Asterias and Capricor: Good News for California's Stem Cell Research Effort

Pat Furlong, CEO of Parent Project Muscular Dystrophy, spoke earlier 

this year about losing her two sons to Duchenne muscular dystrophy

California's $3 billion stem cell agency last week reported encouraging results from two of its clinical trials, news that came as the prestigious journal Nature was declaring that the state effort was in its "last stage."

The trials are being conducted by Capricor Therapeutics, Inc., of Beverly Hills, Ca., and Asterias Biotherapeutics, Inc., of Fremont, Ca. Both are publicly traded firms.

The news was reported by The Stem Cellar, the blog of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known.

CIRM declared,

"Asterias Biotherapeutics continues to keep a steady pace and to hit the proper milestones in its race to develop a stem cell-based treatment for acute spinal cord injury."

The agency has pumped $20.7 million into the company's program, including $6.4 million when the research was being performed by Geron Corp. CIRM said that the latest data show that the treatment is safe and should continue with 10 million and 20 million cell doses with new trial participants. CIRM  blog author Todd Dubnicoff said,

"About a month ago, Asterias reported that six of the six participants who had received a 10 million cell dose – which is transplanted directly into the spinal cord at the site of injury – have shown improvement in arm, hand and finger function nine months after the treatment. These outcomes are better than what would be expected by spontaneous recovery often observed in patients without stem cell treatment. So, we’re hopeful for further good news later this year when Asterias expects to provide more safety and efficacy data on participants given the 10 million cell dose as well as the 20 million cell dose."

CIRM's Karen Ring reported on the good news from Capricor, which has received $23.2 million from CIRM, not all of it for Duchenne muscular dystrophy, however. The disease follows a devastating course and significantly reduces life expectancy. Ring wrote,

"The company reported positive results from their Phase I/II HOPE trial that’s testing the safety of their cardiosphere stem cell-based therapy called CAP-1002. The trial had 25 patients, 13 of which received the cells and 12 who received normal treatment. No serious adverse effects were observed suggesting that the treatment is 'generally safe' thus far."

Linda Marban, president of the company said that it plans to seek permission from the FDA to move into one of the agency's programs to expedite making the treatment available.

The announcements on the trial results came during a week when Nature, which reports only intermittently on CIRM, did something of an overview of the California research program. The Nature headlines said,

"California’s $3-billion bet on stem cells faces final test
"Major investment in regenerative medicine enters its last stage — and the money might run out before treatments are ready."

Capricor's stock closed at $3.12 Friday with a 52-week price range of $2.12 to $5.40. Asterias closed at $3.70 with a 52-week range of $2.30 to $5.80.

Below is an Asterias video on its research.

The Journal Nature Says: 'Last Stage' for California's Stem Cell Research Program

The prestigious journal Nature this week is calling it the "final test" for California's $3 billion plunge into development of stem cell therapies for afflictions ranging from cancer to arthritis.

The California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known, expects to run out of cash for new awards in June 2020. The 12-year-old agency was created by a ballot initiative campaign that led voters to believe that nearly miraculous stem cell treatments were just around the corner. So far the agency has not backed a stem cell therapy that is widely available.

For Nature, the situation merited this headline yesterday on its web site,

"California’s $3-billion bet on stem cells faces final test
"Major investment in regenerative medicine enters its last stage — and the money might run out before treatments are ready."

Amy Maxmen wrote the article. She said,

"Now, the pot of money — one of the biggest state investments in science — is running dry before treatments have emerged, raising questions about whether Californians will pour billions more into stem-cell research."

Maxmen continued,

"If they don’t, that could leave hundreds of scientists without support, and strand potentially promising therapies before they reach the market. 'It’s an issue of great concern,' says Jonathan Thomas, chair of the board for the California Institute for Regenerative Medicine (CIRM) in Oakland." 

Maxmen also noted the critical assessment of CIRM in 2012 by the Institute of Medicine and some subsequent changes made by the agency's board. She said,

"Jim Lott, a member of the state board that oversees CIRM’s finances, says that he is not satisfied with the changes. He also argues that CIRM may not have been strategic enough in directing research. 'Some people say if they had a better focus, they might have achieved cures.'"

