Search for a Diabetes Cure: California Stem Cell Agency Hits $60 Million Mark with ViaCyte

The California stem cell agency next week is slated to award  an additional $4 million to ViaCyte, Inc., a San Diego firm that is working with the agency to develop a "virtual" cure for diabetes.

ViaCyte has already received $56 million over the years from the California Institute for Regenerative Medicine(CIRM), as the agency is formally known. The latest award will be used to help prepare for a clinical trial for a new treatment for the highest risk diabetes patients.

In response to a query this morning from the California Stem Cell Report, Paul Laikind, president and CEO of ViaCyte, said that the new product, PEC-Direct, will deliver the same biologic component as used in the firm's current product, which is now in a clinical trial.

Laikind said PEC-Direct will allow direct vascularization, which "is expected to allow for a very robust engraftment and cellular performance."

Because the new device will require chronic immune suppression, Laikind said,

"It is being developed to treat patients with type 1 diabetes that are at high risk for acute complications such as severe hypoglycemic events associated with hypoglycemia unawareness syndrome."

(The full text of Laikind's remarks and research update can be found here.)

The agency's summary of the closed-door review of the Viacyte proposal said,

"There are over 100,000 people in the U.S. with type 1 diabetes so severe that they are at constant risk of hospitalization and/or death. Within months after administration, this product could naturally restore those patients’ blood sugar to normal healthy levels and save their lives." 

In addition to the $4 million, ViaCyte is putting up $994,343 of its own cash.

CIRM's blue-ribbon panel of scientific reviewers has already approved the award, which is part of a $30 million package of applications coming up next Thursday.  The governing board of the agency will ratify the approvals at its meeting next Thursday during a one-hour telephonic meeting.

The largest award, $10 million, will go to Humacyte, Inc., of North Carolina,  to produce an artificial vein for use in hemodialysis as reported yesterday on the California Stem Cell Report. More details of all the applications and review summaries can be found on the meeting agenda.

The session will be audiocast and carried on the Internet on a listen-only basis. Interested parties can participate in the meeting from telephonic locations throughout the state.

The main site for the meeting will be at the Sanford consortium in San Diego. Other locations include the agency's headquarters in Oakland and sites in Davis, South San Francisco(2), Napa, Los Gatos, Sacramento, Irvine, San Francisco and Los Angeles. For specific addresses and instructions for online access, see the agenda.

Text of ViaCyte's Statement on its New Proposed Diabetes Product

The California Stem Cell Report this morning queried Paul Laikind, the CEO of ViaCyte, Inc., of San Diego, about the company's upcoming $4 million award from the California stem cell agency and the award's relationship to the ViaCyte product known as VC-01. Here is the text of his response.

"ViaCyte is continuing development of VC-01 (what we now call PEC-EnCap).  PEC-EnCap is the first encapsulated allogeneic cell therapy to enter the clinic where the device is designed to protect the cells from the host adaptive immune system.

 "We have early clinical demonstration of the feasibility of the PEC-EnCap approach; the Encaptra Drug Delivery Device appears to be functioning as designed and we have shown engraftment and differentiation to beta cells is achievable at 12 weeks.  However, work is continuing to ensure a robust and consistent engraftment before we move to the second cohort of patients and seek to demonstrate efficacy.

 "We can’t overemphasize enough the importance the clinical results we are obtaining, not only for the further development of PEC-EnCap but for the stem cell-derived cell therapy field in general. This important work has, of course, received important support from CIRM. "In parallel with the development of PEC-EnCap we are preparing to initiate clinical development of VC-02 (PEC-Direct).  PEC-Direct delivers the same biologic component as PEC-EnCap, PEC-01 pancreatic progenitor cells, but does so in a device that allows direct vascularization.  This direct vascularization, based in part on what we have learned with PEC-EnCap during the clinical evaluation, is expected to allow for a very robust engraftment and cellular performance.

"Given the open nature of the device, patients implanted with PEC-Direct, as with other transplants, would require chronic immune suppression.  Thus it is being developed to treat patients with type 1 diabetes that are at high risk for acute complications such as severe hypoglycemic events associated with hypoglycemia unawareness syndrome.

 "This high risk patient population is the same population that would be eligible for cadaver islet transplants, a procedure that has been demonstrated as very effective but suffers from a severe lack of donor material and high cost.  PEC-Direct is expected to overcome these limitations by providing an unlimited supply of cells for transplant and a safer more optimized route of administration.

"ViaCyte remains committed to the development of PEC-EnCap which we view as a potentially transformational therapy for the majority of insulin utilizing patients with diabetes, both type 1 and type 2.  PEC-Direct represents a potentially nearer term therapy for the patients at the highest risk."

$10 Million California Stem Cell Award for Creation of a New 'Lifeline" for Kidney Disease Patients

A 2014 interview with Laura Niklason, whose firm, Humacyte, will receive a $10 million award from California. The interview was conducted at the Stem Cells Meeting on the Mesa in La Jolla, Ca.

Highlights
$10 million matched by Humacyte
Three clinical trial locations in California
Humacyte raised $150 million last year

The California stem cell agency is set to award nearly $10 million for a phase 3 clinical trial to produce a new type of "lifeline" for kidney disease patients undergoing hemodialysis.

The $10 million award to Humacyte, Inc., of Morrisville, N.C., will go for final testing and development of an artificial vein that is critical for kidney disease patients who need hemodialysis.

The $10 million will be matched by the privately held firm. The state funds can only be spent for work performed in California to test the vascular access device. Humacyte plans clinical trial sites in Sacramento, Long Beach and Irvine.  

Formal approval of the award is expected to come July 22  at a telephonic meeting of the $3 billion agency's board of directors.

The stem cell agency traditionally does not identify recipients of awards until its board formally ratifies the decisions of its reviewers, which it almost never overturns. The California Stem Cell Report determined the identity  of the recipient using public sources.

