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The former Cheers star, 57, lost five stone in three years as the poster girl for the international diet business.
She is moving on at a time when her weight has ballooned again, prompting speculation that the company was not comfortable with her as its spokesman.
She told People magazine: "After lengthy negotiations, regretfully the Jenny Craig Company and I did not come to an agreement to continue as their spokesperson."
Alley, who starred on Showtime's reality-comedy series "Fat Actress," became a spokeswoman for the Jenny Craig diet program in 2005.
About a year later, Alley donned a bikini to show off her new shape on "The Oprah Winfrey Show."
At the time, Alley had lost 5st and 4lbs, after hitting a high of 15st 7lbs.
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Alley told People that while her experience with Jenny Craig was "extraordinary," she wants "to create something new that will help millions of people end the seemingly never ending fatty-roller coaster ride."
She intends to develop her own weight-loss brand with plans to launch in 2009.
Scott Parker, vice president of marketing for Jenny Craig, said: "We are sorry that she did not accept our offer" to continue appearing in the company's ad campaign.
"We wish her all the best in her future endeavours."
- As reported in The Daily Mail
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