In the world of 21st century Army medicine, the impossible is quickly becoming possible due to the innovative efforts of numerous men and women — including military, civilian and contract support — dedicated to the advancement of products and procedures that may have been lofty ideas only a few short years ago.
“Restoring blood flow is always the first step in dealing with a traumatic injury,” said U.S. Army Lt. Col. David Saunders.
“So it’s our first step in this effort as well.”
Humacyte, an innovator in biotechnology and regenerative medicine, has received a Broad Agency Announcement (BAA) contract award of $3.4 million from the United States Department of Defense (DoD).
As the product manager for Extremity Repair in the Tissue Injury and Regenerative Medicine (TIRM) Project Management Office of the U.S. Army Medical Materiel Development Activity, Saunders understands this unique area of vascular restoration.
The TIRM PMO team’s primary mission is to make wounded service members whole again by restoring form, function and appearance — and the group takes this responsibility quite seriously.
Currently, it is driving the Department of Defense’s investment to harness the potential of the rapidly growing field of regenerative medicine.
For this particular development effort, the team is focused on early limb salvage and is working with industry partners to realize an organic, “human” product that will afford a more permanent solution for the repair of damaged vessels after traumatic injury on the battlefield.
“The lead product being developed is similar to currently available synthetic grafts in some ways, but considerably more sophisticated,” said Saunders.
“It is basically a tube of smooth muscle material — collagen, fibronectin — that has been derived from human blood vessels artificially grown in the lab.
The implant is then decellularized to prevent an immune reaction in the recipient, which could lead to rejection by the body.
“Once implanted, however, the vessel recruits the patient’s own stem cells and begins to resemble a native vessel within a month or two,” Saunders explained.
Saunders said the intent is to use the product as close as possible to the site of injury on the battlefield, providing a permanent vascular repair solution.
Ideally, the graft would be usable at the first level where surgical care is provided to the injured (military Role of Care 2, e.g., the Forward Surgical Team).
Addressing wounds at the earliest opportunity prior to evacuation provides the greatest chance to save the patient and salvage damaged limbs.
“When we talk about permanent repair, we are aiming to develop an implant that remains functional for decades. This is particularly important for young Soldiers,” said Saunders.
As a joint effort between the U.S. Army Medical Research and Materiel Command’s Combat Casualty Care Research Program, the U.S. Army Institute of Surgical Research and industry partners, the project began under an Armed Forces Institute of Regenerative Medicine grant in 2008.
With this funding support from the DoD, it has since progressed to Phase 3 clinical trials for use as a hemodialysis shunt in end-stage renal disease.
“The approach to this initial development strategy [for hemodialysis],” explained Saunders, “is intended to obtain a primary indication in a relatively low-risk therapeutic area with a clear unmet need and a suboptimal current standard-of-care.”
Saunders clarified that upon U.S. Food and Drug Administration approval of its use as a hemodialysis shunt, and with additional DoD funding, the product will be well positioned to secure a secondary, military-relevant indication for arterial reconstruction.
“Because trauma is (thankfully) a relatively small market from a commercial standpoint, a key part of our strategy is to repurpose regenerative medicine products being developed for widespread chronic diseases like stroke, heart attack, kidney failure and arthritis,” he said.
As the product has progressed into the advanced development stage, management has been transferred to USAMMDA’s TIRM PMO.
Serving as the DoD’s advanced development activity for medical products designed to protect and preserve the lives of warfighters, USAMMDA develops new drugs, vaccines, blood products and medical support equipment that enhance readiness, maximizing survival of medical casualties on the battlefield.
Saunders reiterated that saving both life and limb remains the top priority for this effort.
“In the past decade,” he said, “there have been approximately 2,000 amputees that have survived injury and surgery, and another 500 or so that have had a limb saved.”
“If the new effort is successful, we expect that both more lives and limbs will be saved from fast restoration of the vascular supply.”
Thus far, the bulk of research on the new vessel has been performed through the AFIRM consortium, spanning a number of laboratories at academic medical centers throughout the U.S.
The Phase 3 clinical trials in hemodialysis patients are being conducted at more than 30 centers, and Phase 2 trauma trials are planned at six trauma centers across the country.
Saunders said that 20 to 40 vascular trauma patients will be enrolled into the study.
