Cell Therapeutics FDA Panel Primer: What You Need to Know to Be Ready Next Week

Seattle-based Cell Therapeutics will find out in seven days whether it has a legitimate shot at getting a new cancer drug on the U.S. market. This company has a long and controversial history, and it is guaranteed to generate noise over the next week from stock market bulls and bears. So I figured it might be useful to gather some of the relevant facts in advance of this modern version of Roman theater, otherwise known as an FDA advisory panel.

The main event starts at 8 am Eastern time/5 am Pacific on February 10. That’s when the Oncologic Drugs Advisory Committee, a panel of cancer drug experts that advises the FDA, will gather in a suburban Washington, DC, hotel. There, they’ll hear testimony about, and likely vote on, Cell Therapeutics’ application to market pixantrone (Pixuvri) as a new therapy for patients with relapsed, aggressive forms of non-Hodgkin’s lymphoma. The FDA isn’t required to follow the public advice of its expert panels, although it usually does.

Cell Therapeutics (NASDAQ: CTIC) has survived more than one near-death experience in the past, and CEO Jim Bianco has described 2009 as a “tight-wire act.” So pretty much the whole farm is riding on this panel vote. The company, which ran down to less than a couple of weeks of cash at one point last year, doesn’t have any marketed products generating cash at the moment and nothing besides pixantrone with a legitimate shot at imminent FDA approval. Amazingly, it has burned through more than $1.4 billion of capital since its founding in 1991 without ever becoming profitable. Yet the company has been so prodigious at convincing investors to keep writing checks, and so popular with the fast-money crowd, that it now has an astonishing 574 million shares outstanding. That’s more than Celgene (NASDAQ: CELG), a profitable maker of blood cancer drugs, which has a market capitalization of $26 billion.

James Bianco

James Bianco

The question of little Cell Therapeutics, and whether it will ever get within hailing distance of profitability, really hinges on a single study of 140 patients that doctors review next week.

“We do expect U.S. approval,” Cell Therapeutics president Craig Philips told investors on January 14, during a presentation at the JP Morgan Healthcare Conference in San Francisco.

Before diving into the nitty-gritty of the medical evidence, a little bit of business background is necessary. Cell Therapeutics obtained pixantrone in 2003 when it paid $236 million to acquire Italy-based Novuspharma. The drug is a modified form of an anthracycline chemotherapy. Anthracyclines are potent cell-killing agents commonly used in patients newly diagnosed with lymphomas. They can induce long-term remissions, but they also can cause heart failure if they are used more than once. Novuspharma designed pixantrone to have the cell-killing power of an anthracyline infusion, without damaging the heart.

If the treatment is approved, Cell Therapeutics officials estimate the company can tap into a market of about 10,000 U.S. patients each year who are on at least their third round of treatment for aggressive non-Hodgkin’s lymphoma. Cell Therapeutics uses Cephalon’s bendamustine (Treanda), which costs $44,000 per patient, as a comparable benchmark on price, Philips told investors last month. Assuming Cell Therapeutics captures one-third of the patient population, pixantrone could generate about $150 million annually in U.S. sales. The FDA’s deadline to make a decision is April 23.

The FDA’s advisory panel meetings can dwell on the most arcane and tangential of scientific questions, but the ultimate question usually comes down to whether the panel thinks that the evidence presented for a drug is strong enough to show that the benefit outweighs the risk—or whether more proof from clinical trials is necessary. Adam Feuerstein, an influential biotech columnist of TheStreet.com, published his seven-point case on what he sees as the weak spots in the Cell Therapeutics application.

The 140-patient study on which Cell Therapeutics’ case heavily relies is known as Extend or PIX 301. This study randomly assigned patients to get pixantrone or the physician’s choice of another chemotherapy drug. The study’s main goal was to show the treatment could completely wipe out tumors. The study reached its goal, and the finding was statistically significant. About 20 percent of patients on pixantrone (14 out of 70) had a “complete response” compared with 5.7 percent (4 out of 70) who did that well in the control group.

What about side effects? Patients in the pixantrone group had higher rates of white blood depletion, known as neutropenia, with 41 percent reporting a severe case of that effect, compared with 19 percent in the control group, according to data presented in June at the American Society of Clinical Oncology. An even more severe form of that condition, febrile neutropenia, was found in 7.4 percent of pixantrone patients, compared with 3 percent in the comparison group. There were also more cases of severe cardiac disorders reported among patients who got pixantrone—8.8 percent on the drug, compared with 4.5 percent in the control group.

While cancer drugs are allowed to have greater side effects than a new pain reliever because cancer is a life-threatening disease, it wouldn’t be a surprise if the panel asks tough questions of Cell Therapeutics about the safety of its drug.

Pixantrone has been studied in more than 400 patients overall, Jack Singer, Cell Therapeutics’ chief medical officer, said in a March interview. Singer noted that many of the patients had prior treatments that are toxic to the heart, and that the drug’s “safety profile is about as good as one could hope for.”

One of the key questions the panel is likely to ask is about how long-lasting the remissions are for those patients whose tumors went away. This is one of the reasons many cancer trials are required to use the gold standard measurement of survival time as the primary goal. While complete tumor eradication can sometimes be a promising sign that a drug is working, it’s not always reliable, because cancer can bounce back fast and kill people. Cell Therapeutics doesn’t have statistically significant evidence that shows its drug actually helps patients live longer than some other generic chemotherapy.

If the FDA panel starts pounding the table for that kind of survival data, and says Cell Therapeutics needs to run more trials with a lot more patients before it can get the green light for pixantrone, then this will be a painful blow for the company’s supporters. If Cell Therapeutics can persuade the panel that its data is good enough, then February 10 will be the first day of rebirth at Cell Therapeutics. Either way, the daily stock chart—in which many of those 574 million shares are sure to change hands—will say it all.

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