FDA Issues CRL for Teplizumab, Investigational Candidate to Delay the Onset of T1D
On July 2nd, 2021 the Food and Drug Administration issued a complete response letter (CRL) in response to the biologics license application (BLA) for Provention Bio, Inc’s Teplizumab, a monoclonal antibody and investigational candidate to delay the onset of Type 1 diabetes in at-risk individuals. The FDA’s update for Teplizumab is long awaited as the decision follows the FDA advisory committee’s narrow vote of 10-7 to recommend the approval of Teplizumab back on May 27, 2021.
A CRL is issued when the FDA declines to approve a drug in its current form and has outstanding questions. It is not an outright rejection, but the responsibility now shifts back to the product sponsor(s) — in this case Provention Bio — to address concerns raised.
The FDA’s CRL was received by Provention Bio late evening on July 2nd, 2021. In the FDA’s response, they said that clinical trials had failed to show pharmacokinetic (PK) comparability, a part of the study that involves taking blood samples over a period of time to determine how a substance will handle or hold up in participants’ bodies.
“As PK remains the primary endpoint for demonstration of comparability between the two products, you will need to establish PK comparability appropriately between the intended commercial product and the clinical trial product or provide other data that adequately justify why PK comparability is not necessary,” the FDA said in the CRL.
Later this quarter, Provention Bio expects to collect additional PK data in their ongoing Phase 3 PROTECT trial, a trial that includes patients receiving 12-days of therapy. Once the data becomes available, it will be analyzed by an independent third-party for review.
In addition to the PK considerations, the FDA also noted other product quality considerations, which Provention Bio believes to have addressed in the submitted amendments. The FDA acknowledged in the CRL that the amendments had not yet been reviewed.
The FDA did not cite any clinical deficiencies in the CRL related to efficacy and safety. Provention Bio will have to submit updated safety information when the BLA is resubmitted.
“We know the T1D community is urgently awaiting therapeutic advancements to address their medical needs and believe our collective passion and commitment will continue to drive us forward to meet this goal,” Ashleigh Palmer, CEO and co-founder of Provention Bio said in a press release.
The delay was anticipated by Provention Bio after the company received a regulatory update of Teplizumab’s BLA in April 2021. The FDA noted deficiencies in PK data and said that PKs were not comparable. Since then, the FDA and Provention Bio worked alongside each other to discuss issues concurrently with the ongoing review.
Provention Bio Inc.’s phase 2 clinical trial for Teplizumab, TN-10, found that Teplizumab delayed the onset of Type 1 diabetes by a mean of two years among 76 trial participants between the ages of eight to 49. Provention Bio also found preserved beta cell function, with an average C-peptide AUC of 1.96 vs 1.68 pmol/mol.
Patients were administered Teplizumab through intravenous infusions daily for at least 30 minutes, according to Eleanor Ramos, MD, chief medical officer of Provention Bio Inc. The treatment was given for 14 consecutive days. All participants had stage two Type 1 diabetes.
In the U.S.,1.6 million people live with Type 1 diabetes. Currently, there is no disease modifying treatment that targets the underlying causes of Type 1 diabetes. If approved by the FDA, Teplizumab would become the first disease modifying treatment for Type 1 diabetes delay.
“We will continue to work collaboratively with the FDA to hopefully secure approval of Teplizumab and bring the first disease-modifying therapy for T1D to at-risk patients as soon as possible,” Palmer said.
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