Regulatory Decision Summary for Blenrep

This New Drug Submission (NDS) was filed to obtain market authorization for Blenrep (belantamab mafodotin for injection), used in combination with pomalidomide and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including lenalidomide.

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

Multiple myeloma (MM) is a plasma cell malignancy that is incurable despite the availability of effective therapies across several lines of treatment. The recommended treatment at first clinical relapse of MM is triplet therapy, defined as two novel agents [novel agents refer to proteasome inhibitors (PI), immunomodulatory agents (IMiD), and monoclonal antibodies (mAb)] in combination with dexamethasone. More recently, quadruplet therapy, combining an anti-CD38 mAb with a PI, an IMiD and dexamethasone has become an option in the first line treatment of both transplant eligible and ineligible newly diagnosed MM. The proportion of patients exposed to lenalidomide at first relapse is expected to increase. As triplet and quadruplet therapies are established as first line treatments, new treatment options are essential for RRMM after first line treatment. Blenrep is a BCMA targeting antibody drug conjugate that has been studied in the RRMM setting and may play a role in this setting.

The efficacy of Blenrep, in combination with pomalidomide and dexamethasone (BPd) in RRMM after at least one line of prior therapy including lenalidomide, was demonstrated in a randomized, controlled trial (DREAMM-8). The study demonstrated that administration of BPd resulted in a statistically significant improvement in the primary efficacy outcome of progression-free survival (PFS), compared to pomalidomide, bortezomib and dexamethasone (PVd). The PFS hazard ratio was 0.52, indicating that BPd was associated with a 48% reduction in the risk of progression or death compared to PVd. BPd demonstrated improved outcomes across key secondary efficacy endpoints: overall response rate, duration of response and MRD-negativity rate. At the time of the primary analysis, overall survival (OS) data were immature and did not meet the predefined threshold for statistical significance. The limited robustness of the OS data does not allow a reliable projection for a definitive OS benefit at the final analysis. Note, PFS is an accepted efficacy endpoint for regulatory decision-making in the context of RRMM.

Blenrep is associated with an increased risk of ocular toxicity due to the MMAF component. Ocular toxicity can manifest as corneal adverse reactions, ocular symptoms and reduced visual acuity. Ocular toxicity can recur with subsequent doses of Blenrep. It is the most common cause for Blenrep dose modifications. For ocular toxicity risk mitigation and management, the sponsor has included the following within the Product Monograph (PM): a Serious Warnings and Precautions Box, recommendations for ophthalmic examinations by an eyecare professional at appropriate dosing intervals of Blenrep and whenever clinically indicated (see PM for details). Blenrep dosing guidance based on ophthalmic examination findings is provided in the PM and it is expected that prescribers will implement guidance to use dose reductions and dose delays to manage ocular adverse reactions as well as other adverse reactions. Other adverse reactions associated with the BPd regimen include: infusion-related reactions, thrombocytopenia and infections. These risks are communicated in the agreed upon labeling.

The sponsor has developed a Risk Management Plan in addition to educational materials for patients, prescribers, and eyecare professionals as ocular adverse reaction risk minimization measures.

Overall, the benefit-risk profile for Blenrep for the stated indication is favourable, when administered in accordance with the conditions of use specified in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) is recommended.

The RMP was reviewed. The proposed risk mitigation measures including those related to ocular toxicity, as well as educational materials, are considered acceptable to support routine pharmacovigilance and risk minimization activities for Blenrep.

The evaluation of the chemistry, manufacturing, and control data confirms that the methods and processes for the production, release, and stability testing of belantamab as well as Blenrep drug substance and drug product are well-established and controlled, thus ensuring the consistent manufacture of a safe, pure, and potent product.

The labelling information met all applicable regulations and guidance.

For further details about Blenrep (belantamab mafodotin for injection), please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.