Developers of a cutting-edge lab-grown blood vessel designed to save life and limb in war zones and other emergency scenarios appear to be promoting its use in surgeries far beyond the product\u2019s approved scope. The \u201coff-label\u201d use of these bioengineered tissues comes despite indications of questionable efficacy and potentially catastrophic ruptures.<\/p>\n
The biotechnology firm, Humacyte, has developed an artificial blood vessel, called Symvess, that was approved<\/a> by federal regulators for use in adults with trauma to their arms or legs who urgently need new arteries \u201cto avoid imminent limb loss.\u201d<\/p>\n But at a premier vascular surgery conference this November, Humacyte promoted research presentations<\/a> on alternative uses of its vessels from a clinical trial \u2014 part of a growing trend<\/a> of \u201coff-label\u201d uses of medical devices.<\/p>\n One of those presentations focused on off-label use of the vessels in patients\u2019 torsos, which, according to data<\/a> omitted from a prominent medical article on the product, were unsuccessful in four out of five procedures. In two of those cases, the patient died. The other presentation detailed the use of tissues in surgeries for individuals with kidney failure, procedures that the company previously discouraged the surgeon involved from undertaking.<\/p>\n Humacyte confirmed that both presenters have received compensation from the company in the past, though they were not paid in connection with their conference presentations.<\/p>\n \u201cI find it ethically problematic that several speakers failed to declare from the beginning of their talks that they would be describing usage of the Humacyte graft that was not FDA approved,\u201d said Robert Lee, a vascular surgeon and former medical officer at the Food and Drug Administration (FDA), which attended the November presentations and voiced concerns about the matter during the talks. In September 2024, Lee left<\/a> the federal agency in protest following a ten-year term, after he\u2019d repeatedly warned<\/a> that Humacyte\u2019s blood vessels could rupture<\/a>.<\/p>\n While the FDA went on to approve Symvess three months later for limited uses, it required the surgical graft to be marketed and sold with its most serious<\/a> type of warning for drugs and medical devices, one that states the vessels can rupture, leading to potentially life-threatening bleeding.<\/p>\n The conference presentations followed a New York Times investigation<\/a> earlier this year, raising concerns about the safety and effectiveness of Humacyte\u2019s artificial vessels. A patient advocacy group cited this reporting in a citizen petition<\/a> demanding a full recall of Symvess products, as did a lawsuit<\/a> by Humacyte shareholders claiming the company concealed product risks.<\/p>\n Despite these warnings and concerns, rather than restricting Symvess\u2019s reach, the company now appears to be touting the product beyond the prescribed limits set by the FDA.<\/p>\n This comes amid growing concerns about off-label use of medical devices, according to Hooman Noorchashm, president of the patient advocacy group that submitted the citizen petition and codirector of the Amy J. Reed Medical Device Safety Collaborative, which advocates for safer medical devices, regulatory transparency, and legal accountability.<\/p>\n \u201cIt\u2019s not just one or two products\u201d that are being used for off-label use, said Noorchashm, who has raised safety concerns<\/a> about a breast reconstruction implant that is now being used for off-label purposes despite patient complications<\/a> like infection, persistent pain, and hemorrhages. Once a company gets product approval, said Noorchashm, \u201cthat\u2019s all it really takes to then initiate this process of suggesting, \u2018Hey, maybe we can use it for this off-label purpose, or that off-label purpose.\u2019\u201d<\/p>\n Despite the potential promises of Humacyte\u2019s bioengineered blood vessels, the intervention\u2019s cost, and the contract secured with<\/a> the US Department of Defense, the biotech company had accumulated losses of $702 million as of this September, according to the company\u2019s financial records<\/a>. This month, the company received a $77.5 million<\/a> line of credit from Avenue Venture Opportunities, a global investment firm that specializes<\/a> in \u201cgood companies with bad balance sheets.\u201d<\/p>\n Off-label use of drugs and medical devices can prove valuable as scientists and manufacturers develop new clinical trials to explore the uses and efficacy of novel therapies. But in this case, Lee says Humacyte\u2019s market pressures could be leading the company to push for off-label uses of its signature product for financial reasons.