A biologic therapy that delays the onset of type 1 diabetes was approved by the US Food and Drug Administration on Thursday.
It is the first approved therapy to prevent type 1 diabetes.
ProventionBio and Sanofi’s monoclonal antibody teplizumab, marketed under the brand name Tzield, is given by intravenous infusion.
It’s thought to work by blunting the body’s misguided attack on its own insulin-producing cells. The idea is that protecting these cells buys people more time before they become insulin dependent to manage their condition.
In clinical studies, Tzield delayed progression to full-blown diabetes by just over two years. However, for some study participants, the benefits lasted much longer.
One of them, Mikayla Olsten, was evaluated for diabetes after her 9-year-old sister Mia suddenly had a life-threatening episode of diabetic ketoacidosis and was diagnosed with diabetes. There was no family history of diabetes, and Mikayla was not ill, but she did have four of the five types of autoantibodies that doctors look for to assess a person’s risk.
“They told us if someone has that many markers, it’s not if they develop diabetes, it’s when,” her mother, Tracy, said.
Mikayla was 15 when she entered the study and received teplizumab. She is now 21 and a senior in college. She gets an annual series of tests 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 of autoimmune disease and episodes of uncontrolled blood sugar, the five-year risk of progression to an 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 on insulin, managing her diabetes is an ongoing task.
“She can juggle an awful lot that her peers can’t. She has to plan ahead if she has a basketball game or practice to make sure she’s carbing in and getting her insulin levels down,” Tracy said. “She can’t go a minute or a day without constantly thinking about it, and to be able to give Mikayla an opportunity where she doesn’t have to think about it 24/7 is amazing.”
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 the way to getting it.
“Screening is becoming a really big problem because we know 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 screening” with blood tests to look for markers of the disease.
Tzield is approved for use in people aged 8 years and older who have stage 2 type 1 diabetes. At this stage, doctors can measure antibodies that attack 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 industry but also our medical system is managing autoimmune diseases and especially type 1 diabetes is really sub-par in this day and age,” said Ashleigh Palmer, co-founder and CEO of ProventionBio. “What we do is we wait for the symptoms of the disease to appear in the doctors, and then the doctors chronically treat the patient’s symptoms for life. The problem is that with type 1 diabetes it is too late when the symptoms first appear.”
The treatment consists of a single 14-day infusion course, each lasting 30 to 60 minutes.
The most common side effects reported in study participants were low white blood cell and lymph cell counts, rash and headache.
In type 1 diabetes, a person’s immune system attacks beta cells in the pancreas, which produce insulin, a hormone that helps blood sugar enter cells where it’s used for energy. The attack can take years before symptoms of diabetes appear. Without insulin, blood sugar can build up in the bloodstream and break down endogenous fat and muscle.
Palmer says Tzield stops the disease before symptoms appear by halting the autoimmune disease process and the underlying destruction of beta cells. The treatment essentially restarts the immune system and preserves beta cell function.
“We really don’t have a preventative measure for type 1 diabetes yet, and despite that [the National Institutes of Health] Funded hundreds of millions of dollars over the last 20 years for a program called TrialNet that has tested many, many different things, including this, and some of that came out of that work,” said Dr. Robert Gabbay, Chief Scientific and Medical Officer of the American Diabetes Association. “Finally there’s something that’s delaying the onset of type 1 diabetes and it’s so exciting.”
Unlike type 2 diabetes, which can be prevented with lifestyle changes such as weight loss and exercise, type 1 diabetes is a genetic condition that has not previously had any preventative options.
“For some reason we don’t test for type 1 diabetes, even though biomarkers are available showing that the autoimmune disease process is already underway,” Palmer said. He added that hopes the drug will catalyze the medical system to launch population-based screening during routine childhood well visits to catch 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 these specific antibodies. If antibody levels are high and it appears the person is about to develop diabetes, treatment will delay this process.
“A common question when someone has Type 1 is, ‘Well, what about my child? Will they develop Type 1?’ It’s only about a 5% risk, so most of the time they won’t do it, but if you could find those who would and treat them, that can make a big difference,” Gabbay said.
Delayed diagnosis of type 1 diabetes could have significant implications.
“Obviously, quality of life is significantly impacted, negatively impacted, when you are diagnosed with type 1 diabetes. It’s a disease that never goes away,” Palmer said.
People with type 1 diabetes need to monitor their blood sugar levels around the clock, which affects how they exercise and eat. High blood sugar can lead to diabetic ketoacidosis, in which the body starts breaking down fat for fuel and can cause acids called ketones to build up in the bloodstream. This condition can lead to hospitalization, coma, or death.
In 2019, about 1.9 million people in the United States had type 1 diabetes, including 244,000 children and adolescents, according to the American Diabetes Association. Type 1 affects 8% of all diabetics.
“Type 1 occurs mostly in children and teenagers, and when you’re in the throes of adolescence when you just want to forget you have it,” said Olivier Bogillot, Sanofi’s US general medicine director. “So if you can treat it with just delaying the onset of the disease, you can change the way quality of life is impacted for families and those children.”