Regulatory Decision Summary for Lunsumio

The submission was filed seeking a notice of compliance with conditions for Lunsumio (mosunetuzumab for injection) for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least two prior systemic therapies.

Following review, the indication granted was: Lunsumio (mosunetuzumab for injection) is indicated as monotherapy for the treatment of adult patients with relapsed or refractory follicular lymphoma (Grades 1 - 3a) who have received at least two prior lines of systemic therapy.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

This submission was filed and reviewed under the Notice of Compliance with Conditions (NOC/c) Guidance.

Follicular lymphoma responds well to initial therapy, particularly with immunochemotherapy regimens. However, despite high initial response rates, follicular lymphoma is generally considered incurable with standard treatment approaches. Over time, the disease tends to follow a relapsing-remitting course, with remissions becoming progressively shorter. Therefore, there is a need for additional effective treatments in later lines of therapy.

Lunsumio (mosunetuzumab for injection) is a bi-specific antibody that binds the CD20 receptor, present on both normal and malignant B-cells, while simultaneously binding CD3 on the surface of various T-cell types, which leads to T-cell activation and subsequent B-cell death.

In one phase I/IIb clinical study, GO29781, relapsed/refractory follicular lymphoma (RRFL) patients (n = 90) who received mosunetuzumab monotherapy demonstrated a high rate (60%) of complete response and an overall response rate of 80% as assessed by an independent review facility applying standardized response criteria. Analyses of the duration of complete response (DoCR) and duration of response (DoR) indicate that the responses are durable with the median DoCR not reached by the data cut-off for the trial and the median DoR reported as 22.8 months.

The safety profile is characterized by risks commonly associated with T-cell engaging biologic products such as cytokine release syndrome (CRS) and neurotoxicity including immune effector-cell associated neurotoxicity (ICANS). As well, Lunsumio treatment results in B-cell depletion, neutropenia and can increase the risk of serious infection. Hemophagocytic lymphohistiocytosis (HLH) has occurred in patients treated with Lunsumio. These risks are consistent with other CD20/CD3 bi-specific antibodies. The safety profile is adequately described in the Product Monograph, including in section 3 (Serious Warnings and Precautions), section 7 (Warnings and Precautions), and section 8 (Adverse Reactions). The Dosing and Administration section provides guidance on the management of important adverse reactions, including CRS and ICANS.

Considering the serious nature of the disease and the unmet medical need facing RRFL patients who have received at least 2 lines of prior therapy, high response rates consisting of durable responses are considered clinically meaningful. These data, in combination with a safety profile that is manageable with close monitoring and prompt management, support a favourable benefit-risk assessment for Lunsumio. Uncertainty, with respect to longer term efficacy, exists due to the design of the studies received, which did not include concurrent controls. A randomized, controlled, confirmatory study will be required to be submitted as a commitment to this Notice of Compliance with Conditions.

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

The chemistry and manufacturing information submitted for Lunsumio has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications."

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

For more information on the conditions issued, please refer to the Notice of Compliance with conditions (NOC/c) Website.

Overall, the benefit-harm-uncertainty profile was favourable for Lunsumio, 1 mg/mL, for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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