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FDA Approval for Brentuximab Vedotin

Brand name: Adcetris

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

Hodgkin Lymphoma After Autologous Stem Cell Transplant Failure

On August 19, 2011, the Food and Drug Administration granted accelerated approval to brentuximab vedotin (Adcetris™ for Injection, made by Seattle Genetics, Inc.) for two indications:

The accelerated approval for Hodgkin lymphoma was based on a single-arm multicenter clinical trial (Trial SG035-0003) that enrolled 102 patients who had CD30-positive Hodgkin lymphoma that relapsed after ASCT.

The primary efficacy endpoint in the Hodgkin lymphoma trial, the objective response rate (ORR) of brentuximab vedotin as a single agent as determined by Independent Review Facility, was 73 percent (95 percent CI: 65 percent, 83 percent) with a median duration of 6.7 months (95 percent CI: 4, 14.8).The complete remission (CR) rate was 32 percent (95 percent CI: 23.3 percent, 42.3 percent) with a median duration of 20.5 months (95 percent CI: 12, NE). The partial remission (PR) rate was 40 percent (95 percent CI: 31.5 percent, 49.4 percent) with a median duration of 3.5 months (95 percent CI: 2.2, 4.1).

Systemic Anaplastic Large Cell Lymphoma After Multi-Agent Chemotherapy Failure

The accelerated approval for systemic ALCL was based on a single-arm multicenter clinical trial (Trial SG035-0004) that enrolled 58 patients who had CD30-positive systemic ALCL and had previously received front-line multi-agent chemotherapy.

The primary efficacy endpoint in the systemic ALCL trial, ORR by Independent Review Facility, was 86 percent (95 percent CI: 77 percent, 95 percent) with a median duration of 12.6 months (95 percent CI: 5.7). CR rate was 57 percent (95 percent CI: 44 percent, 70 percent) with a median duration of 13.2 months (95 percent CI: 10.8 ). PR rate was 29 percent (95 percent CI: 18 percent, 41 percent) with a median duration of 2.1 months (95 percent CI: 1.3, 5.7).

The most common adverse reactions (at least 20 percent) 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 percent of patients. The most common (more than 2 percent) 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 a maximum of 16 cycles, disease progression, or unacceptable toxicity.

Drug Warnings Issued

On January 13, 2012, the FDA notified the public that two additional cases of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that can result in death, have been reported with the lymphoma drug brentuximab vedotin. Due to the serious nature of PML, a new Boxed Warning highlighting this risk has been added to the drug label. At the time of brentuximab vedotin's approval in August 2011, one case of PML was described in the Warnings and Precautions section of the label.

In addition, a new Contraindication warning against use of brentuximab vedotin with the cancer drug bleomycin due to increased risk of pulmonary toxicity has been added to the drug label.

The signs and symptoms of PML may develop over the course of several weeks or months. They may include changes in mood or usual behavior, confusion, thinking problems, loss of memory, changes in vision, speech, or walking, and decreased strength or weakness on one side of the body. Patients who develop any signs and symptoms of PML should notify their healthcare professional immediately. Healthcare professionals should hold brentuximab vedotin dosing if PML is suspected and discontinue brentuximab vedotin if a diagnosis of PML is confirmed.

The FDA recommends that healthcare professionals refer to the current brentuximab vedotin drug label for the latest prescribing recommendations. Patients should contact their healthcare professional if they have any questions or concerns about brentuximab vedotin.

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

  • Updated: July 1, 2013