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Spider-Man: Brand New Day brought in $927m (£687m) of global ticket sales to make it the second-biggest opening weekend ever as it shot past its estimated $225m production budget.
The superhero movie - starring real-life husband and wife Tom Holland and Zendaya - is only behind Avengers: Endgame, which took in more than $1.2bn in its opening weekend in 2019.
Brand New Day also set a second-best North American record, with box office takings of $335m.
The film's strong performance gives a much-needed boost for Disney ahead of the highly-anticipated December release of Avengers: Doomsday, after a string of Marvel movies underperformed in recent years.
Brand New Day, which opened in cinemas last week, picks up a few years after 2021's Spider-Man: No Way Home as Peter Parker continues to fight crime in a world that has forgotten he is the masked superhero.
The latest instalment of the hugely popular franchise received largely positive reviews, with some calling it Holland's best Spider-Man performance yet.
The film is Marvel's last big-screen outing before Doomsday, the long-awaited culmination of multiple superhero story arcs after Avengers: Endgame.
Marvel films released since Endgame have struggled to attract the same broad audiences as they did at their peak.
Big budget films like The Marvels and The Thunderbolts recouped their production costs but were among the studio's lowest-grossing films.
Spider-Man remains one of Marvel's most lucrative franchises, with No Way Home making nearly $2bn in ticket sales.
Cinema attendance has slowed since the Covid-19 pandemic, which accelerated the shift to home-streaming options like Netflix.
But the big screen has staged something of a comeback this year, with the North American box office takings on track to pass $10bn for the first time since 2019.
That was helped by blockbuster hits by including Toy Story 5, Michael, and The Super Mario Galaxy Movie - which have made more than $1bn each.
July releases Brand New Day and The Odyssey - director Christopher Nolan's take on the epic Greek poem - are also on track to top the $1bn mark.
Indie horror flicks Obsession and Backrooms emerged as surprise successes, bringing in more than $390m each despite their modest budgets.
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