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its drug-development efforts to focus on the most promising programs. The company now has three compounds in clinical trials.
Sapacitabine is the most advanced of those compounds. The drug, called a “nucleoside analog,” works by interfering with DNA synthesis in cancer cells. That, in turn, induces the arresting of the cells’ division cycle. Unlike the most commonly used chemotherapy treatments for AML, which are infusions that have to be given in medical clinics, sapacitabine is a pill that patients can take at home. There have been side effects in trials, such as nausea, but the drug has been tolerable enough for some patients to take it for 12 cycles—as opposed to just two cycles with standard chemotherapy, Rombotis says.
AML is a rare disease, but a potentially lucrative market opportunity. The disease strikes about 13,000 patients a year, most of them elderly. The most commonly used treatment is a chemotherapy regimen that is too toxic for many older adults to handle. Most patients die within a year of diagnosis, Rombotis says, which is why so many oncologists have been angling to get their sickest patients into trials of sapacitabine. “If we shift the natural progression of the disease, this will be a blockbuster,” he predicts.
Cyclacel hasn’t discussed the pricing of its drug or predicted the overall size of the market. But Genzyme once predicted the AML market to be $600 million a year—a reasonable estimate, Rombotis says, when you consider that similar treatments are priced around $50,000 per treatment cycle. Cyclacel is also developing sapacitabine for myelodysplastic syndromes (MDS) and lung cancer—both of which are even bigger market opportunities than AML, Rombotis says.
The first hint of what Cyclacel’s drug might achieve in AML will emerge at ASCO. Physicians and analysts alike will be looking carefully at the 30-day and 60-day mortality data. In AML, Rombotis says, 30-day mortality rates of 10 percent or less are considered okay. Anything between 10 and 20 percent is worrisome, and 20 percent or more is a “no go,” he says. “At 60 days, we look at mortality as an indicator of efficacy,” Rombotis adds. “If you don’t start to move the curve at 60 days, you’re not going to get there.”
Drug cocktails to fight cancer have become popular over the past decade, so Rombotis hopes that combining sapacitabine with decitabine will produce a more potent—but more tolerable—treatment than the standard chemotherapy regimens. Unlike other cocktails, in which several treatments are given simultaneously, Cyclacel’s treatment regimen consists of alternating one-month therapies: decitabine infusions, then sapacitabine pills that the patients take at home, then decitabine, and so on.
It will take several more years for Cyclacel to prove definitively that its treatment can make enough of a difference in AML to win over the FDA. But Rombotis and his colleagues are inspired by patients in their trials that have achieved seemingly impossible recoveries. During a meeting at Cyclacel’s headquarters, Rombotis brought along the company’s 2008 annual report, which featured Marvin Arnold, a Texan who participated in an early trial of sapacitabine. He was 81 years old when he was diagnosed with AML and placed in the trial. “This man had two more birthdays,” Rombotis says, holding up the annual report that pictures Arnold on the cover.
Rombotis knows Cyclacel will ultimately have to prove that its treatment improves survival by at least three months on average. “Ideally, we want to push survival out beyond six months,” he says. “Otherwise we’re not going to make a dent in this disease.”