The Nature piece covered familiar ground for readers of the California Stem Cell Report. But she had further news from Bob Klein, a Palo Alto, Ca., real estate investment banker. Maxmen wrote,

"Bob Klein, the property developer who put Proposition 71 on the ballot and established CIRM, isn’t waiting for the money to run out. He leads an advocacy group, Americans for Cures, which will soon poll voters  to see whether they would approve another $5 billion in funding. If it looks like at least 70 percent of Californians support that plan, he’ll start a campaign to put another initiative on the ballot in 2018.

"Klein hopes that Californians will rise in support of science at a time when the Trump administration has proposed drastic cuts to the NIH budget. If public enthusiasm is not so strong, Klein says, he’ll aim for the 2020 elections, when voter turnout should be higher because it will coincide with the next presidential race."

Maxmen concluded with this comment from Eric Verdin, president of the Buck Institute on Aging in Novato, Ca., which has received nearly $35 million from CIRM.

“It would be a catastrophe for California if people say CIRM did not do what it was expected to do. They’ve built the foundation for the field and attracted people from around the world — you can’t just now pull the plug.”

California Stem Cell Agency Plumps Its Program as It Eyes Need for More Funding

California's 12-year-old stem cell agency today launched a "statewide outreach tour" that is aimed "partly" at building support for pumping $5 billion more into the program which is nearing the end of its financial life.

The agency has billed the one-hour, public program in San Diego as a "patient advocate event." Reporter Bradley Fikes of the San Diego Union-Tribune discussed the event in an article this morning that was headlined:

"Should Californians give more money for stem cell research?"

In addition to being sponsored by the California Institute for Regenerative Medicine (CIRM),  as the agency is formally known, the event is backed by UC San Diego, which has received $177 million from the agency.

Fikes said the event is the first in a series that is "is partly meant as a way to persuade voters to further support the institute with more funding."

He continued,

"Jonathan Thomas, CIRM’s chairman, said the San Diego event and others like it in other parts of the state are meant to update patients and all Californians about how their money has been spent, and to hear from the public."

Robert Klein, the multimillionaire real estate investment banker who led the 2004 ballot campaign that created the $3 billion agency, said last month that he expects that a public opinion poll this fall will show strong support for adding $5 billion to the effort. It is scheduled to run out of cash for new awards in June 2020 and perhaps sooner.

The 2004 campaign cost $34 million. Klein has not publicly discussed his plans to raise money for the ballot effort.

The agency has yet to finance a commercially available stem cell therapy.

UC Irvine Stem Cell Blog: Troubling New Federal Law on Stem Cell Research

The stem cell blog at UC Irvine this week published a piece that warned that a new federal law aimed at speeding commercialization of stem cell therapies is worrisome and could lead to harm to patients and damage the entire field of research.

The April 10 article was written by Navied Akhtar, a Ph.D. candidate in the biomedical engineering department.

Akhtar's topic was the 21st Century Cures Act. He wrote that the law, signed by President Obama and which had a broad range of supporters,

"...utilitizes evidence from clinical experience to 'help to support the approval of a new indication for a drug approved under [accelerated approval]' and 'to help to support or satisfy post approval study requirements.' The only requirements written in for accelerated approval past a 'reasonable likelihood' that there will be clinical benefit, is that one or both of two requirements are met: (1) That the manufacturer conducts studies after accelerated approval to verify the predicted effect on mortality or other clinical benefit and (2) That the manufacturer submits copies of marketing materials for the drug during the preapproval period." 

Akhtar said that the law 

"will allow for what is effectively anecdotal evidence to be used as actual evidence to support the requirement for accelerated approval. Furthermore, the verbiage surrounding the term 'surrogate endpoint' is loose at best. The idea of a surrogate endpoint is to produce a clinically relevant point in which to be able to measure the efficacy and safety of a drug. In the Cures Act, the definition of what constitutes a surrogate endpoint is left rather open-ended. It reads as such: "The term ‘surrogate endpoint’ means a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is not itself a direct measurement of clinical benefit, and is known to predict clinical benefit and could be used to support traditional approval of a drug or biological product; or is reasonably likely to predict clinical benefit and could be used to support the accelerated approval of a drug or biological product.' It is worrisome to write that this endpoint can be a marker that is not a direct measurement of clinical benefit, but is known to predict clinical benefit. This leaves open a large workaround for accelerated approval of drugs that may have no business being approved."

