Objective
The main objective of this project is to achieve agreement with FDA on the design and other features of the confirmatory trial. This will respond to FDA’s invitation to submit a protocol and supporting data and information for the confirmatory trial as part of a meeting process.
Background Rationale
A cardiovascular and blood pressure treatment called verapamil has been shown to preserve insulin-making beta cells, slowing down T1D progression in young people with new-onset T1D, according to the results of a clinical trial funded by JDRF and announced earlier in 2023. Verapamil is a generic drug that has been available for a number of years. Given the well-characterized safety profile and the new data in T1D, there is a reasonable probability, though not a guarantee, that FDA could approve verapamil for patients with recent-onset T1D without further pre-approval clinical data, though FDA would require post-approval clinical data as a condition for such an approval. FDA indicated at the May 29, 2024 Type C meeting organized by the applicant that it would be willing in principle to consider an AA NDA for verapamil for recent- onset T1D, provided that it accepted the design of a confirmatory trial, whose findings could be reported post-approval, The FDA urged the applicant to return to discuss the design of such a confirmatory trial with the FDA, which is the precise object of this current project.
Description of Project
This project aims to accomplish the next step towards obtaining FDA Accelerated Approval (AA) of a New Drug Application (NDA) for verapamil as a disease-modifying treatment for recent-onset type 1 diabetes (T1D). Verapamil is a long-marketed cardiovascular and antihypertensive drug for which two recently published trials demonstrated preservation of insulin secretion in patients with recent-onset T1D.
The first step was achieved by the applicant in the May 29, 2024 FDA Type C meeting (supported by Breakthrough T1D). FDA agreed in principle that data from the published trials could support an AA NDA for verapamil for recent-onset T1D, conditional on committing to a post-approval confirmatory trial of a design acceptable to the FDA. The FDA encouraged the applicant to quickly follow up with another FDA meeting to discuss the proposed design of such confirmatory trial, and this follow up FDA meeting is the subject of this project.
In the absence of an explicit approval of this indication, access to verapamil by T1D patients who could otherwise benefit from it will be limited by reluctance on the part of physicians to prescribe the product “off label” due to questions about the clinical evidence as well as by medico-legal concerns. The ongoing monitoring of safety and efficacy data would also be hampered without an approved product. Furthermore, the FDA has not issued clear guidance on its expectations for the evidence needed to approve a disease-modifying treatment for T1D. The complete draft protocol with a statistical analysis plan (SAP) summary to be submitted to FDA as part of this project is also expected to establish precedents for other T1D interventions.
Anticipated Outcome
FDA has agreed in principle to review an AA NDA for verapamil aimed at an indication to preserve insulin-making beta cells in young people with recent-onset T1D, contingent on agreement on the design of the proposed confirmatory trial. With this agreement, we would then propose to prepare and file such a NDA, and if approved, market and distribute verapamil on label for T1D in a broadly accessible way for T1D patients.
Relevance to T1D
If an approved verapamil label for recent-onset T1D patients can be achieved, verapamil will be more accessible and more widely used than would be the case without approval. FDA’s approval of this indication could also serve as guide for developing and seeking approval for T1D indications of both new and already approved therapies.