Cell therapy, new PD devices, bioartificial kidneys set a new direction for kidney care
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In an editorial published in the Clinical Journal of the American Society of Nephrology, nephrologists Mark E. Rosenberg, MD, and Tod Ibrahim, MD, detailed problems the specialty may face in the coming decade.
“Nephrology is unique. Having saved the lives of millions of people with kidney failure and advocated successfully for the federal government to cover every American on dialysis, the specialty now faces challenges that obstruct advances in care and innovation,” they wrote. “[T]he federal government underfunds research into kidney disease compared with other diseases, venture capital has little interest in a disease that affects 850,000,000 people worldwide and less innovation exists around kidney disease.”
The title of the editorial, “Winning the war on kidney disease,” which was published in 2019, echoes some of the frustration device makers have about bringing new technology to the kidney care market.
“Funding for the NIH increased 37% between fiscal years 2015 and 2020, while kidney research funding increased by approximately half that percentage during that period,” Holly J. Mattix-Kramer, MD, MPH, wrote in an editorial for Healio | Nephrology News & Issues. “Funding for kidney-related research and disease prevention under the National Institute of Diabetes and Digestive and Kidney Diseases was approximately $700 million in fiscal year (FY) 2020, less than 2% of NIH funding, while traditional Medicare spending on patients with chronic kidney disease reached $130 billion, or approximately $1 in $5” of Medicare health care costs, she wrote. “This is unacceptable when 15% of the U.S. population has [chronic kidney disease].”
Facing the challenge
Nephrologist Bruce Culleton, MD, has spent most of his career in kidney care working for device companies, developing value-based care initiatives and educating patient care teams. As CEO for biotech company ProKidney, he sees potential for improving kidney care with a new innovation: renal autologous cell therapy (REACT or rilparencel).
“I am a ‘jack-of-all-trades’ in the kidney space and a master of none in some ways,” Culleton told Healio | Nephrology News & Issues. “I still think there is room for innovation in the device space, and for innovation in dialysis. But I think it is going to be incremental.”
Culleton, who took the job as CEO about a year ago, and ProKidney are focusing their research dollars (the company went public in mid-2022) on treating patients with type 2 diabetes and advanced chronic kidney disease with cell therapy to preserve kidney function.
In the case of ProKidney’s therapy, renal cells are retrieved by biopsy from patients who have type 2 diabetes and are in late stage 3b to 4 CKD. At the ProKidney manufacturing facility in Winston-Salem, cells from the biopsy are expanded, and after a cell-selection process, the final autologous product, rilparencel, is cryopreserved for injection into the kidney cortex with CT guidance.
In a study published in Blood Purification in 2023, ProKidney enrolled 10 adults with an eGFR of 14 mL/min/1.73 m2 to 20 mL/min/1.73 m2 into a single-arm open-label trial. “Following a percutaneous kidney biopsy, an ex vivo expansion of selected renal cells that constitute rilparencel was injected into the cortex of the biopsied kidney with CT image guidance. Each participant received two doses of rilparencel at 6-month intervals,” the researchers wrote.
The results showed that the need for dialysis was delayed. “At 15 months, [two]patients (20%) have eGFR slope stability and have not commenced renal replacement therapy,” they wrote.
When ProKidney began phase 2 trials in 2017, nephrologists did not have much in the toolbox to slow progression of CKD, Culleton said. “There have been a number of advances in the CKD space in the last 4 to 5 years. I think it is great for patients, and it is good for [ProKidney] too. We know there are patients who will continue to progress ... we are really positioned for patients with GFR less than 30 [mL/min/1.73 m2] with the idea of finding ways to keep them off dialysis – or keep them stable for a kidney transplant.
“I think it’s complementary” to new drug therapy for patients with CKD, Culleton said.
Culleton credits the Kidney Health Initiative (see sidebar) with providing the impetus to expand kidney research in the United States. “They really broke down some of the regulatory barriers to getting new drugs on the market for CKD,” Culleton said.
ProKidney presented results in May from its RMCL-002 multicenter phase 2 trial at the European Renal Association meeting in Stockholm. Patients participating in the trial had an eGFR between 20 mL/min/1.73 m2 to 50 mL/min/1.73 m2 and were randomized to one of two groups: those who received rilparancel shortly after kidney biopsy, and those whose treatment with rilparencel was deferred for at least 12 months after kidney biopsy. The time between first and second rilparencel injections was approximately 6 months.
“Subjects randomized to the deferred treatment arm experienced less decline in kidney function after rilparencel treatment versus standard of care,” David Gerber, MD, of the University of Cincinnati College of Medicine and colleagues wrote in a conference abstract. “Kidney function stabilized in a subgroup of subjects with stage 4 CKD and severe urine albumin-creatinine ratio. Observed procedure and product-related [serious adverse events] SAEs were tolerable and consistent with expected events from percutaneous kidney interventions,” the authors wrote.
