California's $76 Million Bet: Something Called CAR-T, Cancer and Promises

CIRM-funded researcher Saul Priceman of the City of Hope discusses the CART-T frontier, April 2019. Video by American Association for Cancer Research

California's state stem cell agency has now invested $76 million in treatments sometimes described as "miraculous," whose costs can run upwards of $1.5 million. 

The push into the much-heralded CART-T therapy field is part of the agency's effort to fulfill its 15-year-old campaign promise to state voters to turn stem cells into cures. 

The California Stem Cell Report this week took a look at the  CAR-T slice of the agency's $3 billion research pie in the wake of news that Medicare would now cover major portions of the cost of the cancer-fighting technology.

The decision applied to only two specific therapies. But Seema Verma, the top Medicare executive, said CAR-T was
"an important scientific advancement" and would provide help for "some patients who had nowhere else to turn."

Maria Millan, president of the stem cell agency, called the announcement a big step forward. In an email to the California Stem Cell Report, she said,

“We are encouraged by the announcement that the Centers for Medicare and Medicaid will provide coverage for hospital costs related to CAR-T therapies. This is a major step to providing access to these life-saving treatments for patients in need.”

The CAR-T therapies approved by Medicare can run close to $500,000 plus hundreds of thousands more for related costs. One estimate is that total cost of a CAR-T treatment could hit $1.5 million. 

Their medical promise of CART-T is that it's a cure -- not an ongoing treatment, which also can raise total costs exponentially. The idea behind the therapy is that it powers up a patient's immune system to destroy cancer cells in a targeted fashion.  

"Drugmakers note CAR T-cell therapy is designed to be given just once and to be a potential cure for patients who have run out of other options. But not all patients benefit from it and because it is so new, it’s too soon to know whether it will deliver long-term cures," Laurie McGinley wrote in the Washington Post last week. 

California's stem cell agency, formally known as the California Institute for Regenerative Medicine(CIRM), has approved 11 awards involving CAR-T therapies ranging from basic research to clinical trials. The amounts of the awards run from less than $2 million to nearly $20 million, which went to Poseida Therapeutics, Inc., of San Diego, Ca.

The company has received a total of nearly $24 million from CIRM for its CAR-T work. In May, the Food and Drug Administration approved Poseida's CIRM-backed product as an orphan drug treatment for multiple myleoma, a disease that affects 300,000 Americans every year. The company reports that its Phase Two clinical trial for the treatment is now underway.

Poseida's work has attracted the interest of Big Pharma. In March, Novartis pumped $75 million into the company in a fund-raising round that totalled more than $142 million.  (See here for more information on Poseida.)

Last month, in another CART-T venture, the stem cell agency added more millions to an effort at the City of Hope by Saul Priceman, a breast cancer researcher. He told the CIRM board,

"For the past 20 years, City of Hope has focused intensely on developing CAR-T cell approaches for treating the most intractable solid tumors. In the early 2000s, we were the first to demonstrate solid tumor CART-T cell therapy treatment in patients. And recently we were the first to report our remarkable response for patients with glioblastoma."

CIRM directors added more than $9 million to the $1.4 million already provided to Priceman.

In announcing the award, CIRM CEO Millan said, 

“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news. There are few options for patients with breast cancer brain metastases (the target of Priceman's research).

"Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months.  CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”

CAR-T is a gene therapy, which has raised some questions about whether it fits within the scope of the stem cell agency, which was created by a ballot measure in 2004, Proposition 71.  

Kevin McCormack, senior director of CIRM communications, said in response to a query, 

"The programs we’ve funded fit into Proposition 71 because (1) HSC (hematopoietic stem cell) derived CAR-T, (2) CAR T’s enriched for TSCM (stem cell) or gene-engineered T cells qualify as a 'vital research opportunity' as outlined in the proposition." 

Here are links to the CAR-T awards by their CIRM application number, which is very useful in searching for additional information on each grantee's research.

Tran1-10258, $5.6 million, Ezra Cohen, UC San Diego; Clin2-10395, $19.8 million, Matthew Spear, Poseida; Clin1-10999, Devon Shedlock, Poseida; Clin2-10248, $12.8 million, Christine Brown, City of Hope; Clin2-10846, $11 million, Crystal Mackall, Stanford; Clin1-11223, $3.8 million, Xiuli Wang, City of Hope; Disc2-11107, $1.4 million, Saul Priceman, City of Hope; Clin2-11574, $9.3 million, Priceman, City of Hope; Disc2-10748, $1.7 million, Scott Kitchen, UCLA; Disc2-11157, $1.4 million, Lili Yang, UCLA, and Clin2-11380, $4.7 million, Theodore Nowicki, UCLA.

City of Hope video

California's "Huge Ecosystem" for Stem Cells: The View from Europe

Some folks in Europe are worried about stem cell research, particularly about organizations like California's $3 billion stem cell agency.

The alarm was sounded just yesterday in Horizon, which calls itself  "The EU Research and Innovation Magazine."

The article in question (the second most popular on its web site at midday today) was headlined:

"Europe is in danger of being out-innovated in regenerative medicine"

Ton Rabelink, Arno Massee Fotografie

The piece consisted of an interview with Ton Rabelink, professor of internal medicine and head of Leiden University in the Netherlands. He cited the California agency as a "huge ecosystem" for developing much needed stem cell therapies.
nephrology at

Rabelink said that the European Medicines Agency is wrestling with finding the "the right mechanisms to support the field."

‘It is very important that they do this because the regulatory landscape in the US and Japan has changed over the past two or three years to accommodate recent advances. For example, Japan has an early access programme for treatments that seem promising but are not yet proven to work. If they appear safe in say, 40 patients, then doctors can start applying them. The US has created the 21st Century Cures Act that allows for clinical trials for stem cell therapies and fast-track access to market for those that appear effective."

Rabelink said,

"The risk is that if we don’t organise locally here in Europe, we’ll end up having to buy these treatments from those countries. We’ve already seen this with genetically modified cells, so-called CAR cells, to attack tumours in leukaemia. The treatment works quite well but costs about €500,000 ($582,670) per patient.

"It's very interesting to look at what happens in the rest of the world. You really need ecosystems — academia, but also legislatures, manufacturing and, of course, finance. The US has huge ecosystems like CIRM, the California Institute for Regenerative Medicine, which was founded through taxpayers’ money following a referendum, and invests about $250 million per year in this space. (The agency actually was created by a ballot initiative, which is much different than a referendum.)

The Dutch researcher continued,

"The situation in Japan is even more remarkable. The early breakthroughs were made by a Japanese scientist so they consider regenerative medicine almost as their national invention. And, of course, Japan has an ageing population so the concept is very appealing. The government set up a planned economy around regenerative medicine and adapted its regulatory framework, putting national systems in place to oversee quality and safety and organising private-public collaborations, bringing together academic institutions and big pharma. Fujifilm, which was originally a photographic company, is devoting resources to stem cell research and using its film technology to make biomembranes.’