CIRM Creates FDA Committee

Gern Talk, a web site devoted to discussions of matters related to Geron, has picked up a recent piece by patient advocate Don Reed along with our report, "Harsher Realities," on the FDA hold on Geron's clinical trials.

Reed raised his previous concerns regarding the most recent FDA action. But he also had a note about a discussion involving the FDA hearings last month dealing with clinical trials and stem cells.

That discussion occurred at the meeting of the board of directors of the California stem cell agency. Reed said that Robert Klein, chairman of the California stem cell agency "expressed concern" about

"...a possibility that the FDA might put in a condition that embryonic stem cell trials might only be allowed for dying patients. This would be a disaster, meaning that human trials for embryonic stem cells to heal blindness as well as paralysis and other non-life-threatening conditions could not go forward. He asked for volunteers on the board to be on a special FDA committee. Board members Jeff Sheehy and Leeza Gibbons very kindly volunteered for the chore!

"But the overall response from almost everyone (and these are supporters of the research, good people, whose opinions I respect) was that the situation would be handled on the basis of scientific merit, and the safety of the patients, nothing more. Again and again people said, no, no, everything is fine, don’t worry."

Jesse Reynolds of the Center for Genetics and Society also had something to say on the Biopolitical Times on Geron:

"Those of us who support embryonic stem cell research should urge caution, not haste. A botched clinical trial will set the field back years, if not decades."

CIRM Affordable Access Bill Easily Clears Senate

On a unanimous 40-0 vote, the California State Senate has passed legislation to ensure affordable access to CIRM-financed stem cell therapies and to require a study that could lead to reforms in the agency's complex and unique structure.

The measure (SB 1565) by Sen. Sheila Kuehl(see photo), D-Santa Monica, now goes to the Assembly for further action.

The bill was on a "special consent" calendar Thursday, indicating that no controversy existed concerning it. There is no indication that there was any debate on the measure. The California stem cell agency has taken no position on the legislation.

For more on the bill, see the "patient advocate" item below.

The Harsher Reality of the FDA Hold on Geron

At least one analyst is minimizing the impact of the FDA's hold on Geron's clinical trials for its human embryonic stem cell product.

Ren Benjamin, an analyst with Rodman & Renshaw in New York, told Bloomberg News earlier this week said that he thinks the company will "be able to work through the issues with the FDA."

However, the reality is likely to be a tad harsher. The hold is the second pronounced signal in two months from the FDA that it wants to proceed with extreme caution on hESC trials. And the action has stirred some concerns in the patient advocate community, which has pressed for more speed on the research.

Even prior to the Geron hold, Don Reed, vice president for public policy for Americans for Cures, worried about the FDA posture on his blog, stemcellbattles.com. He wrote on May 6,

"The FDA hearings on embryonic stem cells have been (in my view) deeply politicized, setting the stage to block human trials, an enormous setback."

He continued,

"A laundry list of new conditions may send...Geron, Advanced Cell Technology, and Novocell, and the entire embryonic stem cell research field back to the drawing board, conceivably for
decades."

Reed referred to the FDA hearings last month during which the bugaboo of teratomas was raised by the FDA. Monya Baker of Nature's Niche stem cell blog covered the meeting. On April 11, she wrote that the consensus from attendees at the meeting was that the FDA "seems cautious about moving forward, but not spooked."

But then came the FDA hold this week. It had to be a bitter pill for Geron. Thomas Okarma, CEO of the company, said that the company had spent four years working with the FDA and amassed 21,000 pages of documents to alleviate the agency's concerns.

Geron's stock took a big hit on the day the hold was announced, dropping to a 52-week low of $3.76. It stood at $3.97 at the time of this writing, compared to a 52-week high of $9.85.

Geron has been mum since Okarma's statement along with Novocell and Advanced Cell Technology, although we have asked for comments from all three. We are likely to hear more from Geron after it receives the FDA's written concerns.

As for analyst Benjamin's somewhat optimistic position, his firm is a market maker in Geron stock, which means that it has a stake in the company's well-being.

Affordable Access to CIRM Therapies: A Patient Advocate's Position

For a patient advocate's take on legislation aimed at ensuring affordable access to CIRM-financed therapies, take a gander at the May 13 posting by Don Reed on his blog, stemcellbattles.com.

Earlier this week, Reed (see photo) was the only person to testify before the state Senate Appropriations Committee on the measure, aside from the bill's author, Sen. Sheila Kuehl, D-Santa Monica.

