Stem cell agency OKs firm’s clinical trial lauded by Giuliani

California’s stem cell agency last week awarded $750,000 to a New Jersey firm to help finance a clinical trial for the firm’s proposed Covid-19 treatment — a therapy that has been hailed by President Trump’s personal attorney as having “real potential.”

The firm is Celularity, Inc. Its president and co-founder is Robert Hariri, who describes himself as a longtime friend of Rudy Giuliani, Trump’s personal lawyer. The speedy passage of Celularity’s proposed product through the federal drug approval gauntlet has attracted attention from the New York Times as well as the respected STAT biomedical online news service and other media.

The proposal barely scraped through the review process with a score of 85 out of 100, one point above the cutoff line.

The headline on a STAT article on March 31 said, “Rudy Giuliani wants FDA to fast-track a stem cell therapy for Covid-19; critics see political meddling.”

Last Friday, directors of the taxpayer-funded stem cell agency, formally known as the California Institute for Regenerative Medicine(CIRM), approved Celularity’s $750,000 application with no discussion. The proposal barely scraped through the review process with a score of 85 out of 100, one point above the cutoff line. It was the second time this spring that CIRM reviewers had considered the proposal. The first time it was rejected with a score of 84.

It is not uncommon for CIRM directors to approve once-rejected applications after they have been improved and resubmitted.

CIRM’s approval on Friday was routine. It came during a meeting at which directors endorsed a $5.5 billion ballot measure this fall to refinance the agency. The directors’ practice is to rubber stamp — with very rare exceptions — the decisions of its out-of-state reviewers, who operate behind closed doors and do not have to publicly disclose their economic, professional or personal conflicts of interest.  The names of specific reviewers on specific applications are also not disclosed.

In March, Hariri  was interviewed by Giuliani for his podcast show and discussed the Covid treatment.

The reviewers’ decisions come to CIRM directors minus the names of applicants. But in this case, Celularity sent a note to the board in early May, which made its name public.

Celularity is a two-year-old firm that was co-founded by Hariri, who has also been involved with Celgene and Human Longevity, Inc. Celularity’s governing board includes a former commissioner of the Food and Drug Administration under President George Bush and head of the National Cancer Institute, Andrew Andrew von Eschenbach; John Sculley, former CEO of Apple, and Peter Diamandis, founder and chairman of the X Prize Foundation.

In March, Hariri  was interviewed by Giuliani for his podcast show and discussed the Covid treatment. The STAT article cited the interview, which began:

“Rudy Giuliani, President Trump’s personal attorney, is urging the Food and Drug Administration to fast-track clinical trials of an experimental stem cell therapy in Covid-19 patients, prompting fears of political meddling in a scientific process meant to protect patients.

“In recent days, Giuliani has used his Twitter account and podcast to tout the stem cell treatment being developed by a New Jersey biotech company, Celularity, despite scant evidence to date that its therapy will benefit Covid-19 patients.”

“I think it’s important to note that all applications have to undergo a rigorous scientific review and only those that meet the highest standards are approved.” —  Kevin McCormack

The article continued,  “Later on Twitter, Giuliani said Celularity’s therapy, CYNK-001, has ‘real potential’ and ‘trials need to be EXPEDITED.’ In a response to a tweet from one of his followers, Giuliani replied, ‘Let’s hope FDA can recognize that their cumbersome process designed to keep us safer, if it is not altered dramatically in times of great need, can result in unimaginable loss of human life.’”

In response to a query Sunday from Capitol Weekly, Kevin McCormack, CIRM’s senior director of communications, said, “I think it’s important to note that all applications have to undergo a rigorous scientific review and only those that meet the highest standards are approved. The board’s decisions are based on science not politics.”

Hariri has a significant public presence, both on TV news shows and online.  His Twitter home page describes him as a “surgeon, scientist, aviator, futurist.” (For a look at some of his appearances, see here, here and here. 

Hariri is also a significant contributor to Republican political causes. In 2018, he gave $100,000 to a super pac in New Jersey called Integrity New Jersey, according to OpenSecrets.

California stem cell scientist Paul Knoepfler of UC Davis, who produces a stem cell blog, first wrote about Celularity in 2018 and raised concerns about whether the company was hyping its product. Other scientists weighed in on Knoepfler’s blog as well. In March, Knoepfler raised questions about the science behind Celularity’s Covid proposal, both on his blog and in comments to STAT and the New York Times.

Knoepfler wrote, “The notion of an NK cell treatment for COVID-19 is interesting and worth consideration, but at the same time in my view there’s not much data behind it yet so it’s very early days. There’s much we don’t know.”

Friday’s public summary of the application review said 13 of the anonymous reviewers voted for it.

Knoepfler also was concerned about harm to patients during a clinical trial. Those concerns were additionally raised in CIRM’s first review of Celularity’s application (CLIN2COVID19-11857). The review summary said, “This therapy seems to have a potential for high risk (hypersensitivity reactions, potential neurotoxicity and graft vs. host disease) for this indication unless patients are very sick. In particular, the cytokine release syndrome that could happen with this therapy may be the largest issue.”

The syndrome can cause what is known as a cytokine storm, an overreaction of the body’s immune system, and can be fatal.

In a news release, the stem cell agency described the Celularity proposal: “This trial will use blood stem cells obtained from the placenta to generate natural killer (NK) cells, a type of white blood cell that is a vital part of the immune system, and administer them to patients with COVID-19.  NK cells play an important role in defense against cancer and in fighting off viral infections.  The goal is to administer these cells to locate the active sites of COVID-19 infection and destroy the virus-infected cells.”

Friday’s public summary of the application review said 13 of the anonymous reviewers voted for it. Two were against. The earlier vote by the review group was 5-9, with five in support.

The summary of the most recent review said in part:

• “The relative benefit versus risk of exacerbating disease is compelling.
• “Could be a major breakthrough, but would be expensive.
• “Unique idea, but concerns about limited correlative studies.

On the negative side, the summary said, “Is the risk benefit ratio sound? The patients currently treated at this early time point appear to be safe. “  Regarding whether the rationale was sound, another reviewer was summarized as saying, “Maybe. It is not clear if NK cells will help treat COVID-19 or exacerbate it.”

The CIRM governing board does not see the full application, only the public review summary. They are not told the names of the applicants, although in many cases it can be found.

CIRM is restricted by law to funding activities in California. The agency on Sunday confirmed that the CIRM-financed work by the New Jersey firm would take place within the state but did not identify specific locations.