Sunday, November 27, 2016

Dubious Stem Cell Therapies Attract Coverage in California's Capital

The leading newspaper in California's state capital this weekend published a lengthy piece exploring the world of unproven stem cell therapies, including one being offered in its own backyard. 

Reporter Claudia Buck of The Sacramento Bee wrote,
"For long-suffering patients...stem cells offer tantalizing hope. In the last few years, more than 570 stem cell clinics have popped up nationwide, advertising treatment for a range of maladies, from autism and Alzheimer’s to neuropathy and Parkinson’s disease, according to a recent UC Davis study. About 113 of those are operating in California. 
"But do they really work? According to most stem cell experts and the federal government, there’s no way to know yet."
Buck quoted Kevin McCormack, spokesman for the California stem cell agency, as saying,
“It’s quite clear that these people are offering treatments that haven’t been tested in clinical trials. It’s a little concerning,”
Buck wrote,
"'My view is that it’s a giant human experiment that doesn’t have FDA approval,' said Paul Knoepfler, a UC Davis stem cell expert, who co-authored the study identifying the 570 clinics. 'I don’t know how much patients are aware of how uncertain the benefits and risks are. As a scientist, it’s worrisome.'"
Knoepfler, who publishes a blog on stem cell matters, has written in the past about advertising in The Bee by a stem cell business called Nervana. The firm was mentioned in Buck's article, which, however, did not note that Nervana has taken out full page advertisements in the past in The Bee.

Knoepfler's most recent piece on Oct. 21 also noted that the firm had taken out a full page ad in the San Diego Union Tribune as well.  The UC Davis researcher said at the time,
"I don’t believe there is a solid, medical or scientific basis for what they are selling."
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Stem Cell Suspense to End Dec. 5 for Four California Researchers

Four California stem cell researchers could well receive a total of $16.6 million in awards next week from the Golden State's 12-year-old stem cell program.

The researchers were caught in a bit of a snafu earlier in November when the $3 billion agency appeared to come up $1.6 million short. The story about the snag also involved quorums, priorities and fiscal discipline, more than is necessary to discuss right here in this item. But you can read all about it here. 

The two researchers identified so far are Yadong Huang of the Gladstone Institutes, Jill Helms of Stanford and Ankasa Regenerative Therapeutics of La Jolla.  The identities of the others are being withheld by the stem cell agency.

Whether all four will receive funding will be determined on Monday Dec. 5 when the stem cell agency's board will hold a telephonic meeting out of its base in Oakland. The agenda gave no indication of how the agency plans to overcome the difficulties that stymied it on Nov. 17.

The public can attend the meeting at the agency's headquarters in Oakland or from telephonic locations in Napa, Beverly Hills, Elk Grove, Los Gatos, Irvine, Sacramento and two each in South San Francisco and San Diego.

The session is also expected to be audiocast on the Internet. More information and addresses can be found on the agenda. Sphere: Related Content

Monday, November 21, 2016

Quartet of Researchers Snagged in Budgeting, Parliamentary Web at $3 Billion California Stem Cell Agency

Highlights
Fiscal discipline at CIRM
The 10 percent solution
A quorum shortage pops up

Four California scientists who are ready to kick off highly rated projects to treat everything from Alzheimer's to rotting jaw bones became tangled last week in a financial and procedural briar patch involving the directors of the $3 billion California stem cell agency.

The basic problem, however, was simple. Money.

The agency had budgeted only $15 million for this latest round of awards last Thursday. But the four applications -- already approved by the agency's reviewers -- totalled $16.6 million. Typically, the agency's full board rubber stamps in public the decisions of its reviewers, who act behind closed doors without disclosing their economic or professional interests. The board has reversed approvals by reviewers on only four occasions out of hundreds of awards over the past 12 years, according to the agency.

Last week, the chairman of the agency, Jonathan Thomas, began the public discussion by declaring that the board should go through the applications one by one and vote on them. When the money ran out, that would finish action on funding for November.

Fiscal discipline was cited as the main reason for such a course.

Steve Juelsgaard 
Wait a minute, said Steve Juelsgaard, a member of the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. He asked for the amount of
funding already being provided for the afflictions targeted by the proposals. If research in a particular area was already heavily supported, perhaps approving another award in that area was not necessary, Juelsgaard reasoned. However, the agency staff could not provide those figures at the time of the meeting.

A lengthy discussion followed involving several scenarios. One would have cut each award by 10 percent but approve all four.  But that could mean that the proposals would be altered from the versions that were approved by the reviewers. (However, the board is not legally required to accept what the reviewers decide.  Under the terms of the ballot initiative that created the agency, the board has the final say, which is part of the justification for not publicly disclosing the economic interests of reviewers.)

Another proposal would have simply increased the funding for the round. That could not be acted on because it required 10 days advance public notice.

