UPDATE 2-Sanofi, Bristol shake up alliance as patents end

* Bristol to return rights to Plavix, Avapro to Sanofi

* Bristol to keep Plavix rights in U.S.

* Sanofi to make $200 mln terminal payment to Bristol in 2018

* Sanofi shares down 0.8 pct (Adds detail, background) By James Regan

PARIS, Oct 3 (Reuters) - Drugmakers Sanofi and Bristol-Myers Squibb plan to revamp their 15-year-old alliance from Jan. 1 in response to lost exclusivity on two key drugs and the arrival of generic competition in major markets.

The move will see Bristol-Myers return rights to blood clot preventer Plavix and blood pressure treatment Avapro/Avalide to the French drugmaker in all markets, the companies said in a joint statement on Wednesday.

This will give Sanofi sole commercial control of the two treatments, although Bristol-Myers will keep rights to Plavix in the United States and Puerto Rico, which will continue unchanged through 2019.

In return, Sanofi will pay Bristol-Myers royalties through 2018 on sales of Plavix worldwide, excluding the U.S. and Puerto Rico, and on sales of Avapro/Avalide. Sanofi will then make a $200 million terminal payment to Bristol-Myers, the groups said.

The French and U.S. drug giants have both had to wrestle with so-called patent cliffs, which have seen top-selling drugs previously protected by patents hit by competition from cheap copies.

Plavix, designed to help reduce the risk of a future heart attack or stroke, had been the world's second-biggest selling prescription medicine for several years with annual revenue reaching about $9 billion at its peak.

Earlier this year, Sanofi predicted a $1.85 billion dent in net income from the impact of generics on Plavix and Avapro. The company is now banking on emerging markets, diabetes, vaccines, animal health, its takeover of biotech Genzyme and new products in the hunt for alternative growth.

Late on Tuesday, Sanofi announced it would buy Genfar, Colombia's second-largest manufacturer of generic drugs with sales of $133 million last year, of which 30 percent were generated outside the country.

Sanofi is also reshuffling its research operations and said last month it could shed some 900 jobs in France. The company is due to discuss details of the cuts with staff representatives later on Wednesday.

Bristol-Myers is bracing for additional pressure between 2013 and 2015 with the arrival of generic forms of its Sustiva treatment for HIV and its Abilify schizophrenia drug, which together have annual sales of $4 billion.

Among its new medicines, diabetes treatment Onglyza has struggled to register substantial sales in the face of tough competition, while experimental blood clot preventer Eliquis is due to be reviewed in March after U.S. health regulators declined to approve it in June.

Bristol-Myers in August dropped a much-anticipated hepatitis C drug after a patient died of heart failure.

The U.S. group said on Wednesday that the revised agreement with Sanofi would simplify operations and help it focus on delivering drugs in development. The French company said the change "further supports Sanofi's strategic priorities".

The companies added that they had resolved disputes relating to the alliance, and that Bristol-Myers would as a result pay Sanofi $80 million in relation to Avalide supply disruption in the U.S. last year.

Shares in Sanofi, which is France's second-biggest company by market value, were 0.8 percent lower at 67.50 euros by 0726 GMT. The stock is up some 19 percent this year.

(Reporting by James Regan; Editing by David Cowell)

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