Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Depemokimab demonstrated moderate clinical effectiveness in reducing the annualized rate of clinically significant asthma exacerbations in two pivotal Phase 3 trials (SWIFT-1 and SWIFT-2), with statistically significant results (rate ratios of 0.42 and 0.52, both p<0.001). However, the lack of significant improvements in lung function (FEV1) and asthma control (ACQ-5) limits the perceived benefit.
Cost effectiveness
No cost-effectiveness analyses or ICERs specific to depemokimab were identified in the publicly available sources. The absence of economic evaluations raises significant concerns regarding its cost-effectiveness, especially as NICE’s appraisal is still in development.
Quality of life
While the ACQ-5 was used to assess asthma control, the reported responder rates were similar between depemokimab and placebo, indicating no significant improvement in HRQoL. Additionally, no utility values suitable for QALY calculations were identified, which further limits the assessment of quality of life impacts.
Supporting Domains
Safety and Adverse Effects
The safety profile of depemokimab appears favorable, with a pooled analysis showing fewer serious adverse events compared to placebo (5% vs 10%) and no fatal AEs reported. Most adverse events were mild to moderate, indicating good tolerability.
Comparator Selection
The pivotal trials used placebo as a comparator, which is standard for establishing efficacy. However, the lack of head-to-head comparisons against other biologics limits the ability to assess relative effectiveness in the context of existing treatments.
Patient Population and Subgroups
The trial populations were well-defined, focusing on patients with severe eosinophilic asthma. However, the representation of adolescents was limited, and detailed subgroup analyses were not extensively reported, which could affect generalizability.
Care Pathway Integration
Depemokimab is positioned as an add-on therapy to existing asthma treatments, aligning well with current care pathways. The dosing regimen (every 26 weeks) is manageable within existing frameworks, although specific training requirements for administration were noted.
Resource Use and Cost Implications
While the dosing frequency and storage requirements are manageable, no specific cost data were available, and the potential for high resource use remains a concern without clear economic evaluations.
Evidence Quality and Robustness
The evidence is based on two replicate Phase 3 trials with robust designs and clear primary endpoints. However, the absence of long-term data and real-world evidence limits the overall robustness of the findings.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the long-term effectiveness and cost-effectiveness of depemokimab, particularly due to the lack of real-world data and economic evaluations. The potential for access issues based on payer criteria also raises concerns.
