The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for delaying type 1 diabetes by the U.S. Food and Drug Administration should advance efforts to increase screening to cost-effectively identify people at risk of the disease who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved on November 17 as the first disease-modifying therapy to prevent the progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical type 1 diabetes (stage 3) of about 2 years, or even more in some cases.
It is administered by intravenous infusion once a day for 14 consecutive days and is expected to cost around $200,000 for the duration of treatment.
The specific indication is “to delay the onset of type 1 diabetes mellitus stage 3 in adults and pediatric patients 8 years of age and older who currently have type 1 diabetes mellitus stage 2”. In stage 2 type 1 diabetes, the individual has at least two anti-islet autoantibodies and abnormal blood sugar levels, but is still asymptomatic. It is associated with an almost 100% lifetime risk of progression to clinical type 1 diabetes (stage 3) and a 75% risk of developing the disease within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of people with the disease through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But since 85 to 90 percent of people who develop type 1 diabetes do not have first-degree relatives with the disease, broader population screening will be needed to identify eligible candidates for teplizumab.
On an investor call Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” included “raising awareness and screening for autoantibodies in those at risk.” , and finally, routine screening at pediatric well visits for general.” population”, as well as “[healthcare provider] confidence in teplizumab and the desire to prescribe it to their patients.”
Without broad, population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those in stage 2 identified to receive teplizumab. Today, that population is estimated at around 30,000 in the United States, Hoitt said, adding, “With this approval, we hope that more stage 2 patients can be easily identified so that disease progression can be modified”.
During the call, Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per continuous regimen of 14 vials, which should be a dose sufficient for most patients. The company has also launched a program called COMPASS to help patients manage insurance reimbursement, as well as providing financial assistance for some.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said Medscape Medical News that clinicians should not doubt the value of delaying the onset of type 1 diabetes, even if it does not completely prevent it.
“It’s the first drug ever to treat the underlying disease. There’s this undercurrent that insulin is enough. Why would you take the extra risk of immunotherapy? Type 1 is hard to live. I think sometimes the clinical community doesn’t understand that insulin is not enough. It’s very difficult, and it’s important to open that door… We strongly believe that the time to onset of diabetes type 1 is clinically significant. We hear that from every family we’ve spoken to. Clinicians should appreciate that and not overlook it.”
How would the screening be done?
Although the path to universal screening for type 1 diabetes risk is still unclear, much thought and research has gone into it even before teplizumab and other immunomodulating agents showed promise in preventing diabetes. sickness.
Data from a universal school-child screening program implemented in Bavaria, Germany, and a screening program in Denver, Colorado, suggest that even without such intervention, identifying those at high risk of developing type 1 diabetes could be cost-effective by educating the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person will progress to developing diabetic ketoacidosis ( ACD) before diagnosis.
Another study that used data from the United States and Western Europe found that screening for islet autoantibodies associated with type 1 diabetes in children at ages 2 and 6 years would identify most of those who develop the disease in mid-adolescence.
However, using a genetic risk score at birth to identify those who would pass autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, Washington, Told Medscape Medical News.
The score – based on human leukocyte antigen (HLA) haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of type 1 diabetes cases in children among the top 10% of all newborns. Thus, only the wealthiest 10% would then receive the most expensive autoantibody tests.
“I have been working with UK colleagues for 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I am convinced this is the most cost effective solution. It is relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful, an approach must be cost-effective. Payers are willing to pay for newborn screening, but not so much to test 100% of children for antibodies,” Hagopian said.
He is currently working with Washington State Newborn Screening Laboratories to demonstrate the feasibility of the approach using dried blood samples from actual newborn screening after obtaining informed consent from mothers in postpartum wards. of several hospitals. People deemed high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think he actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually the strategy will be added to the Recommended Uniform Screening Panel (RUSP) for universal newborn screening programs, as recommended by the U.S. Department of Health and Human Resources. Social services.
“Newborn screenings for other diseases are routinely carried out. Most are far less common than type 1 diabetes. So while our approach is less than 100% sensitive, this condition is much more common than the many inborn errors of metabolism, we “I’m still going to identify many cases… That’s my hope as to how universal screening for type 1 diabetes will pan out. I see how it could work very well.”
A two-pronged approach to screening may work better
Meanwhile, JDRF, which has supported teplizumab research along with others working in the field, is focusing on both genetic testing and autoantibodies, Kowalski said.
“JDRF works on both avenues – testing children at birth for genetic predisposition and also antibody testing. We have huge programs focused on antibody testing in the general population.”
Kowalski said that while the two-pronged approach is certainly worth exploring — and JDRF does — he also thinks universal autoantibody testing could be cost-effective if done efficiently, such as with less testing. expensive than that used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that do broad autoantibody screening of all children. We hope that it will be very profitable if we switch to cheaper tests.”
He noted that the proportion of children with new-onset type 1 diabetes who had DKA increased from 40% before COVID-19 to 50% in the early days of the pandemic. On the other hand, “With screening you can reduce that to almost zero, like they did in Bavaria. Here [in the US]a visit to intensive care for DKA [costs] $100,000.”
While JDRF and others have been working on this file for years, the new availability of teplizumab will be “multiple in helping things…I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be quite simple that there is a huge benefit to delaying disease from a short-term and long-term cost perspective. This is the first time we have a drug with a price tag attached to it.
But that might not happen quickly, Kowalski warned. “I think there’s a … series of events that have to happen to drive towards universal screening. Here in the United States it’s complicated because we have a very different healthcare system with all these different payers, public and private.
During the investor call, Hoitt said Provention Bio is also exploring the use of Tzield in younger patients and newly diagnosed patients, as well as the potential benefits of a new dosage or combination with other other treatments.
Hoitt is an employee of Provention Bio. Kowalski is an employee of JDRF. Hagopian said he received study funding from Janssen.
Miriam E. Tucker is a freelance journalist based in the Washington DC area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR‘the Shots blog and the Diabetes Forecast magazine. She’s on Twitter @MiriamETucker.
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