Corixa Corp. said it is requesting an appeal of the FDA's complete review letter questioning the net clinical benefit and safety of the company's lead cancer product, known as Bexxar.
In a complete review letter dated March 12, the FDA informed Seattle-based Corixa that additional clinical studies would be necessary to win marketing clearance for Bexxar, a radioimmunotherapy being developed for the treatment of low-grade or transformed low-grade non-Hodgkin's lymphoma. (See BioWorld Today, March 14, 2002.)
Following receipt of the letter, Corixa and its partner, GlaxoSmithKline plc, of London, submitted detailed responses to the agency and scheduled a meeting to work through the problems, Steven Gillis, Corixa's CEO and chairman, told analysts and reporters participating in a conference call early Wednesday morning. That meeting ended in a continuing difference of opinion, however, leading Corixa to file a request for dispute resolution under the Food and Drug Administration Modernization Act (FDAMA).
Corixa's stock (NASDAQ:CRXA) fell 77 cents Wednesday, or 12.3 percent, to close at $5.48.
Gillis said the company is preparing its formal request and, once submitted, the agency is compelled to respond within 45 days. The company will ask the FDA to refer the application to the Oncologic Drugs Advisory Committee (ODAC), a recommending body.
Jim DeNike, Corixa's director of corporate communications, would not speculate on how fast the company might be assigned a meeting date, but analysts predicted late this year or sometime in early 2003.
Brian Rye, a biotech analyst with Raymond James & Associates Inc. in Nashville, told BioWorld Today that an ODAC meeting would be a step in the right direction.
"We are hoping they can get before ODAC; at least that way they can get their foot in the door," he said. "We view this announcement as positive in the context that we have not had any sort of sense of the next step with Bexxar. This has been such a troubled regulatory path and we view any sort of potential meeting as positive."
Research notes released by Thomas Dietz, an analyst with Pacific Growth Equities in San Francisco, went a step further, saying, "We continue to believe that if put to an ODAC panel, Bexxar will be found to have a positive risk/benefit."
In September 2000, San Francisco-based Coulter Pharmaceuticals Inc. and then-partner SmithKline Beecham plc submitted a BLA for Bexxar that was accepted in November of that year. Corixa inherited Bexxar in late 2000 when it took over Coulter in a stock swap valued at more than $900 million. Once the drug was in Corixa's hands, the FDA requested additional safety and efficacy data, prompting Corixa to ship a tremendous volume of data in September 2001. It was widely believed that ODAC would review the application in February 2002, but the agency couldn't schedule the meeting because it was unable to study all the material Corixa submitted. (See BioWorld Today, Oct. 17, 2000, and Jan. 11, 2002.)
However, the FDA has confirmed that data submitted in the biologics license application prior to the March 12 letter enabled the agency to "sufficiently characterize the safety of Bexxar in order to permit an assessment of net clinical benefit."
Gillis said since Bexxar's safety profile doesn't appear to be troubling the agency, instead the problems likely focus on efficacy and the unmet medical need.
"It is our contention that Bexxar does give the high-level durable response that is seen across multiple trials that has not been seen with other products in this indication," he said.
Bexxar is an antibody specific to the CD20 antigen on B cells conjugated to radioactive iodine-131. It attaches to a protein found only on the cell surface, including non-Hodgkin's lymphoma B cells. Similar products are Rituxan and Zevalin, both made by San Diego-based IDEC Pharmaceuticals Inc.
In its company statement, Corixa said the FDA "continues to request additional studies to more carefully assess the true incidence of adverse events and assess for factors that may correlate with an increased incidence of adverse events."
An applicant is not permitted to submit additional data or information as part of the request for the dispute resolution. However, DeNike said if the appeal is granted, Corixa could provide the FDA with additional information to support its contention that Bexxar meets an unmet medical need. Furthermore, a company statement said the FDA has provided guidance as to what additional information must be submitted to support Corixa's claim that Bexxar provides a level of durable response.