Provention Bio’s teplizumab for delaying type 1 diabetes (T1D) will have to grapple with formulating and implementing an effective screening strategy and its ensuing costs, experts said.

There is no precedence for a T1D-delaying therapy, so developing protocols to identify eligible patients will involve a learning curve, experts noted. Because the treatment is a monoclonal antibody (mAb), its expected high price and the extensive screening required to determine eligibility will likely present payer challenges, they added.

The screening strategy will likely rely on the strategy used in the Phase II trial, which forms the basis of Provention’s BLA filing. Phase II participants had first- or second-degree relatives with T1D, and screening entailed testing for multiple autoantibodies and dysglycemia.

In clinical use, testing should be further tailored to the individual, particularly to children who have a greater risk, experts noted. Without knowing how long it takes to develop T1D, experts recommended regular screening to catch high-risk candidates early. However, experts suggested a range of optimal testing frequencies.

Provention has a PDUFA date of 2 July for teplizumab’s approval, and an FDA advisory committee (AdCom) meeting is tentatively scheduled on 27 May. The AdCom will likely deal with safety questions given the limited data made available thus far, but it may find enough momentum for a positive decision due to its efficacy, this news service reported on 25 March.

If it is approved based on the Phase II criteria, teplizumab would be limited to relatives of T1D patients, and a significant number of people who could benefit from teplizumab would be excluded, experts noted. Honing the screening criteria based on age or the titer of autoantibodies may be a way to further expand the eligible population, but the logistics and reimbursement of such an endeavor will likely be challenging, experts noted.

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Provention declined a request for comment.

Screening a key player in paradigm shift

Over time, the cost of screening candidates for teplizumab eligibility could become significant, said Dr Zan Fleming, a former FDA official and president, healthcare consultancy Kinexum, Harpers Ferry, West Virginia. Because there are currently no official guidelines for screening people at risk for T1D, the medical community will need to develop its own protocols, said Dr Emily Sims, paediatric endocrinologist, Riley Hospital for Children, Indianapolis, Indiana.

The screening strategy used by TrialNet, which ran the Phase II teplizumab study, to test children for T1D risk could serve as a real-world model for determining eligibility for teplizumab, said Sims. As per TrialNet’s protocols, children who are relatives of T1D patients are tested for diabetes-related autoantibodies. If they have one antibody, they are rescreened annually. If they have multiple antibodies, they undergo glucose impairment testing annually.

Similarly, the Phase II participants were tested for diabetes-related autoantibodies, and those who tested positive for at least two were given an oral glucose tolerance test. First-degree relatives were ages 8–45 years, while second- or third-degree relative had to be ages 8–20 years.

In the real-world setting, after a positive antibody test, the glucose screening schedule could range between every three and 12 months and should be tailored to the person depending on the number of antibodies, clinical judgement and if there were any metabolic abnormalities, said Dr Hertzel Gerstein, professor, Department of Medicine, McMaster University, Hamilton, Canada. Sims agreed, noting the lifetime risk of T1D for a 50-year-old with multiple autoantibodies is significantly lower than for a one-year-old, making the optimal testing frequency for each individual different.

It is not known how long it takes from testing positive for the antibodies to T1D onset. As such, individuals need to be­­ monitored regularly, said Dr Milos Mraz, endocrinologist, Institute of Clinical and Experimental Medicine, Prague, Czech Republic.

Screening costs will factor into teplizumab insurance coverage decisions, but value-based agreements between health plans and the company for both could be a place to start, noted R Brett McQueen, PhD, assistant professor, Centre for Pharmaceutical Outcomes Research, University of Colorado Anschutz Medical Campus. A mail-order autoantibody test can cost up to $55 and requires a second test to confirm positive results. Direct-to-consumer oral glucose tolerance tests cost between $42 and $89, according to public information.

One potential strategy involves risk-based agreements where Provention will cover screening costs in exchange for a health plan reimbursing the full cost of the drug, McQueen said. Alternatively, plans could cover the screening, and once a patient is identified and on teplizumab, there could be a rebate related to those screening costs, he said.

Payers are traditionally reluctant to cover preventative care, noted investigator Dr Kevan Herold, professor, endocrinology, Yale School of Medicine, New Haven, Connecticut. However, given the economic implications of delaying T1D in young children, there is value in covering teplizumab, he noted. On average, managing T1D costs $2,500 per year with insurance, according to public information. Since people with multiple autoantibodies and impaired glucose are guaranteed to develop T1D, the traditional cost-benefit paradigm for preventative care is changed, said Herold.

In most EU countries, national healthcare systems would probably cover screening costs, said Dr Edoardo Mannucci, associate professor of Endocrinology, University of Florence, Italy. Those costs will be added to the costs of the drug for its pharmacoeconomic assessment, he added. A recently released analyst report stated Provention is comfortable with pricing assumptions being in line with single-course multiple sclerosis drugs, in the range of $100,000 per patient.

However, it may be harder to show teplizumab’s clinical benefit in comparison to mAbs for chronic diseases, Fleming said. The age at which a person is diagnosed with T1D plays a role from a quality-of-life and value perspective, McQueen noted. It is crucial for the company collecting this data to quantify this, he said. The Phase II study found teplizumab delayed T1D onset by a median of three years.

Expanding niche population comes with challenges

Based on recent data, about 15% of T1D patients have close relatives with T1D, so the Phase II screening strategy would miss almost 85% of those who will go on to develop the disease, said Dr Michael Nauck, head of Clinical Research, Diabetes Division, Medical Department I, St. Josef-Hospital (Ruhr-University Bochum), Germany.

Herold advocated for universal paediatric screening for autoantibodies; 2–4 year-olds could be tested once and again between five and seven years. While people could develop autoantibodies later, this system would catch most high-risk individuals, as around two-thirds of T1D patients develop the disease before the age of four years, he added.

A universal preschool screening program in Bavaria could serve as a model, Herold said. McQueen also noted the Autoimmunity for Kids screening program at the Barbara Davis Center for Diabetes in Colorado as another project as being potentially instructive.

Payer concerns over wider screening can be mitigated through risk-based agreements, McQueen said. He pointed to the example of what has been attempted in opening up prenatal screening to women ages under 35 years.

Teplizumab presents a tremendous value to those at risk for developing T1D, but insurance plans will face tradeoffs, if all individuals in a certain age range are screened to identify the small population of people who are at risk for T1D, he noted. The aforementioned Bavarian program screened 90,632 children between ages two and five years, and 280 were identified as having multiple autoantibodies.

Either testing costs need to be lowered or clinical effectiveness needs to be judged based on advanced metrics assessing clinical benefit, like diabetic ketoacidosis reduction, McQueen noted. The Bavarian program helped reduce the risk of diabetic ketoacidosis (Ziegler, et al., JAMA 2020, Jan 28;323(4):339–351).

Manasi Vaidya is a Associate Editor and William Newton is a Healthcare Reporter for Clinical Trials Arena parent company GlobalData’s investigative journalism team. A version of this article originally appeared on the Insights module of GlobalData’s Pharmaceutical Intelligence Center. To access more articles like this, visit GlobalData.