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The 35-year-old will replace VR46 Racing Team rider Fabio Di Giannantonio at the upcoming Malaysian Motorcycle Grand Prix.
Di Giannantonio will undergo surgery on his left shoulder in Rome as part of preparation for the 2025 season.
Iannone last competed in the premier class in 2019 with Aprilia before being served a four-year doping ban for the prohibited substance Drostanolone.
This year, Iannone returned to professional riding with Team GoEleven in the Superbike World Championship.
The Italian scored a podium on his series debut and recently scored his first win at Motorland Aragon.
“Riding the world champion bike is exciting,” said Iannone.
“MotoGP is the most technological and high-performance bike, I’m honoured that they thought of me and I felt like I had to say yes to this opportunity immediately as soon as it was offered to me.
“The challenge is certainly crazy, complex and demanding, as I haven’t ridden a bike in this category for years and without having done tests or similar.
“I’m excited to be able to work with Ducati and the Pertamina Enduro VR46 Racing Team, both for the very high level and for the friendship since years.
“I thank Valentino Rossi, Alessio Salucci, Pablo Nieto, Gigi Dall’Igna, Claudio Domenicali and Mauro Grassilli.”
Alessio Salucci, VR46 team director, said Iannone’s strong showing in WSBK had put him at the forefront of their minds when looking for a replacement for Di Giannantonio.
“I am very happy to confirm that Andrea will race with our colours on the Ducati Desmosedici GP,” said Salucci.
“First of all, Andrea has shown to be in great shape, he closed the WorldSBK season on a high and has always remained close to Ducati.
“He is a great friend of the VR46 family, both mine and Vale’s. We are very happy to welcome him to the Pertamina Enduro VR46 Racing Team and to see him back on a MotoGP bike.
“It’s a really great story! At the same time, we all wish Fabio the best of luck as he will undergo shoulder surgery this week and we can’t wait to see him back on track in 2025.”
The Malaysian Motorcycle Grand Prix takes place across November 1-3.