According to the National Institute of Diabetes and Digestive and Kidney Diseases,

"A vascular access is a hemodialysis patient’s lifeline. A vascular access makes life-saving hemodialysis treatments possible. Hemodialysis is a treatment for kidney failure that uses a machine to send the patient’s blood through a filter, called a dialyzer, outside the body. The access is a surgically created vein used to remove and return blood during hemodialysis."

The Humacyte device, photo Humacyte

A summary of the closed-door review of the application described the product as a "human acellular vessel" that "has the potential for less frequent clotting, abandonment and infection." The summary said current technology is "fraught with complications."

Humacyte was founded in 2004 and raised $150 million last year in venture capital, according to an article last month by Meghana Keshavan on the STAT online biomedical news service. 

In the piece, Keshaven described the process of growing the vessels. She said each has "its own little plastic sack, which serves as a sort of womb for the vessel as it grows. Each bag’s connected to a central bioreactor tank that pumps out all the nutrients it needs — a carefully crafted 'soup' of vitamins, amino acids, and chemicals called cytokines that feed cells directions about how they’re supposed to grow."

Keshaven continued,    

"The lab-grown blood vessels are currently being studied in hemodialysis, a procedure that uses implanted veins as a conduit to remove waste from the blood of patients with kidney failure. Last month, promising results from a 60-patient midstage trial of Humacyte’s product were published in The Lancet."

Humacyte currently is recruiting 350 patients and expects to have preliminary results by July of next year. In response to a question this morning, Jeffrey Lawson, chief medical officer of the firm, said, 

Shannon Dahl,
co-founder Humancyte

Juliana Blum,
co-founder Humacyte

"We currently are engaged on using at least 3 clinical sites in California that should start enrolling patients (Sacramento, Long Beach and Irvine). We also have a number of manufacturing support programs based in California."

Founders of the firm include  Laura Niklason, professor of biomedical engineering and Yale, and Shannon Dahl and Juliana Blum, vice president of the firm.

More Than a Minor Headache: The Stem Cell Snake Oil Problem vs. Legitimate Research

Just two weeks ago, the headlines from Bloomberg News offered a glowing view of the prospects for stem cell therapies and the industry. The story in the online publication, which counts nearly 9 million readers monthly, said,

"Stem cell crusader sparks new hope....Regenerative medicine could be a $120 billion industry by 2030"

But only three days later, that article was overwhelmed by a wave of stories with a much different flavor. They carried reports of unproven therapies, possibilities of fraud, lack of regulation and fearful, expensive consequences for desperate patients.

That theme continued even as recently as this past weekend as The Economist carried a piece headlined,

"A dish called hope: The flourishing, unregulated industry in expensive, experimental treatments"

So which is it? Hope for legitimate cures and oodles of cash for stem cell companies? Or "hope" for treatments that do not work and have sometimes damaged both the bodies and wallets of the patients?

The situation is more than a minor public relations headache for the supporters of stem cell research, be they patients, stem cell companies or the $3 billion California stem cell agency, which is on a campaign to ease federal regulation of stem cell clinical trials.

For all practical purposes, the public generally does not make much of distinction between the legitimate research conducted by institutions such as Stanford and the so-called "miracles" reported about the late hockey great Gordie Howe and others. It all goes into the same cognitive bag. The stories about mysterious and fearsome tumors found in little-known patients attract little widespread attention.

But UC Davis scientist Paul Knoepfler and bioethicist Leigh Turner of the University of Minnesota ripped open that bag with their study last month that reported for the first time that nearly 600 dubious stem cell clinics are peddling their unproven therapies across the country.  Their report supported the view that the stem cell field is rife with snake oil merchants. For the general public, which does not delve deeply into medical research, the perspective could well be described as, "You seen one stem cell therapy, you seen 'em all."

Does this mean that these clinics should be ignored and shoved quietly off into a corner in order to avoid besmirching legitimate efforts? Of course not. It certainly appears that the FDA and other  state regulatory bodies can do a better job. But stiffer regulations are not going to come anytime soon, despite an FDA hearing on the topic in September.

However, the situation DOES mean that folks like Knoepfler and Turner should continue to speak out along with many other scientists who do not want their efforts blackened by the snake oil men. Researchers can work with their institutions' PR departments to place op-ed pieces, find speaking engagements and gin up TV and radio interviews. Blogs, like the one produced by Knoepfler, can be started. The International Society for Stem Cell Research should revive its public education efforts to help patients and the general public understand the facts about stem cell research. It should also reinvigorate its warnings about dubious therapies, which were throttled back a few years ago, reportedly after legal threats were made.

California's stem cell agency has a special concern. It is trying to "de-risk" development of therapies  by a variety of means and lure biotech and Big Pharma into the stem cell game in a bigger way. This summer the agency is offering $75 million to entice a private partner into the state's first-ever, public-private partnership to create a stem cell cure.

The private sector has shied away from the stem cell business, as the stem cell agency's CEO, Randy Mills, has remarked on multiple occasions. One of the reasons involves the public climate and perception of the field. It is hard for companies to invest hundreds of millions of dollars or billions when the stem cell field is burdened with public perception and regulatory obstacles.

Selling the stem cell story in a realistic way is not necessarily an easy task. Nuances must be respected, but excitement is also needed. Balancing it all is a challenge for the men and women in the trenches. But without a good push, development of therapies will be slower, and, as Mills has noted, people will undoubtedly die who likely would have benefited from a more timely treatment.

A Scientist's Comment: Deal Directly with FDA Rather Criticizing It in the Media

The following comment on FDA regulation of stem cell research was submitted via email by a longtime scientist in the field, who asked to remain anonymous. 

