Roche's CD79b-Targeted Antibody-Drug Conjugate Polivy Submitted for Approval in Japan for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

July 04, 2020 News /Bio ValleyBIOON/ -- Chugai Pharmaceutical, a Japanese pharmaceutical company controlled by Roche, recently announced that it has submitted a New Drug Application (NDA) for Polivy (polatuzumab vedotin) to the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In Japan, the MHLW granted orphan drug designation to Polivy in November 2019.

Polivy is a first-in-class antibody-drug conjugate (ADC) targeting CD79b, approved in the United States in June 2019FDAAccelerated approval, in combination with bendamustine and rituximab (hereinafter referred to as BR regimen), for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) who have previously received at least two therapies; in the European Union, the drug received conditional approval in January 2020, in combination with the BR regimen, for the treatment of patients ineligible for hematopoieticStem Cellspatients with R/R DLBCL undergoing transplantation. In the United States and the European Union, Polivy has been granted orphan drug designation for the treatment of DLBCL, as well as Breakthrough Therapy Designation (BTD) and Priority Medicines (PRIME) status, respectively.

It is worth noting that Polivy is the first chemoimmunotherapy approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Compared with the commonly used BR regimen, Polivy in combination with BR significantly improves clinical outcomes in patients. DLBCL is an aggressive hematologic malignancy that typically becomes more difficult to treat with each recurrence. Approximately 40% of previously untreated DLBCL patients experience relapse after standard therapy, leaving limited subsequent treatment options; Polivy provides an important therapeutic option for these patients.

This application in Japan is based on the results of a multicenter, single-arm Phase II study in Japan (Study JO40762/P-DRIVE) and a multicenter, global Phase Ib/II study (Study GO29365). The former study evaluated the efficacy and safety of Polivy in combination with bendamustine plus rituximab (BR) therapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), while the latter study compared the efficacy and safety of Polivy combined with BR therapy versus BR therapy alone in patients with relapsed or refractory DLBCL. In addition, a double-blind, placebo-controlled, global Phase III study (Study GO39942/POLARIX) is ongoing. This study is being conducted in previously untreated patients with DLBCL and is evaluating the efficacy and safety of Polivy in combination with rituximab, cyclophosphamide, doxorubicin, and prednisolone (R-CHP) versus the R-CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone) as first-line treatment for DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is a histological subtype of non-Hodgkin lymphoma (NHL), classified as an aggressive disease. DLBCL is the most common type of NHL, accounting for 30–40% of all NHL cases. It frequently occurs in middle-aged and elderly individuals, predominantly affecting those over the age of 60. It has been reported that this diseaseDiagnosisThe median age was 64 years.Rituximab combined with chemotherapy is the standard first-line treatment regimen for DLBCL; however, approximately 40% of patients relapse due to insufficient treatment response. Despite autologousStem CellsAutologous stem cell transplantation (ASCT) is recommended for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL); however, approximately half of these patients are unable to undergo ASCT due to failure of salvage chemotherapy prior to transplantation. Furthermore, there is currently no standard treatment regimen established for patients who are ineligible for ASCT due to factors such as advanced age or comorbidities. Therefore, there is an urgent need for more effective novel therapeutic options for relapsed or refractory DLBCL.

Polivy was developed by Genentech, a member of the Roche Group, using SeattleHeredityThe company is developing an ADC technology, a first-in-class ADC specifically targeting CD79b. It consists of a humanized anti-CD79b antibody conjugated to the anti-mitotic agent MMAE (monomethyl auristatin E) and is currently under development for the treatment of several types of non-Hodgkin lymphoma (NHL). CD79b is highly and specifically expressed in most types of B-cell NHL, making it a promising target for the development of new therapies. Polatuzumab vedotin binds specifically to CD79b and disrupts these B cells, maximizing the destruction of cancer cells while minimizing impact on normal cells.

The global Phase Ib/II study GO29365 was conducted in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who were ineligible for hematopoietic stem cell transplantation and had previously received multiple therapies (median: 2). The data demonstrated that, compared with the BR group, the Polivy + BR group achieved a substantially higher complete response rate (CR: 40% vs. 18%), more than doubled overall survival (median OS: 12.4 months vs. 4.7 months), and significantly prolonged duration of response (median DOR: 10.3 months vs. 4.1 months; HR = 0.44).In terms of safety, the most common adverse events in the Polivy+BR group and the BR group included:Anemia, thrombocytopenia, neutropenia, fatigue, diarrhea, nausea, and fever. (Bioon.com)

Original Source:Chugai Files a New Drug Application for Polatuzumab Vedotin for the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma