The "Pirates of the Caribbean" star initially boarded the Universal Studios project in 2016, signing on to revamp H.G. Wells' classic tale of a chemist who embarks on a killing spree after using a dangerous drug that renders him invisible, but it appears Depp has since stepped down from the role of the crazed leading man, according to Variety.
The news emerges as studio officials reveal they have tapped "Insidious Chapter 3" director Leigh Whannell to take charge of the monster remake, reuniting him with Blumhouse Productions boss Jason Blum, who also produced the filmmaker's 2015 supernatural hit and 2018 thriller "Upgrade".
"Throughout cinematic history, Universal's classic monsters have been reinvented through the prism of each new filmmaker who brought these characters to life," said Peter Cramer, Universal's president of production. "We are excited to take a more individualised approach for their return to screen, shepherded by creators who have stories they are passionate to tell with them."
Wells' novel has been adapted for the screen numerous times since it was published in 1897, with the most famous film version released in 1933, starring Claude Rains as The Invisible Man.
The reboot is intended to be part of the studio's monster movies revamp series, which began with the 2017 release of "The Mummy", featuring Tom Cruise as Nick Morton and Russell Crowe as Dr. Henry Jekyll.
However, the big-budget blockbuster fell flat with critics and was considered a box office bomb after projected losses were reported to be up to $95 million (£72 million), despite grossing $410 million (£312 million) worldwide.