Bubble Baby Families Denied 'Compassionate Use' of Life-Saving Therapy

"SOS" Rejected by Orchard Therapeutics

A gene therapy company backed by millions of dollars from the state of California has withheld “compassionate use” of a life-saving therapy sought by parents of children suffering from what is known as the bubble baby disease, according to a patient advocate group and parents. 

The families sounded an “SOS” this spring in a letter to the company, Orchard Therapeutics PLC.

“We implore you to treat this as a desperate call for help to save young lives,” the letter said. More than 20 young children are in “urgent need of gene therapy for ADA-SCID (the medical term for the bubble baby disease),” the letter said. (See text here.)

Disclosure of the rejection of the compassionate use treatment is a new twist in the story about the gene therapy, which has saved some 50 lives during its experimental development for bubble babies.  The news is likely to intensify criticism of the company for its financially driven decisions concerning the bubble baby disease. 

The rare affliction is the result of 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.

The SOS for the curative treatment involves a publicly traded company based in London, Orchard Therapeutics PLC. Last fall, the firm suspended for financial reasons a clinical trial involving the treatment.

The California stem cell agency, officially known as the California Institute for Regenerative Medicine (CIRM), has supported the research with more than $40 million, including the latest trial, which was being conducted at UCLA. The school owns the intellectual property behind the therapy and has licensed it exclusively to Orchard. 

One year ago, Orchard pushed away from the therapy, which is called OTL-101, during a company restructuring. Last October, the company curtailed the CIRM-funded trial after deciding other potential products would be more profitable. 

One parent, Andrea Fernandez, whose child was rejected for compassionate use of the treatment, said last week on the boy’s Facebook page, “Sometimes you want to believe not everything is money when it comes to life saving options for children, but you are wrong. Everything is about money, and you have to advocate hard….”

She was not alone. Two other families also interviewed this week by the California Stem Cell Report expressed frustration, sadness and unhappiness concerning Orchard’s conduct. The genetic therapy should be “released back to CIRM” and made available to children who need it to survive, said a non-profit, patient advocate group called SCID Angels for Life. 

Responding to questions, the group said Orchard has been less than transparent, refused to disclose its criteria for compassionate use and has rejected all such applications.   (See text of comments here.)

Suspension of the CIRM clinical trial last fall meant that children not already in the trial would not have access to the treatment unless it was available under a federal compassionate use provision, also known as expanded access.

The provision is a “potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product ... for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available,” says the federal Food and Drug Administration.

Here is the full text of Orchard’s comments concerning its rejection of compassionate use.  

“Orchard Therapeutics does have a standing pre-approval access policy, which is available on our website, and outlines the company’s processes and considerations for compassionate use.

“At the same time, we understand the importance of OTL-101 to the ADA-SCID community and have confirmed to our academic partners our willingness to support them with financial and material resources to file their own IND to seek to treat ADA-SCID patients under a separate compassionate use program that would be led and administered by their institution.”

An IND is an investigational new drug application. It can take a year or more even with conventional drugs. Presumably, the process could be speeded up in the case of OTL-101 since a clinical trial was already once underway. 

UCLA  has not yet responded to queries about the Orchard situation.

(Following publication of this item, UCLA replied. Here is the full text of its response: “UCLA is a leader in developing treatments and medications that enhance and save lives, and our commitment to facilitating access to discoveries made in our labs is a reflection of our public service mission. We are in contact with CIRM, Orchard Therapeutics and University College London regarding potential next steps.”)

The state stem cell agency said, “We understand the concerns of The Angels for Life and want to reassure them that Dr. Maria Millan, our CEO, has been working directly with Orchard’s CEO and Don Kohn (the UCLA scientist involved) to facilitate an early access program for patients as they address the challenges that have led to the stall of this program.  

“Furthermore, CIRM has been working with the Orchard team and Don Kohn ever since the initial announcement from Orchard to understand the hurdles and to support steps toward addressing those hurdles.” 

OTL-101 is one of CIRM’s success stories. But research at UCLA, conducted by Donald Kohn, has been underway since the 1980s and has also been supported by other sources, including the federal government. 

Barb Ballard, a board member of the Florida-based Angels for Life, said the bubble baby families were “heartbroken” when they heard the news this spring that Orchard was continuing to “deprioritize” the cure. 

“To date, all applications (for compassionate use) have been turned down by Orchard,” Ballard said. The company “provides no indication of what criteria must be met.”

She noted that Orchard said it has saved $2.5 million for backing away front OTL-101. Ballard said that figure pales in comparison to lifetime costs for families wrestling with the bubble baby disease.  Fernandez’ family is trying to raise $1.5 million on a gofundme page for a different sort of treatment that could be available in Italy.