Regulatory Decision Summary for NINLARO

Primarily based on the results of Study C16010, a randomized, double-blind, placebo-controlled, multicenter phase 3 study in patients with relapsed and/or refractory multiple myeloma who had received at least one prior therapy, Ninlaro in combination with lenalidomide and dexamethasone demonstrated clinical benefit.

In C16010, the Ninlaro regimen provided a statistically significant prolongation in progression-free survival (PFS), the primary endpoint. A second PFS (non-inferential) analysis with more mature data maintained the positive treatment effect, albeit with a reduction in the size of the effect. The estimated size of the PFS benefit (differences in medians of 4-6 months) was considered to be clinically meaningful. Two of four planned analyses of overall survival (OS) have been conducted to date. At the second analysis, with 35% of the required number of deaths for the final analysis, an OS benefit was not demonstrated. The improvement in PFS was supported by improvements in overall response rate, duration of response, and time to response. The addition of Ninlaro to lenalidomide and dexamethasone did not appear to have a negative impact on quality of life.

Improvement in PFS was observed across subgroup populations, including those defined by stratification factors (number of prior lines of therapy, myeloma International Staging System stage, and previous therapy with a proteasome inhibitor), cytogenetics, and thalidomide refractoriness. While results were supportive of a benefit for the full study population, these data also suggested that subgroups with a better prognosis may have derived less benefit when compared to subgroups with a worse prognosis.

Safety data from C16010 indicated that the addition of Ninlaro to lenalidomide and dexamethasone did not substantially increase toxicity of the background regimen. Treatment-emergent adverse events were consistent with reported safety profiles of individual agents in the combination regimen and were tolerable and clinically manageable with monitoring, conventional medical intervention, and dose modification. The most frequently reported Ninlaro adverse drug reactions (≥20%) were diarrhea, vomiting, nausea and constipation; thrombocytopenia; peripheral neuropathy; peripheral edema; and back pain. Very common adverse events that occurred with greater frequency in the Ninlaro regimen treatment group included nasopharyngitis, upper respiratory tract infection, bronchitis, neutropenia, anaemia, decreased appetite, hypokalaemia, dizziness, headache, rash, pruritis, pain in extremity, arthralgia, and fatigue. Additional common adverse events that occurred with greater frequency in the Ninlaro regimen treatment group included herpes zoster infection, liver impairment events, blurred vision, dry eye, and conjunctivitis.

Based on the data reviewed, the benefit-risk assessment for Ninlaro, used in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy, is considered to be positive.

For more information on Health Canadas decision, please view the Summary Basis of Decision.