"Many advertised  'stem cell' treatments use hematopoietic or blood stem cells which are run under a different set of regulations from pluripotent stem cells since they are umbrella-ed under regulations designed to cover blood transfusions and bone marrow transplants.  Pluripotent stem cells are very new, with many unknowns and the potential for triggering tumor growth.   In contrast, clinical use of blood stem cells has been ongoing for over 50 years with special regulations (or lack thereof) grandfathered in.   Unfortunately, the newly touted 'treatments' are not for homologous use of blood stem cells, are unlikely to be therapeutic and may even be dangerous. 

"The FDA has published new draft guidances addressing these issues that will be discussed in open forum this September.  I think it best to bring concerns about FDA regulations to these meetings and to initiate change by talking directly with the agency rather than criticizing them in the press or through Congress.  Like their oversight over the IRS and other federal agencies, Congress’s actions are counterproductive when they add broad, unfunded mandates while cutting funding at the same time.  But perhaps this is their way of shrinking the government and simultaneously dinging them for not doing their work.  A sure route to failure."

Monty Python, $3 billion and Stem Cells in the Golden State

Inquisition scene from Monty Python, photo CIRM/Daily Mail

The headline today from California was nearly irresistible:

"The Spanish Inquisition and a tale of two stem cell agencies"

Not only that, but the headline appeared over an article involving Monty Python, the $3 billion California stem cell agency and the lesser,  $38 million United Kingdom's Regenerative Medicine Platform(UKRMP). 

The "Inquisition" article ran on the California agency's blog. The author was Kevin McCormack, senior director of communications for the California Institute for Regenerative Medicine(CIRM), as the agency is formally known. 

His topic? How the UK and California efforts have performed, according to an article by Stanford's Irv Weissman and Fiona Watt of King's College London, who is a member of the CIRM scientific advisory board, currently "on hold," according to McCormack.  The Watt-Weissman piece was recently published and buried behind a paywall in Cell Stem Cell.

McCormack noted that the article cited location and politics as important in both operations. He wrote, 

"CIRM was created by the voters of California in 2004, largely in response to President George W. Bush’s restrictions on the use of federal funds for embryonic stem cell research. UKRMP, in contrast was created by the UK government in 2013 and designed to help strengthen the UK’s translational research sector....

"Inevitably the two agencies took very different approaches to funding, shaped in part by the circumstances of their birth – one as a largely independent state agency, the other created as a tool of national government.

"CIRM, by virtue of its much larger funding was able to create world-class research facilities, attract top scientists to California and train a whole new generation of scientists. It has also been able to help some of the most promising projects get into clinical trials. UKRMP has used its more limited funding to create research hubs, focusing on areas such as cell behavior, differentiation and manufacturing, and safety and effectiveness. Those hubs are encouraged to work collaboratively, sharing their expertise and best practices."

Irv Weissman, photo wapiti-waters

Weissman and Watt said it was "not unexpected" that CIRM still has not produced a therapy for widespread use. They cited the sometimes decades-long time frame for transforming basic research into a therapy.

Which is where Monty Python comes in, said McCormack. The two scientists picked up a famous line from the British comedy series:

“Nobody expects the Spanish Inquisition – because our chief weapon is surprise.”

Fiona Watt, photo Watt Lab

McCormack wrote,

"They use that to highlight the surprises and uncertainty that stem cell research has gone through in the more than ten years since CIRM was created. They point out that a whole category of cells, induced pluripotent stem (iPS) cells, didn’t exist until 2006; and that few would have predicted the use of gene/stem cell therapy combinations. The recent development of the CRISPR/Cas9 gene-editing technology shows the field is progressing at a rate and in directions that are hard to predict; a reminder that that researchers and funding agencies should continue to expect the unexpected."

Influential Scientific Journal Rips Effort to Loosen Stem Cell Research Rules

The prestigious journal Nature today editorialized against easing federal regulation of stem cell treatments, a major blow to the campaign by the California stem cell agency to speed such therapies to the marketplace.

The headline on the piece said,

"FDA should stand firm on stem cell treatments."

The unsigned editorial declared that those who contend that the Food and Drug Administration (FDA) is holding back "effective therapies" are peddling a false narrative. Nature declared,

"The claim that regulation is too harsh wrongly implies that the FDA is holding back therapies that work. Critics point to decades of preclinical and clinical work with stem cells and the pipelines of stem-cell treatments. With circular logic, they argue that, because the treatments have not been approved, there is something wrong with the approval system."

The $3 billion California stem cell agency has been lobbying for months for changes in FDA regulation. Randy Mills, president of the California Institute for Regenerative Medicine(CIRM) as the agency is formally known, said back in December that "patients are dying" because the FDA is  being "so careful about safety."

Mills has said the fast-track process in Japan is worth considering. However, Nature said,

 "It is not a fit and proper model to export, chiefly because it grants 'conditional approval' to treatments with minimal safety data and little attention to efficacy."

Nature was also critical of the Regrow Act, a legislative effort to overturn the FDA's current processes. CIRM has not taken a position on that bill.

Nature concluded,

"The FDA should strive to keep this debate on the proper topic — how to create a more efficient system that still scientifically evaluates whether treatments are safe and efficacious. To fall short would be a setback for science, and for patients."

The journal's editorial did not mention CIRM or Mills by name. It did cite the recent article by UC Davis stem cell researcher Paul Knoepfler and Leigh Turner, an associate professor of bioethics at the University of Minnesota, documenting the existence of 570 dubious stem cell clinics in the United States.

'False Hopes, Sizable Profits' -- The Nation's Largely Unregulated Stem Cell Clinics

Locations of stem cell clinics identified in Knoepfler/Turner study
Graphic by Cell Stem Cell 

The biggest stem cell story in the country this week reported that at least 570 dubious stem cell clinics exist throughout the nation that could pose a danger to both the pocketbooks and health of patients.

California led the nation with 113 clinics, with Beverly Hills having the most (18) of any city. The clinics promise to cure or ease afflictions ranging from autism to Alzheimers through the use of scientifically untested treatments.

