California’s plan for ‘miraculous’ cures — at $49,000 per hour

California is planning on spending $49,000 an hour, 24 hours a day, seven days a week during the next year to help scientists develop what some describe as “miraculous” cures and treatments for currently deadly afflictions.

The spending plan was approved with no fuss last month while state lawmakers and the governor wrestled more noisily with a $308 billion state budget that included such intractable problems as homelessness and affordable housing and lesser matters such as traffic fines and cannabis business tax credits.

The state’s effort to find cures and treatments is led by the California Institute for Regenerative Medicine (CIRM), commonly known as the state stem cell agency. It is a 17-year-old enterprise that funds both stem cell and gene therapy research.

The awards are just tiny examples of research funded by CIRM, which will ultimately cost taxpayers an estimated $12 billion.

Its research budget for the 2022-23 fiscal year totals $427 million, much of which is handed out on a monthly basis by 19 members of CIRM’s governing board. The amount is up from $290 million awarded during the 2021-22 fiscal year.

Some of the gene therapies being explored with CIRM funding, as well as by researchers elsewhere around the world, have been described as “miraculous.” One headline on Bloomberg said  “Welcome to the Age of One-Shot Miracle Cures.”

The scope of CIRM’s research is wide, ranging from cancer and heart disease to cartilage replacement and incontinence. An $8 million grant made this spring is supporting a clinical trial that uses a cancer-killing virus to destroy hard-to-treat tumors. Two other grants ($1.6 million and $1.3 million) are separately trying to create cartilage to repair damaged joints and stave off arthritis.

CIRM has helped to finance 80 clinical trials, most of them in the last decade. No therapies have emerged so far for general application.

The awards are just tiny examples of research funded by CIRM, which will ultimately cost taxpayers an estimated $12 billion. The figure includes paying back the principal on state bonds and the expense of interest on those bonds. The bond revenue is CIRM’s only source of research financing. The cash flows directly to the agency, courtesy of the ballot initiative that created it in 2004, and does not go through the usual state budget process. The initiative excluded CIRM from normal legislative and gubernatorial oversight.

The biggest chunk of CIRM’s 2022-23 spending — $169 million — will go for clinical-stage work, including the trials that are the last step in testing a proposed therapy before it can be authorized for general use. CIRM has helped to finance 80 clinical trials, most of them in the last decade. No therapies have emerged so far for general application.

In addition to the clinical stage awards, another $70.4 million is budgeted for what is called translational research, which is aimed at moving basic research discoveries closer to clinical trials. The translational stage is so risky financially that it is referred to as “the valley of death.”

Basic research, which CIRM calls discovery, is backed with $106 million. Another significant category is infrastructure, which totals $80 million. The biggest share of that is expected to help overcome major obstacles in manufacturing cell and gene therapies.

As for who receives CIRM’s billions, the agency counts nearly 800 recipients. They mostly come from institutions that have or had representation on its board.

Just last month, CIRM directors awarded $25 million to 19 scientists in a basic research round that involves science far removed from being used to treat patients. But, says Maria T. Millan, president and CEO of CIRM,  “Every therapy that helps save lives or change lives begins with a researcher asking a simple question, ‘What if?’”

CIRM’s awards are made through a competitive process. The agency sends out a request for applications for a specific program. The applications are reviewed and scored behind closed doors by out-of-state scientists who are selected by CIRM. Patient advocates who are members of the CIRM board score the diversity component of the application. The scientific reviewers do not have to publicly disclose their financial, personal or professional conflicts of interest. The CIRM staff, however, conducts a conflict review.

The scientific and diversity scores are sent to a 19-member subcommittee of the governing board, which does not have access to the full applications, only a brief summary of the review. Also not disclosed are the names of the applicants and their employers. The subcommittee rarely rejects the positive decisions of its reviewers. Sometimes the panel, however, will elevate a rejected application to approval.

The agency may have difficulty in handing out the entire $427 million during the next 12 months.

As for who receives CIRM’s billions, the agency counts nearly 800 recipients. They mostly come from institutions that have or had representation on its board. As of 2020, more than 80 percent of the CIRM cash has gone to institutions that have links to current or past members of its governing board. Board members are barred from voting on applications on which they have a conflict of interest. However, they do participate in developing and voting on “concept” plans for award rounds that could benefit their institutions.

The agency may have difficulty in handing out the entire $427 million during the next 12 months. CIRM had planned to award $474 million during the last 12 months but fell far short of that goal. About $162 million allotted for 21-22 awards has been pushed into this fiscal year. In other cases, CIRM approved only a portion of the funds budgeted to be awarded.

The speed at which the money is distributed is important. Without cash, the pace of the research slows, and CIRM has a limited life span. When its current $5.5 billion runs out in about a decade, it will need to seek more billions. That task most likely will require another ballot initiative along with results from CIRM that show that it has produced therapies that resonate with voters.

And that is not to mention the patients who are waiting for cures. As one CIRM annual report put it: “We act as if lives depend on it, because they do.”
—
Editor’s Note: David Jensen is a retired newsman. He has written about the stem cell agency since 2005 on his newsletter, The California Stem Cell Report, and is the author of “California’s Great Stem Cell Experiment.”