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FDA Alerts

Pharmacist's Applications to Practice

HOPA, through the Publications Committee, will review new drug updates and provide analysis and research on the application of these new drugs or indications.

The letters “PAP” after drugs listed below indicates that they include this additional analysis.  


November 16, 2017–Obinutuzumab (GAZYVA®, Genentech, Inc.) granted regular approval in combination with chemotherapy, followed by obinutuzumab monotherapy in patients achieving at least a partial remission, for the treatment of adult patients with previously untreated stage II bulky, III, or IV follicular lymphoma (FL).

February 26, 2016–Obinutuzumab (Gazyva® Injection) approved for use in combination with bendamustine followed by obinutuzumab monotherapy for the treatment of patients with follicular lymphoma


November 16, 2017

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125486s017s018lbl.pdf

On November 16, 2017, the Food and Drug Administration granted regular approval to obinutuzumab (GAZYVA®, Genentech, Inc.) in combination with chemotherapy, followed by obinutuzumab monotherapy in patients achieving at least a partial remission, for the treatment of adult patients with previously untreated stage II bulky, III, or IV follicular lymphoma (FL).

Approval was based on a multicenter, open-label, randomized phase 3 trial (GALLIUM) for patients with previously untreated non-Hodgkin lymphoma, including 1202 patients with FL. Patients were randomized 1:1 to receive either obinutuzumab + chemotherapy or rituximab + chemotherapy, followed in responding patients by obinutuzumab or rituximab maintenance for up to 2 years. Of the patients with FL, 91% had stage III-IV disease, 44% had bulky disease, and 79% had at least intermediate-risk disease. The chemotherapy backbone was bendamustine in 57%, CHOP in 33% and CVP in 10%. With a median follow-up of 38 months, progression-free survival, as assessed by an independent review committee, was statistically significantly improved in the obinutuzumab arm, with an estimated hazard ratio of 0.72 (95% CI: 0.56, 0.93; p=0.0118) compared to the rituximab arm. Median progression-free survival was not reached in either arm. As assessed by CT, the arms had similar overall response rates (91% with obinutuzumab, 88% with rituximab) and complete remission rates (28% and 27%, respectively).

Among the 1385 patients evaluated for safety, the obinutuzumab arm had higher incidences of serious adverse reactions (ARs; 50% compared to 43% in the rituximab arm), grade ≥ 3 ARs (79% vs. 72%) and fatal infections (2% vs. < 1%). The most common ARs in the obinutuzumab arm (incidence ≥ 20% and ≥ 2% greater than in the rituximab arm) included infusion reactions, neutropenia, upper respiratory tract infection, cough, constipation and diarrhea. The most common grade ≥ 3 ARs (incidence ≥ 5%) observed more frequently with obinutuzumab were neutropenia, febrile neutropenia, thrombocytopenia and infusion reactions. Recipients of bendamustine had higher incidences of serious and fatal infections than recipients of CHOP or CVP.

In patients with previously untreated FL, the recommended dose-schedule of obinutuzumab is 1000 mg intravenously on days 1, 8 and 15 of cycle 1; 1000 mg on day 1 of cycles 2-6 or cycles 2-8; and then 1000 mg every 2 months for up to 2 years.

Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125486s017s018lbl.pdf

FDA granted priority review to obinutuzumab for this indication. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.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).


February 26, 2016

http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125486s013lbl.pdf

On February 26, 2016, the U. S. Food and Drug Administration approved obinutuzumab (Gazyva® Injection, Genentech, Inc.) for use in combination with bendamustine followed by obinutuzumab monotherapy for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximab-containing regimen. Obinutuzumab was previously approved for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia.

This new approval was based on demonstration of an improvement in progression-free survival (PFS) in a randomized, open-label, multicenter trial in patients with FL who had no response to or have progressed during or within 6 months of a rituximab-containing regimen. This trial compared 6 cycles of obinutuzumab plus bendamustine combination therapy followed by continued obinutuzumab monotherapy for up to 2 years with 6 cycles of bendamustine therapy.

Efficacy was assessed in 321 patients with follicular lymphoma randomized to either obinutuzumab plus bendamustine (n=155) or bendamustine (n=166). The median age was 63 years (range 34-87). Patients had received a median of 2 prior therapies (range 1-10). The independent review assessed median PFS was 13.8 months in the bendamustine arm while the median PFS was not reached in the obinutuzumab plus bendamustine arm [HR 0.48 (95% CI: 0.34-0.68), log-rank test p-value < 0.0001).

This trial also enrolled 46 patients with marginal zone lymphoma and 28 with small lymphocytic lymphoma who were also included in the safety analysis. The most common adverse reactions (greater than or equal to 10%) in the safety population treated with obinutuzumab plus bendamustine followed by obinutuzumab monotherapy were infusion reactions, neutropenia, nausea, fatigue, cough, diarrhea, constipation, pyrexia, thrombocytopenia, vomiting, upper respiratory tract infection, decreased appetite, arthralgia, sinusitis, anemia, asthenia and urinary tract infection. Serious adverse reactions were reported in 38% of patients treated with obinutuzumab plus bendamustine followed by obinutuzumab monotherapy. The most common serious adverse reactions (greater than 2%) were febrile neutropenia, neutropenia, infusion related reactions, sepsis, pneumonia and pyrexia.

The recommended dose and schedule for the regimen follows:

  • Obinutuzumab: 1000 mg by intravenous infusion on days 1, 8 and 15 of cycle 1; on day 1 of cycles 2-6 (28-day cycles); and then every 2 months for 2 years.

  • Bendamustine: 90 mg/m2 by intravenous infusion on days 1 and 2 of cycles 1-6.

This application was granted Priority Review. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125486s013lbl.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).

 

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