4. Letairis

First approved in 2007 as a treatment for pulmonary arterial hypertension, Letairis' patent will expire next year.

4. Letairis/Volibris
Gilead Sciences/GlaxoSmithKline
2016 sales: $1.04 billion

Gilead Sciences is mostly known these days for its hepatitis C cures and HIV meds, but the big biotech also has two of the top-selling branded cardiovascular drugs on the market.

Coming in at number 4, Letairis is an endothelin receptor antagonist that was first approved in 2007 as a treatment for pulmonary arterial hypertension (PAH). In 2015, Letairis was approved to treat PAH when paired with tadalafil, the key ingredient in some erectile dysfunction drugs but which is also approved to lower blood pressure in PAH patients.

But generics makers are breathing down Gilead’s neck. Several have filed to make generics of Letairis as soon as the drugmaker’s patent shield falls next year. By 2022, Evaluate Pharma projects the drug will only generate $84 million for the Foster City, California-based company. That is a bad turn of events for Gilead, which has also seen the once-colossal sales for its hep C franchise cornerstone drugs Sovaldi and Harvoni deflated by competition and their own success at curing the disease.

It is one reason CEO John Milligan is feeling the pressure to pull off a transformational M&A deal, as he said on an earnings call recently.

“We are facing some headwinds in 2018 and beyond on other patent expiries we'll have. … So that puts some downward pressure on that non-HCV revenue base and so that makes it challenging for us to grow without some sort of acquisition in those areas,” Milligan told investors.

4. Letairis