PRVB (Provention Bio) has announced that the Teplizumab FDA Approval for Diabetes Type 1 review has been extended by three more months. The expected date is 17th November 2022.
Teplizumab FDA Approval for Diabetes type 1:
Provention Bio is testing Teplizumab, a humanized anti-CD3 monoclonal antibody, for use in the treatment and averting the onset of type 1 Diabetes Mellitus.
Teplizumab was tested in individuals who were at risk of developing diabetes type 1. These included relatives of people with established type 1 diabetes who had at least two autoantibodies and abnormal oral glucose tolerance tests.
Teplizumab delayed the onset of diabetes type 1 compared to placebo medicine by almost two years.
The overall incidence of Diabetes in the overall population was greater in the first year as mentioned in the table below [Ref]:
|Years of Interventnion||Percentage of Patients progressing to Diabetes (42)|
A 2-week treatment of Teplizumab delayed the onset of diabetes in individuals at high risk of developing diabetes type 1.
The development of overt diabetes in individuals who received Teplizumab vs placebo was delayed as mentioned in the table below [Ref]:
|Diabetes Diagnosis||19 (43%)||23 (72%)|
|Diabetes Diagnosis Per Year||14.9%||35.9%|
|Median time to diagnosis||48.4 months||24.4 months|
|The first year of Intervention||7% developed Diabetes||44% developed Diabetes|
Teplizumab for Treating Diabetes Type 1
Type 1 diabetes is a chronic disease in which the immune system kills the beta cells in the pancreas that produce insulin.
In patients with type 1 diabetes, several therapies have postponed the loss of insulin production, but more must be done to prevent clinical progression prior to diagnosis.
Teplizumab prevented high-risk subjects from developing clinical type 1 diabetes.
Telpizumab FDA Approval
Teplizumab FDA Approval Status in 2021
In 2021, the biologics license application (BLA) for Teplizumab in type 1 diabetes was submitted by ‘Provention Bio’. It was rejected on July 2nd. FDA sent the business a complete response letter (CRL).
Teplizumab was compared to a therapeutic drug developed for previous clinical studies in a single, low-dose pharmacokinetic/pharmacodynamics (PK/PD) associating study in healthy patients.
This was emphasized by FDA in the CRL to Provention Bio. The study’s inability to show PK comparability, according to the FDA, was recognized.
The FDA reportedly stated in the CRL that “PK remains the primary endpoint for demonstration of comparability between the two products.”
Hence, they needed to establish PK comparability between the intended commercial product and the clinical trial product appropriately. The data must adequately justify why PK comparability is not necessary.
Provention Bio was expected to put forward PK/PD findings from a PK/PD sub-study in Phase III which was based on the trial associated with patients with newly diagnosed Type 1 Diabetes.
The data from phase III will be evaluated by impartial third parties. Third parties were involved to maintain the integrity of this trial.
Provention Bio will submit the findings, together with further relevant data and analysis, to the FDA after the review is complete.
Additionally, the FDA also included a number of other factors related to drugs in the CRL. However, the business is confident that these problems have already been resolved in BLA revisions or will be soon.
The regulator also stated that prior to approval, some flaws discovered during a general inspection at a manufacturing facility utilized by Provention Bio must be corrected.
However, according to the manufacturer, teplizumab is not responsible for these shortcomings. The CRL made no mention of any clinical flaws connected to the effectiveness and safety information provided for teplizumab in the BLA.
Teplizumab FDA Approval Status in 2022
Nov. 17, 2022, is the new PDUFA deadline. Teplizumab will be the first type 1 diabetes disease-modifying drug if it is authorized.
The FDA has extended its examination of Provention Bio’s teplizumab’s biologics license application (BLA) for the prevention of type 1 diabetes in patients at risk.
The extended user fee goal date was originally set for August 17, 2022, but it is now Nov. 17, 2022. According to a corporate press statement, the FDA intends to convey proposed labeling and, if necessary, any post-marketing requirement or commitment requirements by October 17, 2022, assuming no significant flaws are found during the review period.
In the phase 3 PROTECT project, the company is also testing teplizumab in patients with recently discovered insulin-dependent type 1 diabetes.
Provention Bio anticipates reporting the study’s top-line data in the second half of 2023. However, the study’s enrollment goal was met during the third quarter of 2021.
The FDA views the resubmitted BLA as a comprehensive, class 2 response to the July 2021 action letter. The agent has been given an August 17, 2022 user fee objective date.
The FDA in their letter mentioned the failure of Provention Bio to demonstrate pharmacokinetic (PK) comparability in the clinical studies.
They referenced low-dose PK/PD bridging research in healthy volunteers that compared proposed commercial products made from pharmacological compounds produced for previous clinical studies that failed to demonstrate PK comparability.
Teplizumab’s benefit-risk profile for delaying clinical T1D was supported by the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) in a vote that took place in May 2021.
Members of the committee who voted in favor underlined the critical clinical need, while those who opposed it expressed concerns about the target group and the small amount of evidence available.
However, Teplizumab had already received Breakthrough Therapy Designation from the FDA. The treatment would be the first disease-modifying treatment for T1D if it were authorized.