Sanofi Walked Away From Makarys Own Fast-Track Program. Thats How Bad the FDA Has Become.

Sanofi Walked Away From Makary's Own Fast-Track Program. That's How Bad the FDA Has Become.

When FDA Commissioner Marty Makary says political leaders should never overrule career scientists at his agency, he means it. He's said it on television. But somewhere between that interview and the decision on a type 1 diabetes drug called Tzield, his own appointed regulator apparently did exactly what he said was a disaster.

Sanofi asked the FDA to pull Tzield from Makary's fast-track review program in early May, after the person Makary put in charge of evaluating drugs — acting Center for Drug Evaluation and Research Director Tracy Beth Høeg — disagreed with the career reviewers who had recommended approval, according to sources familiar with the dispute who requested anonymity due to fear of reprisal. The FDA missed its April 21 goal date. Sanofi confirmed the request to remove Tzield from the program but declined to discuss the regulatory status. As of this week, no decision had been issued.

The program in question, the Commissioner's National Priority Review, is a voluntary FDA pathway where drugmakers apply to have their products reviewed in one to two months instead of the usual ten to twelve. Makary announced it in June 2025 as a signature achievement of his tenure, designed to get treatments for serious conditions to patients faster. Sanofi applied to put its type 1 diabetes drug Tzield through that program, and the FDA accepted it based on what the agency called "a large unmet medical need."

Tzield is not an obscure compound. It was the first drug approved to delay the onset of stage 3 type 1 diabetes, a condition that typically lands children and adults in insulin-dependent care for life. Approved originally in November 2022 for people with stage 2 disease, Sanofi's October 2025 application sought to expand the label to include adults and children as young as 8 with stage 3 disease — meaning people already diagnosed and facing imminent insulin dependence. Sanofi had enrolled roughly 1,000 patients in its clinical development program and presented Phase 3 PROTECT trial data showing the drug preserved beta cell function.

Instead they got caught in an institutional dispute.

Høeg, whom Makary appointed as acting CDER director in December 2025, is the fifth person to hold that job in a single year. She arrived from the Office of the Commissioner, where she served as Senior Advisor for Clinical Sciences. Her appointment followed the retirement of Richard Pazdur, a 25-year FDA veteran who had been convinced to take the CDER role just weeks before he left. Pazdur himself had replaced George Tidmarsh, appointed in July 2025.

The concerns Høeg raised on Tzield involved safety signals detected during review, including two seizures, one blood clotting event, and one death, according to reporting from January when the agency first pushed back its decision date. Høeg specifically flagged risks of Epstein-Barr virus reactivation and cancer risk, according to STAT News. Tzield's label already carries a warning for serious, life-threatening viral reactivations including EBV and CMV. Sanofi says three malignancies have been observed across 30 years of clinical development and that in each case "no causal relationship was established between the malignancies and teplizumab." The company also says no causal relationship has been established with the single fatal outcome. More than 1,000 patients have been treated with the drug over three decades of development, the company said.

The irony is difficult to miss. Makary told CNBC's David Faber in an interview aired May 5 that FDA commissioners overruling agency scientists has been a "disaster" every time it has happened. He cited the Aduhelm Alzheimer's approval and the Covid vaccine booster for young healthy kids as examples. He said the agency has not made "corrupt sweetheart deals." The interview was posted the same week Sanofi made its pull request public. By then, Høeg had reportedly already intervened.

This is not an isolated incident. In July 2025, Richard Pazdur — then still in his role as director of the Oncology Center of Excellence — reportedly stepped in late in the review of Replimune's melanoma drug RP1, undercutting staff reviewers who had supported approval. Replimune received a rejection letter. The company was rejected again last month after a second application. Makary has defended both rejections, telling CNBC that nine Wall Street Journal opinion pieces have asked him to approve the drug. "I don't work for Replimune, I work for the American people," he said.

The CNPV program itself is barely a year old. Announced in June 2025, it was designed to compress review times for drugs meeting one of five national health priorities: public health crisis response, innovative breakthrough therapies, large unmet medical needs, onshoring and supply chain resilience, and affordability. The program has already produced several approvals — including a gene therapy for genetic hearing loss in April and a new molecular entity in March — and Makary has held it up as a signature achievement of his tenure. A public hearing is scheduled for June 4.

For patients with stage 3 type 1 diabetes, the stakes are concrete. Stage 3 is when the pancreas can no longer make enough insulin and daily injections become necessary. Tzield, given at that stage, aims to slow further beta cell destruction and preserve whatever function remains. The PROTECT Phase 3 trial showed a statistically significant slowing of C-peptide decline compared to placebo — a surrogate for the ability to produce one's own insulin. Delaying that progression, even by months, means fewer daily injections, fewer hypoglycemic emergencies, and more time in school or at work without the constant management burden that defines established type 1 diabetes.

Whether those benefits outweigh the risks Høeg cited is a genuine scientific question. The FDA's own label acknowledges the viral reactivation risk. Whether a political appointee should be making that call over the recommendation of career reviewers is a different question — and the one Makary said he would never let happen.

The drug is still pending. Sanofi has not withdrawn its application. The sBLA remains under review. But Sanofi has asked out of the one program that was supposed to give Tzield the fastest possible path to patients. Whatever Makary's program was supposed to be, it has stopped being one of them.