Date: Aug 09, 2022 Author: Andrew Jacobs Source: New York Times (
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August 2022: ViaCyte Inc acquired by Vertex Pharmaceuticals (NASDAQ:VRTX) - itself an SBIR involved firm in its earlier years - in a reported $320M cash transaction.
Albeit on a limited basis and - for first time (in 2000) and long after firm's founding in 1992 - ViaCyte (by various other names: Cythera Inc~Novocell Inc~Neocrin) is usefully understood as an SBIR-involved entity. From the outset organized around diagnosis and treatment of diabetes, the underlying therapy addressed by management had been based on differentiation of stem cells into pancreatic beta cell precursors, with subcutaneous implantation in an encapsulation device.
Data in the firm's many publications early demonstrated these cells can produce therapeutically relevant levels of insulin in response to blood glucose and sustain diabetic animals.
Management's early goal - at the time - was described as a product able to free both Type 1 and Type 2 diabetic patients from long-term insulin dependence, while reducing/ eliminating hypoglycemic, microvasculature, and weight-related cardiovascular complications.
Even a cursory survey of the firm's published scientific literature, suggests the small firm's personnel as among those who first
* described directed differentiation of human pluripotent stem cells into pancreatic endoderm cells (PEC)
* and the first to demonstrate the potential of these cells as able to produce insulin in response to increased blood glucose in preclinical models.
ViaCyte personnel have subsequently -- and more recently -- shown that PEC cells further differentiate in vivo, in both preclinical and clinical studies, to the constituent cell types of the human pancreatic islet.
In the three decades since she was first diagnosed with Type 1 diabetes, Lisa Hepner has clung to a vague promise she often heard from doctors convinced medical science was on the cusp of making her body whole again. "Stay strong," they would say. "A cure is just five years away."
But the cure has yet to arrive, and Ms. Hepner, 51, a filmmaker from Los Angeles, remains hobbled by her body's inability to make insulin, the sugar-regulating hormone produced by the pancreas. "I might look fine to you," she said, "but I feel crappy 70 percent of the time."
Staying healthy can be exhausting for many of the 37 million Americans with some form of diabetes. There's the round-the-clock monitoring of sugar levels; the constant, life-sustaining insulin injections; and the potential threats from diabetes' diabolical complications: heart disease, blindness, kidney damage and the possibility of losing a gangrenous limb to amputation.
"'The cure is five years away' has become a joke in the diabetes community," Ms. Hepner said. "If it's so close, then what's taking so long? And in the meantime, millions of us have died."
That attenuated sense of hope drove Ms. Hepner to spend nearly a decade following the fortunes of ViaCyte, a small San Diego biotech company working to create what would essentially be an artificial pancreas. If successful, its stem-cell-derived therapy would eliminate the pin-pricks and insulin injections that circumscribe the lives of the 1.5 million Americans with Type 1 diabetes. Vertex Pharmaceuticals, a Boston biotech company developing a similar therapy, has already made significant headway.
Since its theatrical debut in June, "The Human Trial," the documentary she produced with her husband, Guy Mossman, has electrified the diabetes community, especially those with Type 1, a disease that the uninitiated often conflate with the more common Type 2.
Unlike Type 2, which tends to emerge slowly in adulthood and can sometimes be reversed early on with exercise and dietary changes, Type 1 is an autoimmune disease that often strikes without warning in childhood or adolescence.
Type 1 is also far less prevalent, affecting roughly 10 percent of those with diabetes. A pancreas transplant can cure the disease, but donated organs are in short supply and the surgery carries substantial risks. In most years, only a thousand transplants are done in the United States. To ensure the body does not reject the implanted pancreas, recipients must take immunosuppressant drugs all their lives, making them more susceptible to infections.
Therapies developed from human embryonic stem cells, many experts say, offer the best hope for a lasting cure. "The Human Trial" offers a rare glimpse into the complexities and challenges of developing new therapies -- both for the patients who volunteer for the grueling clinical trials required by the Food and Drug Administration, and for the ViaCyte executives constantly scrambling to raise the money needed to bring a new drug to market. These days, the average cost, including the many failed trials along the way, is a billion dollars.
At a time when the soaring price of insulin and other life-sustaining drugs has tarnished public perceptions of the pharmaceutical industry, the film is also noteworthy for its admiring portrayal of a biotech company whose executives and employees appear genuinely committed to helping humanity. (Limiting the cost of insulin remains politically volatile. On Sunday, during a marathon vote on the Democrats' climate and health bill, Republicans forced the removal of a provision with a $35 cap on insulin prices for patients with private insurance, though the cap remained in place for Medicare patients.)
"The Human Trial," which can also be viewed online, has become a rallying cry for Type 1 patients, many of whom believe only greater visibility can unleash the research dollars needed to find a cure.
Those who have seen the film have also been fortified by seeing their own struggles and dashed hopes reflected in the journeys of the film's two main subjects, Greg Romero and Maren Badger, who became among the first patients to have the experimental cell pouches implanted under their skin.
