A biologic therapy that delays the onset of type 1 diabetes won approval from the US Food and Drug Administration on Thursday.
It is the first treatment approved for the prevention of type 1 diabetes.
The monoclonal antibody teplizumab, to be marketed under the brand name Tzield, from ProventionBio and Sanofi is given through intravenous infusion.
It is thought to work by turning down the body’s misdirected attack on its own insulin-producing cells. The idea is that protecting these cells buys people more time before they become dependent on insulin to manage their condition.
In clinical trials, Tzield delayed the progression to full-blown diabetes by just over two years. But the benefits have lasted much longer in some of the study participants.
One of them, Mikayla Olsten, was screened for diabetes after her 9-year-old sister, Mia, suddenly developed a life-threatening episode of diabetic ketoacidosis and was diagnosed with diabetes. There was no family history of diabetes, and Mikayla was not sick, but she had four of the five types of autoantibodies that doctors look for to assess a person’s risk.
“They told us that when someone has that many markers, it’s not if they’re going to develop diabetes, it’s when,” said her mother, Tracy.
Mikayla was 15 years old when she joined the study and received teplizumab. She is now 21 and a senior in college. She gets an annual battery of tests to check her pancreas and blood markers, and Tracy Olsten says her condition hasn’t progressed in six years.
According to a scientific statement from the Juvenile Diabetes Research Foundation, the Endocrine Society and the American Diabetes Association, when a person has markers of autoimmune disease and episodes of uncontrolled blood sugar, the five-year risk of progression to insulin-dependent symptomatic disease. 75%. The lifetime risk of developing insulin-dependent diabetes is almost 100%.
So far, Mikayla seems to be beating those odds.
Tracy said that for Mia, who is dependent on insulin, managing her diabetes is a constant task.
“She has a tremendous amount of juggling that her peers don’t have to do. She has to plan ahead when she has a basketball game or practice to make sure she carb-ups and lowers her insulin levels,” Tracy said. “She can’t walk for a minute or a day without thinking about it nonstop, and being able to give Mikayla the opportunity where she doesn’t have to think about it 24/7 is amazing.”
Aaron Kowalski, executive director of the Juvenile Diabetes Research Foundation, says the main challenge in prescribing Tzield will be finding people who need it. The drug is approved for people who have no symptoms of the disease and may not know they are on the way to getting it.
“Screening becomes a very big issue, because what we know is that about 85% of type 1 diagnoses today are in families that don’t have a known family history,” Kowalski said. “Our goal is to do general population screening” with blood tests to look for markers of the disease.
Tzield is approved for use in people 8 and older who are in stage 2 of type 1 diabetes. At that stage, doctors can measure antibodies that attack insulin-producing beta cells in the person’s blood, and they have abnormal blood sugar levels, but the body can still make insulin.
“The way not only the industry, but our medical system goes about managing autoimmune diseases, and especially type 1 diabetes, is really suboptimal in this day and age,” said ProventionBio co-founder and CEO Ashleigh Palmer. “What we do is we wait until the symptoms of the disease come to the doctors, and then doctors treat the patient’s symptoms chronically for a lifetime. The problem is that with type 1 diabetes, once the symptoms appear, it’s too late.”
The treatment comes in a single 14-day course of infusions each lasting 30 to 60 minutes.
The most common side effects reported in the trial participants were low white blood cell and lymphocyte counts, rash and headache.
With type 1 diabetes, a person’s immune system attacks cells called beta cells in the pancreas that produce insulin, a hormone that helps blood sugar enter cells, where it is used for energy. The attack can happen for years before any symptoms of diabetes appear. Without insulin, blood sugar can build up in the blood and break down the body’s own fat and muscle.
Palmer says Tzield stops the disease before symptoms appear by stopping the autoimmune disease process and the underlying destruction of beta cells. The treatment essentially restarts the immune system and preserves beta cell function.
“We don’t really have any preventative measures for type 1 diabetes to date, and that’s despite it [the National Institutes of Health] funded hundreds of millions of dollars over the last 20-plus years of a program called TrialNet that has tested many, many different things, including this, and some of this came out of that work, said Dr. Robert Gabbay, chief scientific and physician for the American Diabetes Association. “Finally, something is delaying the onset of type 1 diabetes, and that’s so exciting.”
Unlike type 2 diabetes, which can be prevented with lifestyle changes such as losing weight and exercising, type 1 is a genetic disease that has had no prevention options until now.
“For some reason, we don’t screen for type 1 diabetes, even though there are biomarkers that show the autoimmune disease process is already underway,” Palmer said. He added that the hope is that the drug will catalyze the medical system to start population-based screening during routine childhood visits to intercept the disease and delay its onset.
With Tzield, doctors would test individual family members of people with type 1 diabetes to see if they have the specific antibodies. If the antibody levels are high and it appears that the person is about to develop diabetes, treatment will delay that process.
“If someone has type 1, a common question that comes up is ‘well, what about my child? Are they going to develop type 1?’ It’s only about a 5% risk, so more often than not they won’t, but if you could find the ones that would and treat them, that could make a big difference, Gabbay said.
A delayed diagnosis of type 1 diabetes can have a significant impact.
“Obviously the quality of life is significantly impacted, negatively impacted if you are diagnosed with type 1 diabetes. It’s a disease that never goes away,” Palmer said.
People with type 1 diabetes must monitor their blood sugar levels around the clock, which affects how they exercise and eat. High blood sugar can lead to diabetic ketoacidosis, where the body begins to break down fat for fuel, and can cause a build-up of acids called ketones in the blood. That condition can lead to hospitalization, coma or death.
As of 2019, about 1.9 million people have type 1 diabetes in the United States, according to the American Diabetes Association, including 244,000 children and adolescents. Type 1 affects 8% of all people with diabetes.
“The prevalence of type 1 is mainly in children and teenagers, and when you’re in the throes of youth, when you just want to forget you have it,” said Olivier Bogillot, Sanofi’s head of US generic drugs. “So when you have the ability with a treatment to just delay the onset of the disease, you can change the way the quality of life is affected for families and for these children.”