FDA Slaps Stem Cell Firm Linked to Nebraska Infections

The FDA has identified Las Vegas-based EUCYT Laboratories as the company whose exosome products sickened patients in Nebraska late last year, according to a recent warning letter.

The agency also warned EUCYT for marketing an exosome product COVIXO that it claimed could treat COVID-19.

Paul Knoepfler, PhD, a stem cell expert at the University of California Davis, wrote in a blog post that the June 4 letter "is one of the more lengthy warnings that I've seen recently" as it highlights some 13 "major observations."

"Remarkably, the letter uses forms of the words 'fail' or 'failure' 30 times," Knoepfler wrote.

Last December, public health officials in Nebraska warned clinicians that several patients had developed severe infections after receiving unapproved exosome products. Fewer than five patients had become seriously ill, with some developing sepsis.

At the time, Nebraska public health officials said all patients had received an exosome product derived from C-sectioned placentas; the FDA then issued a "public safety notification" about unnamed exosome products. EUCYT's involvement only became public with the June 4 warning letter, which stated that "FDA issued that public safety notification following multiple reports of serious adverse events experienced by patients who were treated with XOsomes."

When FDA conducted inspections at EUCYT's manufacturing plant last November, it found violations including deficient donor eligibility practices, unvalidated manufacturing processes, deficient environmental monitoring, and inadequate aseptic practices.

From April 2018 to November 2019, EUCYT failed to thoroughly investigate 152 sterility failures, according to the FDA warning letter. In those cases, it identified the contaminating organism but destroyed the batches without more detailed investigations.

It also failed to implement corrective or preventive actions in those cases. In one instance, FDA said, the company failed to investigate one lot of product after it failed sterility testing for E. coli. It discarded the lot without conducting a thorough investigation of other lots manufactured on the same day -- and FDA found that another lot made that day was later tied to a report of a patient testing positive for E. coli.

EUCYT chief executive officer Travis Bird did not return a MedPage Today request for comment.

As for the company's COVID-19 exosome product, the FDA warning letter quotes the company's website as saying the product "drives cellular functionality including augmenting the type 1 interferon pathway ... that is important for anti-SARS-CoV-2 activity." It also claims that the "unique mechanism of action for COVIXO enables each patient to generate their own adaptive immune response against SARS-CoV-2, including memory T cells and antibodies, which will further protect each patient from subsequent exposures and infections."

A document with these claims was downloadable from the EUCYT website on June 1, but no longer appears.

Other companies have marketed exosomes for COVID-19 as well, including one California-based company that pushed inhaled exosomes that could be delivered directly to patients' doorsteps so they didn't have to violate stay-at-home orders.

FDA said neither of EUCYT's exosome products would qualify for the agency's homologous use exemption and must be regulated as drugs that would need to be reviewed and approved. Neither product currently has an approved biologics license application or an investigational new drug application (IND) on file, although a EUCYT press release on May 8 said an IND for COVIXO was "pending approval."

The company markets a host of other stem cell products derived from birth tissue, which FDA also said do not meet criteria for the homologous use exemption and must be regulated as drug products. These include its VidaCord, VidaGel, VidaStem, and VidaFlo product lines.

Following the June 4 warning letter, EUCYT no longer lists available products on its website. Visitors are now invited to contact the company for information.

MedPage Today has previously reported on a growing trend of hospitals implementing placenta donation programs and potential links to unapproved stem cell products.

While exosomes are being evaluated in legitimate research studies, some clinics -- often those peddling unapproved stem cell therapies -- are offering exosome therapy for all kinds of conditions. One site for a clinic in San Diego describes the treatment as "the ultimate anti-aging hack." Delaware Integrative Medicine advertises exosome therapy as being helpful for patients with "chronic inflammation, autoimmune disease, Lyme disease, and other chronic degenerative diseases."

But stem cell researchers say exosomes -- packages of proteins and RNAs that can be transferred from cell to cell -- are nowhere near ready for routine clinical use.

"Overall, it's crystal clear that exosomes are generally drug products requiring pre-approval from the FDA prior to use in patients," Knoepfler wrote on his blog. "And the agency is willing to take relatively quick action against non-compliant exosome firms."

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