FDA Gives OK to Polivy plus Rituxan-Bendamustine Combo to Treat Advanced DLBCL

FDA Gives OK to Polivy plus Rituxan-Bendamustine Combo to Treat Advanced DLBCL

The U.S. Food and Drug Administration (FDA) has approved — with conditions — Genentech‘s Polivy (polatuzumab vedotin-piiq),  used in combination with Rituxan (rituximab) and bendamustine (a chemotherapy), to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had gone through at least two prior therapies.

The approval — called accelerated approval by the FDA — allows medications addressing an unmet need in a serious  condition to come into use if they show benefit on surrogate or interim measures made in a clinical trial. But its continued use and full approval requires a further showing of efficacy in a confirmatory study.

Polivy is a first-in-class antibody-drug conjugate that binds to CD79b, a protein normally found on the surface of most immune B-cells involved in certain types of non-Hodgkin’s lymphoma (NHL). Once bound to CD79b, Polivy is designed to release a toxic substance that kills malignant B-cells without harming healthy cells.

“Despite meaningful progress in the treatment of diffuse large B-cell lymphoma, treatment options are very limited when the disease is refractory to or recurrent after multiple regimens,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a press release. “Today’s approval of this Polivy combination will provide a novel treatment that is both immediately available and very much needed for people with this aggressive disease.”

The decision to grant accelerated approval to the Polivy combo was based on findings from the global, open-label Phase 1b/2 trial (NCT02257567).

The study was designed to assess the benefits of adding Polivy to Rituxan and bendamustine (BR combo) or bendamustine and Gazyva (obinutuzumab) in heavily pre-treated patients with follicular lymphoma (FL) or DLBCL who were not eligible for a stem cell transplant.

A total of 80 DLBCL patients continued in the Phase 2 part of the trial, and were randomly assigned to either Polivy plus the BR combo, or the BR combo alone (a standard treatment for these patients) for a fixed treatment duration of six 21-day cycles.

Researchers evaluated the percentage of individuals achieving complete (tumor eradication), partial (significant tumor size reduction), and objective (tumor reduction to a predefined amount) responses, as well as the duration of their response to the combo therapy without disease worsening.

They found that 40% of those given Polivy plus BR achieved a complete response at the end of treatment, compared to 18% of those treated with the standard BR regimen.

Likewise, a significantly higher percentage of patients (45%) treated with Polivy in combo had an objective response at of treatment end, compared to 18% in the BR combo group.

Among triple combination patients who achieved a complete or partial response, more than half (64%) had responses lasting at least six months, compared to about a third (30%) in those given the standard BR combo. Responses lasting a year were recorded in 48% of these triple combo patients, and in 20% of those receiving the standard regimen.

“The approval of Polivy in combination with bendamustine and Rituxan offers patients with relapsed or refractory diffuse large B-cell lymphoma a new treatment option and new hope for improving patient outcomes,” Meghan Gutierrez, chief executive officer at the Lymphoma Research Foundation. “New medicines can transform the way healthcare providers approach this type of blood cancer and we commend those who contribute to accelerating research for the benefit of patients.”

Adverse events were reported about 5% more frequently in triple combination patients, and included low white and red blood cell counts, low platelet levels, numbness, tingling or pain in the hands and feet, diarrhea, fever, decreased appetite, and pneumonia.

Polivy was designated a Breakthrough Therapy the FDA and given PRIME (priority medicines) designation by the European Medicines Agency (EMA) in 2017 as a potential treatment of patients with relapsed or refractory DLBCL.

Polivy has become the ninth therapy candidate in Genentech’s hematology portfolio to be approved by the FDA.

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