Funding scarce
To help drive innovation, HHS collaborated with the American Society of Nephrology in 2018 to create Kidney X, distributing millions of dollars to manufacturers and start-ups interested in developing new products for kidney patients. Congress is now considering whether to keep the program funded. Legislators have proposed a $20 million appropriation for 2025.
HHS recently launched the KidneyX Sustainability Prize. “Today’s life-sustaining dialysis technology consumes large amounts of water and power, putting patients at risk during resource shortages,” according to a press release. “In a single year, hemodialysis globally requires 265 billion liters of water and uses 1.62 billion kW/h of power. Dialysis further requires a high volume of exceptionally clean water, with up to 70% of water rejected during the filtration and purification process.”
HHS will select up to seven winners to receive an equal share of up to $7.25 million in early 2025.
While KidneyX has helped to spur interest in new devices and bring in new researchers, funding products from the development stage, through clinical trials and to the marketplace requires more resources, Shuvo Roy, PhD, a member of the department of bioengineering and therapeutic sciences at the University of California San Franciso (UCSF), told Healio | Nephrology News & Issues. Roy, along with other researchers at the UCSF and Vanderbilt University, have begun developing the Kidney Project’s iBAK device, an implantable bioartificial kidney. He said recent advances on the device have been positive. “We have been able to place the mechanical component, the hemofilter, in series with the cellular component, the bioreactor, and show function of the device to produce urine, albeit on a small scale, without the need for immunosuppressive drugs and without the need for anticoagulation,” Roy said. “So the next step would be to do more testing to show the device works at a clinical scale, so we can make a request to the FDA to do human trials.”
That means the researchers need to build patient-sized prototypes and conduct long-term animal studies – an expensive proposition. In 2023, the Kidney Project was awarded a $1 million Artificial Kidney Prize from KidneyX for advancing its prototype bioartificial kidney toward a full-sized, human scale. The funding was helpful, Roy said, but building multiple prototypes reliably and reproducibly brings its own challenges.
“We have recognized that there is a need to focus on manufacturing innovations,” Roy said. “Industry partners to build these prototypes at scale aren’t there yet. Many of the medical product manufacturers are unfamiliar with the semiconductor silicon technology necessary for the iBAK device.”
In a question and answer document provided by the Kidney Project, the research group estimates that a working artificial kidney is about 5 years away from being ready for clinical trials, but the researchers estimate they need another $10 million to complete preclinical development. “Our goal is to have a device commercially available by the end of the decade, but again this depends on our funding situation, and it is also possible that unanticipated technical challenges could slow us down,” the research group wrote.
Innovation in transplant
Moving into new territory in kidney transplant leans on technology being developed at companies like eGenesis. The Cambridge, Massachusetts-based research organization recently received $191 million in financing to pursue a first-in-human kidney transplant study.
“This funding will advance our lead kidney program, EGEN-2784, to a first-in-human study for kidney transplant,” Michael Curtis, PhD, CEO of eGenesis, said in a press release.
Supporters of the eGenesis vision include dialysis providers DaVita Inc. and Fresenius Medical Care.
“This announcement from eGenesis marks a step toward a future in which the supply of transplantable organs is less of a rate limiting step in improving the quality of life for all patients with kidney disease,” Benjamin E. Hippen, MD, FASN, FAST, global head of clinical affairs for the global medical office and chief medical officer, care delivery at Fresenius Medical Care, told Healio | Nephrology News & Issues.
Portables
In November 2023, AWAK Technologies announced that its kidney disease progression prediction (KDPP) AI model for CKD patient care received breakthrough device designation by the FDA. The KDPP model helps to assess the risk of kidney disease progression and initiation of renal replacement therapy (dialysis or transplant), within a period of 1 year, 2 years and 5 years, according to a company press release. It is the second breakthrough designation for the company from the FDA. The first was for its Automated Wearable Artificial Kidney Peritoneal Dialysis (AWAK PD) device.
The company recently raised $20 million for additional research and development. “We are excited about expanding our activities into the United States, the largest dialysis market in the world,” Abel Ang, chairman of AWAK Technologies, said in the release.
“The company completed its first human trials with the AWAK PD device in 2018,” Mandar Gori, MS, MBA, chief business officer for AWAK Technologies, told Healio | Nephrology News & Issues. “The trial involved 10 patients. Each patient had up to nine sessions delivered back-to-back.” The patients were treated in an in-center setting, and the AWAK device was connected and monitored by staff, Gori said.
