Chugai Subsidiary of Roche Secures Japanese Approval for Polivy (polatuzumab vedotin) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

March 24, 2021/BioValleyBIOON/--Chugai Pharmaceutical, a Japanese pharmaceutical company under Roche Holding, recently announced that the Ministry of Health, Labour and Welfare (MHLW) of Japan has approved Polivy (polatuzumab vedotin) 30 mg and 140 mg intravenous infusions, in combination with bendamustine (lyophilized formulation) and rituximab (BR regimen), for the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

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 (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 relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) who have undergone transplantation. In the United States, the European Union, and Japan, Polivy has been granted orphan drug designation for the treatment of DLBCL, and respectively by the U.S.FDAGranted Breakthrough Therapy Designation (BTD); granted Priority Medicines (PRIME) designation by the European Medicines Agency (EMA).

Notably, Polivy is the first immunochemotherapy approved for the treatment of relapsed or 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.

In Japan, the regulatory approval of Polivy was based on the results of a multicenter, single-arm Japanese Phase II study (JO40762/P-DRIVE study) and a multicenter global Phase Ib/II study (GO29365). The former study evaluated the efficacy and safety of Polivy in combination with BR therapy for patients with relapsed or refractory DLBCL, while the latter study compared the efficacy and safety of Polivy plus BR therapy versus BR therapy alone in patients with R/R DLBCL.

The randomized Phase II portion of the GO29365 study, in 80 patients ineligible for autologousStem CellsThe efficacy and safety of Polivy + BR versus BR were compared in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who had undergone autologous stem cell transplantation (ASCT). The results showed a substantially higher complete response rate in the Polivy + BR group compared to the BR group (CR: 40% vs. 17.5%). Among the 39 patients treated with Polivy, 36 (92.3%) experienced adverse reactions. The most commonAdverse Reactionsas: neutropenia 53.8% (21/39), thrombocytopenia 41.0% (16/39), diarrhea andAnemia33.3% (13/39) each, fatigue and nausea 23.1% (9/39) each, and fever and peripheral neuropathy 20.5% (8/39) each.

In the P-DRIVE study, the efficacy and safety of Polivy plus BR were evaluated in 35 patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) who were ineligible for autologous stem cell transplantation (ASCT). The results showed a complete response (CR) rate of 34.3%. Among the 35 patients treated with Polivy, 33 (94.3%) experienced adverse reactions. The most commonAdverse ReactionsAnemia 37.1% (13/35), nausea 31.4% (11/35), thrombocytopenia and neutropenia each 25.7% (9/35), constipation/thrombocytopenia/neutropenia each 22.9% (8/35), malaise and decreased appetite each 20.0% (7/35).

Currently, a global, double-blind, placebo-controlled Phase III study (GO39942/POLARIX) is ongoing. This study is being conducted in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) and is evaluating the efficacy and safety of Polivy in combination with rituximab plus CHP (cyclophosphamide, doxorubicin, and prednisolone) versus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) as first-line treatment for DLBCL.

DLBCL (Image source: meddic.jp)

Diffuse large B-cell lymphoma (DLBCL) is a histological subtype of non-Hodgkin lymphoma (NHL) and is 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 at that time was 64 years. Rituximab combined with chemotherapy is the standard first-line treatment for diffuse large B-cell lymphoma (DLBCL); however, approximately 40% of patients relapse due to inadequate 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 ineligible for ASCT due to failure of salvage chemotherapy prior to transplantation. Furthermore, there is currently no standard treatment regimen established for patients who are not candidates for ASCT because of 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 SeattleGeneticsThe 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 being developed for the treatment of several types of non-Hodgkin lymphoma (NHL). CD79b is highly specifically expressed in most types of B-cell NHL, making it a promising target for the development of new therapies. Polatuzumab vedotin targets and binds to CD79b, disrupting these B cells while maximizing damage to cancer cells and minimizing impact on normal cells.

Data from the Phase 3 POLARIX trial evaluating Polivy as first-line treatment for DLBCL were expected in 2021. Other ongoing studies include combination regimens of Polivy with Gazyva/Gazyvaro (obinutuzumab), Venclexta/Venclyxto (venetoclax), and the CD20xCD3 bispecific antibodies mosunetuzumab and glofitamab, to determine the potential of Polivy to deliver clinical benefits in areas of unmet medical need. (Bioon.com)

Original Source: Chugai Obtainsapproval for Polivy for the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma