FDA Grants Accelerated Approval to Brentuximab Vedotin
Friday, August 19, 2011
The US Food and Drug Administration granted accelerated approval to brentuximab vedotin (Adcetris™ for Injection, Seattle Genetics, Inc.) for two indications:
- The treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates.
- The treatment of patients with systemic anaplastic large cell lymphoma (ALCL) after failure of at least one prior multi-agent chemotherapy regimen.
The accelerated approval of the Hodgkin lymphoma indication was based on a single-arm, multicenter, clinical trial (Trial SG035-0003) to evaluate the objective response rate (ORR) of brentuximab vedotin as a single agent. Patients who enrolled in the trial (n=102) had CD30-positive Hodgkin Lymphoma that relapsed after ASCT.
The primary efficacy endpoint in the Hodgkin lymphoma trial, ORR by Independent Review Facility, was 73% (95% CI: 65, 83) with a median duration of 6.7 months (95% CI: 4, 14.8). Complete Remission (CR) rate was 32% (95% CI: 23.3, 42.3) with a median duration of 20.5 months (95% CI: 12, NE). Partial Remission (PR) rate was 40% (95% CI: 31.5, 49.4) with a median duration of 3.5 months (95% CI: 2.2, 4.1).
The accelerated approval for the systemic ALCL indication was based on a single-arm, multicenter, clinical trial (Trial SG035-0004) enrolling 58 patients who had CD30-positive systemic ALCL and had previously received front-line, multi-agent chemotherapy regimens.
The primary efficacy endpoint in the systemic ALCL trial, ORR by Independent Review Facility, was 86% (95% CI: 77, 95) with a median duration of 12.6 months (95% CI: 5.7, NE). CR rate was 57% (95% CI: 44, 70) with a median duration of 13.2 months (95% CI: 10.8, NE). PR rate was 29% (95% CI: 18, 41) with a median duration of 2.1 months (95% CI: 1.3, 5.7).
The most common adverse reactions (≥20%) noted in both trials were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting. Serious adverse events (SAEs) were reported in 31% of patients. The most common (>2%) SAEs reported were peripheral motor neuropathy, urinary tract infection, and abdominal pain. Refer to the prescribing information link below for further details of safety profiles of the individual trials.
The recommended dose and schedule for both indications is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Treatment may be continued until maximum of 16 cycles, until disease progression, or unacceptable toxicity.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125388s000,125399s000lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).