In a recently completed second trial, patients used the wearable/ultraportable device at home, and treatment times varied, Gori said. “Some patients used it for a week, others for a month,” Gori said. The device weighs about 7 pounds.
Gori said the next step is conducting a pivotal clinical trial in the United States using the AWAK-PD device in an effort to submit an application to the FDA.
Product improvements
Developing ground-up devices like the AWAK PD may have a long regulatory path to the kidney care market. Steve J. Lindo, CEO and co-founder of Simergent, is developing a new PD machine, called Archimedes, that he said resolves some of the problems of the current technology. “We really do think this is a game changer, but I think it starts upstream of the patient,” Lindo told Healio | Nephrology News & Issues. “We made it so much easier for patients to use. We have rich graphics and animations, we walk [patients] through every single step. Everything from connecting the tubing set to the machine to troubleshooting potential alarm conditions is displayed on the screen.”
The Archimedes is also on wheels, so it is mobile within the home, Lindo said. A recent survey published in Kidney360 earlier this year and co-authored by Lindo indicated that noise, setup time and a lack of in-home mobility were the key issues patients had with current PD machines. Drain pain and peritonitis concerns were also major complaints in a separate study, Lindo said. “I don’t think any of these items alone are going to be the single driver” for patients to select an Archimedes machine for PD, Lindo said, “but in combination it solves all the major issues around home dialysis.”
Other companies are developing PD-like devices, including iREN, an Israeli company that has a small portable device that provides short exchanges. Itasca, Ill.-based Byonyks Medical Devices raised $9 million to develop its X1 PD cycler, available in southeast Asia. An X2 model is awaiting FDA approval.. The company is also working on a product that can make PD dialysate at the patient’s bedside. “We will be eliminating 120 million PVC bags and 75 million tubing sets that go into the landfill,” Rod Kenley, the company’s chief innovative officer, said at a presentation in 2023 at a company-sponsored med tech summit.
Vascular access
New products have been developed in the last several years that are aimed at improving vascular access, including devices that reduce catheter infection risk and help speed up maturation for arteriovenous fistulas.
“After relatively little innovation in devices for HD vascular access over the past 5 decades, opportunities for technological advances seem promising in the near future,” Tushar J. Vachharajani, MD, and colleagues wrote in the American Journal of Kidney Diseases. “The global epidemic of CKD and kidney failure has ignited several interesting developments that are in the pipeline.”
The authors cite several projects that have progressed to clinical studies, including a pneumatic compression device called Fist Assist (Fist Assist Devices LLC) and the VasQ (Laminate Medical Technologies) to promote arteriovenous fistula (AVF) maturation; the av-Guardian (Advent Access) vascular access system for guiding cannulating needles into the AVF, and BioNanomatrix, a gel product made by Endomimetics designed to prevent tissue growth and stenosis in the vein segment of the AVF.
In their editorial, Rosenberg and Ibrahim said patients with kidney disease should demand innovation. “Every American must demand kidney health. The federal government must fund research into kidney disease at the same level as comparable diseases, such as cancer and diabetes,” they wrote.
“Nephrology’s current leaders must electrify the health professionals of the future.”
- References:
- HHS launches $7.25 million KidneyX Sustainability Prize. https://www.hhs.gov/about/news/2024/09/12/hhs-launches-7-25-million-kidneyx-sustainability-prize.html. Published Sept. 12, 2024. Accessed Sept. 22, 2024.
- Kramer H. Kidney community must push for more research dollars https://www.healio.com/news/nephrology/20211104/kidney-community-must-push-for-more-research-dollars. Published Nov. 8, 2021. Accessed Sept. 21, 2024.
- The Kidney Project: Creating a bioartificial kidney as a permanent solution to kidney failure. https://pharm.ucsf.edu/kidney/device/faq. Published Feb. 16, 2024. Accessed Sept. 22, 2024.
- ProKidney announces strategic updates to its phase 3 program to accelerate rilparencel’s registrational path to potential approval in the U.S. https://investors.prokidney.com/news-releases/news-release-details/prokidney-announces-strategic-updates-its-phase-3-program. Published Sept. 3, 2024. Accessed Sept. 22, 2024.
- Rosenberg M, et al. Clin Jrnl Am Soc Neph. 2019; doi:10.2215/CJN.10180819.
- For more information:
- Bruce Culleton, MD, can be reached at bruce.culleton@prokidney.com.
- Mandar Gori, MS, MBA, can be reached at mandar.gori@awak.com.
- Steve J. Lindo can be reached at sjlindo@simergent.com.
- Shuvo Roy, PhD, can be reached at shuvo.roy@ucsf.edu.
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