Table 7.
Managed access agreement in England for gene therapies
| Managed Access Agreements | Kymriah DLBCLa | Kymriah ALLb | Yescarta (both indications)c | Zolgensmad |
|---|---|---|---|---|
| General concerns | Most plausible ICER for Kymriah compared to salvage chemotherapy is uncertain, but Kymriah has the plausible potential to satisfy the criteria for routine use if this uncertainty could be reduced | Most plausible ICER for Kymriah is higher than the threshold range and Kymriah does not meet the criteria to be a ELT | Most plausible ICER for Yescarta compared to salvage chemotherapy is uncertain. The range of ICER estimates show that Yescarta has plausible potential to be cost-effective and collecting further data on PFS, OS and IVIG use will reduce uncertainty in the evidence |
- Robustness of the economic modelling: the model assumes that everyone with pre-symptomatic SMA and up to 3 copies of the SMN 2 gene would develop type 1 SMA, whereas a substantial proportion of this population would be expected to develop other types of SMA - Data that would address other uncertainties (e.g. generalizability of trial evidence) cannot be collected within a reasonable timeframe and any additional data collection would be burdensome for patients and clinicians |
| Uncertainties | OS: immature data that do not fully support the curative nature of Kymriah | OS: immaturity data that not fully support the curative nature of Kymriah | OS: median overall survival not been reached in pivotal trial (ZUMA-1) | |
| Proportion of patients who would need treatment for B-cell aplasia with IVIG and duration of the treatment | Subsequent stem cell transplant rates | PFS and OS: timeline over which that the curves for progression-free survival and overall survival may converge is not available | ||
| Proportion of patients who would need treatment for B-cell aplasia with IVIG and duration of the treatment | Use of IVIG: need for IVIG in a real-world setting remains uncertain, even data from the follow-up of pivotal trial (ZUMA-1) demonstrated that IVIG was rarely used (8.3% patients) | |||
| Data collection and sources for the post- HTA evidence |
OS - Long-term data coming from the follow-up of pivotal trial (JULIET—Final Clinical Report expected on Aug 2023) - Routine population-wide datasets (NHS SACT) |
OS - Long-term data coming from the follow-up of pivotal trial (ELIANA—Final Clinical Report expected on Jun 2023) |
OS - Long-term data coming from the follow-up of pivotal trial (ZUMA-1) (5-year data available in Q1 2022 and confidentially reported to NICE) |
Different endpoints for two cohort of patients (SMN2 and SMN3) patients - Long-term data coming from the follow-up of the Clinical Trial (SPR1NT), that will be incorporated into an evidence submission and the new economic (expected for July 2022 but not tracked on NICE's website so far) Baseline patient characteristics, including gender, age, date of diagnosis, and SMN2 copy number - NHS England Blueteq system |
|
IVIG - Long-term data coming from the follow-up of pivotal trial (JULIET—Final Clinical Report expected on Aug 2023) - Integrated dataset (MDSAS and NHS England’s Blueteq) |
Stem cell transplant rates BMT Registry (stem cell transplant rates) (it is anticipated that there may be difficulties in linking these to national datasets, to identify patients treated with Kymiriah) |
Timeline convergence of OS and PFS - Long-term data coming from the follow-up of pivotal trial (ZUMA-1) (5-year data available in Q1 2022 and confidentially reported to NICE) |
||
|
IVIG Not specified, but the NHS England’s Blueteq is mentioned |
IVIG - Long-term data coming from the follow-up of pivotal trial (JULIET—Final Clinical Report expected on Aug 2023) - Integrated dataset (MDSAS and NHS England’s Blueteq) |
ALL Acute Lymphoblastic Leukemia, BMT Bone Marrow Transplant, DLBCL Diffuse Large B-Cell Lymphoma, ELT End of Life Treatment, ICER Incremental Cost-Effectiveness Ratio, IVIG Intravenous Immunoglobulins, MDSAS Medical Data Solutions and Services, OS Overall Survival, PFS Progression-Free Survival, SACT Systemic Anti-Cancer Therapy, SMA Spinal Muscular Atrophy
Sources
aNICE. Cancer Drugs Fund Managed Access Agreement. Tisagenlecleucel for treating relapsed or refractory diffuse large B cell lymphoma after 2 or more systemic therapies [TA567] (https://www.nice.org.uk/guidance/ta567/documents/committee-papers-4)
bNICE. Cancer Drugs Fund Managed Access Agreement. Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged
up to 25 years [TA554]
cNICE. Cancer Drugs Fund Managed Access Agreement. Axicabtagene ciloleucel for treating diffuse large B cell lymphoma and primary mediastinal B cell lymphoma after 2 or more systemic therapies [TA559]
dNICE. Managed Access Agreement. Onasemnogene abeparvovec for pre-symptomatic 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene and up to 3 copies of the SMN2 gene [HST15]
(https://www.nice.org.uk/guidance/hst15/resources/managed-access-agreement-pdf-9191290285)