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All Dark Horse Genetics strains + parents and ancestors. Arrows\/Colors: All arrows in this map start at Dark Horse Genetics . After a rough classification (brown) they will point to the

Seattle Genetics’ Dark Horse Drug Candidate

It’s approaching the homestretch.

[Correction: 10:05 am Pacific] The buzz around Seattle Genetics (Nasdaq: SGEN) has been about whether it will finally prove, after more than a decade, that an “empowered antibody” can be an effective treatment for cancer. But while fewer people are watching, the company is eagerly awaiting clinical results for a traditional antibody that also has the potential to help cancer patients live longer — and could generate real cash.

The lesser-known drug is called lintuzumab, or SGN-33. This is a so-called “naked” antibody, a Y-shaped protein that’s genetically engineered to zero in on a specific marker on cancer cells that’s seldom found on healthy cells. In this case, the drug is made to hit a marker on tumors of patients with acute myeloid leukemia. Sometime between late this month and August, the company expects to rip off the blind from a study of 210 patients, which will say whether the new drug can help some very sick, elderly patients live a few months longer with acceptable side effects.

Acute myeloid leukemia is a fast-growing, aggressive form of cancer that often strikes people over the age of 60, and makes them too frail to withstand the high-dose chemotherapy they are prescribed. Life expectancy, based on past studies, is usually about 4-6 months. Seattle Genetics decided to swing for the fence in this tough-to-treat group of people after preliminary studies showed that a “mid-teens” percentage of patients saw some degree of partial or complete tumor shrinkage, and there were anecdotal reports of people living longer, CEO Clay Siegall says. If the company can prove its drug helps people live longer with this nasty malignancy, then Seattle Genetics could be in a position to offer this new drug for sale in the not-so-distant future. The disease kills an estimated 8,950 people a year in the U.S., according to the American Cancer Society. [Correction 10:05 am Pacific: An earlier version said lintuzumab could be ready for sale next year, but the company says it hasn’t provided guidance yet on timing.]

“This is a big unmet need, which is partly why we were excited to embark on this trial,” says Siegall. “We’re hopeful this trial will be successful. If it is, it will be exciting for patients and for Seattle Genetics.”

Wall Street isn’t giving this drug much of a chance. One of the bullish analysts covering the company, Cory Kasimov of JP Morgan, said the consensus among investors is that the lintuzumab trial will fail because of the tough patient population and a “lack of convincing earlier-stage data.” Kasimov gives it a 30 percent shot of winning FDA approval and generating peak annual sales of $350 million by 2016.

This big trial began back in September 2007. The company explained some of the rationale a few months later when it presented early stage results at a meeting of the American Society of Hematology. Of 17 patients who got a variety of doses, five patients had complete tumor remission, while two more had a partial shrinkage of their tumors. The drug was well-tolerated, and patients didn’t develop antibodies to attack the drug itself as a foreign invader, which is known to happen.

Those findings were enough for Seattle Genetics to invest some significant money to get a definitive answer from this ongoing trial, which might be enough to persuade the FDA to clear this drug for sale. The study enrolled 210 patients, and randomly assigned them to get a low-dose chemotherapy drug in addition to the Seattle Genetics treatment, or the low-dose chemotherapy alone. The main goal is to show whether the new drug can help patients live longer — the gold standard measurement in cancer trials. The trial is statistically designed to show a 29 percent lower risk of death among patients on the experimental treatment, and Seattle Genetics is hoping to add a couple extra months of median survival time, without any serious added side effects, Siegall says.

The trial is designed in such a way that researchers, and the company, are blinded to the results to prevent any biases that might skew the study until at least 186 patients who entered the study have died. Then, statisticians will look at which patients got the new drug compared with the standard therapy, to see if there was any benefit. The initial findings will be issued by press release, and then the company will go into more detail at a medical meeting, Siegall says.

It’s possible that if the data for the Seattle Genetics drug is compelling enough from this single study, the company could use it as the basis to whip up an application to the FDA, Siegall says. It’s also possible that it could form part of a body of evidence for the drug, and provide the spark for another rigorous study to prove the drug’s worth, he says.

There are no other drugs on the market for acute myeloid leukemia that hit the same target as the Seattle Genetics drug, since Pfizer (NYSE: PFE) announced yesterday that it is pulling gemtuzumab ozogamicin (Mylotarg) off the market.

Strangely enough, the Pfizer drug was a trailblazer in the field of “empowered antibodies” that Seattle Genetics is seeking to reinvent today with a next-generation form of the technology. The scientists at what was then Wyeth created Mylotarg as a way to combine the targeting ability of an antibody with a potent toxin attached to give it more tumor-killing kick. The drug ultimately was a poor seller, partly because the linker wasn’t really stable enough to ensure the toxin got exactly where it needed to go in the tumor.

A decade of research and development later, Seattle Genetics has applied new chemistry techniques for empowered antibodies for a variety of forms of cancer. But with acute myeloid leukemia, among elderly patients who are especially frail, the notion is that a simpler “naked” antibody like lintuzumab, without any extra toxin, might be an effective way to disrupt tumors without causing serious side effects.

The company has spent a lot of time and money on getting this answer, as it completed enrollment in the study in February 2009, and stopped treating the last patient 12 months later. Suspense, naturally, is building at the company on whether this dark horse drug candidate is a winner or not.

“Our goal is to see a meaningful improvement in survival,” Siegall says.

It's approaching the homestretch.