The study is the first effort to get a handle on the size of an industry that has been little regulated by the Food and Drug Administration (FDA) but appears to promise almost miraculous results.

Results of the study were reported yesterday in the Washington Post, the Los Angeles Times, Fox News, The Sacramento Bee and many other outlets.  A search at midday today on Google turned up 7,230 citations, including articles in France, Mexico and Italy.

One of the authors of the study from the journal Cell Stem Cell is Paul Knoepfler, a stem cell scientist at UC Davis.  He has long campaigned for more action dealing with some of these clinics. In September 2015, he wrote on his blog about what he called "predatory clinics."

"These clinics prey on vulnerable patients and their families. The clinics use hope as a marketing tool. A weapon.

"As the number of such clinics has mushroomed in the US and elsewhere the risk to both patients and to the larger stem cell community proportionately rises too. We are in a situation today where the dangers from such clinics have never been higher."

Co-author of the study, Leigh Turner of the University of Minnesota, said in an article in The Bee by Adam Ashton,

"The problem is that so much of the information that’s provided by the industry, so many of the marketing claims being made, they’re not particularly accurate. They’re not trustworthy, and they don’t have any meaningful science behind them."

In a story by Karen Kaplan in the Los Angeles Times, Turner said,

"There is an obvious need for the FDA, FTC (Federal Trade Commission), state medical boards and other regulatory bodies to play a more effective role in regulating the marketplace for stem cell interventions.' Without it, these clinics are able "to peddle false hope for sizable profits.'"

Randy Mills, president of California's $3 billion stem cell agency, said in The Bee that the Knoepfler/Turner study "highlighted a 'broken system' at the FDA that lets some clinics proceed with almost no oversight while requiring others to undergo studies that could tie up their services for decades. He said there are likely far more clinics offering stem cell therapies than Knoepfler and Turner identified, with many of them operating discreetly.

"'There’s so much stuff going on today, but it’s going on because that’s the system the FDA set up and that’s the system the FDA incentivizes,' he said."

Knoepfler noted a bit of irony yesterday concerning the study in a posting on his blog, The Niche. He wrote, 

"I’m glancing over at the (Scientific American) article (on the study) just now and BOOM I see an ad for a stem cell clinic appear at the top and it is even one of the ones in the database we created for our article. The ad is focused on selling stem cells to treat autism in children, an area that raises a lot of questions.

"How can it be a good thing to have an ad for a stem cell clinic right next to the article about the challenge of stem cell clinics in America? The way the web works these days, perhaps it isn’t so surprising that articles having anything to do with stem cells will often be accompanied by ads for stem cell clinics. This one just really stuck out to me today because of the context."

Google and other media outlets routinely place advertisements for these stem cell clinics on many Web sites and blogs, including this one. Some of the newspapers carrying stories about the Knoepfler study also carry ads for such clinics. 

California Stem Cell Hooha: Testy Media Exchange Triggered by Criticism of the State's Agency

A sharp exchange erupted this week on a mainstream California media site after the state's $3 billion stem cell agency was taken to task for lobbying the federal government to ease its regulation of research on stem cell therapies.

The flap involved allegations of lies and questionable motives. Along the way certain death was mentioned, and one writer was accused of "stealing hope" from seriously ill persons. Personal animus charges were raised along with questions about ill-informed rhetoric.

The hooha was set off by an op-ed piece by UC Davis stem cell scientist Paul Knoepfler who wrote an op-ed in the San Francisco Chronicle (see here and here). It chastized the agency and its president, Randy Mills, for a risky and "political" effort to change regulations by the federal Food and Drug Administration. Knoepfler said patients could be put at risk.

The piece triggered harsh comments that were carried by the Chronicle at the end of the article. In addition to Knoepfler, individuals involved in the exchange included Jeanne Loring, head of the stem cell program at the Scripps Institute in La Jolla; Judy Roberson, a Sacramento patient advocate for Huntington's disease, and a person identified only as "Jeff." He wrote,

"What's Knoepler's real beef?....Poor Paul is not getting the money from CIRM he used to get. So his attitude is 'screw patients,' I want my lab funded like it used to be. Nauseating!!!"

CIRM is the abbreviation for the formal name of the state stem cell agency, officially known as the California Institute for Regenerative Medicine. Its board includes Jeff Sheehy, who told the California Stem Cell Report that he is not the Jeff commenting on Knoepfler's article.

The anonymous "Jeff" said, 

"Has any of (Knoepfler's) research led to a development candidate that might lead to a treatment in the future? Or is he just a stem cell scientist opining about something he knows very little or nothing about(the FDA)? Maybe he 'heard' something from somebody and that gave him just the hook he needed to attack CIRM and Mills, both of whom he obviously has personal animus towards."

Loring largely sided with Knoepfler. She also wrote,

"Jeff, why are you questioning Paul's motives? What are your motives? Do you work for CIRM? As you know, a person's profession doesn't define his/her sphere of knowledge. If something is important to you, you can research it and gain expertise."

Roberson, who favors the CIRM effort to loosen regulations to bring therapies into widespread use, said patient safety is important. She also said,

"But for patients and their families with a 100 percent fatal genetic disease like Huntington's disease, we can withstand some risk because we are facing a gut-wrenchingly long, gruesome death anyway. We have no chemotherapy, no surgery, no radiation and sadly, no hope. We have NOTHING! And we'll continue to have nothing for many more decades if the FDA continues doing business as usual."

Another reader, William Barnes, said,

"I suggest that Dr. Knoepfler consider how it feels to be suffering and near certain death and be denied a possible cure because Dr. Knoepfler doesn't think it's in their best interest....Let the individual patient decide! It’s their life! Why should the decision about someone’s life, possibly your loved one, be made by a distant and dispassionate academic?"

