Sunday, May 20, 2018

A Stem Cell "Nose Job" and Updates on Regulation of Questionable Stem Cell Clinics

Tracking the latest on dubious stem cell clinics, the feds and the implications across the nation can be a bit of consuming task, if you are interested in that sort of thing.

But one Internet site does a pretty good job of keeping up with it. Here is what popped up last week on The Niche, which is based out of UC Davis.
  •  A Q&A with a Georgia law professor concerning the federal crackdown on unregulated stem cell clinics. 
  • A quick look at activities regarding the state of Washington's new law on stem cell clinics, the failed state regulatory attempt in the stem cell "hot bed" that is Florida plus questions about enforcement of California's new stem cell clinic law. 
  • A video of a presentation by an unregulated stem cell clinic which discussed a product described as a  "magic concoction" that is sprayed up the patient's nose.  
Paul Knoepfler is the UC Davis stem cell researcher who produces The Niche and has long written about the dubious clinics that have proliferated across the nation, with the most in California. 
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Thursday, May 10, 2018

Feds Crack Down on Unregulated 'Stem Cell' Clinics, Including One in California

The Food and Drug Administration has moved to shut down two businesses that offer "stem cell" treatments, including one operation based in California,  following reports that some patients were blinded by treatments.

The lawsuits yesterday were characterized as "historic" by one California stem cell researcher, who has been reporting on unregulated and unproven "stem cell" treatments for several years. 

The firms involved are U.S. Stem Cell in Florida and California Stem Cell Treatment Center and its proprietors, physicians Mark Berman, a cosmetic surgeon, and Elliott Lander, a surgeon and urologist. The California enterprise has locations in Beverly Hills and Rancho Mirage with affiliates in 100 locations around the country.

Michael Hiltzik wrote in the Los Angeles Times,
"The lawsuits are the most aggressive steps yet taken by government regulators against rapidly proliferating stem-cell treatment clinics pitching scientifically unproven therapies to desperate patients, some with terminal illnesses. The lawsuits were filed at the request of the Food and Drug Administration, which last year announced that it would take a stern approach to what it described as the manufacture and use of unlicensed drugs."
Researcher Paul Knoepfler of UC Davis has been raising questions about unregulated and unproven stem cell treatments for a number of years. Writing yesterday on his blog, he called the federal action "historic." He said the suits could mark "a turning point for dealing with the for-profit stem cell clinic problem in the U.S."

Here are links to other stories on the lawsuits, which received national attention: Washington Post, The Associated Press and STAT. The Associated Press was carried by the New York Times and many other outlets online. The Times also carried this story by its own reporters.  Here is a recent column by Hiltzik on the California Stem Cell Treatment Center. The headline on the colum says "Patient lawsuits, federal investigations and a 'virtual' PhD: Inside a would-be stem cell empire." 

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Wednesday, May 09, 2018

Removing the Barriers to Widespread Use of Stem Cell Treatments

If you are really interested in delivering stem cell therapies to the marketplace, the place to be early next month is in Los Angeles at a major, international conference that will examine the bottlenecks that stand in the way of bringing the treatments to the public at large.

The California stem cell agency, which is spending $3 billion to create therapies, says that "key unresolved issues" must be addressed before safe and effective therapies reach the mainstream.

The stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), is co-sponsoring the two-day event June 5 and June 6 with the The International Alliance for Biological Standardization.  The session is drawing speakers from around the world. 

Abla Creasey, CIRM photo
Earlier this year, Abla Creasey,  vice president of therapeutics and strategic infrastructure at the agency, said, 
“The field of stem cell research and regenerative medicine has matured to the point where there are over 900 clinical trials worldwide. It is critical to develop a system of effective regulation of how these stem cell treatments are developed and manufactured so patients can benefit from future treatments.”
Her comments appeared on the agency's blog, The Stem Cellar, in an item written by Geoff Lomax, senior officer for CIRM strategic initiatives. Lomax also quoted Martin Pera, a professor at the Jackson Laboratory in Maine and who also directs the International Stem Cell Initiative Genetics and Epigenetics Study Group, and Robert Deans, chief technology officer of Blue Rock Therapeutics, Inc.,  of Cambridge, Mass.

