The FDA approved an anti-CD3 antibody that delays type 1 diabetes onset!
A milestone for managing type 1 diabetes: Tzield (teplizumab)
The treatment of type 1 diabetes (T1D), a chronic autoimmune disease that affects millions worldwide, is about to undergo a revolution. Thanks to Tzield (teplizumab), a recently FDA-approved drug developed by Provention Bio, managing the disease and delaying symptom onset by nearly three years is now possible.
Tzield (teplizumab) – A Game-Changing Therapy for Type 1 Diabetes
Tzield (teplizumab) is the first CD3-directed IgG1 monoclonal antibody to receive marketing authorization for an autoimmune condition. Tzield delays the onset of T1D by targeting the CD3 molecule on T cells and depleting autoreactive T cells (which attack beta cells in the pancreas) from circulation. While Teplizumab does not cure T1D, it offers patients at risk a much-needed treatment option.
Teplizumab Mechanism of Action, adapted from Provention’s Investor Presentation
The Journey of Anti-CD3 Antibody Therapeutics
Anti-CD3 antibodies have been studied as a potential treatment for type 1 diabetes since the 1960s and 1970s. The first clinical approval of a monoclonal antibody (mAb), Orthoclone OKT3, led to severe cytokine release syndrome and eventual withdrawal from clinical use in 1985. Technological advancements in the 1990s led to the development of modified CD3-specific mAbs showing potential for treating autoimmune diseases. Clinical trials of CD3-specific mAbs have shown slower deterioration of β-cell function with no evidence of severe systemic inflammation.
Over 20 years in the making
Teplizumab had a long and tumultuous journey to approval. In the mid-1990s, animal studies showed that anti-CD3 antibodies could prevent or induce remission of diabetes by exhausting autoreactive T cells. Eli Lilly partnered with MacroGenics in 2007 for a phase III trial in 500 patients with recent-onset type 1 diabetes. However, in 2010, the trial failed to meet its primary endpoint, and Lilly dropped the drug.
In 2019, a small NIH-sponsored phase II trial gave Teplizumab new life. Researchers randomized 76 at-risk participants to a 14-day course of the antibody or placebo and found that the median time to the diagnosis of type 1 diabetes was longer in the antibody arm. The results were promising enough for Provention, which acquired the antibody in 2018, to submit it for FDA approval. In 2021, the FDA narrowly voted in favor of approval, but ultimately requested further study. It has since been approved to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients with stage 2 type 1 diabetes.
FDA Approves a Drug That Can Delay Type 1 Diabetes, source: The New York Times
What's Next for Tzield (teplizumab)?
The journey of teplizumab highlights the challenging path from concept to market for new therapeutics. Despite the setbacks, researchers and companies persisted in their efforts to develop a treatment that could delay or prevent type 1 diabetes. Ongoing phase III trials will provide further insight into the potential impact of teplizumab, and the evolving landscape of diabetes research offers opportunities for continued innovation in the field.
As the field of biologics research continues to expand, companies like Nanome are taking steps to make drug discovery more efficient and effective. Nanome offers a software platform for drug discovery, enabling researchers to visualize, design, and simulate molecules in 3D. To support biologics research, Nanome is developing features specifically for large molecules - the Antibody Representation plugin and the Cryo-Em plugin - making the software more versatile and better suited to the needs of researchers working with complex biologics. By leveraging virtual reality technology, Nanome helps accelerate the discovery and development of novel biologics, which have the potential to transform treatment of a wide range of diseases.
References
Dolgin, E. Drug for delaying diabetes wins landmark approval. Nat Biotechnol 41, 6–7 (2023)
Anti-CD3: the agonist and the ecstasy (2021)
FDA Approves First Drug That Can Delay Onset of Type 1 Diabetes (2022)