In a recent town hall meeting, Karim Mikhail told Food and Drug Administration staff that he was normal.
“I am with you on planet Earth,” he said in June. “I understand very well what everybody is going through.”
Typically, such an acknowledgment would be unremarkable. But Mikhail is acting director of the FDA’s Center for Biologics Evaluation and Research, where the previous leader, Vinay Prasad, was decidedly outside the norm.
Prasad was mercurial, pushing at least seven subordinates out of their positions and repeatedly overruling career scientists to limit vaccine availability. Hundreds of workers left CBER during his tenure as morale slumped. And he earned the ire of the rare disease community, rejecting at least five drugs that advocates and the FDA itself previously considered promising. Prasad did not respond to multiple requests for comment.
Mikhail, a former pharmaceutical executive who joined the FDA as a senior adviser to the commissioner in 2025, is now tasked with fixing CBER. Already, his more even-keeled approach has been a lifeline for staff, according to five agency officials who spoke on the condition of anonymity because of fear of reprisals.
“Everybody is still a little skeptical, because I don’t think anybody’s going to trust any political appointee right now,” one official said. “But Karim seems normal, no hubris. He’s in touch with the problems and seems action-oriented.”
Agency officials said Mikhail is focused on hiring replacements for employees who have left and fixing basic operational problems, like a backlog of staff travel requests. He’s in office Monday through Thursday, commuting home to Florida on the weekends. He’s been less involved with review work than Prasad, officials told STAT.
At the town hall, Mikhail said he views his role as the “conductor of the orchestra.”
“I don’t perceive my role as playing the music on a daily basis,” Mikhail said. “In an orchestra, you don’t find a conductor leaving his space to go play the violin just because the violin section didn’t play well.”
Perhaps most importantly to workers, he said his first priority is boosting morale after a difficult year.
Still, Mikhail may not hold his role permanently. The White House is close to selecting a new FDA commissioner, who could adopt yet another approach to running the agency, including new personnel. Acting FDA commissioner Kyle Diamantas has said he doesn’t want the top job permanently, and officials told STAT it doesn’t seem like Mikhail plans to stay.
“He seems fine, but how long is he going to last and what’s next?” an agency employee asked. “They’re all acting.”
The FDA didn’t answer STAT’s question about whether Mikhail plans to stay in his CBER role. Mikhail declined an interview via an FDA spokesperson. The agency has posted a hiring notice seeking both internal and external candidates for CBER director.
“As Acting Director of the Center for Biologics Evaluation and Research (CBER), Karim Mikhail provides strong organizational leadership and direct oversight of the Office of Therapeutic Products during this leadership transition,” said FDA spokesperson Benjamin Nichols.
New thinking on rare disease
There are signs that Mikhail and Diamantas are paying close attention to the rare disease products coming through CBER, which became a sore spot under Prasad.
The two officials met with rare disease patient advocacy groups at a closed-door meeting in June, along with four other FDA leaders. At the meeting, the leaders promised to listen to patients and to stay consistent.
Prasad and former FDA commissioner Marty Makary were criticized by advocates for multiple high-profile rejections, including for therapies that previous FDA leaders had deemed approvable. Since Prasad left in March and Makary left in May, the agency has reversed at least five of these decisions.
“There’s no question that our new acting commissioner and center director understood that pressure from the rare disease community was instrumental in Marty and Vinay taking the exit,” one agency official told STAT.
Nichols, the FDA spokesperson, said the agency’s recent decisions on rare diseases are not “reversals.”
“It is inaccurate to characterize recent regulatory actions involving rare disease therapies as a ‘reversal,’” Nichols said. “Consistent with FDA’s established regulatory processes, the agency reconsidered applications after sponsors resubmitted them with previously identified deficiencies addressed.”
Publicly, Prasad told stakeholders he was willing to be flexible when reviewing therapies for rare disease. But the decisions made during his tenure said otherwise.
He canceled an advisory committee meeting meant to discuss Capricor’s cell therapy for Duchenne muscular dystrophy. Not long after that, the agency rejected the drug. The FDA twice rejected an experimental therapy for advanced skin cancer from Replimune. The agency delivered a surprise rejection to a rare blood cancer therapy developed by Pierre Fabre Pharmaceuticals and Atara Biotherapeutics, told UniQure its Huntington’s disease therapy was not approvable, and rejected Regenxbio’s gene therapy for a deadly childhood brain disorder.