Pera said,
“Participants at this meeting will survey and discuss the state of the art in the development of definitive assays for assessing the safety of pluripotent stem cell based therapies, a critical issue for the future of the field. Anyone active in cell therapy should attend this meeting to contribute to a dialogue that will impact on research directions and ultimately help to define best practice in this sector.”
Deans said,
“I believe standardization will be an increasingly crucial element in securing commercial success for regenerative cell therapies. This applies to all facets of development, from cell characterization and patent protection through safety testing of final product. Most important is the adherence of players in this sector to harmonized standards and creation of a scientifically credible market to the capital community.”
Here is a link for registration.
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Monday, May 07, 2018

Golden State's Stem Cell 'Value:' Bubble Boy Disease and Bringing a Therapy to Market

California's $3 billion stem cell agency today performed a double, PR whammy in an effort to create a greater public understanding of the "key role" it can play in the most expensive and critical steps in creating a therapy that is widely available to the public.

The agency's pitch comes as it faces its potential demise in two years unless it is successful in raising more funds for its operations.

Donald Kohn, UCLA photo
The agency's starting point today involved research for cures for an affliction that has received highly visible, albeit intermittent, coverage over the past several decades. The fatal affliction is often referred to as the "bubble boy" syndrome or, more accurately, SCID,  Severe Combined Immune Deficiency.

In this case, it involves UCLA scientist Donald Kohn, a British firm, Orchard Therapeutics, Inc., opening new facilities in California (Menlo Park and Foster City) and a $20 million award. The cash, however, is only a relatively small piece of the state's immune deficiency investment. 

$141 million for immuno deficiencies

Over the years, Kohn's research has been backed by at least $52 million from the taxpayer-financed California Institute for Regenerative Medicine (CIRM), as the agency is formally known. Overall, it has pumped more than $141 million into immune deficiency disorders, not all of which is directly related to SCID. 

Responding to a query, Kevin McCormack, senior director for CIRM communications, said,
"We’re a lot more than just a pretty face you know. We feel we’re helping change the face of medicine."
Or as Maria Millan, president of CIRM, said both in a news release and in an article on the agency's blog, The Stem Cellar: 
"We invest when others are not ready to take a chance on a promising but early stage project. That early support not only helps the scientists get the data they need to show their work has potential, but it also takes some of the risk out of investments by venture capitalists or larger pharmaceutical companies."
She continued, 
"Our funding and partnership has enabled the smooth transfer of Dr. Kohn’s technology from the academic to the industry setting while conducting this important pivotal clinical trial. With our help, Orchard was able to attract more outside investment and now it is able to grow its pipeline utilizing this platform gene therapy approach.”

De-risking stem cell therapies

In biotech, all this is referred often as "de-risking" and helping research advance beyond the "valley of death," the stage at which conventional financing for research becomes exceedingly difficult to secure. Both have been goals of the agency for some time and are part of what Millan refers to as the agency's "value proposition." 

Boosting public recognition of the value created by CIRM is likely to be a key element in winning approval of a proposed $5 billion bond initiative in 2020, seeking more cash for the agency. The agency estimates that it will run out of money for new awards at the end of next year. 

The agency noted the significance of the deal that GlaxoSmithKline(GSK) made last month with Orchard.  Although the agency tends to focus strongly on medical and scientific achievements, today's PR hit had a stronger emphasis on business matters. Without a successful business model, it is unlikely that any CIRM research will reach the general population.

California's key role

CIRM said,
"Under the deal, GSK not only transfers its rare disease gene therapy portfolio to Orchard, it also becomes a shareholder in the company with a 19.9 percent equity stake. GSK is also eligible to receive royalties and commercial milestone payments. This agreement is both a recognition of Orchard’s expertise in this area, and the financial potential of developing treatments for rare conditions."
Mark Rothera, Orchard photo 
The agency quoted the CEO of Orchard, Mark Rothera, as saying,
"The funding and advice from CIRM allowed Orchard to accelerate the development of OTL-101 and to build a manufacturing platform to support our development pipeline which includes 5 clinical and additional preclinical programs for potentially transformative gene therapies."
The GSK-Orchard deal, CIRM said, was "good news for both companies and for the patients who are hoping this research could lead to new treatments, even cures, for some rare diseases. It was also good news for CIRM, which played a key role in helping Orchard grow to the point where this deal was possible."
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Friday, May 04, 2018

Alpha Clinic Kickoff: Launch of Capricor Trial for Duchenne in $50 Million California Stem Cell Network

UC Davis this week inaugurated its Alpha Clinic program, part of a $50 million, statewide network created by California's 13-year-old stem cell research agency.

The school kicked off its program with the start of a "HOPE-2" clinical trial for Duchenne muscular dystrophy – a fatal genetic disorder mainly affecting boys and young men. About 200,000 persons worldwide suffer with the affliction. There is no cure. Treatment options are limited.

