As Amgen Inc. has grown larger, the company has started to take on the attributes, as well as the problems, of a large pharmaceutical firm.

With the multinational scope and multibillion-dollar revenue seen at only a few biotechnology companies, the Thousand Oaks-based giant operates more like a traditional drug company these days than the small biotech firm it once was.

And now, Amgen is reluctantly blazing a new trail for biotechnology companies.

"Amgen's going to be one of the first companies to go through a pharmaceutical-type restructuring," said Eric Schmidt, an analyst with Cowen and Co. who covers biotechnology.

Much of Amgen's fate hinges on its big blockbuster drugs. Four drugs bring in most of its revenue.

That's why the recent hit in sales to the company's top selling drug, anemia drug Aranesp, has set the company into a close evaluation of how it's operating.

Though Amgen maintains its anemia drugs are safe when used as recommended, studies raised questions about their safety. Those questions led to the Food and Drug Administration adding a warning to anemia drug labels.

Pair that with reduced insurance coverage, and Aranesp sales were down 19 percent in the United States from a year ago during the second quarter.

Amgen also has to worry about the possible approval of a new anemia drug from competitor Roche that could pull sales away.

Cuts in construction

All of the turmoil is pretty unusual in the biotech community.

"We haven't had too many of these," Schmidt said. "Most biotherapeutics grow and grow and grow until they go generic."

Not many of those drugs have gone generic or had significant safety issues, two issues traditional drug firms know all too well.

The big pharmaceutical companies have had popular drugs drop in sales once a patent expires. They've also dealt with issues of questionable safety, as seen with Vioxx.

Many have started making drastic cuts to deal with those issues. Pfizer is cutting 10,000 jobs, has closed manufacturing sites and cut research spending.

"It sounds harsh, but nothing is sacred when it comes to drug companies looking to save money when faced with heavy sales losses," Mitra Thompson, research analyst with Global Insight in London, said in an e-mail.

Amgen has not announced any work force reduction plans, though rumors of layoffs have been rampant in the community. Amgen has about 20,000 employees worldwide, including 8,200 in Ventura County.

Amgen's most visible cuts so far are in construction. The company has put plans for a $1 billion manufacturing center in Ireland on hold and revised expansion plans for manufacturing facilities in Puerto Rico. The company also has reined back research facility expansion.

Investor Steve Silverman said he was upset there weren't more changes. Silverman is a private investor who holds a large amount of Amgen stock in a family trust.

Silverman, who has often called on the company to remove Chief Executive Officer Kevin Sharer and offer shareholders a dividend, said Amgen needs to cut programs that aren't going to become the big blockbuster drugs it needs. He said the company is spending billions on researching products that may never make it to market.

"There's so much superfluous junk," he said. "That's killing us."

In the company's second-quarter earnings call, Sharer said the company was willing to make changes if necessary.

"Certainly in any company, there are opportunities to do things differently, have different priorities," he said during the call. "We're prepared to do that if we need to."

Sharer said the company has to be careful about how it makes any changes.

"The question is the short term and the long term and getting the balance right between delivering now and preparing for the future," he said.

Discovering and developing a new drug can take from 12 to 15 years and cost $800 million, according to a Journal of Health Economics study often cited by the pharmaceutical industry. Out of 10,000 compounds in the lab, only one ever makes it to the pharmacist's shelves.

Higher level of uncertainty

Gary Pisano, a professor of business administration at Harvard Business School, describes it as a "tension" between the business and science sides of a biotechnology company.

Pisano wrote "Science Business: The Promise, The Reality, and The Future of Biotech" late last year. In a podcast interview after the book's release, he talked about the industry's unique challenges.

A key difference between biotechnology companies and more traditional companies is that there is a higher level of uncertainty in drug research that demands a more long-term outlook than just meeting Wall Street expectations, he said.

In the past year, Amgen has upped its spending in research and development, in large part to fund large clinical studies. That might be an area that could get trimmed back again, Schmidt said.

He expects to see more expense reductions and cost cutting at Amgen, including the possibility of layoffs.

Least likely to be touched

In its latest filing with the Securities and Exchange Commission, Amgen reported it was addressing its operating expenses.

"We will refocus spending on critical R&D (research and development) and operational priorities and seek greater efficiencies in how we conduct our business while continuing to make significant innovative R&D investments and build the framework for the company's future growth," the filing reads.

Amgen expects further growth in research and development expenses this year to support large studies and develop early-stage compounds. But the company acknowledges in the filing that it might have to adjust its research and development investment plans.

One decision facing Amgen is whether it should continue to look at new treatment areas for Aranesp or concentrate on younger but more promising compounds, Thompson said.

With the challenges that could permanently reduce the demand for those kinds of anemia drugs, "it might make more sense to examine other options," she wrote.

The projects the company has the most hope for, such as its promising osteoporosis drug, denosumab, are the least likely to be touched, Schmidt said.