The board ultimately approved a Juelsgaard motion to slice roughly 10 percent from each award with the condition that applicants come up with matching funds to bring the total to the level approved by reviewers.

Yadong Huang, Gladstone photo
One applicant, Yadong Huang from the Gladstone Institutes, said, however, that non-profit research organizations were already hard-pressed and could not necessarily come up additional cash. His $5.9 million application (TRAN1-09394) was top-ranked by reviewers and targeted Alzheimer's.

Jill Helms, Linked In photo
Another applicant, Jill Helms, chief scientific officer of Ankasa Regenerative Therapeutics, Inc., of La Jolla, spoke on behalf of the company's application (TRAN1-09270) to target osteonecrosis, an affliction that "causes jaw bones to rot and thigh bones to snap." She urged the board to give priority to applications that already had co-funding. Her $3.7 million application contained a 20 percent co-funding component.

Helms, who is also a Stanford University medical school professor, unsuccessfully asked the CIRM board in 2015 to overturn a negative recommendation by reviewers.

During the two-hour telephonic meeting, the board did approve conditionally two awards under the matching-fund requirement. They were for the Alzheimers proposal and one dealing with sickle cell disease (TRAN1-09292).  The identity of the chief scientist on the sickle cell proposal was not disclosed by the agency under its longstanding policy and tradition within the research field.

Jeff Sheehy, Science photo
The board failed to complete action on the two others because it  lost the quorum that is required to do business legally. That came after a motion by board member Jeff Sheehy to reject one of the four applications failed on a 3-8 vote. Sheehy said another related proposal was already being funded by the agency and that the time to translate the research into a therapy  "would be enormous." The $2.5 million application  (TRAN1-09288) up for consideration last week involved cartilage repair.

Thursday's meeting was being conducted telephonically. After Sheehy lost his motion, he did not respond to telephonic queries from the board. The meeting was nearing its scheduled end at noon. Other board members also failed to respond, and the meeting was adjourned minutes later.

Juelsgaard and some other members said it was important for board members to stick around for the full meetings. Juelsgaard said,
"For gosh sakes, this is something that you signed up to do."
Termination of CIRM board business because of quorum problems regularly occurred some years ago. (See herehere and here.) But since Thomas has been chairman the issue has rarely popped up.

Thomas indicated the board would try to schedule a special telephonic meeting to deal with the four applications. It also has a face-to-face meeting scheduled for Dec. 13 in Oakland. Both meetings legally require 10 days advance notice.

The review summaries on the applications are consolidated in this CIRM document along with their scores and more information.
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Friday, November 18, 2016

$3 Billion California Stem Cell Agency Now Involved in 23 Clinical Trials

The California stem cell agency yesterday pumped $38 million into three clinical trials with the hope that it will lead to therapies for colorectal cancer, "bubble boy" syndrome and a form of high blood pressure.

The action brought to 23 the number of current clinical trials in which the $3 billion agency is participating via funding in whole or in part, according to information on its Web site. It is hoping that one of those trials will produce its first widely available stem cell therapy.

The trials deal with afflictions ranging from HIV and Huntington's Disease to blindness and skin cancer.

The agency's cash for new awards will run out in about three years. The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has been in business since 2004 when voters created the agency through a ballot initiative.

Yesterday's funding was expected and largely reported earlier this week by the California Stem Cell Report (see here and here). Yesterday, the agency's board simply ratified -- in a matter of minutes -- decisions in October by its grant review group, which makes the de facto decisions on awards behind closed doors and without publicly disclosing the economic and professional interests of reviewers.

Here is a link to the press release from the agency and a link to its blog item. Here are links to the review summaries of each proposal: colorectal, bubble boy and blood pressure.

The summaries were the only information that the board had in approving the three grants.

During its telephonic meeting yesterday, the board also became entangled in a budgeting and priorities debate involving four translational research proposals, all of which the agency now says are hanging fire. An effort is being made to schedule a special board meeting soon to deal with the issue, but it requires 10-days advance public notice. The California Stem Cell Report will have a full report later on the situation. Sphere: Related Content

Wednesday, November 16, 2016

Correction

The $20 million "bubble boy" item on Nov. 16, 2016, incorrectly reported that co-funding on the award totalled $8.9 million. The correct figure is $18.2 million. Sphere: Related Content

Tuesday, November 15, 2016

California Pumping $20 Million into Stem Cell/Gene Therapy for 'Bubble Boy' Syndrome

June 2016 video from UCLA

Highlights
30 out of 30 cured
$18.2 million in matching funds
Cells to be frozen
UK's Orchard Therapeutics partnering

California's stem cell agency is ready to award $20 million on Thursday to a UCLA researcher to assist in his 30-year search for a widely available cure for what has come to be known as the "bubble boy" syndrome-- severe combined immunodeficiency (SCID).