In addition to his research, Knoepfler produces a blog, The Niche, on stem cell science, regulation and policy. He took up the blog after a nasty bout with prostate cancer when he was in his 40s. Knoepfler is also the author of "Stem Cells: An Insider's Guide," a book aimed at helping patients understand stem cell science. 

The Case of the FDA's $330,000 Stem Cell Pigs

Judy Roberson at podium, Bob Klein, former chairman of the California stem cell agency at left, Claire Pomeroy, former
UC Davis vice chancellor and agency director at right. UC Davis photo

Judy Roberson is a registered nurse from Sacramento, Ca., who has long been active with the California stem cell agency on behalf of patients with Huntington's disease. She lost her husband to the always fatal, inherited brain disease, and members of her family are at risk.

Roberson appeared before the governing board of the $3 billion California Institute for Regenerative Medicine (CIRM), as the agency is formally known, earlier this month to applaud its efforts and those of its CEO, Randy Mills, to persuade the federal Food and Drug Administration to ease its regulation of proposed stem cell therapies. Here is the text of her statement. 

"The Northern California Huntington's disease (HD)  advocacy community says BRAVO to President Randy Mills for his editorial directed at the FDA, "Give Us Our Cures."

"Over 40 HD advocates joined the CIRM Stem Cell Champion campaign in April, promoted by Kevin McCormack (the agency's director of communications), in the hopes that pressure from affected families will prompt the FDA to become open to stem cell therapies and allow the increased risks that naturally go along with new therapies.

"For people with Huntington's disease, which is 100 percent fatal and has zero therapies, we are willing to take on more risk since we're dying anyway.

"The FDA has delayed the fully enrolled, CIRM funded, first-in-human clinical trial using adult stem cells at UC Davis with Drs. Vicki Wheelock and Jan Nolta. The NIH RAC committee enthusiastically approved their novel therapeutic clinical trial. Then the FDA asked for additional animal studies, this time with three pigs at a cost of over $330,000 plus two years of additional research; costs will approach $1 million.

"One HD family from New York has funded one of the pigs, but this gap in funding has shelved this promising research!

"Devastated patients and their families see this add-on research requirement as a delay from the FDA, which means that this fully enrolled trial, with 24 patients who meet today's criteria will progress and may not qualify in two to four years even if this project later receives FDA approval to begin a phase one trial. FDA delays are killing us!

"We need a new FDA 2.0 because doing NOTHING is doing harm!"

California's Battle for Easing Regulation of Stem Cells Attracts Global Notice

Highlights
CIRM CEO Mills mentioned
FDA regulation/Regrow co-mingled
A tale of dubious stem cell treatments

California's $3 billion, 11-year-old effort to produce a stem cell therapy -- largely ignored by the mainstream media -- broke into global cyberspace today in a reasonably significant way.

The agency was featured in a piece on Buzzfeed, an online news operation that has chalked up more than 173 million unique visitors worldwide in the last 30 days.

The article by Dan Vergano focused on the efforts by the California Institute for Regenerative Medicine or CIRM, as the agency is formally known, and others to persuade the FDA to ease up on regulations so that stem cell therapies can be more quickly developed.

Vergano wrote,

"Despite a decade of scientific hype, progress has been slow in proving that these new treatments actually work. Some scientists are particularly frustrated with the slow pace of FDA review. In a Fox News op-ed published last month, for example, C. Randal Mills, the head of the prestigious California Institute for Regenerative Medicine (CIRM), called for the federal government to loosen its safety rules, promising “medical breakthroughs” for arthritis, back pain, and diabetes."

Mills has focused his efforts since last year on FDA regulation. But his campaign is being co-mingled in the media with the Regrow Act, an industry effort that the agency has not taken a position on.

Paul Knoepfler, a UC Davis stem cell researcher, also recently brought FDA regulation and Regrow together in a piece in the San Francisco Chronicle recently. Vergano interviewed Knoepfler for the Buzzfeed article,

"'We have been telling people to cut down the stem cell hype, and then we turn around and have this talk about miracles and beautiful medicine....Wishful thinking here could have a whole slew of dangerous consequences.' Most worrisome, (Knoepfler) said, is that desperately ill patients looking cures might end up with tumors instead."

Jim Gass, NYTimes photo by Carlos Moreno

One such case was chronicled this week by New York Times reporter Gina Kolata. Her hair-raising story told the tale of patient Jim Gass, a 66-year-old lawyer from San Diego. The article began,

"The surgeon gasped when he opened up his patient and saw what was in his spine. It was a huge mass, filling the entire part of the man’s lower spinal column.

"'The entire thing was filled with bloody tissue, and as I started to take pieces, it started to bleed,' said Dr. John Chi, the director of Neurosurgical Spine Cancer at Brigham and Women’s Hospital in Boston. 'It was stuck to everything around it.'"

"He added, 'I had never seen anything like it.'"

Stem Cells, Long Odds and the 'Invisible Hand of Hype'

The headline on the California story pretty much told it all: "Stem Cells: Where Science, Hope and Hype Meet."

It could have added that it is also a meeting place for Big Pharma, Big Academia and Big Politics.

All of those yeasty ingredients are embodied in the $3 billion California stem cell agency, which is plugging away at developing a therapy promised to voters 11 years ago during a $36 million ballot campaign..

The headline appeared on the KQED Web site, a public television and radio outlet in San Francisco. The city, coincidentally, is where the world's largest aggregation of stem cell researchers, the International Society for Stem Cell Research (ISSCR), is meeting today. The conference is also just across the San Francisco Bay from Oakland, where the stem cell agency is headquartered.

Danielle Venton wrote the article for KQED. She covered a bit of the history of the California Institute for Regenerative Medicine or CIRM, as the agency is formally known. She noted that the agency is now participating in 16 clinical trials, although it has yet to chalk up production of a commercial therapy.

