PARIS, April 15 (Reuters) - Nearly three dozen global pharmaceutical companies, in a letter to the head of the European Commission, demanded help to maintain operations in the EU despite threatened U.S. tariffs on imports, including measures to compensate them for the cost of pharmaceutical innovations, French business newspaper Les Echos reported on Tuesday.

In the letter sent to European Commission President Ursula von der Leyen, the companies -- including Pfizer PFE.N, Eli Lilly LLY.N and AstraZeneca AZN.L -- said they face cost disadvantages in Europe versus the United States, where drugs are sold at prices that on average are twice that of some European countries, such as France, Les Echos reported.

U.S. President Donald Trump has said he expects to impose tariffs on imported pharmaceuticals in the near future.

The companies also asked the EU to simplify regulations, noting that companies currently must conduct multi-country clinical trials for drugs, the letter said.

The industry also said in the letter that it takes issue with a fee the sector will soon need to pay to treat wastewater from micropollutants, Les Echos said.

For a decade "the innovative industry has entirely reimbursed the increase in expenses linked to innovative medicines," the letter said, according to Les Echos.

"We hope to work together in the coming weeks to ensure that these proposals become reality to the benefit of Europe's patients and economic development," the letter added.

Last week, European pharmaceutical companies warned von der Leyen in a meeting that U.S. tariffs would hasten the industry's shift toward the United States and from Europe.

The United States is the biggest market by sales for big pharma companies, and Europe and the United States have interconnected supply chains for medicines. EU medical and pharmaceutical product exports to the United States totalled about 90 billion euros ($101.49 billion) in 2023, according to Eurostat.

European pharmaceutical giants have recently been expanding production facilities in the United States.

($1 = 0.8868 euros)

(Reporting by Makini Brice; Editing by Leslie Adler)

((M.Brice@thomsonreuters.com;))