The California scientist is Donald Kohn, of the Broad Stem Cell Research Center at UCLA, who said today that 30 out of 30 babies have already been cured using his type of therapy. Kohn said that the research involving the extremely rare disease could lead to progress in treating other afflictions ranging from sickle cell disease to cancer.

The progress in treating the "bubble boy" disease is much changed from decades ago when the case of David Vetter captured the nation's attention as the boy who was "born into a world he could not touch."  He ultimately died at the age of 12. (This item continues below video.)

Kohn's proposal for an early stage clinical trial would be co-funded with $18.2 million and would test a stem cell and gene product known as OTL-101. It could replace what the stem cell agency said were the "suboptimal," current treatments for  Adenosine Deaminase Severe Combined Immunodeficiency.

The affliction is extremely rare and occurs in less than one in 100,000 births worldwide, according to Wikipedia. Without treatment, children can die before the age of two.

The agency's application review summary said that reviewers were "highly enthusiastic" about Kohn's proposal during their closed-door session last month. The summary said that reviewers, who are from out-of-state and do not publicly disclose their economic interests, "applauded the move to a cryopreserved product that will allow improved patient access to the therapy." They also noted that the costs of the trial are "exceedingly high."

In response to a query by the California Stem Cell Report, Kohn said today via email, 
"Building upon the previous success of our single-site trials for ADA SCID, which have resulted in 30 out of 30 babies cured, our next trial will focus on developing a cryopreserved formulation of the cell product. 
"This has several potential advantages. It will allow the cell product to undergo full testing before the transplant is performed, whereas currently we only have stat viability, sterility and endotoxin assay results, with gene transfer efficiency measurements coming later.
"Additionally, it provides more time to split up the dosing of the conditioning chemotherapy and individually adjust the total dose based on measurement of the individual patient's unique drug clearance activity.
"Finally, this will allow centralization of cell processing, allowing patients to remain at their local hospital for the treatment, with the stem cells traveling to a commercial cell processing site, gene-corrected, frozen and shipped back to their hospital for infusion."
The agency's board is virtually certain to ratify the decision of reviewers at its telephonic meeting on Thursday. It has almost never overturned a positive recommendation by reviewers. 

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), did not release Kohn's name in advance of the Thursday meeting. Its policy, with some notable exceptions, is to withhold that information until the pro forma vote by its governing board. The California Stem Cell Report identified Kohn as the recipient through a number of public documents. The UCLA researcher has already received $32 million from CIRM for his work. 

Kohn has teamed with Orchard Therapeutics Ltd. of Britain, a firm that began operations last May with a $33 million war chest. Kohn is one of the scientific advisors to the company. He said today: 
"This study is being done at the UCLA Broad Stem Cell Research Center in partnership with Orchard Therapeutics Ltd., who have licensed this stem cell gene therapeutic from UCLA and University College London, UK. The general approach of stem cell gene therapy was first done for ADA SCID, which is a highly favorable disease for this treatment. Findings and advances made for this disorder are being applied to many other inherited diseases, such as Sickle Cell Disease, other Primary Immune Deficiencies, Storage and Metabolic Diseases, as well as HIV/AIDS, cancer and leukemia."
The process uses a patient’s own stem cells. Earlier this year, the company said that the cells are "modified with a functioning copy of the missing or faulty gene before being transplanted back into the patient’s body. The use of the patient’s own cells (autologous) removes the need to search for a matching stem cell donor, which can take months or even years," the company said.

Should the treatment emerge successfully from the clinical trials, it will face competition from a rival developed by GlaxoSmithKline that has been approved for use in Europe at a reported cost of $665,000 per patient. Glaxo is expected to seek approval next year for use of the treatment in the United States, which has only about 12 new cases a year, according to the STAT health science news service. However, a document from the U.S. Center for Disease Control places incidence at 40 to 100 new cases each year. 

The public can participate in Thursday's meeting at locations in Oakland, San Francisco, San Diego, Napa, South San Francisco, San Francisco, Beverly Hills, Fresno, Elk Grove, Los Gatos, Sacramento, and Irvine.  It is also being audiocast on the internet. Instructions and addresses can be found on the agenda.

(Editor's note: An earlier version of this item incorrectly reported that co-funding on this award totalled $8.9 million. The correct figure is $18.9 million.)
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Monday, November 14, 2016

$10 Million 'Eat Me' Award: California Stem Cell Agency to Firm Called Forty Seven

The California stem cell agency is set this week to award $10 million to a Menlo Park firm to help finance a clinical trial for a therapy for colon cancer, which is the second leading cause of cancer death in this country.

The cash will go to Forty Seven, Inc., an enterprise using an immune system, "eat me" technology developed at Stanford University by stem cell scientist Irv Weissman. The firm is adding $6.8 million of its own cash to the project. Weissman has received $30 million over the years from the state agency.