<\/p>\n Rather than restricting Symvess\u2019s reach, the company now appears to be touting the product beyond the prescribed limits set by the FDA.<\/p>\n This type of situation raises \u201clegitimate regulatory and ethical questions if required disclosures are not clear and complete,\u201d said Lee. Regarding Humacyte\u2019s press releases about the conference presentations, he asked, were they \u201cprimarily intended to inform the scientific audience attending the conference, or were they directed more towards the investment community?\u201d<\/p>\n In a press release<\/a>, Humacyte states that Symvess \u201cis an investigational product and has not been approved for sale by the FDA or any other regulatory agency\u201d to treat vascular trauma outside of patients\u2019 extremities.<\/p>\n In response to a list of questions, a Humacyte spokesperson wrote in an email to the Lever that \u201cHumacyte does not, has never, and will not promote off-label use of Symvess,\u201d and that the company \u201ccommunicates the results of its clinical trials consistent with federal and state law and FDA guidance on communication of product information.\u201d<\/p>\n When patients\u2019 blood vessels are damaged from severe trauma, like a car crash or battlefield wounds, and transplanting other intact veins isn\u2019t possible, doctors may deploy artificial vessels just a few millimeters thick to restore blood flow. Typical synthetic vessels made of Teflon or polyester can carry a risk of infection and other complications, in part because the human body may react negatively to the foreign materials.<\/p>\n Humacyte\u2019s new vessel, however, is engineered from a polymer tube seeded with millions of human cells<\/a>. These cells eventually produce a flexible tube made up of collagen and other proteins that can be implanted into patients.<\/p>\n This, according to Humacyte, leads to<\/a> \u201clow infection, and low amputation\u201d rates, making them safer and more effective than other synthetic vessels. The company\u2019s founder and CEO, Laura Niklason, told Wired earlier this year that Humacyte has enough human cells banked to make<\/a> between 500,000 and a million artificial blood vessels.<\/p>\n The company\u2019s 2024 FDA approval of Symvess was supported by two earlier clinical trials, including one involving adults with vascular trauma below the neck. According to an article published in the journal JAMA Surgery<\/a> \u2014 a leading academic publication in the surgical field \u2014 the trial<\/a> indicated that the blood vessels had an 84 percent success rate.<\/p>\n However, after reviewing thousands of pages of information, FDA investigators concluded<\/a> that the vascular-trauma trial suggested the artificial tissues were actually successful only 67 percent<\/a> of the time, compared to an 82 percent success rate of other synthetic grafts.<\/p>\n Lee, who was then serving as a vascular consultant for the FDA, wrote<\/a> in a memo that \u201cthis observed failure mode of the [vessel] is unpredictable, catastrophic and life threatening.\u201d Thomas Zhou, a statistician at the FDA, also noted that \u201cneither study met the usual criteria for an adequate and well-controlled trial.\u201d<\/p>\n Lee is a founding president of Echelon Development Group, a private consulting firm specializing in vascular devices. Two individuals on Echelon\u2019s leadership team serve as key advisors to Phraxis, Inc., one of Humacyte\u2019s potential competitors, according to a statement<\/a> by Humacyte.<\/p>\n \u201cNone of the firms that I have worked with are direct competitors to Humacyte and their novel biologic graft,\u201d Lee wrote in an email to the Lever. \u201cFor calendar year 2025, my medical device consulting income will be around $15,000.\u201d<\/p>\n After the New York Times reported<\/a> on Humacyte\u2019s questionable success-rate claims, a group of company shareholders filed a lawsuit<\/a> this May alleging the company deceived investors about the effectiveness of its artificial blood vessel.<\/p>\n \u201cWhile Humacyte touted the product\u2019s safety and its manufacturing readiness, concealed FDA documents and former employee and whistleblower accounts evidenced a starkly different reality: dangerous product failures, systemic manufacturing deficiencies yielding only 25-40% success rates, and a company burning through cash at an unsustainable rate,\u201d the lawsuit reads.<\/p>\n A group of company shareholders filed a lawsuit this May alleging the company deceived investors about the effectiveness of its artificial blood vessel.<\/p>\n According to the ongoing lawsuit<\/a>, FDA investigators also identified safety concerns at the company\u2019s manufacturing facilities in Durham, North Carolina, including \u201cno microbial quality assurance\u201d and \u201cno microbial testing\u201d for certain processes and equipment, in addition to insufficient \u201cquality oversight.