Genentech's ADC Polivy Receives FDA Accelerated Approval, Doubling Complete Response Rate in Relapsed or Refractory DLBCL

Today, the U.S. FDA announced the accelerated approval of Genentech’s antibody-drug conjugate Polivy (polatuzumab vedotin-piiq) for use in combination with bendamustine and rituximab for the treatment of adult patients with refractory diffuse large B-cell lymphoma (DLBCL). The FDA noted that this is the first chemoimmunotherapy approved for this indication.

Diffuse large B-cell lymphoma, abbreviated as DLBCL, is the most common type of non-Hodgkin lymphoma. It is estimated that more than 18,000 new cases of DLBCL are diagnosed annually in the United States. Although the disease can be effectively controlled after initial treatment in many patients, 30%–40% of patients will ultimately experience relapse.

Polivy, an antibody-drug conjugate (ADC) granted accelerated approval today, targets the CD79b protein specifically expressed on the surface of B cells at one end, while being linked to a chemotherapeutic agent at the other. As designed, upon specific binding to and internalization into B cells in vivo, it releases the chemotherapeutic drug to exert cytotoxic effects, thereby controlling cancer progression.

▲ Typical structure of antibody-drug conjugates (Image source: Bioconjugator [CC BY-SA 4.0])

In a Phase 1b/2 clinical trial, the efficacy of Polivy was validated. The trial evaluated 80 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), who were randomized into two groups: one receiving standard treatment with bendamustine and rituximab, and the other receiving Polivy in addition to this regimen. The results showed that the complete response rate in the standard treatment group was 18%. In the Polivy-treated group, this figure reached 40%, more than doubling the rate. Furthermore, among patients in the Polivy group who achieved partial or complete response, 64% maintained their response for more than six months, and nearly half (48%) sustained it for over a year. In its press release, Genentech noted that this is also the only randomized pivotal clinical trial demonstrating a higher response rate compared to this standard therapy.

Based on these favorable results, the U.S. FDA today granted accelerated approval to Polivy in combination with standard therapy for the treatment of patients with refractory lymphoma. Previously, it had received Breakthrough Therapy Designation, Priority Review, and Orphan Drug Designation from the U.S. FDA.

▲This is also the 12th new drug approved by the U.S. FDA this year (Image source: U.S. FDA)

“Antibody-drug conjugates are a novel class of cancer-targeted therapies. Unlike traditional chemotherapy, they can target specific cells,” said Dr. Richard Pazdur of the U.S. FDA’s Center for Drug Evaluation and Research. “The approval of Polivy today provides a new treatment option for patients who have not responded to multiple prior lines of therapy.”

“Despite significant advances in the treatment of DLBCL, therapeutic options remain very limited for patients whose disease becomes refractory or relapses after multiple lines of therapy,” commented Dr. Sandra Horning, Chief Medical Officer and Head of Global Product Development at Genentech. “The approval of Polivy combination therapy today introduces a novel treatment option, providing immediate benefit to patients with urgent unmet needs.”

We congratulate the accelerated availability of this innovative combination therapy to patients and look forward to it bringing new hope to many!

References:

[1] FDA approves first chemoimmunotherapy regimen for patients with relapsed or refractory diffuse large B-cell lymphoma, Retrieved June 10, 2019, from https://www.prnewswire.com/news-releases/fda-approves-first-chemoimmunotherapy-regimen-for-patients-with-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-300864605.html

[2] FDA Grants Genentech’s Polivy Accelerated Approval for People With Previously Treated Aggressive Lymphoma, Retrieved June 10, 2019, from https://www.gene.com/media/press-releases/14795/2019-06-10/fda-grants-genentechs-polivy-accelerated

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