Venton wrote,

"(T)he frustration many voters feel about CIRM may have more to do with the problematic way researchers, institutional communicators and the media talk about scientific progress in general, and stem cells in particular, than it does with the agency’s performance.

Timothy Caulfield

"'There has always been this high-stakes, extreme rhetoric around stem cells,' says Timothy Caulfield, who teaches science and health policy at the University of Alberta. Caulfield says because stem cell research was so embattled, many spoke of its promise in hyperbolic terms.

"'People had to make bold statements about the future of stem cells in order to counteract those that wanted to have strict laws to stop it. So you have to say, ‘This is going to save lives. This is going to cure a variety of diseases.’ Right from the beginning, the late ’90s, you have that language appearing in the popular press.”  

Venton reported that the international scientists' group, the ISSCR, is "trying to tone things down" with new guidelines about how to talk about stem cell research and its impact. She said the effort "may be facing long odds." She quoted Caulfield as saying,

“It’s really the invisible hand of hype. In most cases these pressures are largely unconscious — whether you’re talking about the media, the researchers, the institutions or the funding agencies.”

Stem Cells and the FDA: California's Lobbying for Easier Approval Triggers Opposition

The $3 billion California stem cell agency came in for some sharp criticism last week in an opinion piece in the San Francisco Chronicle that was written by a UC Davis stem cell researcher who said the agency is engaged in politicking that "risks doing much more harm than good."

Paul Knoepfler, the scientist who also produces "The Niche" stem cell blog,  wrote,

"The California Institute for Regenerative Medicine (CIRM) has become politically active under its new president, C. Randal “Randy” Mills. Mills is lobbying for a radical departure in how the U.S. Food and Drug Administration (FDA) vets experimental stem-cell therapies, but such politicking risks doing much more harm than good."

Knoepfler wrapped in an attack on federal legislation known as Regrow Act. Knoepfler said the proposal would "force the FDA to conditionally approve still experimental stem cell therapies with relatively little data supporting them."

Randy Mills at left, USC photo

Knoepfler reported that Mills said he was not anti-FDA. Knoepfler also noted that the agency has not taken a position on the Regrow Act.  Knoepfler said the FDA effort and the Regrow Act are part of a larger effort to weaken the FDA, which has been under regular criticism for decades for moving too slowly.

The stem cell agency's attempt to modify the way the FDA approaches potential stem cell therapies has been underway for months. The California Stem Cell Report carried news on the subject as long ago as last winter(see here and here.)

Mills initiated the lobbying effort with the FDA after an informal survey of California "stakeholders" showed that they perceived the FDA as the No. 1 obstacle to making stem cell therapies available for widespread use.

In an item on the agency's blog, The Stem Cellar, last December, Mills said that “patients are dying” because the federal government is “being so careful about safety,"

Yesterday, Knoepfler provided some personal insight -- a "backstory" -- on what led him to write about the all of this. His piece was carried on his blog and emphasized that he is a "big backer" of CIRM and still is. Knoepfler has received $2.2 million from CIRM. The CIRM web site has 60 links to mentions of Knoepfler on its Web site, including this one below. 

Knoepfler wrote,

"Most of the stem cell scientists that I have talked to (admittedly with a few notable exceptions that include some long time stem cell advocates and scholars) are opposed to CIRM’s lobbying on this front, but are uncomfortable speaking out."

Uncomfortable is a rather mild word for it based on the fact that the agency holds the key to a $3 billion vault containing the hopes of funding for the entire California stem cell community.

We should note that lobbying is not new to the agency. Its former chairman, Robert Klein, had a passion for it. At one point in 2009, he engineered the hiring of an exceedingly well-connected lobbyist named Tony Podesta for $200,000.  Mills has not ventured into that sort of game, however.

Knoepfler has much more to say on the subject of regulation, the need for it and the impact on patients and the dubious stem cell clinics that seem to be multiplying throughout the nation, despite the fact that the FDA has never approved a stem cell therapy for widespread use.

The California Stem Cell Report will be visiting the matters surrounding these issues and the California stem cell agency. Look for more here during the next week or so.

The California Stem Cell Agency: A Business with Scientists as Subcontractors?

The following commentary was submitted by a grantee of the California Institute for Regenerative Medicine (CIRM) in response to its $15 million award earlier this week to Quintiles, a clinical research organization. The person who wrote the item asked to remain anonymous.

Comments from readers are always welcome on the California Stem Cell Report.  They can either be filed directly on an item by clicking on "post a comment" at the end of each item or by sending them to djensen@californiastemcellreport.com. Here is the commentary on the direction of the stem cell agency.Scientis

"With the funding of Quintiles the last piece of the puzzle falls into place. Randy Mills is very proud of the fact that he transformed the company Osiris, which was research oriented, into a product-oriented company.

"Everything he has done since he became president of CIRM has been strategy to turn it into a product-oriented business.

"From start to finish, Mills is refashioning CIRM as a business. The grant applications have now become 'partnering opportunities,' and the researchers receiving those grants take on a role as subcontractors under  CIRM’s control rather than independent scientists.

"With grantees as partners and subcontractors, the next stage in commercialization is to hire a CRO (contract research organization) to funnel through all of the promising products, taking them out of the grantee’s hands.  Quintiles is a huge organization and the $15 million grant is insignificant for them -- they subcontract for drug companies to run clinical trials.  They have no stem cell experience.

"Subcontracting a CRO is a business strategy to avoid investing in employees and technologies the company needs.  The selection of grantees has also become business-oriented:  CIRM is recruiting companies outside California to fund so they can be added to its corporate profile.  Companies have also become the preferred recipients of CIRM grants, even if they are virtual companies set up by academics for the purpose of obtaining CIRM funding.

"CIRM is morphing into a corporation with centralized control, with the hope that the product pipeline will yield something that makes money.  The question is:  was this the intention of Prop. 71?  If so, why wasn’t it always a corporation?" 

