare affliction called the “bubble baby disease” today have some big-time, good news concerning a life-saving genetic therapy that they were once denied as the result of a tangled affair that included private profit and the public funding of cutting-edge scientific research.  

After being halted nearly two years ago, a California state-financed clinical trial that can help the children is now solidly on its way to a new beginning at UCLA. Treatments of the children could begin as early as June. 

The California stem cell agency is expected to provide $5.8 million to resume the trial at UCLA. Millions more are likely to be forthcoming from the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is officially known.

“Everything is about money and you have to advocate hard to try to find a way for them to get the care they need.” — Andrea Fernandez

Despite the success of the trial over the last several years — “100 percent overall survival” of 50 patients — it was abandoned in 2020 by Orchard Therapeutics, PLC, in favor of research that Orchard deemed would be more profitable.  At that time, Orchard had exclusive rights to the therapy, which was developed at UCLA with the support of more than $40 million from CIRM. The 20 families and their children appealed for expanded/compassionate use of the treatment in 2021 but were denied.

One mother, Andrea Fernandez,  wrote about the situation on Facebook. “Sometimes you want to believe not everything is money when it comes to life-saving options for children, but you are wrong,” she said.  “Everything is about money and you have to advocate hard to try to find a way for them to get the care they need.”

As first reported on Capitol Weekly and the California Stem Cell Report last May, the situation involves “ what policy experts call a ‘wicked’ problem, one that is complex and intractable — a knotty tangle of Orchard’s hoped-for profits, cutting-edge medicine, public funding of scientific research, ethics and the lives of babies born without the ability to stave off even minor infections that could take their lives.”

At the heart of the issue are the children born with a genetic immune deficiency known as ADA-SCID. It is often referred to as the bubble baby disease because a child was once treated for the disease by being literally encased in a plastic bubble. Without treatment, the children can die from even common, relatively benign infections.

Resuming the trial involved regulators at the Food and Drug Administration, California’s research agency and University College London. 

The genetic treatment that rebuilds the children’s immune system was developed over decades by Donald Kohn of UCLA and researchers in London. Orchard, which is based in London, purchased an exclusive license for Kohn’s work from the University of California, which handles intellectual property for all its campuses.

But Orchard later changed its focus, shelved the treatment and denied its use for additional patients. 

After stories about the situation began to appear last year on Capitol Weekly and the California Stem Cell Report, Orchard said it would return the license to UCLA. But resuming the trial involved regulators at the Food and Drug Administration, which authorizes clinical trials, and California’s research agency, along with University College London.

CIRM, which is now flush with $5.5 billion from state taxpayers, considers Donald Kohn’s work one of its crown jewels.

In an online video interview on Monday, Kohn said it was necessary to receive approval for what the FDA considered a new trial, not to mention dealing with UC intellectual property overseers, the London parties and CIRM. “It was a very complicated set of discussions,” Kohn said.

But he indicated he was quite pleased to announce that the FDA has sent back his new investigational drug application naming him as the sponsor instead of Orchard.  A new clinical protocol has been approved at UCLA.  And Kohn said that CIRM has approved transferring the $5.8 million to the “new” trial with UCLA from the “old” one with Orchard

Kohn said the funds should be enough to treat three patients. More treatments would require more funding. The agency, which is now flush with $5.5 billion from state taxpayers, considers Kohn’s work one of its crown jewels. CIRM has been publicly enthusiastic about Kohn’s work over the years and is currently working with him on a genetic treatment for sickle cell disease.  

Kohn said the physician for the first patient on the bubble-baby waiting list has been notified about the likelihood of treatment that could begin around the beginning of June if all goes well. He noted that the same FDA department that regulates gene therapy also regulates covid matters, meaning that it has a very full schedule.

UCLA is working on two parallel tracks, one to line up the commercial partner and the other to continue the research, improve it and treat patients.

The ultimate goal is to make the treatment available to all possible patients outside of a clinical trial. That would require a commercial partner, which has not been selected. 

“It is very important to have an industry partner with the appropriate qualifications, interest and successful track record so they can shepard this through an FDA approval process and make it widely available to patients,” Kohn said Monday.

He said UCLA is working on two parallel tracks, one to line up the commercial partner and the other to continue the research, improve it and treat patients. 

In December, CIRM signaled that its directors’ intellectual property committee will reexamine its intellectual property (IP) rules to help avoid the same issues involved in the Orchard case.

CIRM’s IP rules were formulated more than a decade ago at a time when gene therapies were not its horizon.
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Editor’s Note: David Jensen is a retired newsman who has followed the affairs of the $3 billion California stem cell agency since 2005 via his newsletter, the California Stem Cell Report. He has published thousands of items on California stem cell matters.