By Randall Osborne
It's a sad fact of biotech or a happy fact, depending on your point of view that the disease perhaps most feared by most people is the same "indication" (as scientists prefer to say) that may hold the most profit-making potential in the years ahead.
Cancer, of course.
Tissue-wrecking infused chemotherapies aside, nothing really works against cancer, which is more like an army of diseases than just one. Treatments tend to be multiple, too, with physicians alternating and mixing drugs like boxers varying their punches for the most powerful effects.
Lacking the much-sought "magic bullet," doctors use whatever is at hand against cancer. The cost is high in more ways than one, ravaging not only the patients, but also their bank accounts. Then, more often than not, they die.
One of the most insidious and surely fatal forms is pancreatic cancer, which kills more than 75,000 annually in the U.S. and Europe, making it the fourth leading cause of death by cancer in the U.S. where advanced pancreatic cancer carries an average survival rate of four to five months.
"It's undetectable," said Joseph Rubinfeld, chairman and CEO of SuperGen Inc., who believes researchers may finally be barking up the right tree with a class of drugs called camptothecins, derived from the Camptotheca acuminata tree in China.
SuperGen is developing rubitecan, an oral topoisomerase I inhibitor that scientists suspect will work better while avoiding the brutal side effects of existing chemotherapies.
Topoisomerase I inhibitors function by catalyzing the breakup of DNA in cancer cells. Other agents, such as Gemzar (gemcitabine HCL) operate differently. Gemzar is a nucleoside analogue that mimics a natural DNA building block, and interrupts cancer cell replication. Another approved drug, 5-FU, is a fluorinated pyrimidine analogue that blocks DNA synthesis and RNA processing.
Strongly behind rubitecan already is Abbott Laboratories, which last year agreed to a potential $150 million worldwide marketing deal for the drug, undergoing a Phase III study at more than 200 sites, with data expected in the third quarter of this year. SuperGen got $31 million up front, Rubinfeld said.
The Phase III trials, designed to test 1,800 patients, are "going very well," he said. "We're about 60 percent accrued."
Rubinfeld has a long history in biotech he started the oncology branch of Bristol-Myers Squibb Co., and co-founded Amgen Inc. as well as an earlier, distinguished career as an inventor. The biodegradable detergents that Rubinfeld said "saved the Great Lakes" came from his workbench. He also devised Polaroid's 10-second developing method, which spared vacationers from having to wait a full minute for their photographs.
Now, he's all about battling a pernicious disease.
"Everybody wants to be in cancer," said Rubinfeld, who scoffs mildly at the genomics craze, calling the field "sexy, that's all. You have all that data, all that information, and you still have to find a drug. We're into drugs, and we have 20 real drugs in the pipeline," he said.
Not to mention a solid player already on the market. Nipent (pentostatin), for hairy cell leukemia, is a small-molecule purine analogue that acts by blocking the enzyme adenosine deaminase in cells, and doesn't require the presence of surface receptors. Abbott, as part of its deal with SuperGen, becomes the exclusive U.S. distributor for Nipent. SuperGen retains its U.S. marketing rights for the drug.
In March 1999, SuperGen filed a supplemental new drug application requesting approval of Nipent for treating mature T-cell lymphomas, primarily cutaneous T-cell lymphoma and peripheral T-cell lymphoma.
Nipent, along with SuperGen's approved cancer products mitomycin and Surface Safe, a two-step towelette disposable cleaning system used to decontaminate work surfaces where chemotherapeutic preparation is done, had combined sales last year of about $4.5 million.
But rubitecan will be the star, predicted analyst Peter Drake, of Prudential Vector Healthcare. In a report, he cited the drug as having "blockbuster potential," since no oral drugs for pancreatic cancer exist.
Eli Lilly & Co.'s Gemzar, the current standard of care for pancreatic cancer, is only palliative and costs between $11,000 and $12,000 for a standard, six-month treatment cycle. Worldwide sales of Gemzar last year totaled about $456 million. Lilly estimated about a third, or $152 million, was for the treatment of pancreatic cancer.
If oral rubitecan, with its antitumor effects, sells domestically for $10,000 to $15,000, the ultimate market opportunity for pancreatic cancer is $280 million to $420 million.
Prudential Vector, which gave SuperGen a "strong buy" rating, expects approval of rubitecan in 2001, with sales and royalties adding up to about $115 million in 2002.
Maria Phillips, an analyst with Banc of America Securities LLC in New York, said her firm has given the stock a "buy" rating and, with strong results with rubitecan in pancreatic cancer, prospects for SuperGen look good.
"I'd like to be careful in saying that, because we have very little data so far," she said. "There's a definite subset of patients that respond [to rubitecan], and the survival curve is compelling, but there's quite a bit of drug resistance, relapse in cancer."
Like Rubinfeld, Phillips refers to the success story of Taxol (paclitaxel), the cancer drug marketed by Bristol-Myers.
"Taxol came from the National Cancer Institute," she said. "Nobody wanted it, and it went out for bids. Think about that."
The key to fighting cancer so far, Phillips said, is "finding where the activity is, and where does [a particular drug] work, to combine it with something else."
That "something else" might well be Gemzar, she said. Rubinfeld agreed, saying rubitecan likely would first be competitive with other cancer drugs and then would likely be used along with them.
In such a scenario, the size of the market would be much wider, nearly impossible to guess although Rubinfeld does not disagree with a figure of $2 billion. "Taxol is a $1.6 billion market," he said. "It has all kinds of [side-effect] problems, and it's used everywhere."
Rubitecan's "effects will be wide-ranging, but it's not a magic bullet," Rubinfeld said. The drug's low toxicity and oral delivery route means physicians "could combine it with other cancer drugs, and then you might get 60 percent or 70 percent of people responding," he said, and this is where its true potential lies.
Experiments using camptothecins began at the Houston-based Stehlin Foundation for Cancer Research.
"One of our chief consultants, who worked all his life at Bristol-Myers, was on [Stehlin's] board of directors, and he made me aware they were looking for an industrial partner," Rubinfeld said. "He said five major companies had approached them already. I told the Stehlin people, 'If you give it to a big company, it'll probably lie on their shelves. We'll get it out in your lifetime, two or three or four years.'"
Other companies are exploring topoisomerase inhibitors (BioNumerik Pharmaceuticals Inc. and Enzon Inc., for example), but SuperGen's product is the furthest along. In February, the company registered for a public offering to sell 2 million shares, with certain stockholders to offer 700,000 more.
Finding late-stage research products such as rubitecan for in-licensing is a model "pretty tough to pull off," but has brought SuperGen to the brink of profitability, and is an approach investors would be wise to put cash behind, Rubinfeld said.
"When I went to see the Stehlin people, we had about $4 million in the bank," Rubinfeld said. "Now, we've got $150 million. A year ago, we had 40 people, and we'll have 120 people in the next couple of months. We're in much better shape today." *