New CLL Drug Delays Disease by Nearly 1 Year

In Head-to-Head Trial, Serious Adverse Events Much Higher

Nick Mulcahy

November 07, 2013

A week after obinutuzumab (Gazyva) received approval in the United States for the treatment of chronic lymphocytic leukemia (CLL), Genentech has announced more positive news about the drug.

Obinutuzumab, which is indicated for use in combination with chlorambucil for patients with previously untreated CLL, improved median progression-free survival by nearly a year more than rituximab (Rituxan, Genentech) in a head-to-head trial of CLL patients (26.7 vs 15.2 months; hazard ratio, 0.39; confidence interval, 0.31 - 0.49; P < .0001).

Median overall survival has not yet been reached in the 2 treatment groups.

"These new data are important because they showed for the first time that [obinutuzumab] significantly extended progression-free survival when directly compared against [rituximab]," said Hal Barron, MD, chief medical officer at Genentech, in a press statement.

Complete response rates were also better with obinutuzumab than with rituximab (21% vs 7%). In addition, there was a higher percentage of minimal residual disease negativity — defined as no detectable disease in the blood at the end of the treatment course — with obinutuzumab (29.4% vs 2.5%).

These data come from the second stage of CLL11, a phase 3 multicenter open-label study of 663 patients randomly assigned to obinutuzumab plus chlorambucil or rituximab plus chlorambucil.

No new safety signals were observed for either obinutuzumab or rituximab, according to the company.

However, serious adverse events were much higher with obinutuzumab. Grade 3 to 5 adverse events occurred more often with obinutuzumab than with rituximab (66% vs 47%), as did grade 3 to 5 infusion-related reactions (20% vs 4%).

Obinutuzumab is a glycoengineered antibody, which means that specific sugar molecules in GA101 were modified to change its interaction with immune cells.

Obinutuzumab is the first drug with a "breakthrough therapy" designation to receive approval by the US Food and Drug Administration (FDA). That means that obinutuzumab has the potential to offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

These data have been accepted for presentation at the plenary session of the annual meeting of American Society of Hematology in December.

Obinutuzumab was approved with a boxed warning about hepatitis B virus reactivation. Patients should be assessed for hepatitis B virus and their related reactivation risk. The boxed warning includes another concern: the risk of inducing progressive multifocal leukoencephalopathy.

According to the FDA, these are known risks with other monoclonal antibodies in this class, and rare cases have been identified in participants in other trials of obinutuzumab.


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