Review Memo Dismisses Hoeg’s Block on Tzield Approval
FDA has released an unusual internal memorandum detailing how former CDER acting director Tracy Beth Hoeg opposed approval of a Sanofi supplemental BLA for Tzield, only to have her position overturned after her departure from the agency. The sBLA was eventually approved earlier this month
The just-posted memo from now-CDER acting director Michael Davis describes repeated objections raised by Hoeg during FDA's review of the application, which sought accelerated approval of Tzield to delay the decline in endogenous insulin production in children ages 8 to 17 recently diagnosed with Stage 3 Type 1 diabetes.
In May, Sanofi had asked FDA to remove its Type 1 diabetes therapy Tzield from the Commissioner's National Priority Voucher (CNPV) review program following an internal disagreement over the drug’s supplemental application (see earlier story).
According to the document, the application was reviewed discussed three times by the agency's CNPV review council between October 2025 and April. The review team consistently concluded that the pivotal PROTECT study demonstrated a statistically significant benefit on C-peptide, a surrogate endpoint FDA considered reasonably likely to predict clinical benefit, and recommended accelerated approval.
However, Hoeg repeatedly disagreed with the review team's benefit-risk assessment, according to the memo. "At each CNPV Review Council meeting, Dr. Hoeg voiced objection to approval of this application," the memo states. Hoeg disagreed with reviewers' conclusions that the therapy's benefits outweighed potential risks, including diabetic ketoacidosis (DKA), Epstein-Barr virus (EBV) reactivation, and cancer, it says.
The memo reveals that Hoeg met with the review division, office leadership and the Office of New Drugs director on 4/9, where she stated she could not approve the application. Shortly afterward, FDA informed the sponsor that it would miss the 4/21 PDUFA goal date in order to convene an advisory committee meeting to discuss the product's risks and benefits.
The document also describes a February briefing attended by then-FDA commissioner Marty Makary, Hoeg and former CBER director Vinay Prasad, underscoring the level of senior leadership involvement in the review.
After Hoeg's departure from FDA, current acting center director Davis revisited the application and reviewed analyses from multiple FDA disciplines, including endocrinology, infectious disease, oncology, biostatistics and epidemiology. The memorandum states that Hoeg did not leave a written review detailing her analysis or explaining why she disagreed with the review team's conclusions.
The agency said several consult reviews directly examined the safety concerns that Hoeg had raised. Reviews from infectious disease and oncology specialists acknowledged the biological plausibility of EBV reactivation but concluded that labeling changes, including a Boxed Warning, could adequately address the risk, according to the memo. An Office of Surveillance and Epidemiology review requested by Hoeg found that available data did not support a causal link between teplizumab and reported malignancies. Another safety review found no new pediatric safety signals in postmarketing reports.
The memo concludes that all reviews reached consistent findings that the product demonstrated a meaningful effect on an accepted surrogate endpoint and that identified risks could be mitigated through labeling, postmarketing requirements and pharmacovigilance. FDA leadership ultimately sided with the review team and endorsed accelerated approval.
In a particularly notable rebuke of the prior leadership decision, the memo states that FDA would not proceed with the advisory committee meeting requested by Hoeg. Agency officials wrote that none of the review disciplines had concluded that outside expert input was necessary and that convening an advisory committee would only add delay and consume agency and sponsor resources without materially informing the regulatory decision.
The memo provides a rare public look into internal disagreements over drug approvals and highlights the influence Hoeg exercised during her brief tenure as acting CDER director. It also illustrates how several regulatory decisions initiated under former FDA leadership have been reassessed following the departures of Makary, Hoeg and Prasad.