CRISPR/ViaCyte and Genprex Vie for First Diabetes Gene Therapy

A female Researcher works with vials of blood/courtesy of Getty Images

Genome editing has been a hot-button topic in recent years. With the rise of CRISPR technology in the news, this is not surprising for either scientists or investors.

In February 2022, CRISPR Therapeutics and ViaCyte made history, carrying out the first-in-human transplant of gene-edited, stem cell-derived pancreatic cells to treat Type 1 diabetes (T1D).

With results of an animal study published in February 2023, Genprex aims to add credibility to another genome editing approach in the hunt for a functional cure to T1D.  

Based in Austin, Texas, Genprex focuses on developing life-changing therapies for cancer and diabetes.

The company’s pipeline includes three different products under investigation: Reqorsa, GPX-002 and GPX-003. While Reqorsa is seeking indications in cancer in Phase I trials, GPX-002 and GPX-003 are undergoing preclinical trials for diabetes, with GPX-002 targeting T1D and GPX-003 targeting type 2 diabetes (T2D). 

While traditional gene therapies include replacement gene therapy, gene editing and CAR-T for diabetes, Genprex aims to use Adeno-Associated Virus (AAV) pancreatic intraductal infusions to deliver Pdx1 and MafA genes to the pancreas.

Non-Human Primate Study

One month after eight non-human primates (NHPs) were injected with streptozocin to induce diabetes, surgical procedures were performed to provide infusions to the subjects.

Results showed the NHPs had decreased insulin requirements, increased C-peptide levels, improved glucose tolerance compared to baseline and more insulin-positive cells compared to non-treated diabetic controls based on immunohistochemistry.

The researchers assessed blood glucose and insulin requirements. During the untreated diabetes induction period, total daily exogenous insulin levels were between 8 and 10 units and average daily blood glucose levels were between 50 and 100 mg/dL.

After Genprex’s investigational AAV-CMV-Pdx1-mafA construct was injected during the surgical procedure, average daily blood glucose levels spiked to 200 mg/dL initially, but total daily exogenous insulin levels decreased to below 4 units.

Average daily blood glucose levels decreased to around 100 mg/dL 56 days after the operation. Average glucose stimulated insulin secretion remained higher following the operation compared to prior, and eight weeks after the operation, glucose suppression capabilities improved.

At the 3-month mark, NHP2 recent glucose tolerance test results showed there was virtually no difference between treated diabetic NHPs at the 3-month mark versus healthy NHPs.

While this achievement may seem to be revolutionary, there are unknowns that need to be assessed.

Genprex stated the gene therapy could be administered without an operation using routine endoscopic retrograde cholangiopancreatography in humans, but this is a different type of procedure from the one used on NHPs.

In addition, the allure of a quick cure to diabetes may require some cultural acceptance for patients used to lifelong interventions such as oral and injectable treatments.

Finally, Genprex’s human trials have yet to commence, so FDA approval for this type of treatment may not hit the market until the latter half of the 2020s at the earliest.

CRISPR and ViaCyte in Phase I

CRISPR and ViaCyte are slightly further ahead with their diabetes genome editing treatment, VCTX210. This was a key attraction for Vertex, which acquired ViaCyte in July 2022. 

While previous products from ViaCyte such as PEC-Direct require long-term immunosuppression with drugs, VCTX210 is designed to be a more permanent solution without the need for immunosuppressants.

As of February 2023, the companies had completed dosing in Phase I subjects. While this is technically one step ahead of Genprex, the Phase I trial is primarily looking at safety as opposed to efficacy data.

There are also some differences between VCTX210 and Genprex’s products. VCTX210 is an allogeneic, gene-edited, stem cell-derived therapy designed as a best-in-class treatment for T1D and insulin-dependent T2D, while Genprex uses viral delivery.

Regardless of what the future holds for Genprex versus CRISPR/Viacyte, these gene therapy agents hold much promise in the search for a single solution to diabetes. With potential answers for a patient pool that numbers in the hundreds of millions worldwide, keep an eye out for these frontrunners in the next few years.