CladribineCladritab
Not recommended NeurologyRestricted 💬 consumer voice
Treatment of relapsing-remitting multiple sclerosis (RRMS) to reduce the frequency of clinical relapses and to delay the progression of physical disability.
6
Submissions
5 resub
2011–23
On the record
$105k–200k
ICER range
1 sourced ICER · 2011
Cost-min
Cost basis
Decisions on record
- Meeting Nov 2023 Not recommended Relapsing-remitting multiple sclerosis
- Meeting Nov 2021 Not recommended Multiple sclerosis (relapsing-remitting)
- Meeting Jul 2018 Recommended Relapsing remitting multiple sclerosis (RRMS)
- Meeting Mar 2018 Not recommended Indication is for the treatment of relapsing- remitting multiple sclerosis (RRMS) to reduce the frequency of clinical relapses and to delay the progression of physical
- Meeting Nov 2017 Not recommended At time of PBAC consideration: Indication is for treatment of relapsing-remitting multiple sclerosis for a maximum duration of two years. At time of publication: Indication is for the treatment of relapsing-remitting multiple sclerosis (RRMS) to reduce the frequency of clinical relapses and to delay
- Meeting Mar 2011 Not recommended Multiple sclerosis
Access path
- TGA registered · Cladritab
TGA label equal than the PBS population
- Mar 2011Not recommended
uncertainty over usefulness given treatment limited to two years and safety concerns recognised by FDA and EMA…
- Nov 2017Not recommended
Comparator changed: interferon beta-1a (Rebif®) → fingolimod
- Mar 2018Not recommended
uncertainty in the non-inferior efficacy claim of cladribine versus fingolimod over two and four years; insufficient…
- ↻ resubmittedJul 2018Recommended · restricted
- Nov 2021Not recommended
- Nov 2023Not recommended
Clinical claim of non-inferior comparative efficacy and safety over four years not adequately justified; surrogate…
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
The PBAC did not recommend amending the existing equi-effective doses of cladribine and fingolimod for the treatment of relapsing-remitting multiple sclerosis (RRMS), on the basis that the evidence presented did not satisfactorily establish that two years of treatment with cladribine (plus two years of no treatment) is non-inferior to four years of treatment with fingolimod.PSD · Nov 2023
The PBAC considered the nominated comparator of fingolimod was reasonable, consistent with its view when it recommended cladribine at its March 2018 meeting.PSD · Nov 2023
Economic analysis
During the evaluation the sponsor provided an updated CMA workbook for evaluation. The updated CMA included modified cladribine and fingolimod switch data, as the switch data used in the model had initially been inconsistent with the clinical data presented.PSD · Nov 2023
As in the November 2021 submission, the resubmission presented a CMA of cladribine compared to fingolimod over four years. The most notable change in the CMA in the resubmission was the use of PBS 10% sample data to determine treatment switching for cladribine and fingolimod (timing of switching and the treatment received after 19PSD · Nov 2023
Clinical claim
Cladribine is non-inferior to fingolimod in terms of safety over four years.PSD · Nov 2023
EDSS = expanded disability status scale; RRMS = relapsing remitting multiple sclerosis Source: pp13-16, 25 and 36-37 of the resubmission.PSD · Nov 2023
Consumer comments
6.2 The PBAC noted and welcomed the input from individuals (1) and health care professionals (HCPs) (3) via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with cladribine, including the ease of use due to the dosing regimen and oral dosage form.PSD · Nov 2021
Financial management – risk sharing
The resubmission did not present any information relating to Risk Sharing Arrangements.PSD · Nov 2023
Cost-effectiveness
Cost-minimisation analysis; no ICER calculated by design
The PBAC considered the clinical claim of non-inferior comparative efficacy and safety of cladribine for two years (with two year of no treatment) and fingolimod over four years was not adequately justified. PBAC · 2023
ICER / price too highEconomic model disputed ×5Immature survival dataNo head-to-head trial ×2
Decision context
PopulationPatients with relapsing-remitting multiple sclerosis (RRMS)
Why it was knocked back
- Clinical claim of non-inferior comparative efficacy and safety over four years not adequately justified; surrogate outcomes (treatment switch, discontinuation) poorly correlated with relapse; non-randomised data with significant baseline imbalances; propensity score matching did not fully address confounding; limited number of patients with four years of cladribine treatment data (only 9% of cladribine cohort received four years of treatment versus 52% of fingolimod cohort); unknown if all important confounders captured
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2023 | Not recommended | fingolimod | — | Registry · ARR |
| Nov 2021 | Not recommended | fingolimod | — | RCT · Surrogate |
| Jul 2018 | Recommended · restricted | fingolimod | — | RCT · Surrogate |
| Mar 2018 | Not recommended | fingolimod | — | RCT · ARR |
| Nov 2017 | Not recommended | fingolimod | — | RCT · Annualised relapse rate |
| Mar 2011 | Not recommended | interferon beta-1a (Rebif®) | $105k–200k | RCT · OS | PFS | DFS | ORR | QoL | Surrogate | Cost-minimisation | Other | null |
Clinical evidence
Consumer voice
Consumer input from one individual and three healthcare professionals highlighted benefits of cladribine including ease of use from its oral dosage form and dosing regimen, and noted that many patients did not require additional treatment in their third year of therapy.
The comments described a range of benefits of treatment with cladribine, including the ease of use due to the dosing regimen and oral dosage form. Consumer comments · PSD
ease of usetreatment burdendosing regimensustained benefit
Similar precedents
Regulatory · TGA
Label equal than PBS population — Both TGA label and PBAC recommendation specify identical indication: RRMS patients to reduce relapse frequency and delay disability progression.