\u201d<\/p>\n The plaintiffs also allege that executives concealed<\/a> those manufacturing problems in Durham, telling investors that Humacyte had a \u201cvery successful interaction\u201d with the FDA regarding Symvess\u2019s application, subsequently inflating stocks. Shareholders claim this allowed several directors to sell shares at an inflated price<\/a>, including CEO Niklason, who made nearly $39 million.<\/p>\n Humacyte has filed a motion to dismiss the lawsuit, which is currently pending in court.<\/p>\n Regardless of recent controversies, Humacyte announced two presentations about expanded, off-label uses of its product at the recent VEITHsymposium vascular conference in New York. The conference is considered a premier event for vascular specialists, drawing thousands<\/a> of attendees from around the world.<\/p>\n One talk focused on five patients who had received Humacyte\u2019s vessels in their torsos during the Symvess vascular trauma trial. According to the presentation slides<\/a>, two of those patients died, another subsequently had their leg amputated, and in a fourth, the blood vessel eventually stopped working. However, the presentation concluded that vessels\u2019 \u201cuse in torso arterial trauma is feasible,\u201d and that the deaths and other issues were largely driven by \u201ccomplications related to the initial traumatic injury\u201d and infections.<\/p>\n One slide noted that \u201ctorso subjects are not included in the FDA-approved indication.\u201d Lee, however, argues that \u201cespecially when speakers have corporate, financial, or professional ties, a clear declaration of off-label use should be made at the beginning of their presentation with the conflict-of-interest slides,\u201d he said.<\/p>\n According to the Humacyte spokesperson, \u201cHumacyte did not pay Dr. Magee or Dr. Moore in connection with their presentations at the VEITHsymposium but has compensated\/reimbursed them in connection with their role as key opinion leaders<\/a> in the past.\u201d<\/p>\n Notably, the JAMA Surgery article<\/a> on the clinical trial touting Symvess\u2019s 84 percent success rate failed to include any information about the torso surgeries or their outcomes.<\/p>\n According to Ernest Moore, director of surgical research at Denver Health and lead author on the JAMA Surgery article, Humacyte did not provide him with all of this information prior to publication of the article. Moore is one of several of the study\u2019s authors who\u2019ve reported<\/a> receiving grants from Humacyte, while other study authors worked directly for the company, including Niklason, Humacyte\u2019s CEO.<\/p>\n \u201cIt is true that, according to standard practice, Humacyte did not share the tens of thousands of pages of [the company\u2019s submission to the FDA] with every investigator,\u201d noted the Humacyte spokesperson. \u201cThis is because the JAMA Surgery article focused on the extremity patient population, which is the indication that FDA ultimately approved.\u201d<\/p>\n In August, JAMA Surgery issued a correction<\/a> to the article, noting that had the torso surgeries and other uses of the blood vessels been included in the analysis, the studies\u2019 \u201cefficacy and safety findings could have been attenuated.\u201d<\/p>\n Such promotion of off-label use could be a precursor to Humacyte\u2019s next business moves.<\/p>\n \u00a0Moore, meanwhile, led the other Symvess presentation at the vascular conference, during which he described inserting Humacyte\u2019s vessels into four dialysis patients suffering from kidney failure and limited blood flow to their limbs. According to Moore\u2019s presentation slides<\/a>, the procedures suggested the lab-grown blood vessels \u201cmay be a viable alternative\u201d for such surgeries and \u201cdemonstrated durable patency, safety, and freedom from graft-related infection or rupture.\u201d<\/p>\n But according to Moore, Humacyte previously discouraged him from using its bioengineered tissues in this way.<\/p>\n \u201cInterestingly, it was Humacyte who, after a number of these [surgeries], reviewed them and said, \u2018Ya know, we probably don\u2019t think these really qualify, so I don\u2019t think you have to do these [surgeries] anymore,\u2019 so I stopped doing them,\u201d said Moore.<\/p>\n The four surgeries performed by Moore \u201cwere not the primary focus for Humacyte\u2019s commercial strategy,\u201d noted Humacyte\u2019s spokesperson. \u201cAs a result, we asked that Dr. Moore not enroll additional . . . patients.\u201d<\/p>\n Such promotion of off-label use could be a precursor to Humacyte\u2019s next business moves.