CIRM gets first approval of a one-and-done gene therapy

It was a warm spring afternoon on the Sacramento River, not far from where gold was discovered in California more than 178 years ago.

Directors of the state’s genetic research agency were meeting in a hotel room on the river bank, scratching for another sort of gold – not a mineral, but a revolutionary medical therapy. And then the announcement came.

After 21 years of “prospecting,” the California Institute for Regenerative Medicine (CIRM) fetched up its first “nugget” – federal approval of a one-and-done gene therapy for a life-threatening disease.

The announcement marked a historic milestone for CIRM. Until last Thursday, despite two decades of spending billions for stem cell and genetic research in California, CIRM could not point to a single federally approved therapy that it has financed. The news on March 26^th lifted that persistent cloud hanging over CIRM’s performance.

The announcement meant even more for families whose children suffer from an ultra-rare genetic affliction that often leads to early death.

They include the Langenhop family, whose three children – Ava, 10; Olivia, 8, and Landon, 6 – were all born with the life-threatening immune disorder called LAD-1 (severe leukocyte adhesion deficiency-1). The condition puts them at risk of near-constant bacterial and fungal infections.

The three children were treated successfully in 2020 in a clinical trial at UCLA that CIRM funded with $5.9 million in 2019. The treatment by scientist Donald Kohn and his team repaired their immune systems. Today they are leading normal lives, but will be monitored for years.

Rocket Pharmaceuticals, Inc. of Cranbury, N.J., sponsored the treatment, which is known as Kresladi. The company plans to make the treatment available late this year.

Last week, CIRM President and CEO Jonathan Thomas broke the news to CIRM’s weary 35 directors at the end of an eight-hour session in a windowless room.

“I have very significant, hot-off-the-press” news, he said: The Food and Drug Administration (FDA) had approved a treatment supported by CIRM.

“With the first FDA-approved therapy from CIRM funding we are delivering on our commitment to Californians to support the development of new stem cell and gene therapies that save lives,” Thomas commented later in a statement.

Helping CIRM to survive
The go-ahead for commercialization of the treatment is a watershed moment for CIRM. It is attempting to fulfill voter expectations when they created the enterprise in 2004. During a hype-filled ballot campaign, voters were led to believe that miraculous therapies were just around the corner. Treatments could be developed for afflictions that affect half the families in the Golden State, voters were told.

CIRM has now supported 119 clinical trials, the last stage before potential therapies reach the market. CIRM hopes that more treatments will emerge soon. That could help CIRM with its own survival. Its money runs out in a few years. To avoid financial extinction, CIRM will then need refinancing by voters through another statewide ballot initiative.

After 21 years of “prospecting,” the California Institute for Regenerative Medicine (CIRM) has fetched up its first “nugget” – federal approval of a one-and-done gene therapy for a life-threatening disease.

Voters have already approved $8.5 billion in state bonds for CIRM: $3 billion in 2004, when CIRM was created, and another $5.5 billion in 2020. The estimated, full cost of CIRM to taxpayers is $12 billion because of the interest on the money that the state borrows.

The support makes CIRM the largest state-financed research agency in the nation, although it is restricted by law to stem cell and gene therapy research.

CIRM has recently readjusted its priorities to boost the impact of its research. After a year-long study, it established ambitious goals dealing with solving treatment manufacturing problems, providing greater access for patients to clinical trials, working to solve affordability issues and much more.

$111 million awarded last week
CIRM’s nearly 1,600 awards already support a vast array of conditions and afflictions. The agency gives out about $500 million annually for all stages of research. Targets include such leading killers as heart disease and cancer but also include bad knees, which affect millions of people, and incontinence among women, which damages the lives of half the women in the country.

Just last Thursday, CIRM directors awarded $111 million for nine projects involving eye disease, neuropsychiatric disorders, ALS, Pitt Hopkins Syndrome and more.

CIRM is facing increasing demand for financing all stages of research as the Trump administration continues to curtail its research efforts. In one CIRM award round last year, 327 researchers applied for a total of $74 million. CIRM ultimately approved only 24 awards in that round. The agency expects demand to remain high.

The pressure for additional state research funding has led to a $23 billion bond proposal for the November ballot. Authored by state Sen. Scott Wiener (D-San Francisco), the measure (SB 895) cleared its first Senate committee on the same day that the Rocket news was announced.

A CIRM board member, Kim Barrett, vice dean for research at UC Davis, testified before the committee that day, endorsing the bill on behalf of the University of California.

The measure would create a research award organization within state government that would fund grants in areas ranging from stem cell and genetic research to wildfire, agriculture, water and ocean matters. In contrast to the bill, CIRM operates independently of normal state operations. And Wiener’s proposal does not guarantee CIRM funding and could be regarded as making CIRM redundant and unnecessary.

While the Rocket therapy is likely to cost millions of dollars, it will not generate huge amounts of revenue or profit because the number of potential patients is so small – only an estimated several hundred worldwide.

Federal approval of the therapy, however, also came with an FDA “voucher” that will provide for speedier consideration by the federal government of other potential therapies. Rocket expects to sell that voucher to another company for $200 million to $300 million and use the cash to support development of its other gene therapies.

CIRM has a stake in two of those Rocket efforts and has already awarded the company $6.8 million to pay for related research in California.

“Hopefully, an approval like this one will encourage other companies to invest in these kinds of therapies and recognize that there is a pathway to make these commercially available,” Kohn said.

Kohn has received $69.2 million from CIRM for related research dealing with other genetic afflictions including the “bubble baby” disease and sickle cell disease.

The Rocket therapy may not be the only one that CIRM will see approved this year. Capricor Therapeutics, Inc., of San Diego, is hoping its treatment for Duchenne muscular dystrophy will win approval in August. CIRM has invested $3.4 million in that effort.

In 2004, following creation of CIRM via a ballot initiative, national news stories carried headlines about a new California gold rush, one that involved stem cells. But that gold rush has failed to materialize, and the agency remains virtually unknown to California voters. CIRM, however, is moving to spread the word about its virtues with stories about patients like the Langenhop children.

“They say about one in every one million people have LAD-1,” their mother, Alicia, told UCLA. “We really felt like we must be the unluckiest family in the entire world.”

Today she feels much different. “We just feel like we’re so lucky to have this available, to live in a time where science is at this point,” Alicia said. “We couldn’t be happier. We feel really lucky this is the place we were brought to.”

David Jensen is a retired newsman and has covered CIRM for 21 years on his newsletter, the California Stem Cell Report. He authored the book, “California’s Great Stem Cell Experiment,” in 2020.