Akhtar goes on to cite cases of drugs that ultimately proved harmful even after clearing the usual approval process. 

In the case of novel stem cell therapies, he argued, serious mishaps or death because of loose federal standards could endanger progress in the entire field. 

New Top Lawyer Likely Coming Soon to California's $3 Billion Stem Cell Agency

California's $3 billion stem cell agency appears set to announce a new general counsel, a key position that pays nearly $400,000 a year.

The agency has closed applications and has only one candidate to replace James Harrison, who has announced he will be leaving the agency's service at the end of June.

A job opening notice was posted last month seeking applicants for the position, which has an annual salary range of $208,483 to $384,537.

Harrison worked as outside contractor with the Oakland-based agency in an agreement that totalled $575,000 this fiscal year. The agency is expected to run out of funds for new awards in June 2020.

Harrison has been the top lawyer for the agency since its inception in 2004.

California's Unregulated Stem Cell Clinics: Will State Regulators Step In to Cure Abuses?

The state of California has laws regarding substandard and questionable medical care, and now questions are being raised about whether it should step in to deal with the unregulated stem cell clinics that appear to flourishing in the Golden State.

The concerns come as the Los Angeles Times reported during the weekend about an enterprise in La Jolla, StemGenex Medical Group, which describes itself as "the premiere leader in the United States for regenerative medicine." 

The Times' Pulitzer Prize-winning columnist Michael Hiltzik wrote about the case of Jim Durgeloh, 59, a construction contractor from Washington state, who was looking for a solution to his hip problems, as well as other cases. Durgeloh paid StemGenex $15,000 for a treatment.

Hiltzik interviewed Durgelogh who was in Southern California with his wife following treatment. Hiltzik wrote,

"They were preparing to fly home, infused with the hope communicated by the clinic staff, who 'seemed very optimistic,' Durgeloh told me.

"A lawsuit in San Diego federal court suggests that StemGenex may have given the Durgelohs nothing but hope. Three StemGenex patients — two with diabetes and one with lupus — say they were misled by the medical group’s marketing pitch to pay $14,900 each in 2015 and 2016 for therapies that have had no effect.

"The lawsuit, which seeks class-action status, claims that StemGenex has made its money by 'targeting the ill and the elderly' with 'false, fabricated and purposefully misleading' claims about patient satisfaction."

Hiltzik continued,

"StemGenex, in its reply to the ... lawsuit, asserts that the plaintiffs 'cannot prove' that its 'representations regarding the efficacy of its stem cell treatments are actually false.' The plaintiffs, it continues, 'do not cite to a single scientific study that disproves [StemGenex’s] advertised claims.'"

UC Davis stem cell scientist Paul Knoepfler wrote yesterday on his blog about Hiltzik's article. Knoepfler was the co-author of a 2016 study that attracted nationwide attention with the disclosure that 570 unregulated stem cell clinics exist in the United States. California leads the way with 113.

Knoepfler focused on Hiltzik's disclosure that one of the StemGenex physicians, Scott Sessions, was placed on three years probation last February involving treatments not related to StemGenex. Sessions was accused of negligence "related to cosmetic surgery and other procedures he performed on two patients at an unrelated facility in 2011 and 2013."

Knoepfler continued,

"Sessions photo was up on the Stemgenex website...and then suddenly it wasn’t. Hiltzik also mentions that Stemgenex has had other questionable information on its web site in the past.

"With California having the most stem cell clinics selling non-FDA approved interventions of any state I hope the state medical board here will wake up to the fact that it needs to give this arena more attention."

The state has wide-ranging authority to regulate physicians. A document on the state Department of Consumer Affairs web site says that physicians can be disciplined for such things as  "not using accepted, effective treatments or diagnostic procedures," "not referring a patient to a specialist when
appropriate" and "continuing to use a procedure that is unnecessary."