The application to help with an early stage clinical trial was unanimously approved by the agency's scientific reviewers during a closed-door meeting last month. The full board will ratify the action at its telephonic meeting this Thursday. 

The agency, formally known as the California Institute for Regenerative Medicine(CIRM), has almost never overturned a positive decision by its reviewers.

The $3 billion agency does not release the names of successful applicants prior to board action. Forty Seven was identified through the use of public records.

According to a federal Web site,
"This trial will evaluate Hu5F9-G4 in combination with cetuximab. Hu5F9-G4 is a monoclonal antibody which is designed to block a protein called CD47, which is widely expressed on human cancer cells. Blocking CD47 with Hu5F9-G4 may enable the body's immune system to find and destroy the cancer cells. Cetuximab is a monoclonal antibody drug that is used for treatment of certain types of colorectal cancer as well as head and neck cancer."
The idea is to override a tumor's "don't-eat-me" signal and instead trigger the body's "eat-me" response.

California's scientific reviewers expressed high praise for the project. However, they also said,
"The design of the trial itself is fine, but the decision-making process is sub-optimal. It is critical to include clear go/no go criteria for the second phase of the trial and for the data to be evaluated by an independent, objective third party for a decision as it is unclear what toxicities are expected given the proposed new mechanism of action and use of a combination therapy." 
Forty Seven announced last February that it is backed by $75 million from a variety of partners including Google. Others in the venture capital group are Lightspeed Venture Partners, Sutter Hill Ventures (the two leaders on the financing) and Clarus Ventures.

In August, Karen Tkach wrote in BioCentury:
"With companies lining up to block CD47 for cancer, the cell surface protein is emerging as one of the top new targets in oncology. But the list of suitors could be about to get a lot longer as the target could have uses in a much broader range of indications, according to two studies from Stanford University that extend its prospects to cardiovascular disease and transplant biology, and hint at roles in several more diseases."
According to the clinical trial information on a federal Web site, Forty Seven will have clinical trial locations in Grand Rapids, Mich.; San Antonio, Texas, and Nashville, Tenn.  The California stem cell agency is limited to spending its award for work done in California. 

The federal information has conflicting indications on whether patients are currently being recruited for enrollment in the trial.

(In response to a query following publication of this item, Mark Chao, a co-founder and medical
Mark Chao, Stanford photo
director of Forty Seven and co-PI on the trial, said,
"We have been excited about the positive reviews by the CIRM committee and hope to hear good news on Thursday. Thank you for sending this article. With regards to initiating California clinical sites on the trial, this is a very big point of emphasis for us, in particular with CIRM’s mission and are currently working to activate two sites in California (Stanford University and UCLA) for the trial. One of our goals are to bring this therapy to patients within California and have designed our trials with this in mind. Please let us know if there are any further questions we can address. We look forward to a long relationship with CIRM.")
The chair of the study is Chris Takimoto of Forty Seven. The CIRM application number is CLIN2 -09577.
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Friday, November 11, 2016

Trump's 'Ouija' Stem Cell Policy Is Making Scientists Anxious

One of the bulwarks of the mainstream media today weighed in with a hefty assessment of Trump and stem cells, declaring that researchers are "anxious" about what is likely ahead.

Prominently mentioned by ABC News was Vice President-elect Mike Pence, who supported legislation in Indiana banning donation of fetal tissue for research. That law, signed by Pence as governor of Indiana, was temporarily halted by a judge, who questioned its constitutionality.

Alta Charo, a bioethicist and law professor at the University of Wisconsin, was quoted as saying that trying to determine what Trump's stem cell policy might be is a "little bit like using a Ouija board." But she did point to Pence's fetal tissue position.  Additionally, Trump has taken a pro life position on abortion.

Also cited in the article at some length was a spokesman for the $3 billion California stem cell agency, which owes its existence to presidential restrictions on human embryonic stem cell research. ABC reporter Gillian Mahoney wrote,
 "Kevin McCormack, communications director at California Institute for Regenerative Medicine, said reintroducing a funding ban to stymie research would likely be more difficult than it was in the early 2000s when stem cell research was a new field.
"'It would be like putting a genie back in the bottle,' said McCormack.
"Pointing to one case at the University of Southern California, where a paralyzed man regained hand movement after an experimental stem cell therapy, McCormack said any measures that would halt funding or restrict stem cell research wholesale, 'would be like going up to someone and say you can't have that treatment.'
"McCormack did note that more states have provided stem cell funding, including California, which provides grants for the California Institute for Regenerative Medicine. While state funding could help, the NIH provides a huge amount of funding for U.S. medical research, spending approximately $32 billion on medical research annually."
(Editor's note: The state does not provide grants for the stem cell agency. The agency uses state bonds to provide grants to researchers.  The agency's funding flows straight to it without intervention by lawmakers or the governor.) Sphere: Related Content