<\/p>\n Humacyte is currently conducting another<\/a> clinical trial on people with end-stage kidney disease. Next year, the company plans to submit an FDA application for its artificial blood vessels to be used in these patients, according to its most recent financial report<\/a>.<\/p>\n During an investor call<\/a> last month, Niklason noted that there is a \u201chigh unmet need\u201d for kidney patients who would require Symvess. \u201cThese subgroups are not small,\u201d Niklason told investors. \u201cIf you combine all women with men having these risk factors, it\u2019s more than half of the dialysis population.\u201d<\/p>\n Noorchashm, codirector of the Amy J. Reed Medical Device Safety Collaborative, wasn\u2019t surprised that Humacyte is marketing its blood vessels for off-label uses.<\/p>\n \u201cThe reality is that the government of the United States has provided this company with a license to market this particular device for use in vascular operations,\u201d said Noorchashm, who submitted the citizen petition<\/a> to the FDA in April requesting a recall of all Symvess products due to the vessel\u2019s \u201cpotentially catastrophic outcomes.\u201d<\/p>\n \u201cIt takes a long time for companies to get to this point and a lot of investment, so I would fully expect the company and its executives would not want the company to sink,\u201d he said.<\/p>\n Off-label use of drugs and medical devices has been a growing concern for decades and is nearly impossible to track, said Gail Van Norman, a physician and anesthesiology professor at the University of Washington Medicine.<\/p>\n According to an article by Norman on off-label use of drugs and medical devices, such processes can expose patients to treatments that have not been formally tested, increasing potential medical risks and discouraging manufacturers from investing in clinical studies to properly evaluate the safety<\/a> and efficacy of their products.<\/p>\n \u201cAll of this is really arising out of commercial pressure,\u201d Norman said.<\/p>\n While the FDA prohibits<\/a> companies from explicitly marketing off-label uses of drugs and medical devices, \u201cyou can go to a medical meeting and present a study that\u2019s been published in a peer-reviewed journal\u201d as a form of marketing, Norman added.<\/p>\n Meanwhile, Humacyte executives are still telling their investors an encouraging story. In a presentation<\/a> on Symvess, company representatives noted that in the clinical trials that were used for FDA approval, their lab-grown blood vessel \u201cis durable over 36 months of observation in trauma repair\u201d with \u201czero reports of late infection, aneurysm, or mechanical failure.\u201d<\/p>\n To date, sixteen hospitals have ordered Humacyte\u2019s blood vessels, generating hundreds of thousands in product sales, according to the company\u2019s third-quarter financial results<\/a>.<\/p>\n \u201cThis active physician engagement is complemented by our steady drumbeat of strong publications that support Symvess and our technology platform,\u201d Niklason said during a recent investor call<\/a>. \u201cWe\u2019re confident that we will continue to see the benefits of this product validated by further research.\u201d<\/p>\n Earlier this year, Humacyte cut the price of its blood vessels from $29,500<\/a> to $24,250<\/a> per unit and implemented a plan to trim its workforce<\/a> by thirty employees.<\/p>\n \u201cCould financial pressures resulting from low Symvess sales be a reason why there was a focus on the off-label use of this product?\u201d asked Lee.<\/p>\n Either way, he argues, \u201cphysicians and patients should be aware that when a medical product is employed outside of the FDA-approved indications, the agency has not determined that there is an assurance of safety or effectiveness for that new use.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"Developers of a cutting-edge lab-grown blood vessel designed to save life and limb in war zones and other…\n","protected":false},"author":2,"featured_media":366769,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[64,63,137,500],"class_list":{"0":"post-366768","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-healthcare","8":"tag-au","9":"tag-australia","10":"tag-health","11":"tag-healthcare"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/366768","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/comments?post=366768"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/366768\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media\/366769"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media?parent=366768"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/categories?post=366768"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/tags?post=366768"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}