However, due to the challenges of conducting regulated trials in trauma patients, enrollment is anticipated to begin late this year, with completion of the study not anticipated until 2019.
As additional studies to support the arterial reconstruction indication may be required, the projected availability to the warfighter is slated for 2025.
For the DoD and those in Army Medicine, however, this may be too late.
“The DoD is providing additional funding for this later effort because we need a trauma indication as soon as possible,” said Saunders.
“We are working to help accelerate the development for trauma use with an aim to obtain licensure as early as 2020.”
This new $3.4M funding from the DoD will help support the addition of clinical sites for Humacyte’s Phase II vascular trauma trial in the US.
The trial is being conducted to study Humacyte’s investigational human acellular vessel (HAV), or HUMACYL®, to treat patients with traumatic vascular injuries from violent civilian or military events, such as automobile crashes, industrial accidents, or injuries of war.
“We are honored to be recognized and now supported by the Department of Defense for our research and development in patients with vascular trauma,” said Jeffrey H. Lawson, M.D., Ph.D., Chief Medical Officer of Humacyte.
“Vascular trauma remains a major cause of morbidity and mortality among warfighters.”
“While civilian trauma can be significant, the battlefield environment presents an even greater surgical challenge to manage trauma and prevent infection for vascular and non-vascular wounds.”
“This funding will help us continue to make important medical strides in the development of our bioengineered HAV, beyond our ongoing pivotal study for patients requiring hemodialysis.
Utilizing a soldier’s own vessel for vascular reconstruction is frequently difficult or not possible due to the nature and extent of common combat-related injuries.
Furthermore, currently used synthetic materials may be poorly suited for vascular reconstruction in the setting of combat related injuries, due to the extreme risk infection with these injuries,” notes Lawson.
“Our goal is to provide military and civilian surgeons with a safe and effective tool for long-term restoration of blood flow.
The DoD is America’s oldest and largest government agency, with over 1.3 million men and women on active duty, and 742,000 civilian personnel.
Advancing the agency’s mission to provide the military forces with the support needed to deter war and to protect the security of our country, the DoD US Army’s Medical Unit recently began working with Humacyte and other partners in the biomedical space to find solutions for injured warfighters.
(Hear from Laura Niklason, founder Humacyte. She is the Nicholas M. Greene Professor in Anesthesia and Biomedical Engineering at Yale University. Her research focuses primarily on regenerative strategies for cardiovascular and lung tissues. Dr. Niklason’s bioengineered blood vessels are currently undergoing clinical trials, and are the first life-sustaining engineered tissues to be studied under a Phase III trial. Courtesy of WITI build. empower. inspire and YouTube)
In May 2016, Humacyte announced the commencement of the HUMANITY® study, a Phase III study of HUMACYL as a conduit for hemodialysis in patients with end-stage renal disease (kidney failure) who are not candidates for fistula placement.
In September, Humacyte announced the completion of enrollment of 350 evaluable subjects this study.
The company expects 12-month post-implantation patient data from the study to be available in late-2018.
With this data, Humacyte plans to file a BLA to seek marketing authorization for HUMACYL.
(Learn More. Courtesy of hkpark47 and YouTube.)
In addition to its clinical studies for hemodialysis and vascular trauma, Humacyte is developing and plans to seek regulatory approval for additional clinical applications for its HAV, and the company recently announced the commencement of a U.S. Phase II clinical trial of the bioengineered vessel as a bypass graft in patients with peripheral arterial disease (PAD). T
he company is also continuing its efforts in advancing the development of future pipeline products that may improve treatment outcomes for patients suffering from both vascular and non-vascular diseases.
Humacyte, a privately held company founded by Dr. Laura E. Niklason, M.D., Ph.D., in 2004, is a medical research, discovery and development company with clinical and pre-clinical stage investigational products.
Humacyte is primarily focused on developing and commercializing a proprietary novel technology based on human tissue-based products for key applications in regenerative medicine and vascular surgery.
The company uses its innovative, proprietary platform technology to engineer human, extracellular matrix-based tissues that can be shaped into tubes, sheets, or particulate conformations, with properties similar to native tissues.
These are being developed for potential use in many specific applications, with the goal to significantly improve treatment outcomes for many patients, including those with vascular disease and those requiring hemodialysis.