Reed's view is that CIRM's regulations, which can be easily changed unilaterally by CIRM, are sufficient to provide affordability. He also contends that an outside study of CIRM's structure is unnecessary and that its built-in conflicts are only a "convergence of expertise." We should note that last week most of the experts on the panel were barred by law from even discussing -- much less voting on -- $271 million in grants because of their conflicts of interest.

Reed is a regular at meetings of the board of directors of the stem cell agency and is vice president for public policy for Americans for Cures, the private advocacy group directed by CIRM Chairman Robert Klein.

Kuehl's bill, SB 1565, was approved 14-0 by the committee and is now on the Senate floor. In addition to codifying in state law affordable access, the measure would require an independent study of CIRM by a state agency known as the Little Hoover Commission with recommendations for reform.

A note on the analysis from the Appropriations Committee says that the Little Hoover staff contends that the legislature does not have the legal authority to direct its work. An opinion as been requested from the Legislative Counsel's office on the question. However, the Legislative Counsel works for the legislature and is inclined to find ways for lawmakers to do what they want.

Here is a link to the floor analysis available to California state senators as they consider the measure.

(Editor's note: After this item was posted, we learned that the bill passed the Senate on Thursday on a 40-0 vote. It nows goes to the Assembly.)

Complete Okarma Statement on FDA Hold

Here is the full text of the statement by Geron CEO Thomas Okarma(pictured) on the FDA's "verbal" hold on the firm's proposed clinical trials.

"We have not yet received a letter from the FDA explaining the decision to place the submission on hold, so we are unable to comment specifically. Once we have the letter and have had a discussion with the agency, we will communicate our findings and our thinking to shareholders. We are disappointed with this action given the interactions we had with the FDA over four years leading to the filing, and the breadth and depth of the submission, some 21,000 pages, predicated on those discussions with the agency."

The company's entire four-paragraph press release can be found here.

Fresh Comment

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FDA Says Whoa to Geron

The FDA slammed on the brakes today on Geron, which had been hoping to launch clinical trials this year on a treatment for persons with spinal injuries.

News reports said it was unclear why the FDA imposed the clinical hold on the test, but it is good bet that the action could be linked to the FDA's hearings last month on stem cell clinical trials. Cautionary notes seemed to be the order of the day at the session.

Geron said it was disappointed in the action. The company's stock plummeted nearly 20 percent following the news, closing $3.94.

Steve Johnson of the San Jose Mercury News and Monya Baker of the Niche blog for Nature magazine both wrote today about the FDA action.

Baker covered the FDA hearings last month and produced the most comprehensive reports on the proceedings. She has links to all her coverage in her Geron item today, plus a link to her interview with the Marie Csete, chief scientific officer for the California stem cell agency, concerning the issues involved in placing stem cells in persons.

Media Play: Harvesting Organs vs. Building Stem Cell Labs

One of the top five stories last week on Bioethics News was the New York Times report on California's awards of $271 million to build new stem cell labs, according to the site's blog.

The story ranked No. 3 in popularity. However, the blog reported that the piece lagged well behind the No. 1 story, a USA Today article on a New York City plan to equip ambulance crews to prep bodies for organ harvest -- before receiving consent from families.

Half-Billion-Dollar Biotech Loan Proposal Moves to Finance Committee

How do you turn $500 million into as much as $1 billion over 10 years? Loan it to struggling biotech companies that could default on the loans at a rate of up to 50 percent.

Sound too good to be true? Maybe, but that's what the California stem cell agency is projecting for what appears to be the most optimistic scenario for its proposed biotech loan program.

The program came up for discussion last week at the CIRM directors meeting. John M. Simpson of Consumer Watchdog attended the session and filed an item for his group's blog. Simpson wrote that the concept "appears promising" but he still had questions.

"The main one is with CIRM's limited staff, how will loan applications be adequately vetted? Robert Klein, chairman of the stem cell agency's Independent Citizens Oversight Committee (ICOC), has suggested using outside 'designated underwriters.' Lots more needs to be made clear about how that would work and how conflicts will be avoided."

We have written previously about the same concerns. But with the new economic models that were laid out last week, a need has arisen for a sharp-eyed, detached business analysis of the plan. It would also be useful to see that analysis in a form that is reasonably accessible. The documents available so far on the latest agenda of the Biotech Loan Task Force are fairly technical and somewhat incomplete. For example, they do not explicitly lay out a range of scenarios from the best to the worst.

Two fundamental questions are yet to be addressed about the biotech loan program: Is it a "good way" to turn $500 million into $400 million or less -- instead of $1 billion? And what is the likelihood that might occur?

Risk cannot be removed from this intriguing plan, but it should be fully understood.

