An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
First Successful Clinical Trial with Anti-CD40L Antibody is Completed
On October 29, a potentially major advancement for type 1 diabetes treatment was announced by the University of Miami Diabetes Research Institute (UM-DRI), in collaboration with the University of Chicago, regarding the pioneering the use of Tegoprubart (Eledon Pharmaceuticals, Irvine, Calif.), a novel anti-CD40L antibody, as an alternative to Tacrolimus in islet transplantation. UM-DRI’s extensive preclinical research laid the foundation for the FDA-approved human trial which is now underway at the University of Chicago.
Research and subsequent clinical trial results were presented today at the 5th Annual Summit on Stem Cell Derived Islets in Boston, Mass.
Pre-clinical research at UM-DRI, supported in part by the Diabetes Research Institute Foundation (DRIF), was led by Norma Kenyon, PhD, (deputy director and professor of surgery, microbiology, immunology and biomedical engineering at the UM-DRI) and Camillo Ricordi, MD, (director of the Cell Transplant Center and director emeritus of the DRI, professor and chief of the Division of Cellular Transplantation). Their work demonstrated the safety and efficacy of Tegoprubart in large pre-clinical models, paving the way for the FDA-approved clinical trial at the University of Chicago, led by Piotr Witkowski (professor of surgery and director of the Pancreatic and Islet Transplant Program at the University of Chicago).
New Approach, Reduced Toxicity
For patients in the clinical trial, donor pancreatic islets (the mini-organs containing insulin-producing cells) were infused into the liver by a minimally invasive procedure through a catheter placed by the interventional radiologist under local anesthesia. Traditionally, patients undergoing islet transplantation have relied on Tacrolimus, a calcineurin inhibitor with notable side effects. However, this new approach with Tegoprubart has the potential to minimize toxicity while preserving transplanted islet function. This advancement marks a substantial shift, as CD40L antibodies, unlike Tacrolimus, aim to condition the immune system to accept transplanted cells as “self,” thereby lowering the risk of immune rejection and potentially improving insulin production and stability. In pre-clinical trials at UM-DRI, this approach enabled higher rates of insulin secretion post-transplant, with no observed sign of toxicity toward the transplanted islets, kidneys, or other organs.
All trial patients received this novel therapy at the University of Chicago. Two female patients with type 1 diabetes, age 40 and 30, showed excellent control of glucose levels without the need for insulin injections, after decades of inability to control their blood sugar and living in constant danger of debilitating, potentially lethal episodes of low blood sugar (hypoglycemia). A third patient with type 1 diabetes had already received the anti-CD40L therapy with remarkable results that were also presented at the Boston meeting.
“There is clinical evidence from our studies and others conducted by the NIH’s Clinical Islet Transplantation Consortium that demonstrate islet transplantation can reverse diabetes,” said Witkowski. “However, the use of current standard of care anti-rejection medications, specifically calcineurin inhibitors like Tacrolimus, have limited the benefit of these procedures due to well-known associated toxicity to the islets and the kidneys, in addition to neurotoxicity and an increased risk of hypertension. Our initial results indicate that Tegoprubart can effectively protect islets from rejection without the side effects related to current standard therapy.”
Supported by The Cure Alliance (TCA), Breakthrough T1D and the DRIF, this pilot trial highlights decades of dedication by UM-DRI scientists, notably Drs. Kenyon and Ricordi, who have consistently advanced the field of islet transplantation. With longstanding support from the DRIF, UM-DRI remains at the forefront of finding safer, more effective diabetes therapies. This novel antibody approach, developed with Eledon Pharmaceuticals, holds potential for true insulin independence.
“It has been a long journey to help people with type 1 diabetes become free from dependence on insulin,” said Ricordi. “This strategy holds great promise!”
