Image By Tax Credits Via Flickr

Image by Tax Credits via Flickr.

When a big pharma company loses patent protection on a hit drug, it can blow a hole in the company's top line. Just ask investors in Pfizer, sales of whose megablockbuster cholesterol drug Lipitor plunged more than 90% after it lost patent protection in 2011. Pfizer's revenue has been in decline ever since.

Knowing that, we asked our team of Motley Fool contributors to look ahead to 2016 and name a company with a key drug that risks losing patent protection during the year. Read on to see which drugs they called out and see what their owners are doing to help soften the blow. 

Brian Feroldi: Pharma giant AstraZeneca (NYSE:AZN) has a big challenge coming this May, when its top-selling cholesterol-busting drug, Crestor, is slated to lose patent protection. That's a big deal, considering worldwide sales of Crestor topped $5 billion in 2015, which represents more than 20% of the company's total revenue. Losing exclusivity in the U.S. puts the company in a bind, since more than half of Crestor's total sales come from the United States.

To help prepare for the decline, AstraZeneca has been pumping money into R&D to bring new drugs to market, and the company has made a lot of progress. AstraZeneca scored six regulatory approvals in 2015, which included new drugs that hold blockbuster potential, such as Tagrisso, which treats lung cancer, and Lynparza, which treats ovarian cancer.

Beyond its recent approval, the company also boasts a handful of other drugs that are producing great growth. Farxiga/Forxiga, which treats type 2 diabetes, grew sales 137% globally in 2015, and Brilinta/Brilique, an antiplatelet drug that lowers the risk of having a heart attack, grew sales 44%.

These new medicines look like they should pay off big time for the company, which is expecting low- to mid-single-digit revenue and earnings-per-share growth in 2016. That's a heck of an accomplishment for a company that expects to lose patent protection for its most successful drug, and it speaks to its commitment to invest so heavily in new medicines. 

Cheryl Swanson: AbbVie (NYSE:ABBV) will lose patent exclusivity on the composition of its flagship drug, Humira, in December. So what's up? Should AbbVie investors see this stock as a crippled donkey? After all, Humira, the best-selling drug on the planet, makes up two-thirds of AbbVie's sales.

If you listen to AbbVie CEO Richard Gonzalez, there's nothing to fear. AbbVie has over 70 additional patents protecting Humira that won't begin to expire until 2022. With that kind of legal armament, the company hopes to keep competition at bay for six years. In the Q3 2015 earnings call, Gonzalez said,  "Any company seeking to market a biosimilar version of Humira will have to contend with our extensive patent estate, which AbbVie intends to enforce vigorously."

I'm inclined to think competition from new branded anti-inflammatory drugs using novel mechanisms, such as those that target IL-17, may have more of an impact on Humira than biosimilars will. Those include psoriasis drug Cosentyx from Novartis, which demonstrated a clear superiority to Amgen's Enbrel in trials. The drug is a TNF inhibitor, similar to Humira, and could pose a competitive threat. Gonzalez has an answer for the IL-17 drugs as well, claiming they will be "relegated to the failure patient population, because physicians are comfortable" with AbbVie's drugs.

AbbVie is projecting double-digit earnings per share through 2020. But that's dependent on protecting Humira, growing Imbruvica sales ($5 billion projected by 2020), and launching 20 new products or indications in the next four years. If all pans out as Gonzalez expects, AbbVie's loss of its primary patent on Humira will be a non-event. But a healthy dose of skepticism about management promises can be a valuable asset -- so keep an eye on this one.

Sean Williams: One giant drug that'll be kissing its patent protection goodbye in the latter portion of this year is Merck's (NYSE:MRK) Zetia, a statin designed to help patients lower their LDL-cholesterol along with proper diet. In 2015, based on Merck's recently released annual report, Zetia was its second best-selling drug, pulling in $2.65 billion. 

In 2010, Merck entered into an agreement with generic-drug producer Glenmark Pharmaceuticals that will allow Glenmark to begin selling a generic version of Zetia on Dec. 12 this year. This pushed Zetia's expiration date forward by a tad (it originally was April 25, 2017). Although physicians and consumers aren't going to care about whether generic Zetia floods the market given that there's such a broad spectrum of new and foundational LDL-cholesterol-lowering treatments to choose from, it's a sizable blow to Merck. Usually, the introduction of generic drugs wipes out between 50% and 80% of cumulative sales within two years.

Thankfully for Merck, it has other avenues it can lean on, namely Keytruda and Zepatier. Keytruda is Merck's cancer immunotherapy drug that's currently being tested in around 100 combination studies and more than 30 tumor types. It works by helping expose cancer cells that normally hide from detection and supercharging the immune system to find and destroy these cells. With sales of Keytruda growing to $560 million in 2015, and its launch into second-line metastatic non-small-cell lung cancer looking promising, Keytruda could cross the $1 billion mark in annual sales for fiscal 2016.

Similarly, the introduction of Zepatier should allow Merck a taste of the hepatitis C market, which has a long enough tail to support more than a decade of growth. Merck's differentiated product, and its substantially lower wholesale cost, could garner Zepatier a decent amount of market share. Although Harvoni is projected to remain the clear market share leader, my suspicion is that Zepatier's annual sales could hit $1 billion by as soon as fiscal 2017.

Thus, while Zetia's loss will hurt, new product growth could quickly put shareholders' pain in the rearview mirror.

Brian Feroldi has no position in any stocks mentioned. Cheryl Swanson owns shares of Amgen. Sean Williams has no position in any stocks mentioned. The Motley Fool has no position in any of the stocks mentioned. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.