All of these companies are now getting a second chance at approval. The agency will revive the advisory committee meeting for Capricor’s therapy in July. Replimune has resubmitted its application, and Pierre Fabre and Regenxbio have plans to resubmit. The FDA agreed to accept UniQure’s application, which several agency officials had disparaged during Prasad’s tenure. Saol Therapeutics, a company whose experimental mitochondrial disease drug was rejected last August, resubmitted its application in July.
The FDA has seemed more willing in recent months to approve rare disease drugs based on survival analyses and single-arm clinical trials. Many of the drugs listed above were previously rejected for not running randomized, controlled trials. Such trials are the gold standard for clinical data but are often difficult or unethical to conduct for extremely rare diseases.
‘Flexibility’ and safety
CBER under Mikhail has become decidedly more flexible — though he has told staff he takes issue with that word.
“The term ‘flexibility’ makes everybody feel like we’re getting off the main lane of the highway, driving on the shoulder, and about to hit the concrete wall, whether that’s a safety concern for a patient or something else,” Mikhail said. “We need to get out of that attitude.”
Mikhail said he is increasingly focused on safety, and whether the risks of a drug outweigh the risks of the disease it treats. The agency needs a completely new regulatory framework for rare disease, he said, and to “not take something that was designed for a chronic disease affecting millions of patients and sort of apply flexibilities to it.”
Pam Gavin, CEO of the National Organization for Rare Disorders, told STAT she was encouraged by the agency’s recent decisions and appreciated the opportunity to meet with agency leaders in June.
“Because so few rare diseases have FDA-approved treatments, it is vital that the agency use all appropriate regulatory tools to evaluate rare disease therapies,” Gavin said.
Jeff Allen, CEO of Friends of Cancer Research, said leaders and patient advocate groups hashed out prior differences at the meeting and discussed finding a unified way forward.
“There were things that were expressed around wanting to assist the rare disease community and rare disease drug development generally, but there were actions that appeared contrary to that,” Allen said. “They wanted the opportunity to engage with the external patient advocacy community and talk through some of those concerns.”
Quiet on vaccines
The FDA has been far quieter on vaccine issues since a political poll showing that vaccine restrictions are unpopular. Before the shift, Prasad suggested multiple policies that critics said would raise the regulatory bar for vaccines to a level that would make it difficult to manufacture the products.
Prasad, whose thinking on vaccines appealed to health secretary Robert F. Kennedy Jr.’s skepticism of the products, had wanted flu shot makers to run trials each year showing their products reduced infection, rather than the typical approach of showing the generation of antibodies to fight infections. His most consequential decision was limiting Covid-19 shot approval to those over 65 or with preexisting health conditions and asking companies to run randomized controlled trials for the healthy population.
It seems unlikely that Mikhail will follow through on Prasad’s vaccine goals, agency officials told STAT. The agency already seems inclined to approve a new flu vaccine from Moderna that Prasad initially refused to review, overruling staff. “Karim seems to be leaving vaccines alone,” one agency official said.
“On the vaccine side, it’s a completely different paradigm,” Mikhail said during the town hall, contrasting the FDA’s regulatory approach to rare diseases versus vaccines. “We need to weigh things differently. How do we deal with short-term safety versus long-term safety now that we have new technologies? It is evolving.”
Staff reset under Mikhail
Some of the key allies Prasad brought in to help lead CBER are now gone, though Mikhail’s role in their exits is unclear.
Prasad elevated Vijay Kumar, a lead reviewer in the Office of Therapeutic Products, to acting director of that office after pushing out longtime director Nicole Verdun. At the end of June, Mikhail announced that Kumar was stepping down from the role. Kumar told STAT the decision is “completely independent of any internal or external topic or event or circumstance.”
On July 2, Mikhail announced that Mallika Mundkur, another Prasad ally, was leaving the FDA. She was deputy chief medical officer under Prasad, who served as the agency’s chief scientific and medical officer in addition to CBER director.
Others are in new roles. Prasad’s deputy CBER director, Katherine Szarama, is now associate director of regulatory science affairs in the commissioner’s office, officials told STAT.
Prasad also hired Alyson Haslam, a former researcher in his lab at the University of California, San Francisco, with the intention of making her deputy director in the Office of Vaccines. She never took on the role, and several officials told STAT her job was unclear.
Haslam is still in CBER, and her role is still unclear. She did not respond to STAT’s request for comment, and the FDA did not address STAT’s question about her job.
Correction: A previous version of this article said Regenxbio and Pierre Fabre resubmitted their applications. They have not officially resubmitted, though they plan to.