title: U.S. Food and Drug Administration approval: ofatumumab for the treatment of patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab.
abstract: OBJECTIVE
  To describe the data and analyses that led to the U.S. Food and Drug Administration (FDA) approval of ofatumumab (Arzerra, GlaxoSmithKline) for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.
  
  
  METHODS
  The FDA reviewed the results of a planned interim analysis of a single-arm trial, enrolling 154 patients with CLL refractory to fludarabine, and a supportive dose-finding, activity-estimating trial in 33 patients with CLL. Patients in the primary efficacy study received ofatumumab weekly for eight doses, then every 4 weeks for an additional four doses; patients in the supportive trial received four weekly doses. In the primary efficacy study, endpoints were objective response rate and response duration.
  
  
  RESULTS
  For regulatory purposes, the primary efficacy population consisted of 59 patients with CLL refractory to fludarabine and alemtuzumab. In this subgroup, the investigator-determined objective response rate was 42% [99% confidence interval (CI), 26-60], with a median duration of response of 6.5 months (95% CI, 5.8-8.3); all were partial responses. The most common adverse reactions in the primary efficacy study were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. Infusion reactions occurred in 44% of patients with the first infusion (300 mg) and 29% with the second infusion (2,000 mg). The most common serious adverse reactions were infections, neutropenia, and pyrexia.
  
  
  CONCLUSIONS
  On October 26, 2009, the FDA granted accelerated approval to ofatumumab for the treatment of patients with CLL refractory to fludarabine and alemtuzumab, on the basis of demonstration of durable tumor shrinkage.
authors.affiliation: Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA. steven.lemery@fda.hhs.gov
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Lemery
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhang
authors.forename: Mark D
authors.initials: MD
authors.lastname: Rothmann
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Justin
authors.initials: J
authors.lastname: Earp
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Andrew
authors.initials: A
authors.lastname: McDougal
authors.forename: Anne
authors.initials: A
authors.lastname: Pilaro
authors.forename: Raymond
authors.initials: R
authors.lastname: Chiang
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Gootenberg
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005334:Fever / Q000139:chemically induced; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D015337:Multicenter Studies as Topic; D009503:Neutropenia / Q000139:chemically induced; D011014:Pneumonia / Q000139:chemically induced; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000074323:Alemtuzumab; D014740:Vidarabine; C527517:ofatumumab; C024352:fludarabine