Craig McDonald
UC Davis photo
The lead trial investigator, Craig McDonald of UC Davis, said in a news release,
"Collaborating with the Alpha Clinic team enables us to capitalize on their research infrastructure and expertise for clinical trials focused on cell-based therapies.
"It complements the skills of UC Davis’ Neuromuscular Research Unit, which is a national leader in conducting Duchenne trials. We believe this unique partnership could be a model for translating stem cell discoveries into meaningful treatments for patients with muscular dystrophy and other serious progressive neurologic diseases.”
The trial will test the safety and efficacy of a therapy developed by Capricor, Inc., of Beverly Hills -- CAP-1002. The state's stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), in 2016 awarded the firm $3.4 million, part of a total of $17.8 million that the firm has received from the state. CIRM has also awarded another $7 million to Cedars-Sinai for early development work that led to the creation of Capricor.  

(Here is a link to the summary of the review of the Capricor application, CLIN2-08334, submitted by Deborah Ascheim, chief medical officer at Capricor.)

CIRM governing board member Jeff Sheehy said in 2016,
"This is pretty much a pure CIRM product. They came into our first disease team to develop the product. We've supported two of the three clinical trials. So if this turns out to be a major success, this will be a real feather for CIRM. We've been with them all the way. So I'm optimistic."
Linda Marban, president of the firm, said in a news release that the research is "one of the very few clinical initiatives to focus on helping boys and young men whose ability to walk has been seriously impaired by the loss of muscle function that occurs as Duchenne muscular dystrophy progresses."

Capricor is a publicly traded firm, whose stock closed at $1.32 today. The 52-week high on the stock was $4.25 and its  52-week low 63 cents.

The Alpha Clinics are one of the signature programs of the stem cell agency. In addition to Davis, UC San Francisco, the City of Hope, UCLA, UC Irvine and UC San Diego are part of the network. UC Davis last year received $8 million from CIRM to help create its program. 
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Wednesday, May 02, 2018

A California Scientist's Eight-Year Journey into the Byways of Dubious 'Stem Cell' Clinics

You could call it the "Knoepfler Effect."

It has bounced noticeably around the country in recent months, leading to headlines in the Washington Post, the Atlanta Constitution, the Los Angeles Times and other outlets in Florida, Seattle and elsewhere.

It involves the activities of dubious, so-called "stem cell clinics" -- enterprises once ignored by the mainstream media, the Food and Drug Administration as well as other regulators, including California lawmakers, and much of the established stem cell scientific community.

Not so today. Here is a sampling of the recent news coverage:
Paul Knoepfler
UC Davis photo 
Over the last several months, these "stem cell" businesses have come under increasing scrutiny by media and regulators. Much of the credit for the attention must go to Paul Knoepfler, a stem cell researcher and blogger at UC Davis. About eight years ago, he began writing -- largely alone and in isolation -- on his blog about the problem. 

He was convinced that the persons lured into the "clinics" were paying large sums for so-called treatments that did not fulfill their promise and that, in fact, could be dangerous. In one case, Knoepfler went undercover -- sort of. He later tangled politely with the leading newspaper in California's state capital about how it was carrying full page ads from an unregulated clinic.

The watershed moment came in 2016 when Knoepfler and Leigh Turner of the University of Minnesota put a number to the matter -- 570 dubious "stem cell" firms nationwide with California leading the nation with 113. That was the key. Readers and regulators like solid numbers. They help focus attention, providing a hook for action and creating a new understanding.  Knoepfler and Turner's peer-reviewed scientific journal piece was the biggest stem cell story in the country that week.

Knoepfler also learned about the media game. He promptly returned media emails and calls and couched his responses in plain English -- "good quotes," as they are known in the trade.

Knoefler persisted even while some of his peers looked disparagingly at his blogging.  Back in 2012, one told Knoepfler that he was "skeptical of scientific social media with its 'twitting and the blobs(cq)'."

In California, however, his work helped to lead to a new law that forces the "stem cell" enterprises to inform their customers more fully about the nature of what might happen to their bodies.

It is a ticklish business to credit a specific individual with triggering a fresh wave of public attention to new and complex issues, such as stem cells and their dubious exploitation. Turner and others have been involved as well and deserve considerable credit. But Knoepfler was at the forefront and did, in fact, take a few arrows for his work.

