4. Novartis

There are two primary reasons Novartis anticipates flat sales during 2016: Its hallmark cancer drug Gleevec recently came off patent and its Alcon ophthalmic business has seen declining growth rates. Novartis blamed “insufficient innovation, reduced customer focus, and undeveloped capabilities” for Alcon's 1% drop in net sales and 7% fall in core operating income in 2015. To add to the doom and gloom, its recently approved heart-failure drug Entresto — heralded as a “mega-brand” by Bernstein analyst Tim Anderson — has failed to generate significant sales since its approval in July. Indeed, in the last three months of 2015, Entresto only brought in sales of $5 million. Novartis allayed concerns about the slow start, attributing it to limited access; physicians, it said, needed prior authorization to prescribe the drug. On another front, Novartis launched Zarxio, a biosimilar of Amgen's Neupogen, in September. That could prove a boon for Novartis: Neupogen generated 2014 sales of $1.6 billion, with $839 million of that sum in the U.S. Novartis is giving Zarxio the branded launch treatment, too, having established a commercial organization for the cancer drug with a 50-person sales and marketing team.