A Provention Bio therapy for delaying the onset of type 1 diabetes has been proven Refused Regulatory agencies questioned the comparability of the drugs tested in clinical trials with the products that the company plans to bring to the market, so they were approved by the FDA.
The drug teplizumab still has a way forward, and a clinical trial is already underway that can provide the answers the FDA needs. But the FDA’s refusal of antibodies will indefinitely delay the start of the Red Bank, New Jersey-based biotechnology company, which is expected to become its first commercial drug.
Provention shares opened at $6.40 per share on Tuesday, a drop of nearly 23% from Friday’s closing price.
The FDA specifically asked about the pharmacokinetics (PK) of teplizumab-how it is metabolized and absorbed by the body. Provention Bio obtained the drug from its partners Macrogenics and Eli Lilly, supporting the clinical data submitted by Provention to the FDA based on the API produced by Eli Lilly. According to Provention regulatory documents, for APIs produced by biotechnology contract manufacturers, the concentration of teplizumab in the blood decreases over time.
Provention has established its own model to evaluate these differences, and it believes that these differences are not enough to affect the efficacy or safety of its drugs. The FDA is not so sure. According to Provention, the FDA’s full response letter on July 2 stated that a “bridging” study comparing drugs tested in clinical trials with planned commercial products failed to show PK comparability. The complete reply letter is a personal letter and therefore will not be made public. But according to Provention’s summary of this letter, the FDA needs more information.
“Since PK is still the primary endpoint to prove the comparability between the two products, you need to properly establish PK comparability between expected commercial products and clinical trial products, or provide other data to fully prove why PK comparability is not required, “Provention quoted the FDA as saying.
Type 1 diabetes is an autoimmune disease in which the immune system destroys the beta cells of the pancreas, which in turn affects the production of the blood sugar regulating hormone insulin. Currently, the standard of care for type 1 diabetes includes insulin therapy and blood glucose monitoring.
Teplizumab is a monoclonal antibody designed to bind to a cell surface protein called CD3. This protein helps activate T cells and direct various immune responses. Provention stated in its regulatory documents that research has shown that the combination with CD3 triggers can restore immune tolerance and may prevent immune cells from attacking beta cells.
Provention’s submission of teplizumab to the FDA for review is based on a pivotal study of 76 patients. In the results of this phase 2 study, the 14-day course of medication resulted in a median delay of two years in the onset of type 1 diabetes in pre-symptomatic patients compared to placebo. Side effects include low levels of white blood cells called lymphocytes, high levels of liver enzymes, skin rashes, and an immune response called cytokine release syndrome. The results of the study were reported at a 2019 meeting of the American Diabetes Association and published in the New England Journal of Medicine.
In May, an independent advisory committee of the FDA reluctantly recommended approval of teplizumab. Vote 10 to 7 The benefits of drugs outweigh their risks.
Provention expects to generate additional PK data from the ongoing Phase 3 study of approximately 300 children and adolescents newly diagnosed with type 1 diabetes. The company said that the PK data of the study is expected to be released later in the third quarter and will be analyzed by an independent third party to maintain the integrity of the placebo-controlled study. Provention added that it will review the results and then decide whether to submit them to the FDA along with any other relevant data and analysis.
The FDA letter lists some product quality issues, and Provention believes that these issues have been resolved in the amendments it has submitted to it, or can be resolved in a short period of time. The agency also pointed out some deficiencies in the manufacturing facilities. Provention said that those unspecified issues are not related to teplizumab, but need to be resolved before the drug is approved.
Photo courtesy of FDA