Regulatory Decision Summary for Polivy

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.


Product type:

Drug

Medicinal ingredient(s):

polatuzumab vedotin for injection

Therapeutic area:

Antineoplastic Agent

Type of submission:

New Drug Submission

Control number:

232303
What was the purpose of this submission?

 

The purpose of this new drug submission (NDS) was to seek conditional market authorization for Polivy (polatuzumab vedotin) in combination with bendamustine and rituximab for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. The submission was granted advanced consideration in accordance with the Notice of Compliance with Conditions policy. After evaluation of the submitted data package, Health Canada authorized, with conditions, Polivy for the following indication: Polivy (polatuzumab vedotin) in combination with bendamustine and rituximab is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, who are not eligible for autologous stem cell transplant and have received at least one prior therapy.

 

Why was the decision issued?

 

Conditional authorization was primarily based on the results from an international, multicenter, open-label, phase 1b/2 study in patients with relapsed or refractory diffuse large B-cell lymphoma. In the phase 2 study period, a randomized cohort of 80 patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, who are not eligible for autologous stem cell transplant and have received at least one prior therapy were enrolled. Patients received either Polivy plus bendamustine and rituximab (pola+BR arm, n = 40) or bendamustine and rituximab alone (BR arm, n = 40).

The primary objective of the randomized patient cohort was to compare the complete response (CR) rates between patients treated with Polivy in combination with bendamustine (B) and rituximab (R) versus BR alone. The CR rate for patients in the pola+BR arm was 40% versus 17.5% for patients in the BR arm. This was supported by secondary endpoints, including objective response rate, best overall response rate and duration of response.

The most common adverse reactions (AR) reported in clinical trials with Polivy included neutropenia, thrombocytopenia, and anemia. Other commonly reported ARs (>10%) included diarrhoea, abdominal pain, fatigue, pyrexia, pneumonia, weight decreased, decreased appetite, hypokalemia, hypoalbuminemia, hypocalcaemia, peripheral neuropathy, dizziness, cough and pruritis. Patients treated with Polivy also experienced higher incidences of infusion-related reactions, hepatic toxicity, gastrointestinal toxicity, arthralgia and skeletal pain. Overall, patients treated with pola+BR experienced more Grade ≥3 AEs (84.4% versus 74.4%), attributed to higher incidences of neutropenia, thrombocytopenia, anemia, lymphopenia, pancytopenia and pneumonia. Neutropenia and thrombocytopenia were the most common reasons for treatment discontinuation. Four fatal infections occurred in each treatment group. The risks associated with polatuzmab vedotin are considered tolerable and manageable, and have been adequately described in a Serious Warnings and Precautions Box, Warnings and Precautions and Adverse Reactions sections of the product monograph.

Given the study design, there is residual uncertainty regarding the magnitude of the treatment effect with the addition of Polivy to BR. Nevertheless, the observed treatment benefit, in the context of a conditional authorization, demonstrated promising clinical evidence in terms of response rates and duration of response in patients with r/r DLBCL which shows a promising benefit/risk profile for the proposed patient population. As a condition of authorization, the sponsor will be required to commit to file phase 3 trial data to confirm the efficacy of Polivy and the benefit/risk balance in patients with DLBCL.

The recommended dose of Polivy is 1.8 mg/kg.

 

Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.