(Editor's note: Prop. 71 is the ballot initiative that created the stem cell agency in 2004.)

California Stem Cell Agency Awards $15 Million to Quintiles to Accelerate Stem Cell Therapies

BERKELEY, Ca. -- The California stem cell agency today awarded $15 million to a North Carolina firm to create an organization that would be a key in making California the global leader in clinical application of stem cell therapies.

The five-year contract will go to Quintiles, a publicly traded firm that specializes in shepherding research through clinical trials and over federal regulatory hurdles. The governing board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, voted 13-0 to approve the award.

Randy Mills, president of CIRM, said that the plan to create the operation specializing in stem cells in San Diego would speed development of commercial therapies for widespread use. Mills said that effort "may be the best thing that CIRM does." He said it will give the state a "big competitive advantage."

The award requires that Quintiles begin its work on what CIRM calls an "accelerating center" within 45 days. The company expects to base its effort at its existing facility in San Diego.  It said it will scale up employee levels as needed.

Quintiles, headquartered in Research Triangle Park, N.C., is a Fortune 500 firm with 35,000 employees around the world. According to Wikipedia, it is "the largest provider of biopharmaceutical development and commercial outsourcing services."

No stem cell therapies have yet been approved by the Food and Drug Administration. Mills said that novel nature of the therapies means longer review periods of potential therapies that can run into years. Unforeseen issues also surface in the process of testing stem therapies.

Avi Kulkarni, senior vice president of Quintiles, made an unusual public presentation to the CIRM board prior to action by directors. Applicants are almost never allowed to make lengthy public presentations to the board. Three other unidentifed enterprises applied for the award but failed to be recommended by reviewers.

Kulkarni said the goal of his clinical research organization is to improve the probability of success in developing therapies.  He said the stem cell market is poised for "significant growth." But he said the existing models for therapy development do not serve the market well.

Queried  by Anne Marie Duliege, a CIRM board member, Adrian McKemey, also a senior vice president of Quintiles, said that Quintiles has been involved in 10 to 20 clinical trials related to regenerative medicine.  About half of those deal with stem cells, he said.

The board did not discuss concerns by grant reviewers about what they described as Quintiles lack of stem cell experience and their questions involving the top management of CIRM/Quintiles contract.

CIRM grant recipients will be the first beneficiaries of the Quintiles arrangement and will receive discounts on its services that Mills estimated will total $22.5 million.

The Quintiles executives said they expect to be involved with researchers even prior to formally filing applications. They also said Quintiles will assist in bringing additional stem cell efforts into California.

Here is a link to the CIRM press release on the contract.

(An earlier version of this item, based on incorrect information supplied by a Google search, incorrectly identified Quantiles as headquartered in Colorado.)

Delay on Action on Pay-for-Eggs Legislation in California

Legislation to allow women to be paid when they provide human eggs for research was put off in the state Senate Health Committee this week.

The proposal (AB2531) by Assemblywoman Autumn Burke, D-Inglewood, was not taken up Wednesday as scheduled. Burke asked that the hearing be postponed because two members of the committee were absent, according to Ruff Allison, a spokesperson for her office.  Often that occurs when a measure does not have sufficient support among the members of the committee who are present.

The bill is expected to be taken up in the committee next Wednesday.

$15 Million California Stem Cell Agency Award to Firm Lacking Stem Cell Experience

California's stem cell agency is set to award a key, $15 million contract to a yet to be identified business despite an acknowledgement that the firm "lacks expertise in stem cell clinical and product development."

The five-year award is aimed at helping to make California a world leader in clinical application of stem cell research. It is also linked to the ambitious Alpha Clinic program of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based stem cell agency is known. All CIRM projects initially will receive preferential treatment from the awardee although other outside efforts will be serviced later.

The winning firm is supposed to provide regulatory, operational and consultative services to clinical trial sponsors and "accelerate the regulatory review process and the conduct of high quality clinical trials using stem cell treatments," an agency document said.

The agency's blue-ribbon, out-of-state reviewers gave the firm's application a score of 89 out of 100 during a closed door meeting earlier this spring, according to a presentation prepared for the CIRM board meeting next week. The cut-off line was 85. The other three applicants fell below that level.

A summary of the review published by the agency said,

"The applicant lacks expertise in stem cell clinical and product development."

It stated,

"While there is a lack of stem cell experience in the team, there is a clear commitment and plan to aggregate stem cell expertise and leverage knowledge gained over time to build a center focused on accelerating progression of stem cell projects toward commercialization."

Concern was also expressed about top level management. The summary said,

"Reviewers were not convinced that the proposed center director is sufficiently experienced to direct the CIRM Accelerating Center. However, there is great confidence in the parent organization, which alleviated some of the concerns."

Nonetheless, the reviewers' bottom line indicated that they believed their qualms could be overcome. The summary said,

"Reviewers thought the applicant to be highly capable of delivering the required core services and establishing and sustaining the proposed CIRM Accelerating Center. More importantly, reviewers thought the applicant had given great thought about how best to partner with CIRM to accelerate delivery of stem cell treatments to patients with unmet medical needs by leveraging CIRM Infrastructure Programs and offering innovative and impactful preclinical and clinical development resources to both CIRM and non CIRM-funded investigators."

It is customary for the agency to withhold the names of winning applicants until the board formally ratifies the reviewers' decisions. That will come next Wednesday at the board's public meeting in Berkeley. The names of competing applicants are generally withheld indefinitely by the agency, although the agency has made exceptions.

CIRM reviewers make the de facto decisions on all applications, always behind closed doors. In the agency's 11-year history, the agency's governing board has almost never overridden a positive funding decision by its reviewers.

The reviewers' economic and professional interests, however, are not disclosed publicly. At most state agencies, financial decision-makers are required to disclose their economic interests.

