A biologic therapy that slows the onset of type 1 diabetes was approved by the U.S. Food and Drug Administration on Thursday.
It is the first therapy approved for the prevention of type 1 diabetes.
The monoclonal antibody teplizumab, which will be marketed under the brand name Tzield, from ProventionBio and Sanofi, is administered by intravenous infusion.
It is believed to work by fighting off the body’s misdirected attack on its own insulin-producing cells. The idea is that protecting these cells gives people more time before they become dependent on insulin to manage their condition.
In clinical trials, Tzield slowed progression to full-blown diabetes by just over two years. But the benefits 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 so many markers, it’s not a matter of if they’re going to develop diabetes, it’s when,” said her mom, Tracy.
Mikayla was 15 when she entered the study and received teplizumab. She is now 21 and a senior in college. She gets a series of tests every year to check her pancreas and blood markers, and Tracy Olsten says her condition hasn’t improved 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 for autoimmune disease and episodes of uncontrolled blood sugar, the five-year risk of progression to insulin-dependent symptomatic disease is 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 insulin dependent, managing her diabetes is a constant chore.
“She can juggle an awful lot that her peers don’t have to do. She needs to plan ahead when she has a basketball game or practices to make sure she gets more carbs and lowers her insulin levels,” Tracy said. “She can’t go a minute or a day without thinking about it non-stop, and it’s great to give Mikayla the opportunity where she doesn’t have to think about it 24/7.”
Aaron Kowalski, CEO of the Juvenile Diabetes Research Foundation, says the biggest 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 their way to getting it.
“Screening is going to be a really big deal because what we know is that about 85% of type 1 diagnoses today occur in families with no known family history,” Kowalski said. “Our goal is to do a general population study” with blood tests to look for markers of the disease.
Tzield is approved for use in people ages 8 and older who are in stage 2 of their type 1 diabetes. At that stage, doctors can measure antibodies attacking insulin-producing beta cells in the person’s blood, and they have abnormal blood sugar levels, but their body can still produce insulin.
“The way not only the industry, but also our medical system is addressing autoimmune diseases, and type 1 diabetes in particular, is really suboptimal in the current times,” said Ashleigh Palmer, co-founder and CEO of ProventionBio. “What we do is, we wait for the symptoms of the disease to get to the doctors, and then the doctors chronically treat the patient’s symptoms for a lifetime. The problem is that with type 1 diabetes, it’s too late when symptoms first appear.”
Treatment consists of a single infusion course of 14 days each lasting 30 to 60 minutes.
The most common side effects reported in the trial participants were low white blood cell and lymph cell counts, rash, and headache.
In type 1 diabetes, a person’s immune system attacks cells called beta cells in the pancreas that produce insulin, a hormone that causes blood sugar to enter cells, where it is used for energy. The attack can last for years before any symptoms of diabetes appear. Without insulin, blood sugar can build up in the bloodstream and break down the body’s own fat and muscle.
Palmer says Tzield staves off the disease before symptoms appear by stopping the autoimmune disease process and the underlying destruction of beta cells. The treatment essentially reboots the immune system, preserving beta cell function.
“We really don’t have a preventive measure for type 1 diabetes so far, and that despite [the National Institutes of Health] have funded hundreds of millions of dollars over the last 20 years from a program called TrialNet that has tested lots and lots of different things, including this, and some of it came out of that work,” said Dr. Robert Gabbay, chief scientist and physician of American Diabetes Association: “Finally, there’s something that slows the onset of type 1 diabetes, and it’s so exciting.”
Unlike type 2 diabetes, which can be prevented through lifestyle changes such as losing weight and exercising, type 1 is a genetic disease that has had no preventive options until now.
“For some reason, we don’t screen for type 1 diabetes, even though biomarkers are available to show that the autoimmune disease process is already underway,” Palmer said. He added that the hope that the drug will catalyze the medical system to start population screening during routine visits to the children’s wells to intercept the disease and delay its onset.
With Tzield, doctors would screen individual family members of people with type 1 diabetes to see if they have those specific antibodies. If the levels of antibodies are high and it appears that the person is on the verge of developing diabetes, treatment will slow that process.
“If someone has type 1, a common question 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 those who could treat them, it could make a big difference,” Gabbay said.
A late diagnosis of type 1 diabetes can have major consequences.
“Clearly, 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 who are type 1 diabetics need to monitor their blood glucose levels 24 hours a day, which affects how they exercise and eat. High blood sugar can lead to diabetic ketoacidosis, in which the body begins to break down fat for fuel and can cause a buildup of acids called ketones in the bloodstream. This condition can lead to hospitalization, coma or death.
As of 2019, approximately 1.9 million people have type 1 diabetes in the United States, including 244,000 children and adolescents, according to the American Diabetes Association. Type 1 affects 8% of everyone with diabetes.
“The incidence of type 1 is especially prevalent in children and teens, and when you’re in the turmoil of adolescence, when you just want to forget you have it,” said Olivier Bogillot, Sanofi’s chief of general medicine in the US. “So if you have the ability with treatment to just delay the onset of the disease, you can change the way quality of life is impacted for families and for those children.”