l affect all tobacco companies including Altria Group Inc. (MO), the parent company of Philip Morris USA; Reynolds American Inc. (RAI); and Lorillard Inc. (LO). The companies didn't have immediate comment on the final warnings, but in comments previously filed with the FDA they took issue with several aspects of the warnings, including the large size. The pictures and warnings such as "smoking can kill you" will be required to be placed on the top half of cigarette packages with the brand name on the lower portion of the packages. The warnings will be required to cover 50% of the front and back panels of a cigarette pack as well as the top 20% of cigarette advertisements. Reynolds said in comments filed with FDA that "even on acute poisons...the warnings are not of this size and character. The company said, "the function of the 'warnings' is not to warn consumers about the risks from smoking, but to communicate a government message: "Don't buy or use this product." A 2009 law requires larger and more graphic health warnings on cigarettes as part of an effort to discourage people from starting to smoke and to lower current smoking rates. About 20% of Americans smoke cigarettes, according to government figures. Tobacco use leads to about 443,000 deaths each year in the U.S. and is considered the leading cause of premature death. "These labels are frank, honest and powerful depie the stocks of rival developers of obesity drugs that have been rejected by the FDA, Vivus Inc. (VVUS) and Arena Pharmaceuticals Inc. (ARNA). Orexigen, which has no products on the market and loses money, appears to have enough cash and investment securities--roughly $77 million as of March 31--to last through 2012 as it figures out its next steps, said Leerink Swann analyst Joshua Schimmer in a research note. The FDA said Friday it believes a cardiovascular outcomes trial is necessary to ensure that Contrave's benefits outweigh its risks when used in overweight and obese patients. FDA spokeswoman Erica Jefferson noted that Contrave increases blood pressure relative to placebo in studies. A similar blood-pressure risk, together with increased risk of heart attack and stroke, was the basis for the agency's decision last year to ask Abbott Laboratories (ABT) to withdraw the diet drug Meridia from the market. Abbott pulled the drug. The FDA earlier this year rejected Orexigen's application for approval of Contrave, citing the blood-pressure risk and asking Orexigen to run another clinical trial to assess the risk of heart attacks and other cardiovascular outcomes associated with the drug. In response, Orexigen had asked the FDA to consider approving the drug in the near term for a narrowed population consisting of people with lower cardiovascular risk. The approved use could then be expanded after Orexigen completed the cardiovascular outcome trial, if the trial data warranted the expansion, Orexigen proposed. Orexigen said Friday it proposed a trial of 12,000 to 15,000 patients, with a planned interim analysis in early 2013 that could potentially support approval. The full trial would wrap up about three to four years after starting. But the FDA said Orexigen's proposed cardiovascular outcomes trial wouldn't be sufficient to assess cardiovascular risk, and instead laid out requirements that Orexigen said would translate into a trial enrolling 60,000 to 100,000 patients. "We certainly don't believe that this is necessary or feasible," Preston Klassen, Orexigen's head of global development, said on a conference call Friday. FDA spokeswoman Jefferson, however, said the agency doesn't believe it would take a trial of that size, and that FDA didn't come up with those numbers. She declined to say how big the FDA wants such a trial to be. Also, the FDA said it wouldn't consider approving C