TA877 · STA
Recommended as an add-on to optimised standard care (ACE inhibitors or ARBs at highest tolerated doses, and SGLT2 inhibitors) for stage 3 and 4 CKD with albuminuria associated with type 2 diabetes in adults with eGFR of 25 ml/min/1.73 m² or more.
Source documents
Intervention
Conditions
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| ace inhibitors (at maximum tolerated licensed dose) | active drug | Yes | — |
| angiotensin-receptor blockers (arbs) (at maximum tolerated licensed dose) | active drug | Yes | — |
| sglt2 inhibitors | active drug | — | — |
| placebo (plus standard care) | placebo | — | — |
| placebo plus standard care | placebo | — | — |
| standard care including sglt2 inhibitors | active drug | Yes | — |
| standard care with ace inhibitors or arbs | standard of care | Yes | — |
| standard care with ace inhibitors or arbs and sglt2 inhibitors | standard of care | Yes | — |
| placebo | placebo | — | — |
| standard care alone | standard of care | — | — |
| standard care with sglt2 inhibitors | standard of care | — | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| FIDELIO-DKD | RCT | phase 3 | Yes |
| FIGARO-DKD | RCT | phase 3 | Yes |
| FIDELITY | meta_analysis | unknown | — |
Economic model
ICER
Methodological decisions (14)
Whether SGLT2 inhibitors should be included as a relevant comparator for finerenone
Company: SGLT2 inhibitors should not be included as a comparator because they were not established NHS practice at time of company submission; company focused on finerenone as second-line treatment added to ACE inhibitors/ARBs without SGLT2 inhibitors
ERG: SGLT2 inhibitors should be considered a relevant comparator despite not being established at time of trial, because recent NICE recommendations will likely increase uptake
Committee: SGLT2 inhibitors are a relevant comparator, but comparison of finerenone with SGLT2 inhibitors in SGLT2 inhibitor-naive population is missing; finerenone can only be recommended as option in addition to SGLT2 inhibitors or when unsuitable
ICER impact: uncertain_direction
Whether to include FIGARO-DKD and FIDELITY data in addition to FIDELIO-DKD for decision making
Company: FIDELIO-DKD should be the primary evidence base; combining FIDELIO-DKD and FIGARO-DKD data was not pre-specified and questionable statistically
ERG: Company provided insufficient details for critique; additional evidence from FIGARO-DKD could reduce uncertainty around the marketing authorisation population
Committee: Further evidence from FIGARO-DKD and FIDELITY are relevant and appropriate; FIGARO-DKD data support FIDELIO-DKD results but have limitations
ICER impact: uncertain_direction
Whether to include clinical evidence from FIGARO-DKD and FIDELITY meta-analysis in addition to FIDELIO-DKD
Company: Company excluded FIGARO-DKD from initial evidence base because full data was not available; suggested combining FIDELIO-DKD and FIGARO-DKD data was not pre-specified and questionable statistically
ERG: Additional trial data from FIGARO-DKD and FIDELITY pooled analysis would provide insight into marketing authorisation population and reduce uncertainty
Committee: FIDELIO-DKD, FIGARO-DKD, and FIDELITY evidence are all relevant and appropriate for decision making to reduce uncertainty, even though marketing authorisation population represents approximately 90% of FIDELIO-DKD
ICER impact: decreases
Use of time-invariant transition probabilities in Markov model
Company: Time-invariant transition probabilities are appropriate; experts advised against more complex time-varying approach; method is common in CKD modelling and validated against SHARP-CKD-CVD model
ERG: Time-invariant approach is oversimplified; tight confidence intervals reflect this simplification; comparison with trial data over time would be more informative; ranges in SHARP-CKD-CVD represent extremes not confidence intervals
Committee: Effects of time-invariant transitions are uncertain; comparison of model predictions with Kaplan-Meier curves from trial data would be informative; external validation did not represent true external validation
ICER impact: uncertain_direction
How to model previous cardiovascular disease history in baseline population (45.9% of FIDELIO-DKD participants had prior CVD event)
Company: Use simplifying assumption that no patients had cardiovascular events before entering model; model from point of FIDELIO-DKD entry only
ERG: Model using total patient history; suggested ideal approach of 3 sub-models reflecting different CVD history states
Committee: Neither approach optimal; company approach likely resulted in optimistic cost-effectiveness; restructuring into 3 sub-models would reduce uncertainty. Company's updated sub-models did not properly track patients over time in each subgroup as intended
ICER impact: decreases
Sensitivity analysis methodology - parameter uncertainty and sampling approach
