Friday, June 24, 2016

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.'"
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Thursday, June 23, 2016

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.”
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Monday, June 20, 2016

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. Sphere: Related Content

Friday, June 17, 2016

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.)
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Wednesday, June 15, 2016

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.)
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Friday, June 10, 2016

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. Sphere: Related Content

Thursday, June 09, 2016

$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.
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