BETHESDA, MD 01 November 2013—FDA today announced the approval of obinutuzumab as part of a treatment regimen for chronic lymphocytic leukemia (CLL).
for the drug states that it is indicated, in combination with chlorambucil, for the treatment of CLL in patients who have not previously received drug therapy for the disease.
The monoclonal antibody product will be available within about two weeks, according to Genentech, which will market the therapy as Gazyva.
Obinutuzumab targets the CD20 surface antigen on B lymphocytes, resulting in lysis of the cells, including the abnormal B lymphocytes that are typical of CLL.
Obinutuzumab is the first so-called breakthrough therapy to be approved by FDA since the agency began using that designation in 2012, in response to requirements in the Food and Drug Administration Safety and Innovation Act.
According to FDA, 31 drugs were granted breakthrough therapy status between July 9, 2012, and October 25, 2013.
FDA may grant the breakthrough therapy designation at the request of a manufacturer for a drug that is intended for the treatment of a serious or life-threatening disease or condition. To receive the designation, manufacturers must have preliminary evidence that the drug works better than existing therapies.
In a clinical trial involving 356 patients with CLL, obinutuzumab in combination with chlorambucil doubled the median time that patients lived without their disease worsening, compared with chlorambucil therapy alone.
The most common adverse events reported among clinical trial participants who received obinutuzumab and chlorambucil included infusion reactions, neutropenia, thrombocytopenia, anemia, musculoskeletal pain, cough, and fever.
To reduce the risk for infusion reactions, the labeling recommends pretreatment of patients with a glucocorticoid, an antihistamine, and acetaminophen. Specific dosage and timing recommendations for these medications vary depending on the treatment cycle and are described in the labeling.
A boxed warning in the labeling states that patients who are treated with obinutuzumab are at risk for reactivation of hepatitis B virus infection and progressive multifocal leukoencephalopathy, either of which may be fatal. All patients should be screened for hepatitis B virus infection before initiating therapy with obinutuzumab, and treatment should be halted if the virus becomes active.
The labeling recommends that patients receive six cycles of therapy with obinutuzumab, with each cycle being 28 days. Cycle 1 consists of four doses: 100 mg on day 1, 900 mg on day 2, 1000 mg on day 8, and another 1000 mg on day 15. For cycles 2–6, the dose is 1000 mg on day 1 and no doses on the other days.
Instructions for preparing the 100-, 900-, and 1000-mg doses for i.v. infusion are included in the labeling. The doses for day 1 and day 2 of cycle 1 are to be prepared at the same time, with the 100-mg dose administered immediately after preparation and the 900-mg dose stored at 2–8 °C for administration on day 2.
The monoclonal antibody therapy will be supplied in 1000-mg single-use vials that should be refrigerated at 2–8 °C and protected from light and never frozen or shaken.