Lab-Grown Blood Vessel Approval Sparks Debate Over Patient Safety
Biotechnology firm Humacyte, in its evaluation of a lab-engineered blood vessel, aimed to ascertain if blood flowed unrestrictedly through the innovative conduit 30 days post-implantation.
During this period, some of the 54 trial participants encountered complications. Medical professionals lost contact with one individual. Four patients died. Another four underwent limb amputation, including one who developed a blood clot and infection in the synthetic vessel, according to Food and Drug Administration documentation.
Humacyte, a publicly traded company on the Nasdaq, cited these patient outcomes as evidence of success in discussions with investors and in a publication in JAMA Surgery.
Conversely, within the FDA, scientists categorized the fatalities, amputations, and the untraced patient as failures, records indicate, pointing to insufficient data to confirm vessel patency.
FDA Greenlights Vessel Despite Internal Reservations
Despite internal misgivings, the agency authorized the vessels in December without a public study review. Senior officials approved the device over objections from staff members who, FDA records reveal, deemed the study significantly flawed and expressed alarm regarding severe patient consequences linked to vessel malfunctions.
The company is now intensifying its marketing strategies targeting hospitals and military applications.
Standard medical practice for damaged blood vessels involves grafting a vessel from another area of the patient’s body to restore circulation. Artificial vessels are considered when patients lack suitable veins for harvesting due to extensive injuries.
Humacyte’s vessel is fabricated from a mesh framework inoculated with human heart cells. These cells proliferate within a bioreactor over two months. Subsequently, the human cells and genetic material are removed, leaving behind a lab-grown tube primarily composed of collagen derived from aortic cells.
Prior to approval, an FDA medical reviewer highlighted that 37 out of 54 patients were not evaluated in a safety assessment four months after implantation, with many deceased or lost to follow-up. “Significant uncertainty exists concerning the safety and efficacy of this product beyond 30 days,” the FDA report stated.
Dr. Robert E. Lee, a vascular surgeon with three decades of experience treating gunshot wound victims in Detroit, retired from the FDA in protest. His review of over 2,000 pages of company records, conducted during his tenure as an FDA medical officer, revealed that the vessel could unexpectedly rupture. He described these events as “unpredictable, catastrophic, and life-threatening” in his FDA review, portions of which have been recently disclosed.
Concerns Over Vessel Rupture and Safety Data
“That’s an unacceptable hazard for any marginal benefit, if any, this product offers over current standard treatments,” stated Dr. Lee, who served as an agency reviewer since 2015, in an interview. He emphasized the current use of patients’ own vessels or Gore-Tex tubes when available.
An FDA spokesperson stated that the approval “was grounded in a thorough evaluation of clinical trial data demonstrating a clinically significant benefit in restoring blood flow in the affected limb and ultimately limb preservation.”
Humacyte is also innovating grafts for dialysis patients, cardiac bypass surgery candidates, and infants with congenital heart defects.
Dr. Laura Niklason, a Humacyte founder, hailed the approval of Symvess, the vessel’s brand name, as a “milestone for regenerative medicine in general.”
Company Response and Marketing Strategy
Dr. Niklason initiated work on lab-grown vessels decades ago. In its two decades of operation, Humacyte has accumulated over $660 million in debt without generating sales, according to financial disclosures.
In an interview, Dr. Niklason explained that the disagreement regarding classifying patient deaths and amputations as successes or failures arose from the company’s decision to only categorize cases as failures when definitive evidence of blood flow cessation existed. She stated the FDA adopted a more conservative approach to calculating product success rates. “Reasonable individuals can disagree,” she added.
FDA records do not establish a direct causal link between vessel issues and patient fatalities or amputations.
Dr. Niklason clarified that while the company must utilize agency figures in product marketing to clinicians, it can present its more favorable statistics to investment analysts. She also noted the study’s publication occurred prior to the FDA’s decision.
B.J. Scheessele, Humacyte’s chief commercial officer, informed investors this month about ongoing discussions with 26 hospitals to commence distribution. Mr. Scheessele also expressed hopes to sell the vessels to the Department of Defense for battlefield injuries. The U.S. Army committed $6.8 million to Humacyte in 2017, recognizing the product’s potential for wounded soldiers.
Each artificial vessel is priced at $29,500, and Mr. Scheessele indicated the company’s aim to market several thousand annually in the United States.
Origins of the Technology and FDA Scrutiny
Dr. Niklason conveyed in an interview that her motivation for engineering blood vessels was twofold, stemming from her observations of the devastating impact of arterial disease during her early medical career.
She recalled an experience as a medical resident in the late 1990s witnessing a senior physician making repeated incisions in a patient’s limbs to procure a healthy vessel for heart bypass surgery, describing the procedure as “barbaric.”
“To provide a new blood vessel for a patient in need, we typically have to resort to borrowing from another part of their body,” she explained.
