With the marketing authorization of this preventative therapy — a first for any autoimmune condition, and the first medicine since insulin shown to alter the course of type 1 diabetes (T1D) — patients at risk of developing the disease now have a drug they can take to help delay symptom onset.

People with type 1 diabetes require a lifetime of insulin injections. Credit: MEHMET TAYLAN / Alamy Stock Photo

“It’s a game changer,” says Carla Greenbaum, an endocrinologist at the Benaroya Research Institute in Seattle. “It changes that paradigm” of how T1D is handled.

But Tzield does not come cheap. With a sticker price of nearly $200,000 for a full course of treatment, the humanized CD3-directed IgG1 monoclonal antibody from Provention Bio might only be a cost-effective option for at-risk individuals with certain genetic and immune characteristics, studies show. And finding those individuals could prove challenging given that few places have mass screening protocols in place to identify would-be beneficiaries.

Although tests to detect immune markers of preclinical T1D have been available for years, health policymakers generally discouraged their adoption on the grounds that there was little to offer patients whose results came back positive. The arrival of Tzield changes that equation. “Now we have something to do about it,” says Kevan Herold, a clinical immunologist at the Yale School of Medicine in New Haven, Connecticut.

Herold is the chair of TrialNet, an academic consortium that led the registration-enabling trial of Tzield, which measured the time from baseline to T1D diagnosis among people at high-risk who had relatives with the disease. In that 76-person study, drug treatment postponed the onset of symptomatic T1D by a median of nearly three years — from 27.1 months among placebo recipients to 59.6 months among those who got Tzield — with side effects that included blood count abnormalities, rashes and headaches.

The treatment also helped normalize the function of insulin-producing beta cells and altered immune repertoires, with evidence that by inducing partial exhaustion of cytotoxic T cells, it creates a more tolerogenic immune environment. The antibody has the Fc region mutated to minimize target receptor binding that could lead to crosslinking and cytokine release.

Tzield is approved for anyone 8 years of age and older with blood work showing two or more autoantibodies against either pancreatic islet cells or the insulin hormone; patients should also be showing signs of impaired sugar metabolism, as measured by an oral glucose tolerance test or by another method. Recipients don’t need to have a family member with T1D to be eligible for the therapy, as they did to participate in the TrialNet study. But those types of patients are generally easier to identify, since their relatives are already engaging with endocrinologists and other diabetes specialists in the healthcare system. So, to begin with, Provention Bio and its commercial partner Sanofi intend to focus their marketing efforts on that population, a group estimated to include around 30,000 drug-eligible individuals in the United States.

“As a first step, it makes a lot of sense,” says Emily Sims, a pediatric endocrinologist at the Indiana University School of Medicine in Indianapolis. Compared to the general population, people with first- or second-degree relatives who have confirmed T1D are at a 15-fold elevated risk of developing the disease in their lifetimes. What’s more, she notes, “there’s infrastructure there for free testing among these people already.” An estimated 170,000 Americans without a family history of T1D could stand to benefit from Tzield. The challenge becomes finding those individuals.

Moving forward, diabetologists hope to offer widespread population screening for diabetes-related autoantibodies, and a few jurisdictions have run pilot programs to gauge the feasibility of such an approach. Large-scale studies from the German state of Bavaria, for example, and Colorado show it is doable, but whether community-wide screening is cost-effective is another question. “We’re still on the border about whether or not there’s enough evidence to get it into public policy,” says Kimber Simmons, a pediatric endocrinologist at the University of Colorado Barbara Davis Center for Diabetes in Aurora who is co-leading her state’s screening effort.

To expand the antibody’s reach, Provention Bio is running a large placebo-controlled trial to establish its efficacy in youngsters with newly diagnosed T1D. If approved in that context, analysts predict peak sales of the therapy could top $1.5 billion annually. Several academic trials are also ongoing or planned with a range of other drug candidates — low-dose anti-thymocyte globulin, the cytotoxic T lymphocyte antigen 4 (CTLA-4) analog Orencia (abatacept) and the CD20-targeted antibody rituximab, to name a few — both for recent-onset T1D and as disease-delaying agents.

Plus, researchers are beginning to test some therapies at the earliest stages of presymptomatic disease, when diabetes-related autoantibodies show up but people’s blood sugar levels remain normal. As Herold points out, the landmark approval of Tzield “is not the last word on preventing diabetes.”

“The field is wide open now,” he says.