Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Gilteritinib shows a clear clinical advantage over salvage chemotherapy, with a median overall survival increase from 5.6 months to 9.3 months (hazard ratio 0.68; p=0.0013). This significant improvement in primary outcomes indicates a strong therapeutic impact, although there is uncertainty regarding long-term survival, particularly post-stem cell transplant. This strengthens the market access risk assessment and overall reimbursement probability.
Cost effectiveness
The ICER for gilteritinib is reported to be below £50,000 per QALY gained, which is within NICE’s acceptable range for life-extending treatments. The economic model incorporates a patient access scheme, enhancing its cost-effectiveness profile. This informs pricing and reimbursement risk and pharmaceutical reimbursement forecasting.
Quality of life
The oral administration of gilteritinib allows patients to manage their treatment at home, which is a significant quality-of-life benefit compared to inpatient chemotherapy. However, the evidence for HRQoL improvements is not robustly quantified, leading to a moderate rating. These outcomes align with HTA decision predictors and support pricing and reimbursement assessment.
Supporting Domains
Safety and Adverse Effects
Gilteritinib has an acceptable safety profile, with manageable adverse events. The evidence suggests that adverse effects are mostly mild to moderate, aligning well with existing therapies, although some concerns remain regarding the long-term safety post-transplant. This profile reduces payer uncertainty and supports access risk forecasting.
Comparator Selection
The ADMIRAL trial provides a robust comparison of gilteritinib against a range of salvage chemotherapy options, which are appropriate standard-of-care alternatives. The committee concluded that salvage chemotherapy was a suitable comparator. This aligns with HTA comparator analysis and strengthens the market access submission.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population with relapsed or refractory FLT3-mutation-positive AML. However, there are some concerns regarding the small subgroup analyses, particularly for patients with prior FLT3 inhibitor use. This enhances reimbursement likelihood rating and payer relevance.
Care Pathway Integration
Gilteritinib can be integrated into existing care pathways with minor adjustments, primarily due to its oral administration. This facilitates patient management at home, reducing the need for hospital visits. This supports budget impact analysis and facilitates market access feasibility.
Resource Use and Cost Implications
The overall resource implications of gilteritinib are manageable, especially with the patient access scheme in place. However, there are concerns about the potential for high costs associated with hospitalizations and treatment wastage. This supports pricing model stress-testing and payer evidence expectations.
Evidence Quality and Robustness
The evidence base is primarily derived from the ADMIRAL trial, which is a well-designed RCT. However, there are some methodological concerns and uncertainties regarding the long-term survival data, particularly post-stem cell transplant. These outcomes align with HTA decision predictors and support pricing and reimbursement assessment.
Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty regarding long-term survival outcomes, especially after stem cell transplant. The committee noted that while gilteritinib meets end-of-life criteria, the assumptions made in the economic model introduce significant variability. These factors elevate access risk forecasting within HTA evaluation frameworks.
