There's a lot for investors to like about Amgen Inc. (NASDAQ:AMGN) and Biogen Inc. (NASDAQ:BIIB). Both of these biotech stocks have produced tremendous returns over the past couple of decades, and the businesses they represent still generate enormous profits. 

Both of these stocks have outperformed the broad market during the present century, but Biogen provided returns miles ahead of its larger peers. Let's stack these industry titans side by side to see which is poised to offer superior returns in the years ahead.  

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The case for Amgen Inc.

This company's superstar duo, Enbrel and Neulasta, just can't hit the high notes like they used to. The aging treatments make up a combined 42% of Amgen's total product sales, and single-digit losses such as those reported over the past couple quarters will make top-line growth awfully difficult over the next several years.

Amgen's next-generation cholesterol drug, Repatha has finally started marching upwards in recent quarters, but it could stall out in the quarters ahead. One of America's largest pharmacy benefits managers recently dropped Repatha in favor of a rival therapy from Regeneron (NASDAQ:REGN) and Sanofi (NYSE:SNY). That puts a lot of strain on the only other younger products generating significant sales growth right now.

Multiple myeloma therapy Kyprolis rose 17% in the first quarter and could pass the $1 billion mark this year. Denosumab continues to make big contributions as a preventative treatment for people with osteoporosis and cancer. Sales of the bone density drug hit a $3.8 billion annualized run rate in the first quarter, a 14% gain compared to the same period last year.

The company's lead growth drivers could get some assistance from a new migraine drug any day now. The FDA is expected to deliver a decision regarding Aimovig by May 17 that could make it an important new option for headache sufferers that have tried multiple treatments without success. During a clinical study supporting its application, 50% of the patients that took a 140 mg dose of Aimovig reported a 50% or greater reduction in monthly migraine days, versus just 27% of patients in the placebo group. A large addressable population combined with a current dearth of effective treatments is expected to drive annual sales past $1.2 billion by 2022.

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The case for Biogen Inc.

Biogen's top line reached a new high in the first quarter, but investors are worried it's nearing a peak. The company relies heavily on sales of several multiple sclerosis (MS) drugs that have started slipping in the face of new competition. The company's leading growth driver of the past few years, Tecfidera, has flattened out. First-quarter sales of the oral MS therapy rose 3% to an annualized $3.9 billion run rate, but double-digit losses for older treatments led to a 4% contraction of total MS revenue in the first quarter compared to the same period last year.

Biogen leans on its MS franchise for around 67% of total revenue, so a continued slide could create a tough headwind to overcome. The company's new lead growth driver, Spinraza, looked like it was up to the task, but investors aren't so sure anymore. Following its launch at the beginning of 2017, the rare disease drug shot up to a $1.5 billion annualized run rate based on fourth-quarter sales. Unfortunately for Biogen, Spinraza sales in the first quarter of 2018 came in just $1 million higher than the previous three-month period, suggesting a slowdown ahead.

Spinraza's an expensive treatment for a small number of spinal muscular atrophy patients that's effective, but it requires several doses each year at a list price of $125,000 each. Novartis (NYSE:NVS) recently acquired a gene therapy candidate that should have Biogen shaking in its boots because it appears to work with a single dose.

Although Spinraza's trajectory could quickly reverse, Biogen made a smart move by expanding its investment into the company that discovered it, Ionis Pharmaceuticals (NASDAQ:IONS). Unfortunately, Ionis probably won't be adding any candidates to Biogen's ultra-risky late-stage pipeline right away.

Aducanumab is Biogen's most important candidate in late-stage development right now, but several other experimental therapies that prevent plaques of protein fragments from forming in the brain have already failed miserably. Success where others have failed could lead to megablockbuster sales, but at this point, it's still a long shot.

In the numbers

Biogen generated $4.7 billion in free cash flow over the past 12 months, which was impressive, but it hardly holds a candle to the $10.9 billion that Amgen recorded during the same period. Despite strong cash flows today, the market isn't expecting much growth from either of these companies. Biogen trades at just 12.8 times trailing free cash flow, and Amgen is slightly less expensive at just 11.6 times trailing free cash flow.

Even if Amgen were priced at a slightly higher multiple, it would pull ahead in this matchup. That's because Biogen's lead Alzheimer's disease candidate needs to succeed if it's going to outperform Amgen in the years ahead, and that's a mighty big risk.

Even if growth becomes difficult in the years ahead, Amgen shares offer a nice 3% dividend at recent prices. Put it together, and the bigger biotech looks like a much better buy today.

Cory Renauer has no position in any of the stocks mentioned. The Motley Fool owns shares of and recommends Biogen and Ionis Pharmaceuticals. The Motley Fool has a disclosure policy.