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ODAC Cites Clinical Benefits of Bexxar, Safety Concerns

ODAC Cites Clinical Benefits of Bexxar, Safety Concerns

BETHESDA, Maryland—Members of the FDA’s Oncologic Drugs Advisory Committee
(ODAC) gave a mixed review to Corixa’s Bexxar (tositumomab and iodine I-131-tositumomab),
a radioactive-labeled monoclonal antibody intended to treat certain
non-Hodgkin’s lymphoma (NHL) patients.

The committee agreed that the drug showed evidence of clinical benefit in
NHL patients, with unusually high rates of complete remissions (see ONI
January 2003, page 1). ODAC voted 10 to 3 in support of the efficacy of
Bexxar in rituximab (Rituxan)-refractory patients and unanimously supported
its clinical utility in chemotherapy-relapsed and refractory, low-grade NHL,
with or without transformation.

ODAC members, however, expressed concern about whether the clinical trial
data presented to them clearly demonstrated that the drug’s benefits outweigh
its risks, particularly with regard to the occurrence of secondary cancers.
FDA did not ask the panel to vote on whether to recommend that FDA approve
Bexxar.

Corixa has applied to the FDA for two types of approval for the drug. The
company seeks accelerated approval to market the drug as a treatment for
patients with relapsed or refractory low-grade or transformed low-grade NHL.
Corixa also is seeking standard approval to market Bexxar for the treatment
of patients with rituximab-refractory follicular NHL.

During the ODAC meeting, Corixa presented data from two pivotal and three
supportive studies to back its new drug application. The five trials showed
overall response rates ranging from 46% to 63% and complete response rates
ranging from 20% to 33%. Safety data presented by the company from 620 Bexxar-treated
patients showed that 14 of them died from myelodysplastic syndrome (MDS) or
acute myelogenous leukemia (AML), with an annualized incidence for the two
diseases of 2.2% a year.

During the committee’s discussion, chair Donna Przepiorka, MD, PhD, of the
University of Tennessee in Memphis, called the complete response rates for
Bexxar "amazing in patients who have been so heavily pretreated. However, I
am concerned about the hematologic data as well as the potential for leukemia
in these patients. This is certainly not something I would jump to as a
first-line therapy in patients with stage III or IV disease. But definitely
for patients with refractory disease or refractory-relapsed disease, it is
better than anything we can do currently." Her remarks seemed to sum up the
general views of most of her fellow ODAC members.

Bexxar’s monoclonal antibody targets the CD20 surface antigen, which is
expressed on B-cell tumor cells. The antibody is labeled with iodine-131 and
when it attaches to the CD20 antigen, the radionuclide delivers a deadly dose
of radiation to the cancer cell. Bexxar also has an affinity for a few normal
cells.

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