Pancreatic Cancer Test Cost-Effective When Used as a Surveillance Tool in High-Risk Patients Newly Diagnosed with Diabetes
On October 31, ClearNote Health announced the results of a cost-effectiveness analysis on the use of the Avantect Pancreatic Cancer test to manage new-onset diabetes (NOD) patients for their risk of developing pancreatic cancer in the first three years post diabetes diagnosis.
ClearNote Health is an early cancer detection company focused on enabling people at risk for high-mortality cancers to live longer, healthier lives. These findings, developed in collaboration with the Mayo Clinic and the Arizona Centers for Digestive Health, will be presented on November 19 at the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) conference.
Greater than 80% of pancreatic cancer patients present with either type 2 diabetes or impaired glucose tolerance. The increased incidence of pancreatic cancer in patients diagnosed with diabetes has been observed repeatedly in clinical studies, in most cases less than 24 months prior to their diagnosis of pancreatic cancer. Avantect was shown to be cost-effective when used to detect early-stage pancreatic cancer in recently diagnosed diabetes patients 50 years of age or older.
“This health economic analysis is groundbreaking. Modeling suggests more patients would be detected with early stages of the disease, potentially increasing eligibility for life-saving surgical treatment. In collaboration with our research partners, we have shown that monitoring newly diagnosed type 2 diabetes patients 50 and over for pancreatic cancer using Avantect is not only a potential game changer for survival but it’s also more cost-effective for the healthcare system,” said David Mullarkey, CEO of ClearNote Health.
ClearNote Health aims to directly address the unmet need for early cancer detection in high-risk patients. The company’s proprietary epigenomic and genomic methods use a standard blood draw to identify pancreatic cancer signals at its earliest stages by measuring 5-hydroxymethylcytosine (5hmC) levels, copy number variants, and fragment sizes in cell-free DNA.
Positive Preliminary Results Announced from First-in-Human Feasibility Study Using Nanosecond Pulsed Field Ablation to Treat Benign Thyroid Nodules
On October 31, Pulse Biosciences, Inc., announced positive preliminary results from its first-in-human feasibility study using Nanosecond Pulsed Field Ablation for the treatment of benign thyroid nodules. Stefano Spiezia, MD, presented these results today at the 2024 American Thyroid Association Annual Meeting.
The preliminary data demonstrate that nano-PFA pulses effectively delivered by the company’s Percutaneous Electrode System reduced nodule sizes on average by over 50%, without evidence of residual fibrosis or scarring, and provided symptomatic relief within the first month of treatment. The nonthermal and minimally invasive nature of nano-PFA energy has shown potential to mitigate the risk of complications from thermal ablation procedures or surgical removal of benign thyroid nodules.
“I am proud to report that in the treated nodules, we observed significant nodule volume reductions which led to great improvements in symptoms for the patients in our study. We are excited to finish the long-term follow-up, complete the study, and continue the utilization of nano-PFA to advance the standard of care for patients with benign thyroid nodules,” Spiezia says. Chief of Endocrine Surgery Division at Napoli Ospedale del Mare and principal investigator of the study and founder of “Save Your Thyroid” institute.
Pulse Biosciences’ nsPFA Percutaneous Electrode System is currently being investigated by Stefano Spiezia, chief of Endocrine Surgery Division at Napoli Ospedale del Mare, Naples Italy. The study has completed enrollment in the 30-patient first-in-human feasibility clinical trial (NCT06117085) to support the initial safety and effectiveness profile of the nsPFA electrode or needle in treating and reducing the volume of benign thyroid nodules leading directly to a reduction in patient symptoms.
“These groundbreaking results suggest nano-PFA energy can provide symptomatic relief to patients with benign thyroid nodules across the first month after the treatment,” said Burke T. Barrett, Pulse Biosciences president and CEO. “We would like to thank Dr. Spiezia and his team for all the clinical work they continue to do with the System. This feasibility study and our ongoing U.S. pilot program will inform the design of the pivotal trial we intend to commence mid-2025. The study will be designed to support a specific labeling indication to commercialize the system in the United States as a treatment for benign thyroid nodules.”
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