Clinical trials of a much-anticipated compound from Eli Lilly brought mixed results, causing analysts to further cool on the drug.

The Phase III trial, a head-to-head study of prasugrel vs. the Bristol-Myers Squibb/Sanofi-Aventis drug Plavix (clopidogrel), showed a significant increase in fatal bleeding with the Lilly compound compared to clopidogrel. On the other hand, prasugrel trumped Plavix with regard to efficacy in preventing cardiovascular deaths.

Yet the findings of elevated bleeding risk may prove frustrating for Lilly, as they may require the firm to conduct more studies of the blood thinner, possibly delaying US approval.

The results came as the Indianapolis drugmaker is eager to show productivity from its pipeline. Prasugrel, which is being co-developed with Daiichi Sankyo, is the highlight of an FDA submission plan that also includes an inhaled insulin system for diabetes, a long-acting form of diabetes drug Byetta and an extended-release form of the antipsychotic Zyprexa.

Daiichi Sankyo and Lilly are still aiming for submission by year’s end, John Alexander, Daiichi Sankyo’s global head of R&D, said in a statement.

Even so, the prasugrel news had a sobering effect on Wall Street. Sanford Bernstein’s Tim Anderson wrote that its approval is “far from certain.” Indeed, another trial may be needed to assuage regulators of the bleeding risk, which was highest in elderly patients and those with low body weight.

Anderson lowered his prasugrel sales forecast from $1.6 billion in 2012 to $800 million, a 50% reduction, because the TRITON study, read Sunday at the American Heart Association meeting, limits prasugrel to about 20% of the current Plavix-using population—those with moderate-to-high cardiovascular risk—and even then only within a limited audience, he explained. In addition, “excessive bleeding makes it unlikely that prasugrel will be used ‘off label’ in the remaining 80%,” Anderson wrote in a research note.

Another analyst, Jami Rubin of Morgan Stanley, also lowered her sales estimate for the Lilly blood thinner. Her amended outlook came last month after Lilly suspended two smaller prasugrel studies. On Sunday Lilly said it halted enrollment in those trials so that it could work out a dosing strategy to avert problems for those at risk of elevated bleeding.