Regulatory Decision Summary for Polivy

The regulatory decision was based on data from a Phase III controlled double-blinded study where 879 adult patients with previously untreated large B-cell lymphoma (LBCL) were randomized 1:1 to receive either Polivy in combination with rituximab, cyclophosphamide, doxorubicin and prednisone (Polivy plus R-CHP, n = 440) or standard of care rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP, n = 439). Effectively, in this new treatment regimen Polivy replaces vincristine in R-CHOP. Patients were stratified by International Prognostic Score (IPI) 2 or 3-5, bulky disease present or bulky disease absent, and geographical region and were excluded if they presented with > Grade 1 neuropathy or had renal or hepatic impairment.

The LBCL patients randomized to Polivy plus R-CHP had a statistically significant benefit in the primary efficacy outcome measure of progression-free survival (PFS) compared to the LBCL patients randomized to R-CHOP (Hazard ratio: 0.73 [95% Confidence Interval (CI): 0.57, 0.95]). The PFS benefit is considered clinically meaningful even if difference is not large since R-CHOP is an effective therapy in the front-line setting and further delaying progression and time to initiation of subsequent therapies by Polivy plus R-CHP is considered beneficial. Of note, LBCL patients enrolled on study with IPI scores of 3-5 and without bulky disease appeared to derive the greatest benefit from Polivy plus R-CHP over R-CHOP. Refer to the product monograph for complete details.

Polivy plus R-CHP has associated risks and these are documented in the product monograph, including uncertainties of this treatment regimen in individuals who have not been enrolled in clinical studies, with the revised recommendation to avoid using Polivy in patients with moderate or severe hepatic impairment. Events reported at higher incidences with Polivy plus R-CHP over R-CHOP were peripheral neuropathy (14% vs. 9%), diarrhea (31% vs. 20%), infections (50% vs. 42%) including febrile neutropenia (15% vs 9%), anemia (12% vs. 9%), and hepatic toxicities (11% vs. 7%). The important safety concerns associated with Polivy plus R-CHP in previously untreated adult patients with LBCL, along with recommended dosing modifications, have been updated accordingly.

Overall, the benefit-risk profile of Polivy plus R-CHP is considered favourable in adult patients with previously untreated large B-cell lymphoma, when it is used according to the instructions provided in the product monograph.

An updated Risk Management Plan (RMP) for Polivy was reviewed by Health Canada and considered acceptable.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

The overall, the benefit-harm-uncertainty profile is favourable for Polivy and 30 mg/vial and 140 mg/vial strengths for the recommended indication. A Notice of Compliance (NOC) was issued.

For further details about Polivy, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.