March 31 (Reuters) - Shares of U.S. drugmakers fell on Monday after reports that the Food and Drug Administration's top vaccine official had been forced to resign, the most high-profile exit at the regulator amid an overhaul of federal agencies.

Shares of Moderna slumped 12.8% in morning trading, while Novavax and BioNTech SE dipped 9%.

The S&P 500 biotech ETF declined 2.8%, set to add to the roughly 6% drop this year, as the resignation amplified uncertainty among biotech investors.

Peter Marks, who played a key role in President Donald Trump's first term in developing COVID-19 vaccines, will leave effective April 5, the Wall Street Journal and other media outlets reported on Friday.

As director of the FDA's Center for Biologics Evaluation and Research, Marks has publicly supported programs that expedited the development of rare disease treatments and gene therapies during his tenure.

Marks' departure follows the exit of head of the FDA's drug evaluation unit, Patrizia Cavazzoni, roughly two months ago.

U.S. Secretary of Health and Human Services Robert F. Kennedy Jr. — an environmental lawyer who has long sown doubts about the safety and efficacy of vaccines — announced plans to reshape the federal public health agencies.

"Given Dr. Marks' influence on the development of biologics and uncertainty as to who will replace him and how his legacy might continue, his departure will create a significant near-term overhang," said William Blair analyst Matt Phipps.

While a replacement is still unclear, "there is clearly a risk that the candidate's views will be in line with Secretary Kennedy's on vaccines," Phipps said.

The reports on Friday said Marks was given the choice by a Health and Human Services (HHS) official to resign or be fired.

Marks did not respond to a request for comment over email on Monday.

In a letter obtained by the media outlets including the Wall Street Journal and Associated Press, which could not be immediately verified by Reuters, Marks criticized Kennedy's views on vaccines.

"It's no secret that Biotech has been under immense pressure recently given broader macro issues, this unfortunate update does nothing to reassure investors or provide relief," said BMO Capital Markets analyst Evan Seigerman.