The biotech loan program has been sent to the CIRM Finance Committee, which could hold hearings over the next couple of months. The hope is that the biotech loan program could be launched in the disease team program grants in the spring of 2009.

Fresh Comment

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CIRM Response on Audit

Earlier this afternoon we asked Don Gibbons, chief communications officer for CIRM, if the agency had any comment on the state controller's audit(see item below). Here is his response.

"We are thrilled that the auditor found that our policies and procedures are working. The one minor issue related to specialists who call in to assist in grant review and signed conflict forms prior to the call, but not afterward, and that fix was put in place already at the April 9-11 grant review session."

New CIRM Audit and Foxes and Chickens

California's top financial officer today said the "administrative processes and expenditures" of the state's stem cell agency are "proper" and in compliance with the Prop. 71, the ballot initiative that created the agency in 2004.

The audit by the office of state Controller John Chiang made one recommendation. It involved CIRM's grants working group, where specialists failed to follow a policy requiring them to sign post-review certification forms that cover conflicts of interest, confidentiality and non-disclosure of information. CIRM said it agreed with the recommendation and has taken steps to correct the situation.

"Big deal,” said John M. Simpson, stem cell project director for Consumer Watchdog. He added,

"Under Prop. 71, none of these disclosures are open to public review. They should be."

Chiang (see photo), who is a Democrat and was elected by statewide vote, ordered the audit last year following stories about violation of conflict of interest rules by a CIRM director (first reported by the California Stem Cell Report). However, the scope of the audit was limited largely to accounting and compliance matters because that falls within the scope of the controller's office.

Simpson said in a news release that the audit ignored "fundamental flaws" at the agency.

"The problem is that Prop. 71 deliberately created an oversight board that is fraught with conflict," said Simpson.

"The board is dominated by representatives of the very institutions that will receive most of the $3 billion in research funds handed out. Controller Chiang found that CIRM is following Prop. 71’s rules, but those rules specifically put the foxes in charge of the chicken coop."

The audit did refer peripherally to the investigation by the state Fair Political Practices Commission into complaints of conflict of interest violations by CIRM Director John Reed. Chiang and Simpson asked for the FPPC probe, which is not yet complete. The controller's report said,

"The FPPC investigatory procedures may disclose additional issues, facts, and circumstances beyond the matters noted in our review, as our review was not an investigation."

CIRM President Alan Trounson, in a response to the controller's office, said that CIRM was "pleased by the many positive findings."

"It is of overriding importance to us to ensure that California have full confidence in the integrity of the processes we use to commit public funds to stem cell research."

Release of the audit came on the same day as the state Senate Appropriations Committee unanimously approved, 14-0, legislation by Sen. Sheila Kuehl, D-Santa Monica, aimed at ensuring that Californians have affordable access to CIRM-financed therapies. The measure, SB1565, would also require a study next year aimed at policy issues concerning CIRM, including its difficulties with conflicts of interest. The bill now goes to the Senate floor.

Chiang's audit will be reviewed by the Citizens Financial Accountability and Oversight Committee on July 7 in San Diego. That group was created by Prop. 71 to examine CIRM procedures.

CIRM To Invest $66 Million in Intellectual Capital

The California stem cell agency will soon embark on a new, $66 million round of training grants, including some aimed at undergraduates and possibly community college students.

CIRM directors last week approved initiation of the programs, which were overshadowed by $271 million in lab construction grants. Only one news report surfaced on the training effort.

Bradley J. Fikes of the North County Times, which circulates in northern San Diego County, reported about the $18 million effort aimed at roughly 100 students below the doctoral level. He wrote:

"State universities and community colleges got an invitation last week to join California's stem cell research program."

The "Bridges to Stem Cell Research" grants aimed at undergraduates will total roughly $18 million. The program was foreshadowed by a $31 million proposal by the state college system last year, which had the effect of jump-starting the latest effort.

Also approved last week was a $48 million continuation of the training programs already underway for CIRM Scholars. Those grants were the first ever approved by CIRM.

While the training dollars are smaller than those in the lab program, they represent an important investment in intellectual capital. And they come at a time when the state is otherwise scrimping on higher education.

The "Bridges" program triggered a light moment last week at the directors meeting chaired by Robert Klein, a multimillionaire, real estate investment banker.

John M. Simpson, stem cell project director for Consumer Watchdog, reported that Ted Love(see photo), a member of the board of directors and CEO of Nuvelo, Inc., said CIRM should not judge the success of the program by only counting the number of participants that get laboratory jobs.

"Who knows?" asked Love. "Maybe one of these students will end up being a multimillion dollar real estate mogul who supports stem cell research."

