'Socialized Research' and 'Privatized Profits:" California's Gene Therapy Research and Million Dollar Plus Treatments

"One and Done" -- If Companies Actually Go to Market

Only eight days after the California stem cell agency approved its most recent award for its $60 million battle against sickle cell disease came a cautionary note from 3,000 miles away.

The note sounded financial misgivings regarding the proposed, gene-editing treatments that have been highly touted as a possible cure for sickle cell disease, an affliction that occurs predominantly among African-Americans and other minorities. 

The concerns came from the 60-member Congressional Black Caucus. Million-dollar plus price tags were the main matter for the federal lawmakers. “We are troubled that access to these medicines is anything but guaranteed for the patients who would benefit most from them,” the lawmakers said in a letter to the head of the mammoth U.S. Department of Health and Human Services. 

The timing of the July 28 letter appears merely coincidental to the approval on July 20 of an $8.4 million gene-therapy grant by the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is officially known. 

The caucus letter was not directed at CIRM, which is likely not even on the lawmakers’ radar -- at least not yet. Nonetheless, by law, CIRM is very much charged with ensuring the accessibility and affordability of its research.

The Black Caucus’ concerns, in fact, do come into play in connection with California’s newly energized approach to genetic research. The field is hot right now. It promises one-time treatments that generate permanent cures -- so-called “one-and-done” therapies. And Proposition 14 last fall specifically authorized the stem cell agency to dive more deeply into genetic research. 

But the promise of curative treatments can pose special challenges.  

One example involves another gene therapy effort backed with $42 million by CIRM. The therapy in question was developed at UCLA, which licensed it exclusively to Orchard Therapeutics PLC, a publicly traded company based in London.

The CIRM/UCLA/Orchard treatment targeted what is known as the bubble boy disease, a rare genetic immune deficiency. The treatment has saved the lives of 50 persons during its trial. However, Orchard decided to abandon the therapy in favor of other treatments that the firm hopes will be more profitable. Orchard also denied compassionate use of the therapy by 20 children. 

In May, following coverage of the matter by the California Stem Cell Report, Orchard announced that it was giving up the license from UCLA. CIRM and UCLA are now working to push the therapy forward but had little concrete to report as of early last month. 

The new, July 20 award for CIRM’s sickle cell trial involves Donald Kohn, the UCLA scientist who developed the bubble baby treatment. The principal investigator for the effort, however, is  Mark Walters of UC San Francisco. Last spring, UC San Francisco touted the project as the “first-in-human clinical trial of a CRISPR gene correction therapy in patients with sickle cell disease using the patient’s own blood-forming stem cells.” 

In addition to California state funding, federal support is lined up. The CIRM award is expected to be matched by another $8.4 million from the National Institutes of Health, an organization that falls within the Department of Health and Human Services as does the Food and Drug Administration (FDA).

The FDA controls clinical trials and decides which therapies are to be made available to the public. 

The Orchard case has raised questions about whether public funds should be used to support clinical trials for potential, curative gene therapies that could well be abandoned by businesses for financial reasons.

As one California scientist earlier told the California Stem Cell Report, the Orchard case involves “a socialized research process and privatized profit, and profit shouldn’t be the sole consideration when someone actually comes up with a cure.” 

The financial argument for the high prices for curative, genetic treatments is that they will cure the patient and avoid the costs of multiple different treatments, hospitalization plus care over years, if not decades. Businesses argue that they should be “reimbursed” for their expenses of developing the therapies, although they mostly do not become involved until the very last stages of the research.

Those sorts of issues did not come up for discussion during the July 20 CIRM directors’ meeting. CIRM’s intellectual property and ethical standards have not been revisited for years. A “one-and-done” treatment was not even close to being on the table back in 2005 when CIRM intellectual property and research standards were being drawn up.

However, for the first time this year, CIRM is requiring that its grant reviewers judge whether an application meets certain diversity and equity standards, which can involve financial barriers.

The CIRM summary of the grant review session, which is conducted in private by anonymous, out-of-state scientists, had this to say about equity issues and the application from Walters, 

“This proposal demonstrates an understanding of the challenges faced by individuals who are underrepresented, and an acknowledgement of the need to work to create an environment that promotes greater participation (i.e. enrollment in curative therapy trials for SCD can be slowed by barriers that include a lack of information, lack of strong connections to patients from under-represented populations and their providers that foster trust in the investigative team, inadequate outreach directed at patients and their families).”

Beyond that, the summary of reviewer comments did not speak to questions of affordability or accessibility. 

Back in 2004, the ballot initiative that created CIRM gave a nod to affordability and access. Last year, that was stepped up in the initiative, Proposition 14, that refinanced the agency with $5.5 billion. It required CIRM to set up a new, intensive program to ensure that the treatments that it helps to finance are affordable and accessible. Proposition 14 also allotted up to $155 million to develop and implement those efforts.

The affordability program has yet to get off the ground nine months after the passage of Proposition 14. Former state legislator Art Torres, vice chair of the CIRM board, was selected in December of last year to lead the effort. Appointments to the new, statutory 17-member CIRM affordability/accessibility working group are not complete, and it is not listed on the CIRM website along with its other statutory working groups. 

CIRM directors will meet again on Aug. 24 as they continue to try to implement the 17,000-word Proposition 14 with all its new provisions. More information may emerge at that time. Interested parties can direct questions or make comments to the CIRM governing board during the meeting or email them in advance to kmcormack@cirm.ca.gov.

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Labels: Orchard, sickle cell, IP, bioethics, initiative weaknesses, affordability accessibility