A cure for type 1 diabetes has been “just around the corner” for decades now — or so patients have been told. But the moonshot mission has been rough.
ViaCyte knows this well after years 18 years of R&D. With every step of progress, a new mountain of challenges looms. The company puts its head down and troubleshoots through, with backing from private investors, pharma partners, the California Institute for Regenerative Medicine (CIRM) and the Juvenile Diabetes Research Fund (JDRF).
On Wednesday, the San Diego, California-based company announced a new partner; W. L. Gore & Associates, the multi-billion dollar manufacturer of medical and non-medical fabrics and devices, including the iconic GORE-TEX. If Gore can contribute some materials expertise, one more problem could get solved.
The partnership centers around ViaCyte’s flagship islet replacement therapy.
Type 1 diabetes (aka juvenile diabetes) is an autoimmune disease. It accounts for around 5 percent of all diabetes cases. Some 95 percent are caused by so-called adult-onset diabetes, which is a longer-term metabolic disorder.
While genetic and environmental factors are believed to play a role, the ultimate trigger for type 1 diabetes is not known. At some point, the immune system incorrectly recognizes beta cells in the pancreas as foreign or threatening. It begins systematically destroying them and with that, the ability of the body to produce insulin.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Insulin is the key that allows glucose to enter cells. Without insulin, glucose builds up in the bloodstream while cells are effectively being starved. For decades, patients have replaced the missing insulin with a synthetic version. Yet dosing is problematic. Too little insulin and the blood glucose levels rise; too much and the patient becomes hypoglycemic — a potentially fatal condition if the individual isn’t revived with a readily available source of sugar.
Patients must manage this life or death balancing act for the remainder of their days.
ViaCyte hopes to remove the uncertainty with its PEC-Encap combination product. It comprises PEC-01 pancreatic progenitor (stem cell precursor) cells packaged in an immune-protective device called the Encaptra Cell Delivery System.
Once implanted under the skin, the PEC-01 cells further mature into insulin-producing ‘islets’ — beta cells included. Blood can flow around the device, allowing the cells to register blood glucose in real time and produce an appropriate amount of insulin in response.
To preserve the biological package, ViaCyte has been fine-tuning its transplant device, which CEO Paul Laikind likens to a tea bag.
“In the case of PEC-Encap it’s a semi-permeable membrane that is really the active component of the device,” Laikind said in a phone interview. “That membrane is sized such that oxygen, nutrients, glucose, and even proteins can move freely back and forth across the membrane surface. But it is also sized such that cells cannot. So none of the immune cells of the host are able to penetrate and communicate with the cells inside, so to speak, or directly access the cells in the device. And none of the cells inside the device are able to exit.”
That separation is critical for staving off the two-pronged immune response waiting to neutralize the cells.
Once triggered, the immune system of diabetes patients will forever be geared towards destroying beta cells. That’s the autoimmune component. The second issue is the natural immune rejection that occurs when cells or tissues containing foreign DNA are introduced into a transplant patient. ViaCyte uses stem cells derived from an embryo, which triggers this kind of reaction.
Finding a balance between cell preservation and efficacy is hard. According to Laikind, ViaCyte had progressed into Phase 1/2 trials with the PEC-Encap, but after treating around 20 patients it identified an issue with vascularization.
The membrane doesn’t allow the components of blood vessels to pass through — they’re too big. Yet the cells need nutrients and oxygen to survive.
“When it engrafts, what we need is that vascular network to set down on the outside of the device,” Laikind said.
That’s why Gore’s expertise in medical devices is needed.
Another product being forwarded by ViaCyte is a straight transplant of insulin-producing cells. The patient would need to take immune-suppressing medications indefinitely to protect the introduced cells. According to Laikind, the side effect profile of this approach is better suited to patients who struggle to maintain stable blood glucose levels or for the 10-40 percent of patients who have hypoglycemia unawareness. In the latter cases, the individuals are unaware their blood sugar is dropping and thus, can’t halt their descent into hypoglycemia.
Beyond ViaCyte, other companies are attempting to break into the field.
Novo Nordisk, the world’s largest manufacturer of diabetes drugs, has signaled its intent to move into stem cell therapies. Another company, Semma Therapeutics, is eying up clinical trials, having developed a method for efficiently producing beta cells en masse.
Both are several steps behind ViaCyte, which is a blessing and a curse for the San Diego team. The company has raised millions as the flag bearer for a lasting therapy for type 1 diabetes. But it is also the first to encounter unforeseen challenges in the field. It’s those challenges that have slowed the march towards a cure, but progress is undoubtedly being made.
Photo: Hero Images, Getty Images