Since Dr. Niklason initiated dialogues with the FDA in 2015 regarding human trials, the agency consistently identified shortcomings in the company’s vessel usage studies. The trial involved individuals with severe trauma from incidents like gunshot wounds or car accidents, conducted across U.S. and Israeli hospitals. Participants had an average age of 30, with half being Black patients.
Humacyte also supplied vessels to physicians treating injured soldiers in Ukraine.
Conflicting Interpretations of Study Results
By November 9, 2023, Dr. Niklason presented study results to investors during an earnings call in optimistic terms. Initially, she reported a 90 percent blood flow rate through the vessels at 30 days—outperforming existing market alternatives.
She described the outcomes in Ukraine as “remarkable,” stating, “We’re honored to assist our Ukrainian surgeon colleagues in preserving life and limb in this wartime environment.”
However, in subsequent months, FDA reviewers, including Dr. Lee, scrutinized the same studies and reached significantly less favorable conclusions.
Drawing upon his extensive experience as a vascular and general surgeon in Detroit dealing with victims of gunshot wounds, stabbings, car accidents, and similar traumas, Dr. Lee brought substantial expertise to the evaluation process.
He voiced alarm regarding a case in Ukraine involving a patient who experienced bleeding at the surgical site eight days post-vessel implantation. Doctors discovered a two-millimeter perforation in the Humacyte vessel, which they repaired with sutures, according to FDA records. Four days later, recurrent bleeding necessitated graft removal the following day. The review suggested potential infection involvement.
FDA Scientists Question Study Methodology and Outcomes
Out of 71 cases reviewed by Dr. Lee for safety assessment, seven individuals, approximately 10 percent, experienced vessel failures leading to significant bleeding, according to FDA records. Dr. Lee characterized this rate as unprecedented in his experience with Gore-Tex grafts.
“Plastic arteries typically do not present with catastrophic hemorrhage, unexpectedly like this,” Dr. Lee elaborated. “Typically, patients exhibit signs of illness,” such as fever or infection indicators, “offering time for intervention.”
Seeking deeper insights into the cause of these mid-vessel ruptures and to ensure physician awareness, Dr. Lee advocated for a public advisory hearing on the device.
Thomas Zhou, a biostatistician within the FDA’s biologics division, also raised concerns regarding the U.S. study arm and data from Ukraine.
“Neither study fulfilled standard criteria for an adequate and well-controlled trial,” he asserted.
The study involving 16 Ukrainian patients was retrospective and observational, allowing researchers to retrospectively analyze a larger dataset and selectively choose favorable cases. It provided “limited support for efficacy,” partly because the injuries were “predominantly from shrapnel” rather than the severe trauma typical in battlefield scenarios, he elaborated.
The U.S. study was labeled “poorly executed” and underwent “multiple significant modifications” during the trial, the statistical review indicated.
FDA records further show agency scientists discounting patient deaths and amputations as successes, citing lacking information or imaging studies.
Discrepancies in Success Rates and Long-Term Efficacy
Consequently, the FDA determined the vessel’s success rate for the pivotal study to be 67 percent, contrasting with the company’s reported 84 percent, FDA documents reveal. In comparison, existing artificial grafts already exhibited blood flow rates of 82 percent, the review highlighted.
The company also reported an 84 percent success rate at 30 days in a JAMA Surgery article published in November, widely consulted by surgeons. The article claimed the Humacyte vessel “demonstrates improved outcomes” compared to other artificial vessels.
It further asserted Symvess “provides benefits” in “infection resistance.” However, the FDA review found no clinical evidence substantiating this additional advantage.
Dr. Lee’s efforts to persuade FDA leadership to convene a public advisory committee meeting for open discussion and independent expert review of the study results were unsuccessful. Instead, the agency opted to send records to three external reviewers who acknowledged vessel failure as a “serious risk” but suggested “the appropriate patient population” would benefit, according to documentation.
Announcing graft approval on December 20, Dr. Peter Marks, head of the biologics division, characterized the vessels as “innovative products offering potentially life-saving benefits for patients with severe injuries.”
However, the product carries a black box warning—the agency’s most severe—for failures that “can result in life-threatening hemorrhage.” The FDA also mandates ongoing safety data reporting from the company.
Dr. Hooman Noorchashm, co-director of the Amy J. Reed Medical Device Safety Collaborative at Northeastern School of Law, argued the FDA should not have approved a product deemed inferior to existing alternatives by its own scientists.
Expert Criticism and Call for Further Review
“If the graft fails,” he stated, or if detachment occurs at the vessel attachment point, “it is essentially equivalent to the patient sustaining a gunshot wound.”
Dr. Lee expressed hope that the FDA, under new leadership, might still convene a public meeting.
“Every surgeon utilizing it needs to see the information I reviewed,” he concluded.