The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft rejection for Japanese firm Takeda’s Adcetris (brentuximab vedotin), which was previously available via the Cancer Drugs Fund, but will be removed from both lists if the NICE decision is finalised.
Implications | As part of its current scheme to review all drugs previously available for National Health Service (NHS) England funding only via the Cancer Drugs Fund (CDF), the National Institute of Health and Care Excellence (NICE) has issued its first draft rejection, for Takeda’s Adcetris (brentuximab vedotin) for use in CD30-positive Hodgkin’s lymphoma patients, citing insufficient evidence for clinical effectiveness. |
Outlook | Takeda has stated that it does not intend to apply for inclusion in the newly redesigned CDF, meaning that if the NICE draft rejection is finalised, the drug will no longer be available from NHS England, either via NICE or the CDF. This is the third NICE drug reappraisal from the old CDF list, and the first draft rejection, since the first two (Bosulif (bosutinib, Pfizer (US)) and Alimta (pemetrexed, Eli Lilly (US)) received draft approvals for regular funding by NICE. |
NICE has issued a preliminary appraisal consultation document (ACD) advising non-recommendation of Takeda’s Adcetris (brentuximab vedotin) for the treatment of CD30-positive Hodgkin’s lymphoma in adults with: relapsed ore refractory disease after autologous stem cell transplantation (ASCT); increased risk of disease relapse or progression after ASCT; or relapsed or refractory disease after at least two previous therapies, when ASCT or multi-agent chemotherapy is not an option. In these patient populations, there are currently no approved treatments.
The NICE committee ruled that the available evidence of clinical effectiveness was “immature and limited”, particularly for the target patient populations, and that outcomes presented mostly related to the antitumour effect measured as response rate, which is less clinically relevant than progression-free survival and overall survival. Also, NICE said that Takeda’s comparisons of the drug with historical controls were of questionable validity. Treatment with the drug costs GBP69,000–87,000 (USD89,976–113,448) per patient per course. The most plausible incremental cost-effectiveness ratios (ICERs) were GBP56,342 per quality-adjusted life year (QALY) gained for relapsed or refractory disease after ASCT, and GBP590,407 per QALY gained for adults with increased risk of disease relapse or progression after ASCT, both above the range considered cost-effective for NHS funding. The drug did not meet end-of-life criteria, since there was insufficient evidence to show that it extended life by at least three months, compared with standard NHS treatment, and end-of-life criteria for short life expectancy (less than 24 months) did not apply. A patient access scheme (PAS) was not offered by Takeda.
During the appraisal process, Takeda declined to put forward a case for inclusion of Adcetris in the newly redesigned CDF, stating that the patient population was small (around 50–60 eligible patients per year), and that it was unclear whether provision of extra data would change the outcome.
The ACD is open to public consultation until 1 September 2016, and is available here.
The new-look Cancer Drugs Fund
On 29 July 2016, NHS England launched its newly remodelled CDF, which is now intended for the co-ordination and managed access for patients to recently approved cancer drugs in England, during the period of their initial formal appraisal by NICE for routine funding on the NHS (see United Kingdom: 1 August 2016: UK's remodelled Cancer Drugs Fund goes live). It will operate under clear guidelines and with strict budgetary controls. The CDF will fund availability of newly approved drugs awaiting NICE funding decisions, cancer drugs for which managed access and close monitoring are required, and certain off-label drugs for rare conditions. Full guidelines for the new scheme are available here.
The previous incarnation of the CDF had a stronger emphasis on individual patient access to cancer drugs rejected by NICE as too expensive for NHS funding – however, the latter category will no longer be included in the scheme, but will be dealt with on a case-by-case basis via NHS England’s existing individual funding request (IFR) procedure, available across all therapeutic areas.
The NICE reappraisal process for CDF drugs
As a key part of the transition process to the new version of the CDF, all drugs that were listed on the “old” CDF are currently undergoing reappraisals by NICE, which will act as a gatekeeper to the scheme from now on. For each drug, NICE can make three possible decisions:
• Recommendation for routine commissioning via regular NICE guidance
• Non-recommendation for routine commissioning
• Recommendation for use within the CDF (managed access)
For many of the drugs, they can undergo NICE’s rapid reappraisal scheme, which involves a reconsideration of existing date, plus clinical updates and additional information from the producing company (which may include a new discount under a PAS). However, several of the CDF-listed drugs have never been appraised formally by NICE until now, since they were targeted at small populations, with only limited data available for evaluation. From 1 April 2016, NICE has extended its evaluation coverage to all approved cancer drugs, including those it did not review before. Adcetris is one of the latter category, so this is its first NICE appraisal.
The current drug list for the new CDF is available here.
Outlook and implications
Including this one, NICE has now made three draft decisions on ex-CDF drugs. These are:
• Bosulif (bosutinib) (Pfizer, US) for chronic myeloid leukaemia – draft acceptance in final appraisal determination (FAD) for routine commissioning via NICE (see United Kingdom: 7 July 2016: NICE recommends Pfizer's Bosulif for CML in first reappraisal from CDF).
• Alimta (pemetrexed) (Eli Lilly, US) for advanced non-small-cell lung cancer (NSCLC) – draft acceptance in FAD for routine commissioning via NICE (see United Kingdom: 20 July 2016: NICE recommends Lilly's Alimta as maintenance therapy for advanced lung cancer in second reappraisal from CDF).
• Adcetris for CD30-positive Hodgkin’s lymphoma – preliminary draft rejection in ACD for both routine commissioning and CDF provision.
Adcetris will continue to be available to patients on the NHS with CDF funding until a final NICE decision is made, and if rejected at that stage, funding may only be pursued on a case-by-case basis under the IFR scheme.
With the entire CDF drug list under review, it will be interesting to see how many of the ex-CDF drugs eventually enter routine funding, which are reinstated longer-term to the CDF under strictly managed access, and which are removed from routine public funding like this one is likely to be. Although Adcetris only targeted a small number of patients, and was not deemed an end-of-life treatment, it is still one less available option in a patient group with few existing choices, if this NICE decision becomes final.
It is noteworthy that the two positive rapid reappraisals from NICE above both came with newly negotiated PAS discounts from the producing companies – and in this context, Pfizer has already voiced its concern that this should not be regarded as a precedent, and that provision of substantial discounts across the board would be unsustainable. Considering the fixed budget of the CDF (GBP340 million), it can no longer be regarded as a “safety net”, and since pharmaceutical companies would bear most of the risk of a CDF overspend, there is a strong possibility that some patients may well be denied important treatments in the future. Among the upcoming rounds of NICE ex-CDF appraisals over the next few months, there may well be some highly controversial decisions. A continued dialogue with the pharma industry, and refinements to the scheme as it develops, will be essential to ensure that the new-look CDF achieves its aims of facilitating cost-effective cancer treatment.