Relapsed or refractory Hodgkin lymphoma patients could be denied access to innovative medicine

Takeda UK Ltd has announced that brentuximab vedotin (Adcetris^®), a medicine that has rapidly become standard of care for patients with relapsed/refractory Hodgkin’s lymphoma (R/R HL),¹ has received a negative recommendation within draft guidance from the National Institute for Health and Care Excellence (NICE).²

Takeda UK Ltd has announced that brentuximab vedotin (Adcetris^®), a medicine that has rapidly become standard of care for patients with relapsed/refractory Hodgkin’s lymphoma (R/R HL),¹ has received a negative recommendation within draft guidance from the National Institute for Health and Care Excellence (NICE).²

Should this decision be made final within the Final Appraisal Determination (FAD) expected in January 2017, it would mean that patients in England would be denied access to a medicine that has transformed treatment paradigms and given many patients the opportunity to achieve a potential cure with or without a stem cell transplant.³ It would also introduce an inequality of care across the UK, as access to the initial indications for brentuximab vedotin was granted by the Scottish Medicines Consortium and the All Wales Medicine Strategy Group in 2014 and 2015, respectively.^4,5 The Republic of Ireland has also granted access via their National Cancer Control Programme.⁶ Brentuximab vedotin is also available and reimbursed in all other major European countries.

Commenting on the draft recommendation, Dr Graham Collins, Consultant in Haematology, Churchill Hospital, Oxford said: “This draft decision from NICE is hugely disappointing for patients and the clinical community as we are at risk of losing access to a highly effective treatment that has rapidly become standard of care in relapsed or refractory Hodgkin lymphoma.  Losing access would mean a retrograde step in therapy; reverting back to an era where clinicians were limited to managing patients with often ineffective and toxic chemotherapies and limiting our ability to offer patients potentially curative stem cell transplants. It is also concerning that this decision could potentially deny patients at high risk of relapse post-ASCT access to a valuable new treatment approach that has been shown to improve progression free survival in this patient population. I would urge Takeda and the clinical community to work with NICE during this consultation period, to both ensure that all eligible patients in England continue to have access to brentuximab vedotin and that the whole of the UK remains at the forefront of the management and research of Hodgkin lymphoma.”

When it was launched in the UK in 2012, brentuximab vedotin was the first medicine to be specifically licensed for the treatment of R/R HL for more than 30 years.⁷ Over 500 patients have since had access to brentuximab vedotin via the nCDF for the treatment of R/R HL following an ASCT or following at least two previous therapies when ASCT or multi-agent chemotherapy is not a treatment option and access will remain until the completion of this NICE appraisal. Brentuximab vedotin is being reviewed by NICE for the initial launch indications and also for a new indication, granted marketing authorisation by the European Commission in June 2016, for the treatment of patients with CD30+ HL at increased risk of relapse or progression following ASCT.^8–10

Jonathan Pearce, Chief Executive of the Lymphoma Association, said: “The news that Hodgkin lymphoma patients could lose access to a drug that has been available for some time through the former Cancer Drugs Fund is of concern. The decision means patients will be denied access to a treatment option that has been successful for a number of patients and, consequently, will limit positive outcomes for this group of patients some of whom could be cured. We would urge Takeda, NICE and clinicians to work together to reassess the decision and find a cost-effective solution that would ensure patients in England have access to the best possible treatments available and to avoid a postcode lottery across the UK.”

In the ACD, NICE has not recommended the R/R HL post ASCT indication as the committee did not agree with Takeda’s base case cost-effectiveness submission and questioned the mortality benefit vs. historical controls.  In the post two lines setting, NICE has agreed to consider the clinical and cost effectiveness of brentuximab vedotin on the submission of further evidence. In the high risk HL consolidation setting, NICE has expressed interest in seeing further sub-group analysis to reflect the high risk population.

Commenting on the ACD, Jon Neal, Business Unit Director – Oncology, Takeda UK said: “Brentuximab vedotin has been a game changer in the management of relapsed or refractory Hodgkin lymphoma and is the only licensed medicine in this setting. The recently published five year follow up of the pivotal study showed that the median overall survival for brentuximab vedotin was nearly 3.5 years, longer than the historical survival data of less than three years quoted within the ACD.  This is a rare disease that often affects young people and due to the high level of unmet need, brentuximab vedotin was granted a licence based on unprecedented Phase II trial results. This poses a challenge to the NICE methodology which penalises the absence of Phase III data which is often the case for rarer cancer medicines.

Takeda conducted the Phase III randomised double blind AETHERA trial to further enhance the outcomes of patients at increased risk of relapse after ASCT.  Brentuximab vedotin showed a significant improvement in progression free survival of 18.8 months vs placebo and is the first and only medicine to receive a licence in this setting. Despite the committee’s conclusion that this is not a relevant population for routine care in England, Takeda stands firm that there is a clear unmet need especially in high-risk patients who might not be eligible for a subsequent allogeneic transplant.

We will continue to work closely with NICE to provide all relevant information needed to address these observations highlighted within the ACD, with the aim of ensuring that all eligible patients can access brentuximab vedotin in England.”

Takeda encourages all stakeholders to provide comment to NICE on the ACD before the end of the consultation period on 1 September 2016, particularly as this is the last open consultation opportunity for stakeholders to provide comment. Long term funding for brentuximab vedotin in England will then be determined within the FAD that will be published after the second appraisal committee meeting in October.

Brentuximab vedotin is also licensed for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).⁹ NICE will review this indication in a separate single technology appraisal in 2017.

References

1. British Committee for Standards in Haematology. Guideline on the management of primary resistant and relapsed classical Hodgkin lymphoma 2014;164:39–52.
2. National Institute for Health and Care Excellence. Appraisal consultation document. Brentuximab vedotin for treating CD30-positive Hodgkin’s lymphoma. August 2016.
3. Chen R et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 2016: blood-2016-02-699850;  doi:10.1182/blood-2016-02-699850.
4. All Wales Medicines Strategy Group. Final Appraisal Recommendation – 1215: brentuximab vedotin (Adcetris^®) 50mg powder for concentrate for solution for infusion. May 2015. Available at: http://www.awmsg.org/awmsgonline/app/appraisalinfo/1255
5. Scottish Medicines Consortium (SMC). Brentuximab vedotin (Adcetris®). Detailed Advice Document No. 989/14. Published 13 October 2014. Available at: http://www.scottishmedicines.org.uk.
6. Health Service Executive. Adcetris (brentuximab vedotin) 50mg powder for concentrate for solution infusion x1 Vial. August 2014.
7. Jona A. Younes A. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma. Blood Rev. 2010 Nov;24(6):233–8.
8. NICE Single Technology Appraisal. Brentuximab vedotin for treating CD30-positive Hodgkin’s lymphoma Final scope. Available at: https://www.nice.org.uk/guidance/GID-TAG467/documents/lymphoma-hodgkins-cd30positive-brentuximab-vedotin-final-scope2. Last accessed: August 2016
9. Adcetris Summary of Product Characteristics June 2016.
10. European Commission approval for the expanded use of brentuximab vedotin as consolidation treatment in post-transplant hodgkin lymphoma. Available at: http://ec.europa.eu/health/documents/community-register/html/h794.htm. Last accessed: August 2016.