When Humacyte from Biotech Company designed a study to see if the lab's grown blood vessels work, they decided to measure whether they flow freely through the high-tech tube 30 days after being implanted in a person.
As the day went on, some of the 54 patients in the study came into trouble. The doctor lost one follow-up. Four people have died. Four more people were amputated, including those who developed blood clots and infections in the artificial container, according to Food and Drug Administration records.
Humacyte, trading on Nasdaq, counted all these patients as evidence of successful consultations with investors and in a Jama Surgery article.
However, the FDA shows that scientists counted deaths, amputations and lost cases as failures, focusing on the lack of information to determine if the vessel is clear.
Still, the agency approved the vessel in December without public review of the study. The senior official approved it in FDA records that the study found the study worried about the patient's disastrous outcomes when the container fell apart.
Currently, the company is stepping up its marketing efforts to hospitals and using them on the battlefield.
When a patient's blood vessels are damaged, doctors usually find the blood vessels in another part of the body and implant them to repair blood flow. Once the patient is severely injured and harvests the vein, he turns to the artificial container.
Fumashete containers are made from mesh tubes seeded with cells from the human heart. The cells grow in the bioreactor for two months, and at the end of the process, human cells and genetic material are removed. The lab-grown tubes made of collagen developed from aortic cells remain.
Before the vessel was approved, one FDA medical reviewer noted that 37 of the 54 patients were not evaluated in safety checks four months after obtaining the implant. “There is a great uncertainty over 30 days regarding the safety and efficacy of this product,” the FDA report states.
Dr. Robert E. Lee, a vascular surgeon who cared for Detroit's gunshot wounds for 30 years, left the job after a fall from the FDA in protest. Dr. Lee discovered that a vessel could burst without warning in a review of more than 2,000 pages of company records conducted while he was an FDA medical officer. The events are “unpredictable, devastating and life-threatening,” he wrote in an FDA review, some of which were published a few weeks ago.
“This is an unacceptable risk for any benefit if this product exceeds current standard treatment,” Dr. Lee, an agency reviewer since 2015, said in an interview. He noted that doctors are currently using the patient's own container or using tubes made of Gore-Tex.
An FDA spokesperson said the approval was based on a careful evaluation of data from clinical trials that demonstrate clinically meaningful benefits of restoring blood flow to affected limbs and ultimately restoring limb rescue.
Humacyte also develops grafts for dialysis patients, patients undergoing cardiac bypass surgery, and infants with heart-related birth defects.
Dr. Laura Niklason, one of the company's founders, said the approval of the vessel, known as the Symvess, was a “a global regenerative medicine milestone.”
She had begun work to create vessels grown in the lab decades ago. Over the past 20 years, the company had not recorded sales and had more than $660 million in debt, the financial report shows.
In an interview, Dr. Niklason said success or failure occurred after he decided to count cases as a disorder only if blood flow was certain to be blocked, resulting in disagreement about how to label patients' deaths and amputations. The FDA took a more conservative approach to calculating product success rates, she said. “Reasonable people don't agree,” she added.
FDA records do not indicate whether the ship's problems directly caused death or amputation.
Dr. Nikrason said the company must use its agency numbers when marketing products to clients, but it can present more advantageous figures to investment analysts. She also said the study was published before the FDA reached a decision.
The company's chief commercial officer, BJ Scheessele, told investors this month that Humacyte is in talks with 26 hospitals to begin distribution. Scheessele also said the company hopes to sell the ship to the Department of Defense due to battlefield injuries. The US Army gave Humacyte $6.8 million in 2017, accepting the product as an option for wounded soldiers.
Each artificial vessel costs $29,500, and Scheessele said the company hopes it will sell thousands of people each year in the US.
In an interview, Dr. Niklason said there was two interest in vascular engineering. As a young doctor, she had observed that arterial disease was devastating.
She watched her experience as a medical resident in the late 1990s, seeing senior doctors make incisions after incisions of patients' legs and arms, and seeking healthy containers for use in cardiac bypass surgery. She called the procedure “wild bar.”
“We usually need to take Peter to pay for the pole to provide new blood vessels to patients who need it,” she said.