Company: Acknowledged limitations in original analyses; updated transition probabilities for standard care arm to be sampled from Dirichlet distribution
ERG: Original approach had multifaceted issues (grouping parameters, wide bounds, user-specified limits, utility overestimation); questioned why finerenone arm transitions not sampled from Dirichlet distribution like standard care
Committee: Updated approach was improvement but outputs remained uncertain; results should be interpreted with caution. Transition probabilities for CKD progression were critical and not subject to sensitivity analysis initially
ICER impact: uncertain_direction
Missing comparative effectiveness evidence with SGLT2 inhibitors
Company: No head-to-head comparison provided
ERG: Outstanding gap requiring acknowledgement
Committee: Noted as missing comparison; could not recommend finerenone instead of SGLT2 inhibitors, only as add-on; recommended alongside SGLT2 inhibitors
ICER impact: uncertain_direction
Relevance of trial populations defined by eGFR thresholds to marketing authorisation population
Company: Marketing authorisation population represents approximately 90% of FIDELIO-DKD population; trial enrolled only eGFR 25 ml/min/1.73 m2 and above
ERG: Concerned about lack of clarity regarding finerenone use when eGFR is 15-25 ml/min/1.73 m2 (CKD stage 4)
Committee: Marketing authorisation eGFR ranges are appropriate despite not covering all NHS CKD stage definitions; eGFR ranges in marketing authorisation are appropriate for likely finerenone use
ICER impact: uncertain_direction
Whether finerenone should be stopped when eGFR drops below 15 ml/min/1.73m² and after renal replacement therapy starts
Company: Finerenone stopped after renal replacement therapy starts
ERG: No strong preference
Committee: Finerenone stopped after renal replacement therapy starts
ICER impact: decreases
Whether health state-transition probabilities should remain time-invariant beyond the 4-year trial period when modelling over 34 years
Company: Time-invariant transition probabilities appropriate; validation against FIDELIO-DKD supported the approach
ERG: Modelling predictions for time to events should be explicitly compared with empirical Kaplan-Meier curves from trial; concerns about validity over 30 years of assumed fixed probabilities
Committee: Updated transition probabilities were also uncertain; acknowledged company addressed comparison with trial data but noted uncertainty remains for 30-year extrapolation beyond 4-year trial period
ICER impact: uncertain_direction
Whether treatment effects of finerenone combined with SGLT2 inhibitors are additive
Company: Effects of finerenone and SGLT2 inhibitors are independent and additive, based on evidence that background SGLT2 inhibitor use did not reduce finerenone benefit
ERG: Insufficient details provided; uncertain whether effects are truly additive versus additional but not independent
Committee: Uncertain; analyses provide a useful upper bound estimate but true additivity is not known
ICER impact: increases
Whether treatment benefit of finerenone persists beyond 4-year trial follow-up
Company: No treatment waning assumed because relative effect was almost constant over 4 years in trial; company assumes finerenone would be stopped if no treatment effect in practice
ERG: Not explicitly stated
Committee: Treatment effects beyond 4 years are uncertain; company provided scenario analyses with waning effects over 16 years but outcomes of extrapolation beyond 4 years are not known
ICER impact: decreases
Whether finerenone's treatment effect diminishes after the trial period and over what timeframe
Company: No treatment effect waning required; relative effect constant over 4-year trial; would be stopped in practice if no effect observed
ERG: Scenario analyses with 16-year waning considered but arbitrary; 7-year and 9-year discontinuation scenarios potentially more informative
Committee: Uncertainty around treatment waning inherent beyond trial period; company made reasonable attempt to explore; extrapolation beyond 4 years uncertain
ICER impact: decreases
Source of health state utility values for CKD stages
Company: Initially used FIDELIO-DKD trial-based utilities; revised after technical engagement to use TA358 (tolvaptan) utilities for consistency with accepted NICE approach
ERG: Preferred modified trial-based utilities over TA358 utilities which were from 2005 small population without EQ-5D; noted lack of engagement with more recent literature from NG28, NG148, NG203
Committee: Both approaches have advantages and disadvantages; during consultation company updated dialysis, transplant and cardiovascular event utilities to reflect NG28 values; ERG accepted updated utilities as appropriate
ICER impact: uncertain_direction
Evidence gaps
Special considerations
Cross-references