Regulatory Decision Summary for Tevimbra

The purpose of this New Drug Submission (NDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Tevimbra, filed by BeOne Medicines I GmbH, for the following indication:

Tevimbra (tislelizumab for injection) is indicated:

• in combination with gemcitabine and cisplatin is indicated for the first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), and then as a single agent after up to 6 cycles of combination therapy.

After review, the recommended indication is:

Tevimbra (tislelizumab for injection) is indicated:

• in combination with gemcitabine and cisplatin for the first line treatment of adult patients with recurrent or metastatic nasopharyngeal carcinoma (NPC).

A request to file under the Priority Review Policy was denied during the pre-submission process.

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

Nasopharyngeal carcinoma (NPC) is a rare disease in Canada, though higher rates are observed among individuals of Asian ancestry and in Inuit populations. There is an unmet need in this population where, until recently, the only authorized treatment for recurrent or metastatic NPC was cytotoxic chemotherapy comprising platinum-based doublet chemotherapy (most commonly gemcitabine plus cisplatin). Recently, however, PD-1 targeting monoclonal antibodies have become available in Canada for the treatment of recurrent and metastatic NPC in combination with chemotherapy or as monotherapy after disease progression on or after chemotherapy. The authorization of Tevimbra will add to the armamentarium for treatment in this patient population.

Tevimbra, a PD-1 targeting monoclonal antibody, has been studied in a Phase 3, randomized, double-blind, placebo-controlled study in patients with metastatic or recurrent NPC who had not received previous systemic therapy for recurrent or metastatic disease. Eligible patients were treated with Tevimbra in combination with cisplatin and gemcitabine or placebo in combination with cisplatin and chemotherapy. Treatment with Tevimbra resulted in clinically meaningful and statistically significant improvements in Progression Free Survival (PFS) (Hazard Ratio [HR] =0.52 [95% Confidence Interval [CI]: 0.38 to 0.73; p<0.0001]) compared to placebo.

The safety profile of Tevimbra in combination with cisplatin and gemcitabine was consistent with the known and expected safety profiles of the individual components of the treatment regimen. Treatment with Tevimbra can cause immune-mediated adverse reactions, which is consistent with the class of monoclonal antibodies. The risks of treatment with Tevimbra can be mitigated and managed through labelling in the Product Monograph and through routine post-market pharmacovigilance activities. Thus, the use of Tevimbra in combination with cisplatin and gemcitabine provides a clinical benefit over cisplatin and gemcitabine alone, with a manageable safety profile, and offers an additional first-line treatment option for patients with metastatic or recurrent, locally advanced NPC.

An updated Risk Management Plan (RMP) for Tevimbra was reviewed by Health Canada and considered acceptable. Results related to the safety and effectiveness of Tevimbra from ongoing and planned studies will be submitted in Periodic Safety Update Reports (PSURs) as they become available.

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

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

Overall, the benefit-harm-uncertainty profile was favourable for Tevimbra 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 Tevimbra, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.