Since Dr. Nikrason began meeting with the FDA in 2015 about starting a human trial in 2015, the agency has repeatedly found errors in the company's efforts to study the use of vessels. The trial took place in US hospitals and Israel with people suffering from major trauma, including gunshots and car accident injuries. The average age of participants was 30 years old, with half of them black patients.
The Himashte also provided ships to doctors who treat wounded soldiers in Ukraine.
By November 9, 2023, Dr. Nikrason had described the results of his research with investors in brilliant terms regarding the revenue call. Initially, she said the proportion of blood flow through the vessel over the 30-day period was 90%, defeating existing products in the market.
And she said the results in Ukraine were “surprising.” “We are proud to be able to help our Ukrainian surgeon colleagues save lives and limbs in this wartime environment.”
However, over the next few months, FDA reviewers, including Dr. Lee, looked into the same study and concluded that they hardly looked good.
As a Detroit vessel and general surgeon, Dr. Lee has decades of experience with the casualties of gunshots, stab wounds, car accidents and other accidents that could potentially receive such vessels.
He said he was wary of the description of a Ukrainian man who began bleeding at the site of the surgical wound eight days after the vessel was implanted. According to FDA records, doctors discovered a 2 mm hole in the fumasite container and repaired it with sutures. Four days later, the patient bleed again and the graft had to be removed the next day. This review suggested that infection may have played a role.
According to an FDA review, 71 cases, seven or about 10% of Dr. Lee investigated the safety review experienced ship breakdowns, resulting in most bleeding. Dr. Lee said it was unprecedented in the experience with Gore-Tex grafts.
“Plastic arteries, they don't usually present with catastrophic bleeding, but this is unexpected,” Dr. Lee said. “I know the patient is sick,” he continued with fever or other signs of infection. “You know something is brewed, and you usually have time to take care of it.”
We want to gather more information about the root cause of mid-vessel blow-off and make sure that doctors are aware of the possibilities.
Thomas Zhou, a biostatistician in the FDA's Department of Biology, also flagged concerns from data from the US department of research and Ukraine.
“Neither study meets the usual standards of appropriate and well-controlled trials,” he wrote.
The study of 16 patients treated in Ukraine was retrospective and observational, allowing researchers to look back at the larger data pool and select the best case. It showed “limited support for effectiveness.” He said this was because the injury was “skewed into a shrinking injury,” and therefore it wasn't the devastating wound that is commonly seen on the battlefield.
According to a statistical review, the US study was “inadequately conducted” and reported that it had undergone “several major changes” during the trial.
Records also show that FDA scientists dismissed the patient as a successful death and amputation, citing a lack of information and imaging research.
The FDA concluded that the success rate of the vessel for its important survey was 67% rather than 84% for the company. In comparison, the blood flow of the artificial graft was already at 82%, the review says.
The company also reported a success rate of 84% over 30 days in an article published in JAMA Surgery in November. This is widely read by surgeons. The article stated that the fumasite container “shows improved results” over other artificial containers.
He also stated that this symbiosis “provides a benefit” to “infection resistance.” The FDA review stated that there was no clinical evidence of any particular effect.
Dr. Lee failed to convince top FDA officials to hold a meeting of public advisory committees where independent experts can discuss and review their findings. Instead, they decided to send the records to three external reviewers instead. An external reviewer identified the failure of the Humasite ship “as a serious risk,” but added that the document would benefit from a “appropriate patient population.”
When announcing the approval of the graft on December 20th, Dr. Peter Marks, head of the biology department, called it “an innovative product that offers potentially life-saving benefits to seriously injured patients.”
However, the product comes with a black box warning (the most serious agent) against the failure that “may lead to life-threatening bleeding.” The FDA also requires us to continue reporting safety data.
Dr. Furman Norshashum, co-director of Amy J. Reed Medical Device Safety Cooperation at Northeastern School Law of Law, said the FDA should not approve products that scientists deemed inferior to existing options.
“If the graft falls apart,” he said, or if it's cut to where it's attached to the container, “it's basically like a patient being shot.”
Dr. Lee said he hopes the FDA, which has new leadership under the Trump administration, will still hold a public meeting.
“Every surgeon who uses it needs to see what I did,” he said.
