Polatuzumab Vedotin: First Global Approval.

in Drugs by Emma D Deeks

TLDR

  • Polatuzumab vedotin is a drug that targets a protein on the surface of B cells, which are a type of white blood cell that helps fight infections. The drug works by binding to the protein and then entering the B cell, where it releases a chemical that kills the cell. Polatuzumab vedotin has been approved by the US FDA for use in combination with other drugs to treat a type of cancer called diffuse large B-cell lymphoma (DLBCL) in adults who have already tried other treatments. The drug is also being studied for use in other types of cancer, such as follicular lymphoma (FL) and non-Hodgkin lymphoma (NHL).

Abstract

Polatuzumab vedotin (polatuzumab vedotin-piiq; Polivy™) is an antibody-drug conjugate comprising a monoclonal antibody against CD79b (a B cell receptor component) covalently conjugated to the anti-mitotic cytotoxic agent monomethyl auristatin (MMAE) via a cleavable linker. After binding to CD79b on the B-cell surface, polatuzumab vedotin is internalized and the linker is cleaved, releasing MMAE into the cell, where it inhibits division and induces apoptosis. Polatuzumab vedotin is being developed by Genentech (a subsidiary of Roche) for the treatment of haematological malignancies. In June 2019, the US FDA granted accelerated approval to polatuzumab vedotin, in combination with bendamustine plus rituximab, for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have received at least two prior therapies. Use of the compound in combination with bendamustine plus rituximab is also under regulatory review for relapsed/refractory DLBCL in the EU and is in ongoing phase 1b/2 development in this setting or relapsed/refractory follicular lymphoma (FL) in several countries. Various other polatuzumab vedotin combination therapy regimens are also in phase 1b/2 development for relapsed/refractory non-Hodgkin lymphoma (NHL) [including DLBCL and FL] or in phase 2 or 3 development for previously untreated DLBCL, while polatuzumab vedotin monotherapy has been in phase 1 development for relapsed/refractory B-cell NHL in Japan. This article summarizes the milestones in the development of polatuzumab vedotin leading to this first approval for its use in combination with bendamustine plus rituximab for relapsed/refractory DLBCL.

Overview

  • Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b on B cells and inhibits cell division and induces apoptosis. It is being developed by Genentech for the treatment of haematological malignancies, including DLBCL, FL, and NHL. The compound has been in phase 1b/2 development for relapsed/refractory DLBCL and FL, and is currently under regulatory review for this indication in the EU. Polatuzumab vedotin has been granted accelerated approval by the US FDA for the treatment of adults with relapsed/refractory DLBCL in combination with bendamustine plus rituximab. The article summarizes the milestones in the development of polatuzumab vedotin leading to this first approval.
  • Methodology and Subject Demographics
  • The article does not provide specific details on the methodology used for the development of polatuzumab vedotin or the subject demographics of the study.
  • Primary Objective and Key Findings
  • The primary objective of the article is to summarize the milestones in the development of polatuzumab vedotin leading to its first approval for the treatment of relapsed/refractory DLBCL in combination with bendamustine plus rituximab. The article highlights the key findings of the study, including the accelerated approval of polatuzumab vedotin by the US FDA for this indication.
  • Comparative Analysis and Findings
  • The article does not provide specific details on the comparative analysis of polatuzumab vedotin with other treatments for relapsed/refractory DLBCL.
  • Implications and Future Directions
  • The article highlights the significance of the accelerated approval of polatuzumab vedotin by the US FDA for the treatment of relapsed/refractory DLBCL in combination with bendamustine plus rituximab. The article also suggests that polatuzumab vedotin is under regulatory review for this indication in the EU and is in ongoing phase 1b/2 development in several countries. The article also mentions that various other polatuzumab vedotin combination therapy regimens are in phase 1b/2 development for relapsed/refractory NHL or in phase 2 or 3 development for previously untreated DLBCL. Polatuzumab vedotin monotherapy has been in phase 1 development for relapsed/refractory B-cell NHL in Japan.
  • TLDR
  • Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b on B cells and inhibits cell division and induces apoptosis. It has been granted accelerated approval by the US FDA for the treatment of adults with relapsed/refractory DLBCL in combination with bendamustine plus rituximab. The compound is under regulatory review for this indication in the EU and is in ongoing phase 1b/2 development in several countries. Various other polatuzumab vedotin combination therapy regimens are in phase 1b/2 development for relapsed/refractory NHL or in phase 2 or 3 development for previously untreated DLBCL. Polatuzumab vedotin monotherapy has been in phase 1 development for relapsed/refractory B-cell NHL in Japan.
  • Key Insights
  • The key insights from the article are:
  • - Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b on B cells and inhibits cell division and induces apoptosis.
  • - Polatuzumab vedotin has been granted accelerated approval by the US FDA for the treatment of adults with relapsed/refractory DLBCL in combination with bendamustine plus rituximab.
  • - Polatuzumab vedotin is under regulatory review for this indication in the EU and is in ongoing phase 1b/2 development in several countries.
  • - Various other polatuzumab vedotin combination therapy regimens are in phase 1b/2 development for relapsed/refractory NHL or in phase 2 or 3 development for previously untreated DLBCL.
  • - Polatuzumab vedotin monotherapy has been in phase 1 development for relapsed/refractory B-cell NHL in Japan.

Comparative Analysis & Findings

  • The article does not provide specific details on the comparative analysis of polatuzumab vedotin with other treatments for relapsed/refractory DLBCL.
  • - Polatuzumab vedotin has been granted accelerated approval by the US FDA for the treatment of adults with relapsed/refractory DLBCL in combination with bendamustine plus rituximab.
  • - The article highlights the key findings of the study, including the accelerated approval of polatuzumab vedotin by the US FDA for this indication.

Implications and Future Directions

  • The article highlights the significance of the accelerated approval of polatuzumab vedotin by the US FDA for the treatment of relapsed/refractory DLBCL in combination with bendamustine plus rituximab. The article also suggests that polatuzumab vedotin is under regulatory review for this indication in the EU and is in ongoing phase 1b/2 development in several countries. The article also mentions that various other polatuzumab vedotin combination therapy regimens are in phase 1b/2 development for relapsed/refractory NHL or in phase 2 or 3 development for previously untreated DLBCL. Polatuzumab vedotin monotherapy has been in phase 1 development for relapsed/refractory B-cell NHL in Japan.
  • - Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b on B cells and inhibits cell division and induces apoptosis.
  • - The article highlights the key findings of the study, including the accelerated approval of polatuzumab vedotin by the US FDA for this indication.
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