The despair that drives them to become human guinea pigs can be hard to watch. Mr. Romero -- whose father also had the disease, went blind before he was 30 and then died prematurely -- confronts his own failing vision while grappling with the pain of diabetes-related nerve damage. "I hate insulin needles, I hate the smell of insulin. I just want this disease to go away," Mr. Romero, 48, says numbly at one point in the film.
Type 1 can leave patients feeling alienated and alone, in part because of flawed assumptions about the disease. Tim Hone, 30, a medical writer in New York who has been living with Type 1 since he was 15, said friends and acquaintances sometimes suggested that he was responsible for causing his illness. "I've had people scold me and say that if I went on a diet and stopped eating Snickers bars I could reverse my disease," Mr. Hone said.
The stigma often drives people with Type 1 to hide the disease. In his quest to feel "normal" at college, Todd Boudreaux said, he avoided telling friends about his illness, a decision that could have had dangerous ramifications in the event of a seizure brought on by low blood sugar levels.
Greg Romero, one of the subjects in the documentary. "I hate insulin needles, I hate the smell of insulin. I just want this disease to go away"; he said.
"I didn't want to be defined by my illness, and I didn't want to be seen as weak, but having Type 1 does make you different and it's important that everyone around knows so they can help if you have severe low blood sugar," said Mr. Boudreaux, 35, who lives in Monterey, Calif., and works for the nonprofit group Beyond Type 1.
Ms. Hepner, too, has spent much of her life downplaying the disease, even with her husband, Mr. Mossman. She recalled his confusion early in their relationship when he awoke to find her discombobulated and drenched in sweat, the result of hypoglycemia, or low blood sugar. The more Mr. Mossman, a cinematographer, learned about the disease, the more he pressed her to make the film.
For years, Ms. Hepner stood her ground, worried about drawing unwanted attention to her health. "It's a competitive world out there and I just didn't want people to think, 'Oh, she's not thinking straight because her blood sugar is high,'" she said.
But over time, the ubiquity of pink-ribbon breast cancer awareness campaigns and highly publicized efforts to cure Alzheimer's made Ms. Hepner realize her filmmaking skills could change public perceptions of Type 1, a disease that is nearly invisible, in part because many people who have it do not look sick.
She hopes to change other misperceptions, including the notion that diabetes is a relatively inconsequential and "manageable" illness, one that has been popularized by Big Pharma's feel-good drug television commercials that feature self-assured patients playing tennis and basketball and piloting hot air balloons.
In fact, the industry spends a fraction of its research dollars on finding a cure, with the rest directed toward developing medications and devices that make it easier to live with the disease, according to the Juvenile Diabetes Cure Alliance.
The payoff from those investments is undeniable. For those who can afford them, continuous glucose-monitoring devices can obviate the need for self-administered finger-prick testing, and the machines can be paired with iPhone-size insulin pumps that eliminate much of the guesswork over dosing.
Ms. Hepner has profound appreciation for the wonders of insulin: At one point in the film she pays homage to its inventor, Frederick Banting, during a visit to his home in Canada. But she notes that insulin-dependent diabetes is no picnic. Many people without insurance cannot afford the thousands of dollars it costs annually for the drug, forcing some to skimp and ration. And a miscalculated or ill-timed dose can lead to seizures, unconsciousness and even death. Even with all the advances in care, only about 20 percent of adults with Type 1 are able to maintain healthy blood sugar levels, according to a 2019 study. On one occasion, Ms. Hepner woke up in the I.C.U. after her insulin pump failed.
"We need to stop trying to normalize this disease because, let's face it, having diabetes isn't normal," she said. "It's the other pandemic, one that killed 6.7 million people last year around the world."
Despite her frustrations, it would be inaccurate to describe Mr. Hepner and her film as pessimistic. At the risk of giving away too much, "The Human Trial" ends on a hopeful note. And despite a number of near-brushes with bankruptcy, ViaCyte succeeded in gaining the funding to keep the laboratory lights burning.
Then there is more recent news that did not make it into the film. Last month, ViaCyte was acquired by Vertex, the competing biotech company that has been developing its own stem-cell treatment. That treatment has shown early success, and last year the company announced that a retired postal worker who took part in clinical trials had been cured of Type 1 diabetes.
After almost a lifetime of hearing a cure was just around the corner, Dr. Aaron Kowalski, chief executive of the JDRF (Juvenile Diabetes Research Foundation), the world's biggest funder of Type 1 research, counts himself as an optimist. A dozen more drug companies are pursuing a cure than a decade ago, he said, and the organization this year plans to spend $100 million on cure research. "It's not a matter of if this will happen, it's a matter of when," said Dr. Kowalski, who is a scientist and has had the disease since childhood, as has a younger brother. "Our job is to make sure it happens faster."
Until that day, he added, people with diabetes, both Type 1 and Type 2, could use a little empathy and understanding.
Andrew Jacobs is a health and science reporter, based in New York. He previously reported from Beijing and Brazil and had stints as a metro reporter, Styles writer and national correspondent, covering the American South. @AndrewJacobsNYT
A version of this article appears in print on Aug. 9, 2022, Section D, Page 5 of the New York edition with the headline: The Long, Long Wait for a Diabetes Cure.