The California Stem Cell Report asked Knoepfler for his brief thoughts about his stem cell adventures. He replied,
"Some highlights include times when patients decided not to get risky stem cells for themselves or their kids. I also have enjoyed getting to know so many cool people from diverse backgrounds all over the world I’ve only met because of the blog.
"Seeing things like the new California stem cell clinic law sprout up is exciting too, especially as now other states are trying to follow our state's lead it seems and maybe pass even better legislation. I’m also hopeful to have positive impact at the national level such as by somehow working a miracle to get the FDA to do more overall, but we’ll see how that turns out. 
"If that all sounds too cheery, then as my grandma might have said back in the 70s, 'It’s not all peaches and cream.' 
"There have been downsides too like various threats from clinics or their fans. I also feel like at times I’ve stepped in it with something I wrote or said when I could have avoided headaches if I had been wiser. Anyone can do that, but when you do it publicly such as on a blog then it’s got more bite to it. Doing all this stuff has risks to it. But overall it’s been worth it."  
A final note: People often shrug at the likelihood that they can make change in society. Many scientists as well shy from speaking out publicly, surrendering the public arena to snake oil peddlers. But the "Knoepfler Effect" stands as evidence that persistence and first-class work can, in fact, make a real difference in science and public policy. 
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Friday, April 27, 2018

California Hits More Than Half-Billion Dollars in Stem Cell Clinical Trials

The stem call agency has an interactive dashboard on its web site, part of which is seen above.
The California stem cell agency this week boosted the number of its clinical trials to 48 -- representing an investment of $553 million -- with the hope of producing its first widely available stem cell therapy and staving off its own demise.

In a 14-minute, telephonic meeting Thursday, directors of the agency ratified three new awards totalling $32 million and increasing its trials from 45. The applications had been approved earlier behind closed doors by the agency's out-of-state reviewers.

The action left the agency, known formally as the California Institute for Regenerative Medicine (CIRM), with $224 million in uncommitted funds, CIRM said in response to a query. The agency was provided with $3 billion when it was created in 2004 by California voters. The $224 million figure could rise $278 million with "recovery" from cancelled grants.

Nonetheless, CIRM expects to run out of cash for new awards by the end of 2019. It is attempting to raise $220 million privately to tide it over until November 2020, the date when voters may be asked to approved an additional $5 billion in bond funding.

Thursday's brief meeting generated no fresh discussion about the financial future of the agency, which is unique in California history and operates with no oversight by the governor or the legislature. Nor was there any discussion of the applications for research funds. 

CIRM said in a news release this morning that while the agency has backed 48 trials, only 42 are active. It has also funded early stage research in 11 additional projects that moved later into the "clinical trial stage" without additional CIRM support. 

The directors made their award decisions Thursday based on a brief CIRM staff presentation and summaries of the reviews of the applications. 

Links to the summaries, the winners and their awards are below. Go to the summaries by clicking on the application number. Updates on the status of CIRM research can also be found as it progresses by searching on the application number.

Sangamo Therapeutics, Inc., of Richmond, Ca., was awarded $8 million to "test a new therapy (phase one/two) for beta-thalassemia, a severe form of anemia (lack of healthy red blood cells) caused by mutations in the beta hemoglobin gene."

The agency said,
Edward Conner
Sangamo photo
"Patients with this genetic disorder require frequent blood transfusions for survival and have a life expectancy of only 30-50 years."
The company, which announced a secondary stock offering of more than $200 million this week, is providing $15 million in co-financing. Its stock closed at $16.75 on Friday. Its 52-week high is $27.50 and its low $4.25. 

The principal investigator is Edward Conner, chief medical officer of the firm, and the application number is CLIN2-11031

The company said in a news release that the work also involved Bioverativ.

Stanford University researchers received $12.3 million and provided $2.3 million in matching funds for a a phase one trial for a CAR-T therapy for "patients with B cell leukemias who have relapsed or are not responding after standard treatments, such as chemotherapy."

Maria Millan, president of CIRM, said in the news release,
Crystal Mackall
Stanford photo
“When a patient is told that their cancer has returned it can be devastating news. CAR-T cell therapy is an exciting and promising new approach that offers us a way to help patients fight back against a relapse, using their own cells to target and destroy the cancer.”
The principal investigator is Crystal Mackall and the application number is CLIN2-10846

(Here is the link from Stanford on the award. The link was added on April 30 to this item after its initial publication.)

Morton Cowan
UCSF photo
UC San Francisco researchers received $12 million (with no co-funding) for a phase one trial to test a treatment "to restore the defective immune system of children born with severe combined immunodeficiency (SCID), a genetic blood disorder in which even a mild infection can be fatal" and which is often known as "the bubble baby disease."

CIRM said it has"funded two other clinical trials targeting different approaches to different forms of SCID. In one, carried out by UCLA and Orchard Therapeutics, 50 children have been treated and all 50 are considered functionally cured."

The principal researcher is Morton Cowan and the application number is CLIN2-10830.

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