"It brought the house down," Simpson said.

Requests for applications for the training program are expected to be posted on the CIRM website in June. Cash should start flowing in 2009.

Media Coverage, Lab Needs and a Proposal for a New CIRM Mantra

Here are a few more links to some of the Internet coverage concerning the CIRM meeting this week during which directors awarded $271 million in lab construction grants for stem cell research.

Chronicle of Higher Education -- Jeffrey Brainard put together a bit of an overview, including discussion of conflicts of interest at CIRM.

The Niche, blog of Nature Reports Stem Cell – Monya Baker touches on some of the aspects of the media coverage and the need for the labs.

The Biopolitical Times, blog for the Center for Genetics and Society – Jesse Reynolds critiques stories by the Los Angeles Times and San Francisco Chronicle on the lab awards.

Consumer Watchdog -- John M. Simpson says the CIRM board of directors should begin each meeting by repeating the following quotation from Claire Pomeroy, one of its members and dean of the UC Davis School of Medicine, "All Californians are paying for Prop. 71 so all should benefit from it."

Consumer Watchdog Rethinks Stand on Klein's Private Contact with Grant Applicants

The man who probably has spent more time than any other independent observer physically watching the affairs of the California stem cell agency now believes that CIRM Chairman Robert Klein did not violate the agency's no-contact rule with grant applicants. We disagree.

It is a change of position for John M. Simpson, stem cell project director for Consumer Watchdog. Earlier he responded to questions from the California Stem Cell Report about Klein's actions, which you can read all about here, by saying there could have been a technical violation.


Simpson now says,

"Upon further reflection, I don't believe Bob Klein violated the Facilities Working Group bylaws when he played a role in negotiating discounts if applicants take all the CIRM money upfront.

"First, the applications were no longer before the Facilities Working Group. The group's work was done.

"Second, the discussions weren't focused on specific applications but on a discount rate that would apply to all equally if accepted.

"Not that it's relevant to whether there was a technical violation, it's also the case that everyone at the meeting -- including me - understood from the discussions that Klein would be involved in the negotiations."

However, the ban in the bylaws does not permit conditions. Drafted by CIRM's outside counsel, James Harrison, the single sentence states flatly:

"Members of the Facilities Working Group shall not communicate with an applicant about an application to CIRM."

The facilities group work is not really done until the CIRM board of directors act. The board has absolute authority over grant approval, as CIRM likes to point out. Directors could well send a recommendation back to a review group for reconsideration.

Another possibility: Sometimes, reviewers make a recommendation that basically says a grant should be funded if there is enough cash. Let's say a reviewer, following the review group action, decides that the applicant needs a little guidance to help bring about directors' approval. He or she could contact the applicant and give them suggestions on how to successfully approach the directors. Under Simpson's construct, that certainly would be permissible.

In this particular case, Klein's proposal to stretch CIRM funds was inventive and successful. But, in our view, he violated the bylaws to do it, although it seems at this point to have created no harm. Nobody is arguing he performed a dastardly deed.

However, bylaws are in place for a reason. If they are violated on relatively minor matters, what does that mean ultimately for CIRM's credibility and integrity.

CIRM Conflicts: Comments from the Cerberus

The California stem cell agency is bit of a strange beast politically and governmentally speaking. It was deliberately created that way by those who drafted Prop. 71, which established the agency in 2004.

While the trend in government in the past few decades has been towards minimizing conflicts of interest, the voter-approved initiative installed them in spades when it created CIRM's 29-member board of directors. And there is virtually nothing that the ordinary branches of government, such as the governor or the legislature, can do about it. To alter the law concerning CIRM requires a state constitutional amendment or a nearly equally unattainable super, super-majority vote of the legislature –70 percent.

John M. Simpson, stem cell project director for Consumer Watchdog, commented on the conflicts today in his blog after attending two days of meetings of the directors earlier this week. Here is part of what he wrote:

"Only seven members (out of the 29 positions) could vote on the overall grant awards Wednesday -- all the rest had to recuse themselves. They couldn't even talk about the proposals. Besides the members of the board who hold their seats by virtue of their academic roles, several patient advocate members were conflicted because they work for academic institutions that had requests pending. One member is a UC regent."

One of the justifications for placing persons with conflicts on the board was to tap their knowledge and expertise. Obviously, that did not occur earlier this week. Instead they were gagged by state law.

The conflicts and recusals also meant that it would only take a majority of four to hand out $271 million in taxpayer funds. No vote tally was announced by CIRM in its press release, but it is fair to assume that all seven voted in favor of the grants, a foregone conclusion since last December.

