In an expected and recoverable setback for Prevention Bio, the FDA issued a full response letter for the company’s type 1 diabetes drug teplizumab on July 2, after finding that the commercial product did not have pharmacokinetic comparability to that made for clinical trials Active ingredient showed.
The company that purchased teplizumab from Eli Lilly and showed signs of an in-depth CRL by announcing the FDA’s PK concerns in April found that the FDA told the company, “Because PK is the primary endpoint for demonstrating comparability between the two Products must adequately establish the PK comparability between the intended commercial product and the product for the clinical trial or provide other data that adequately justify why a PK comparability is not required. “
Prevention said it expects relevant additional PK / PD data from an ongoing Phase III trial to be collected later this quarter, and then it will decide whether that data will be submitted to the FDA for PK comparability to support or otherwise justify why this comparability is not necessary.
While the FDA recently overruled its advisory board with Biogen’s high-stakes approval of Aduhelm, this CRL is not similar to this situation due to the minor nature of the issues to be resolved. The FDA’s Endocrinological and Metabolic Drugs Advisory Committee voted 10-7 in May for FDA approval of teplizumab, which delayed the onset of type 1 diabetes by a median of two years compared to placebo.
On the issue of safety, panelists expressed concerns and appeared confused about the higher incidence of diabetic ketoacidosis in the patients receiving treatment compared to placebo, as well as the three deaths in the treatment arm in the confirmatory studies (not in the pivotal study) zero in the placebo arms. All seemed to agree that if the drug was approved, long-term safety data would be required and that the label should be limited to the population included in the pivotal study.
The FDA asked the company to submit a security update as part of its BLA follow-up. If this re-filing is successful, approval for teplizumab would complete the decades of development that began when Lilly acquired the drug from former UCSF scientist and CEO of Sonoma Biotherapeutics Jeffrey Bluestone, who began working on it about 35 years ago.
While the agency raised no clinical or efficacy concerns, the FDA cited several additional issues related to product quality, Provenion said, which it believes have been resolved with changes already submitted and the FDA confirmed it has not yet been reviewed.
As for potentially unexpected results, a recent inspection, not just of teplizumab, uncovered certain deficiencies in a fill / finish facility used by the company that need to be addressed prior to approval.
The biotech analysts at SVB Leerink said in a statement to investors this morning: “While we expect weakness in PRVB shares today [the company’s stock declined by more than 26% on Tuesday], We believe that the lack of issues beyond PK comparability and CMC / manufacturing avoids a potential worst case scenario in which clinical issues with teplizumab could jeopardize its path to approval in at-risk populations and / or new cases. “
Editor’s Note: This article has been updated to include a comment from SVB Leerink to indicate that Jeffrey Bluestone is the CEO of Sonoma Biotherapeutics.