Image source: U.S. Food and Drug Administration.

The holy grail of the drug development process is uncovering a drug capable of blockbuster sales. In layman's terms, we're talking about $1 billion or more in annual sales.

As you might imagine, the deck is already stacked against drug developers even getting a drug approved by the Food and Drug Administration. Medscape suggests that just one in 5,000 to 10,000 preclinical compounds will actually make it to pharmacy shelves. Of those drugs that are approved, a vast majority will not generate $1 billion or more in annual sales.

Sales of these blockbuster drugs could easily double
Blockbuster drugs are truly few and far between -- but some appear only to be getting started. Although peak sales estimates are highly subjective, I'd contend that the following therapies, which are already generating $1 billion in annual, or extrapolated, sales, are primed to see their revenue double from current levels, if not more.

As a word of caution, in addition to peak sales estimates being subjective, the biotech space is notorious for fierce competition. Although I'm suggesting that the following blockbuster treatments could see their sales double, it's always possible a more effective and/or safer treatment could come along and displace them at a moment's notice. So keep that in the back of your mind.

Without further ado, sales of these four blockbuster drugs could still have ample room to grow.

1. Xtandi
When it comes to efficacy in treating metastatic castration-resistant prostate cancer, Xtandi, which was developed by Medivation (NASDAQ:MDVN) and Astellas Pharma, tends to blow its competitors out of the water.

Image source: Astellas Pharma.

Approved in both first-line and second-line indications for mCRPC, Xtandi handily outperformed the placebo in the clinical trials that led to its approvals from the Food and Drug Administration. In the more recent PREVAIL trial in men with no prior history of treatment, Xtandi reduced the risk for death by 29%, lowered the risk of radiographic progression by 83%, and delayed the treatment time to initiating chemotherapy by a whopping 17 months! The improvement witnessed in first-line overall survival was also deemed statistically significant.

In 2015, Xtandi is projected to generate more than $1 billion in sales in the U.S., and in the neighborhood of half a billion in overseas markets. By 2020 to 2025, Xtandi's global peak annual sales could head as high as $5 billion.

2. Eliquis
Developed by Bristol-Myers Squibb (NYSE:BMY) and Pfizer (NYSE:PFE), blood-thinner Eliquis was heralded as a blockbuster as soon as its late-stage clinical results were announced. On an extrapolated basis Eliquis is certainly in that elite blockbuster category, with $355 million in worldwide sales in Q2 alone.

Image source: Bristol-Myers Squibb.

However, sales of Eliquis didn't get out of the gate cleanly. In 2013, and even early in 2014, a lack of physician education and insurer coverage seemed to stymie Eliquis' growth. However, a beefed-up marketing campaign -- Eliquis was one of 2014's most marketed drugs -- and improved physician education, have made quite the impact since mid-2014.

What's really to like about Eliquis is that, in a head-to-head, double-blind study against mainstay blood-thinner Warfarin, patients taking Eliquis exhibited fewer strokes, less major bleeding, fewer hemorrhagic strokes, and fewer deaths than the Warfarin control group. Game, set, match, Eliquis!

Assuming Eliquis' beefed up marketing continues to pay off, and the duo of Pfizer and Bristol-Myers is able to explore expanding Eliquis' label, there's no reason Eliquis can't reach $3 billion-plus in annual sales within five years.

3. Revlimid
Among the drugs listed here, Revlimid is already the biggest in terms of revenue generation. Last year, this multiple myeloma drug sold by Celgene (NASDAQ:CELG) was responsible for $5 billion in sales, or about two-thirds of Celgene's total 2014 revenue. Although Celgene has diversified its pipeline in recent years -- in fact, an argument could be made that Celgene's cancer drug Abraxane also be included in this list – it's still very much reliant on Revlimid for future growth.

Image source: Celgene.

The key to Revlimid's growth is a combination of its pristine pricing power and its label expansion. Already approved in its bread and butter first- and second-line multiple myeloma indications, Revlimid is being examined in more than a half-dozen other indications. These include for multiple myeloma maintenance therapy, non-deletion 5q myelodysplastic syndromes, first-line follicular lymphoma, relapsed/refractory indolent lymphoma, and first-line diffuse B-cell (ABC-subtype) lymphoma, just to name a few. If Revlimid can snag these new indications and continue to maintain or grow its market share in multiple myeloma, there's reason to believe it could hit $10 billion in annual sales by as soon as 2020.

4. Invokana
Among newer therapies that are extrapolating out as blockbuster drugs, but still have plenty of room for growth, I'd suggest keeping an eye on next-generation type 2 diabetes therapy Invokana, developed by Johnson & Johnson (NYSE:JNJ). Based on $340 million in worldwide sales in Q3 2015, Invokana is pacing nearly $1.4 billion in sales annually.

Image source: Johnson & Johnson.

What makes Invokana so interesting is that it's an SGLT-2 inhibitor. Unlike prior-generation type 2 diabetes therapies, which work in the liver or pancreas, SGLT-2 inhibitors block glucose absorption in the kidneys, allowing patients to excrete extra glucose through their urine. Additionally, SGLT-2 inhibitors come with the welcome side effect of weight loss. Not all type 2 diabetics are overweight, but the correlation between being overweight and diabetic is high.

The big question will come in 2017 when Johnson & Johnson reports on its long-term cardiovascular outcomes trial for Invokana. Recently, Eli Lilly and collaborative partner Boehringer Ingelheim announced that their SGLT-2 inhibitor Jardiance was superior to the current standard of care in the EMPA-REG OUTCOME study, reducing the risk of cardiovascular events in high-risk CV patients. If Invokana can match this efficacy in its trial, I suspect it could come close to $3 billion in peak annual sales.

Let's remember that type 2 diabetes prevalence is on the rise, so SGLT-2 inhibitors, as a whole, could be an area of high growth for investors in the coming decade.

If you're looking for investing ideas in the biotech sector, it certainly couldn't hurt to start with the developers behind these blockbuster drugs.

Sean Williams has no material interest in any companies mentioned in this article. You can follow him on CAPS under the screen name TMFUltraLong, track every pick he makes under the screen name TrackUltraLong, and check him out on Twitter, where he goes by the handle @TMFUltraLong.

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