CIRM's board of directors have only overturned the positive decisions of its grant reviewers on one occasion and never on their negative decisions, which raises other good government issues. Discussion of that will have to wait for another day.

Pravda to Marin: A Look at Media Coverage of CIRM's Stem Cell Grants

The California stem cell agency's $271 million lab construction effort gained additional attention today, ranging from Pravda in Moscow to Merced in the fields of California's agricultural central valley.

Some stories, including those in the New York Times and on the Xinhau news service, did not use CIRM's $1.1 billion figure for the total impact of the grant program, which includes additional contributions required by CIRM of the applicants and other expenditures that are linked to the labs.

Many of the stories in California focused sharply on the local angles in the program, rather than the national and international implications. In an odd story, Pravda, for reasons difficult to understand, zeroed in on UC Davis.

One editor for an international news organization told us he considered the grant announcement a "local" story, which I told him was shortsighted. Adding 800,000 square feet in research facilities to house 2,200 scientists is likely to have a significant impact in the global stem cell arena for decades to come.

Here in California, it was important news locally as well.

Terri Somers of the San Diego Union Tribune reported primarily about the San Diego Consortium for Regenerative Medicine and its $115 million research center. CIRM is popping for only $43 million of the total. She wrote:

"'The fact that we want to build a stem cell research facility here in San Diego and the state is willing to give us $43 million to help make that happen is pretty good,' said Louie Coffman, the consortium's vice president. 'Forty-three million dollars is a pretty good head start.'"

While Coffman is out beating the bushes for cash, he said the consortium plans to seek a loan. The facility includes extra lab space that it could rent to pay off debt.

Richard Halstead of the Marin Independent Journal also reported on the fundraising tasks ahead. He said,

"Now that it has the grant, the Buck Institute must figure out where it is going to find the other $20.5 million it will need to construct the building, plus at least another $1.4 million to stock it with equipment.

"'That is a big question,'said James Kovach, president and chief operating officer of the Buck Institute."

Halstead continued:

"Kovach said he will pursue several options simultaneously. He said philanthropic foundations that have adopted a results-oriented approach - 'what has been termed venture philanthropy' - should be interested in funding such a project."

Overall, a search this morning on the term "California stem cell laboratoraties" generated roughly 60 to 70 stories on Google News. Here are links to other stories: San Francisco Chronicle, Sacramento Bee, San Jose Mercury News, North County Times (San Diego area), Merced Sun Star, Madera Tribune, GlobeSt.com, Santa Cruz Sentinel, Earthtimes and Entrepreneur.com.

Fresh Comment

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Beating the $1.1 Billion Stem Cell PR Drum

Most recipients of California stem cell largesse were quick to post news releases today dealing with their construction efforts backed by the state's stem cell agency.

UC San Francisco offered the most razzle-dazzle with multiple renderings, a campus map and a video. UC Irvine had a video as well. All the news releases offered a quick look at the specific impact at each location. More and technical details can be found in the applications themselves on the CIRM web site.

Here are links to all the recipient press releases we could find late this afternoon.

Buck Institute
San Diego Stem Cell Consortium – no release at the time of this writing
Stanford
UC Berkeley
UC Davis
UC Irvine
UCLA – no release at the time of this writing.
UC Merced
UC San Francisco
UC Santa Barbara
UC Santa Cruz
University of Southern California

NY Times, San Diego UT and More on Golden State's Stem Cell Labs

The New York Times and some California media carried stories this afternoon on the landmark, $1.1 billion lab construction program triggered by the California stem cell agency. More is expected on Thursday.

Andy Pollack of the New York Times wrote:

"California has awarded $271 million in grants to build 12 new stem cell research centers in the state, even as one of the political rationales for the building program might soon disappear."

Pollack reported that California stem cell Chairman Robert Klein and others say, however, that "even if the restrictions were lifted, new laboratory space would be needed to expand research and to recruit scientists, who are already flocking to California because of the availability of research financing."

Terri Somers of the San Diego Union-Tribune wrote an online piece this afternoon that will probably be updated in the print version Thursday morning.

KNBC TV (channel 4) and three other Los Angeles TV stations (7, 11 and 18) covered the news conference and presumably will have coverage this evening. Here is a link to the KNBC online version.

The San Francisco Chronicle and San Jose Mercury News this afternoon used The Associated Press story. They may staff written stories tomorrow.

The Sacramento Bee carried a staff-written online piece and is also likely to have more later.

Ron Leuty of the San Francisco Business Journal weighed in with a piece that was circulated nationally via the national news network linking business journals.