Assistant Managing Editor

Shares of Cell Therapeutics Inc. tumbled 39.6 percent after FDA briefing documents, emerging ahead of Wednesday's advisory panel, suggested that the company's abbreviated pivotal study of pixantrone might not be enough to warrant the drug's accelerated approval in relapsed/ refractory aggressive non-Hodgkin's lymphoma.

That news seemed to affirm Wall Street's worries last month, when an oddly-timed $30 million stock and warrant sale - on top of $140 million raised in a series of 2009 offerings - left investors wondering whether bad regulatory news was coming down the pike. Investors sent shares down 11 percent that day. (See BioWorld Today, Jan. 15, 2010.)

The Seattle-based company's stock (NASDAQ:CTIC) fell another 42 cents to close Monday at 64 cents.

FDA staff also raised questions concerning safety data, particularly cardiac toxicity, but it's the shortened Phase III study - stopped after 140 patients rather than the planned 320 due to slow recruitment - that could get the most attention at the Oncologic Drugs Advisory Committee meeting, especially since the briefing documents stated that the trial's earlier-than-expected conclusion invalidated the special protocol assessment.

So, even though pixantrone met its primary endpoint, showing that 25 percent of patients treated with the anthracycline drug demonstrated a complete response vs. 5.7 percent of those given comparator agents, it's possible the panel will ask for additional data. The FDA, which usually follows the advice of its advisory panels though it's not bound to do so, has set an April 23 action date for pixantrone.

In 2007, Cell Therapeutics met with the FDA to report trouble enrolling patients. The company cited reluctance on the part of investigators, who preferred to use either multi-agent chemo or supportive care in the third-line NHL population, and said only 66 of the 189 sites opened for the trial had actually accrued patients.

The company said it decided to conduct a full analysis of the trial instead of a previously planned interim analysis, based partly on FDA guidance that a primary endpoint analysis could be acceptable for a new drug application if it was able to demonstrate statistical significance between treatment arms.

But in the briefing documents, reviewers stated that "higher levels of evidence is usually required in trials which discontinue prior to the final analysis."

Safety issues likely will come up at Wednesday's meeting as well. Reviewers pointed specifically to cardiotoxicity, a well-known side effect of anthracyclines. Cell Therapeutics has maintained that pixantrone has shown consistently fewer cardiac side effects compared to existing anthracyclines because it's designed to reduce the production of free radicals, and data published recently in Blood showed a significant reduction in cardiac cell toxicity with pixantrone vs. marketed anthracyclines.

Pixantrone's overall safety database showed that cardiac failure events Grade 3 or higher occurred in six of 197 patients (3 percent) who received the drug as a monotherapy and in four of 151 patients (3 percent) receiving pixantrone in combination treatment regimens.

Cell Therapeutics holds all rights to pixantrone, though it has been seeking a partner, while also waiting to see whether Basel, Switzerland-based Novartis AG will exercise its option to license the drug for commercialization under the companies' 2006 collaboration. (See BioWorld Today, Sept. 19, 2006.)

For the past few years the firm has focused most of its efforts on pixantrone. In addition to raising money via stock and warrant offerings, Cell Therapeutics also sold its rights to radioimmunotherapy drug Zevalin (ibritumomab tiuxetan) to Irvine, Calif.-based Spectrum Pharmaceuticals Inc. for $31.5 million last year, and in 2008, cut 62 jobs at its Bresso, Italy, facility to save $14 million in annual costs. (See BioWorld Today, Nov. 12, 2008, and Feb. 9, 2009.)

The company also is developing Opaxio (paclitaxel poliglumex), which is in Phase III in patients with previously untreated non-small-cell lung cancer.

Published  February 9, 2010