Countdown's on as FDA Accepts BLA for Provention Bio's Diabetes Delay Drug

diabetes_John Fredricks/NurPhoto via Getty Images

John Fredricks/NurPhoto via Getty Images

Provention Bio announced that the U.S. Food and Drug Administration has accepted its biologics license application (BLA) resubmission for teplizumab, a drug intended to delay clinical Type I Diabetes (T1D) in at-risk individuals. The FDA has assigned a user fee goal date of Aug. 17, 2022, at which time the agency will decide if the therapeutic meets standards for approval.

Getting to this stage has proven rocky for Provention Bio. In July 2021, the FDA issued a Complete Response Letter (CRL) for teplizumab, citing that the company’s studies of the drug failed to demonstrate pharmacokinetic comparability, a primary endpoint. At the time, Provention Bio agreed to revisit its data and use pharmacokinetic modeling to adjust the 14-day dosing regimen for the commercial product to match exposure to clinical material used in a previous clinical trial.

Following the CRL, the company resubmitted its BLA for teplizumab in January. Now, the fate of teplizumab is in the FDA’s hands as the agency reviews all data and materials submitted to determine if the therapeutic is fit for the market.

Teplizumab is the first-ever disease-modifying therapy intended to delay the onset of T1D, an autoimmune disease in which the body’s T cells attack healthy beta cells that produce and secrete insulin. T1D is a growing problem, with an estimated five million people in the U.S. being diagnosed by 2050. Those at the highest risk for the disease are people with two or more T1D-related autoantibodies and abnormal blood sugar levels.

Teplizumab has provided promising results throughout Provention Bio’s pivotal TN-10 study, which delivered a single 14-day course of the therapeutic to people at high risk for developing T1D. The therapeutic delayed insulin-dependent, clinical-stage disease by at least two years, with findings published in March 2021 showing that the therapeutic delayed T1D diagnosis by a median of five years. After the trial, the percentage of those who were free of diabetes in the teplizumab group was double that in the placebo group. Teplizumab also indicated that those treated showed improved rates of insulin production.

The drug also shows favorable safety and tolerability profiles, although it poses a risk of cytokine release events and lymphopenia, reducing lymphocytes in the blood. However, the drug is not taken chronically, making adverse events manageable and short-lived. Additionally, the FDA CRL letter to Provention Bio addressed no issues with the drug's clinical safety.

Teplizumab works by helping to reduce the loss of beta-cell functioning, leading to the delay of T1D onset. It is an anti-CD3 monoclonal antibody that modifies CD8+ T lymphocytes, which are cells essential for immune defense and thought to be an important effector cell in the attack of beta cells.

At least two other drugs are currently being tested to prevent T1D, including hydroxychloroquine (HCQ) and abtacept (orencia), both of which are approved by the FDA for the treatment of other autoimmune diseases, including systemic lupus erythematosus and certain types of arthritis. Clinical trials and studies are ongoing for both drugs.

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