Biotech’s Victory on Hold : Amgen Is Among 3 Firms Claiming a Breakthrough in Blood Science, While Wall Street Yawns and Waits

Thrombopoietin was given its unwieldy name before anyone was sure it existed. For decades, this mystery hormone was the Holy Grail of blood science--believed to be a mere speck in the vast reaches of the blood system, but one with awesome power to make blood clot.

Now, three biotechnology companies, including Thousands Oaks-based Amgen Inc., say they’ve found the speck, and cloned it.

The announcements, made within a month of each other, represent a breakthrough for science and hope for thousands of cancer patients, whose blood often loses the ability to clot during treatment. Doctors now rely on risky transfusions to keep such patients from bleeding to death, and they’re elated at the news about thrombopoietin. “We all want to get our hands on it,” said Stephanie Williams, a doctor who treats cancer patients in Chicago.

Financial analysts, though, are more stoic. As promising as the discovery appears to be, it is five years or more from the market. Wall Street is more interested in what new products these companies have to offer now.

And for Amgen, that’s not much. Under the leadership of chief executive Gordon Binder, the company is still going strong with two, hugely successful products it developed in the late 1980s. Thanks to those two blood cell-producing drugs, Epogen and Neupogen, 14-year-old Amgen is now the world’s premier biotechnology company, with a 1993 profit of $383.3 million on revenue of $1.37 billion.

Sales of Neupogen alone were $719.4 million in 1993. If thrombopoietin is approved, most analysts estimate its sales could range from $250 million to $500 million per year. Demand could be even higher if it turns out that higher doses of chemotherapy--which might become more common with the drug in use--are effective in fighting cancer.

The long process of getting approval for thrombopoietin starts with animal tests. Then, the Food and Drug Administration requires three separate phases of clinical trials on humans, followed by an FDA review. The process can take years, and for new, genetically-engineered products, development costs are typically $250 million to $400 million, according to Amgen.

Analysts say they are looking for a more immediate encore to Epogen and Neupogen that would propel Amgen’s growth through the end of the decade, after sales of its existing products level off.

Thrombopoietin “has captured people’s imagination . . . but in terms of the commercial aspects, this is still a long way off,” said Edmund A. Debler, an analyst at the health-care investment firm Mehta and Isaly in New York. “Amgen’s (research) pipeline is still weak.”

It’s a criticism that’s been leveled at Amgen before.

Although Amgen is still credited for its stunning rise, some now say its streak has faded. Debler, the analyst, said the problem is this: Although Amgen should continue to be profitable, a gap in its growth may come in the late 1990s because the company has come up with no new, blockbuster products that will hit the market by then. This, despite a mammoth budget for research: Amgen’s research-and-development budget totaled $255 million last year.

This problem can’t be solved by thrombopoietin, which has come too late to tide Amgen over for the rest of this decade, Debler said. Neupogen and Epogen “made Amgen the company of the ‘80s. But what will make them the company of 2000?”

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Such nay-saying is the curse of success, responded Amgen’s senior vice president for research, Daniel Vapnek. While acknowledging that thrombopoietin is “the most exciting thing we have now,” Vapnek was adamant that there is nothing wrong with Amgen’s science.

Rather, he said, the problem is undue expectations built upon the company’s explosive entry into the market. Biotechnology “is a home-run business,” he said, and Amgen hit two early on with Neupogen and Epogen. “It’s difficult to come up with products like that on a regular basis,” said Vapnek.

Whether thrombopoietin will be another home run depends on how well Amgen fares against its competitors in the race for a patent.

South San Francisco-based Genentech, and Seattle-based Zymogenetics Inc., a subsidiary of Novo Nordisk A/S of Denmark, published their findings on thrombopoietin in the June 16 issue of the British journal Nature. Amgen--which is working on thrombopoietin with the pharmaceutical arm of Japan’s Kirin Brewery--published its report July 1 in the American journal Cell. All three appear to have isolated the same molecule and are now poised to begin the various stages of clinical trials.

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Because all three companies published their results so close together, a protracted patent process, possibly ending in a court battle, seems inevitable, said Debler, the analyst. In this country, “it will probably come down to opening up the lab books to see who found it first,” he said.

Alternatively, the companies could avoid a court battle by settling among themselves and marketing the drug jointly, added Debler. But that would mean sharing the potential profits from sales of the drug.

The route to market may be quicker if thrombopoietin proves as effective as early signs indicate. The three companies appear to have cloned the same highly specific, highly potent molecule that the body manufactures to stimulate the production of certain blood cells called platelets.

Platelets are wafer-shaped cells that cause blood to clot. Without them, you would bleed to death, either after cutting yourself, or through spontaneous internal bleeding that can’t be stopped once it’s started.

Platelets pose big problems for cancer patients undergoing certain types of chemotherapy, which involves bombarding the body with poisonous drugs that kill cancer cells. “They try to give the dose that kills the tumor without killing the person,” explained Don Foster, a molecular biologist at Zymogenetics and senior author of the Nature paper.

Chemotherapy can lead to the loss of certain blood cells. Patients who lose too many white blood cells get infections; those that lose too many platelets have problems with bleeding.

Drugs are available that help replenish white blood cells--including Amgen’s Neupogen. But so far, there is no corresponding drug to replenish platelets.

That means doctors must limit doses of chemotherapy to give the blood a chance to restore platelet levels--hence, the grueling back-and-forth race of cancer treatment, in which chemical attacks on tumors are reined in just long enough to give the blood a breather.

Doctors try to give the body an edge by using other, secondary treatments, such as platelet transfusions. But these are difficult, risky and expensive.

Worse, some patients develop immunity to platelet transfusions, creating a profound dilemma for patient and doctor.

The choice is often to continue chemotherapy and hope the patient doesn’t bleed to death, said Gary Schiller, a doctor who treats leukemia and other cancer patients at UCLA’s Bowyer Oncology Center. “Sometimes there are miracles.”

Doctors believe that doses of thrombopoietin could induce a frenzy of platelet-making in the blood, allowing chemotherapy to resume. That could eliminate the need for platelet transfusions.

Other possible applications of the drug could include speeding recovery of cancer patients after bone marrow transplants and treatment of various blood disorders.

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For now, hopes for thrombopoietin are high--some say unduly so for a substance that was just a name and a mystery until recently.

“It clearly is the right thing. . . . This is the missing puzzle piece in how the bone marrow manufactures blood cells,” enthused Zymogenetics’ Foster, noting that the substance yielded a 400% increase in platelet production when administered to mice.

But that confidence may take a while to reach Wall Street: “The medical experts get excited,” said Joyce Lonergan, an analyst at the investment firm Cowen & Co. in New York. “But you become jaded as a biotech analyst.”