The review process in this case did deviate somewhat from other past practices.  CIRM applicants are normally evaluated based only on a written submission. In this case, however, applicants were permitted to make a 20-minute, face-to-face presentation to reviewers, who then had a chance to ask questions. The agency's regular practice is to withhold the identity of specific reviewers from applicants.

The goal of the "Accelerating Center" is to speed submissions to regulators and assist with clinical trial management, the tests that are conducted before regulators will approve a therapy for widespread public use. The center is also supposed to deal with data management, biostatistical and analytical services.

It will be a key component in the Alpha Clinics Network, a $34 million CIRM project. The Alpha Clinics were pushed forward with the intent of making the Golden State the global leader in stem cells, although the plan was scaled down financially from an original $70 million. (See here and here for more).

Three centers were funded: a combined project involving UCLA and UC Irvine and one each at the City of Hope in Duarte in the Los Angeles area and UC San Diego.

Here is a link to a CIRM presentation made for applicants in the $15 million Accelerating Center round. Here is a link to the CIRM request for applications.

Here is a link to  CIRM's Alpha Clinics Network page with interviews of some of the leaders in the program.

The Human Egg Business: California Lawmakers Consider Paying Women for Research Eggs

If you are interested in the buying and selling of human eggs, you might want to take in a California legislative hearing tomorrow in Sacramento.

Up for action in the state Senate Health Committee is a measure that would permit paying women who provide the eggs if they do so for the purposes of research. The compensation is condemned by some because of the risk of providing the eggs, which requires heavy hormonal stimulation. But legalizing payment is sought by others as an aid to science and  as a matter of equality for women.

Currently women cannot legally be paid in California for providing eggs for research but they can be paid for providing them for fertility purposes. Compensation can range upwards of $50,000, according to an analysis by the Health Committee.

The legislation, AB2531 by Assemblywoman Autumn Burke, D-Inglewood, is sponsored by the fertility industry, which is largely unregulated.  A similar measure was vetoed in 2013 by Gov. Jerry Brown who said,

"Not everything in life is for sale nor should it be."

Burke's bill passed the Assembly April 28 on a 65-3 vote. It now requires full Senate approval before going to the governor.

Opposition to the measure includes Dorothy Roberts, a nationally recognized bioethicist who serves on the research standards group of the California stem cell agency. Also opposed is the Center for Genetics and Society in Berkeley. Marcy Darnovsky, executive director of the group, said this spring, 

"Offering large sums of money encourages women in need to gamble with their health. It’s what bioethicists call 'undue inducement.'"

She noted that the proposed law conflicts with the standards of the California stem cell agency and recommendations of the prestigious National Academy of Sciences.

According to the Senate analysis by Melanie Moreno, Assemblywoman Burke says,

"AB 2531 ensures that women are treated equally to all other research subjects - allowing them to actively evaluate their participation in research studies and be paid for their time, trouble and inconvenience when they do participate. Given that compensation is allowed in 47 other states, and there is no evidence of abuse, it’s time to reconsider our ban, just as New York did." 

For more on paying women for their eggs, see here, here, here and here.

California's Stem Cell Agency Approves Nearly $19 Million Operational Budget

CIRM's budget comparisons. The column in the center reflects estimated final spending for this year.

A key committee of the California stem cell agency today approved an $18.9 million operational budget for its next fiscal year, a nearly 10 percent increase over its current level of spending.

The money will go for such things as salaries, meetings, travel and office supplies at the $3 billion state enterprise. It does not affect the size of its grant program, which has seen the agency hand out roughly $2 billion since 2005.

The increase of 10 percent largely reflects its failure to fill vacant positions at the Oakland-based organization, which has a staff of about 55.

The spending plan was approved unanimously by the Finance Subcommittee of the agency's governing  board with little discussion during a 20-minute teleconference meeting. The budget is expected to be ratified by the full board at its meeting June 15 in Berkeley. It will take effect July 1.

For more on the budget and the agency's unusual 6 percent budget cap, see here and here.

$18.9 Million Spending Plan for California's Stem Cell Agency, Up Nearly 10 Percent

The California stem cell agency is set to approve tomorrow an $18.9 million operational budget for its coming fiscal year to pay for such things as employee salaries and pencils, an increase of nearly 10 percent over its current spending levels.

The budget will come before the Finance Subcommittee of the agency's governing board, which is expected to approve the proposal with few changes. The full board is expected to ratify the budget at its meeting June 15 in Berkeley.

The $3 billion agency operates under 6 percent spending cap imposed by Proposition 71, the ballot measure that created the research effort in 2004. The agency has $180 million (6 percent of the $3 billion) to spend on operational matters over its life, not including research grants. It has run through roughly $105 million.

When the $180 million is gone, that is the end of the money unless the agency can wangle extra cash from the legislature or private sources. Funding for both expenses and research grants is expected to run out in 2020.

CIRM documents show that the 10 percent budget increase over estimated spending for this fiscal year is tied largely to the fact that the agency did not hire as many persons as expected during the current fiscal year.  In the budget proposal, presented by Finance Director Chila Silva-Martin, the agency said it plans to fill out its staff about 55 in the coming year, although retention issues are likely to surface in the next few years because of the lack of funding beyond 2020.

Also playing a role in the bigger budget is a step up in the number of grant review sessions.

The largest expenditure for the fiscal year beginning July 1 -- $13.3 million --  is for salaries and benefits. The figure is up from $11.5 million for the current year. The second largest expense categories come from outside contracting and application reviews and meetings. Both categories have nearly identical totals -- about $1.8 million each. Outside contracting is about the same as last year but reviews and meetings are up from $1.4 million.

The public can listen in on tomorrow's session via a toll-free number. A teleconference site where public comment is possible is located in Irvine. That site is in addition to the main location in Oakland. Full details can be found on the agenda.