Sanofi was encouraged by the UK National Institute for Health and Care Excellence’s (NICE) November 2024 announcement of the appeal results for the reimbursement of Sarclisa (isatuximab) plus pomalidomide and dexamethasone (Isa-Pd) as a fourth line treatment in relapsed refractory multiple myeloma. Following what were viewed as “negative recommendations” made as a result of regulatory practices being unable to keep pace with innovations in the lab, NICE agreed to a third review of Isa-Pd, acknowledging challenges in evaluating innovative combination therapies and the need for flexibility in such assessments.
The ICARIA-MM study demonstrated significant benefits of Isa-Pd in improving progression-free survival and overall survival compared to pomalidomide and dexamethasone alone. Yet there remains a lag in accessing cancer medicines in England (compared to European standards). Whilst acknowledging the challenges in current assessment and funding frameworks for combination therapies, as well as a need for greater flexibility in certain situations, Anju Bhalla, Head of Oncology and Haematology, Sanofi UK and Ireland, highlights the importance of treatment availability for managing multiple myeloma and remains committed to maintaining access to isatuximab plus pomalidomide and dexamethasone (Isa-Pd) as an important fourth line option. Here she discusses the appeal process, its outcomes, and her hopes for lessons learned. Anju Bhalla (Sanofi) reactively provided these responses following Medicine Maker's request.
What were the key points upheld in Sanofi's appeal against NICE's initial decision, and what does this success mean for the broader landscape of combination therapies in the UK?
The appeal committee recognized that NICE’s methods for evaluating medicines have changed in recent years, moving away from its ‘end-of-life’ criteria to a ‘severity modifier’, meaning Isa-Pd is being re-appraised for routine NHS commissioning against different criteria to which it entered the Cancer Drugs Fund (CDF).
Additionally, the key combination drug pomalidomide was assessed as cost effective by NICE under NICE's old methods (which applied a higher cost-effectiveness threshold), although it is unlikely to be under NICE's new methods. At the time NICE changed its methods, Isa-Pd was the only combination of three drugs in the CDF whose backbone treatment was already recommended under the previous higher threshold. As such, the appeal committee has requested that NICE consider applying flexibility outside its usual processes.
Sanofi appealed that there was no indication that the appraisal committee understood that applying NICE’s standard methodology meant that isatuximab cannot be cost effective even at zero price. The committee acknowledged that it wasn’t clear within the final draft guidance.
Could you share more about the challenges posed by the NICE framework, and what reforms Sanofi hopes to see?
Welcome progress has been made by the Association of the British Pharmaceutical Industry (ABPI), NICE, NHS England, and the Competition and Markets Authority through the publication of guidance for companies – but unresolved issues remain.
Ultimately, the issues revolve around inflexibility in the way NICE assesses new medicines. For combination medicines, the challenges revolve around the value assessment, pricing, and funding that hinder patient access to (and development of) innovative medicines. These include cost-effectiveness barriers; for example, the thresholds for reimbursement are the same for combination medicines as they are for single medicines. The cost-effectiveness of the full combination is assessed regardless of whether the backbone medicine(s) have already been priced at the limit of cost-effectiveness. As such, reimbursement of combinations, for which the backbone is close to or at the threshold of cost-effectiveness, is extremely difficult.
There are also pricing barriers, or indication-based agreements that are currently the exception. These are difficult to secure under existing guidance, and this difficulty is a significant barrier for combinations as, in many situations, the price for the backbone medicine(s) has already been established, placing the onus on the manufacturer of the add-on therapy to demonstrate cost-effectiveness. Greater allowance for indication-based agreements would enable different prices to be negotiated per indication, enabling greater value for each separate indication/combination.
Ultimately, Sanofi would like to see NICE introduce greater flexibility within its processes to ensure medicines that provide demonstrable patient benefits can stand a fair chance of reimbursement. To fully resolve the combination therapies access challenge, all barriers must be resolved, not just one element.
How will stakeholder collaborations contribute to the case for Isa-Pd?
We are grateful for the strong support from the clinical and patient community. Alongside Sanofi, patient organizations such as Myeloma UK, along with clinical groups including the UK Myeloma Society, have also been challenging NICE’s negative final draft guidance. These groups, who work with patients every day, have been significant voices in showcasing the need for continued access to Isa-Pd and building the case for its reimbursement. Multiple unresolved issues around the value assessment, pricing and funding of combinations threaten access to and development of innovative medicines in combination. NHS England, the UK government, and NICE must work with patient groups and the pharmaceutical industry to agree a framework that supports a flexible reimbursement and pricing framework for combination therapies. We are pleased to be working with NICE and NHS England to navigate a way forward.
How does Sanofi plan to address the potential impact on patients awaiting treatment during the appraisal process?
There is no impact on patients awaiting treatment while the appraisal process is still ongoing and until the Final Guidance is published. Isa-Pd will continue to be available to eligible new patients in England and Wales through the Cancer Drugs Fund. Isa-Pd is available to all eligible multiple myeloma patients in Scotland and is not impacted by any outcome from NICE.
How does Sanofi plan to address disparities between the UK and Europe?
We are concerned that the current NICE approach means Isa-Pd may not be available to patients in England should NICE issue negative final guidance, while patients in other countries (including Scotland) will continue to have access. It is important we understand and address the fundamental issue at the core of NICE’s reimbursement processes that is preventing some innovations being reimbursed. Whilst there are certainly lessons and insights we can glean from our European neighbors, it is important we find a solution that is right for NICE and NHS England.
How does the Isa-Pd case fit into Sanofi's broader strategy in oncology, especially in making innovative treatments accessible in complex healthcare systems?
Combination therapies are a cornerstone of cancer care and further progress against this devastating disease will likely be achieved through making these combination treatments available to patients. Isa-Pd is a valuable fourth line option for relapsed and refractory multiple myeloma patients who have limited alternatives at this later stage of their cancer. Overcoming access barriers for innovative combination therapies has the potential to offer improved outcomes for patients as early as possible, leading to a better chance of survival and improved quality of life.
What do you hope will be the major lessons learned from this appraisal process?
Medical advancements like isatuximab have the potential to transform cancer outcomes. However, NICE’s health technology appraisal process must evolve if it is to keep pace with the speed of scientific advances.
We hope this appraisal makes the government, NICE, and NHSE recognize the need to review and update its existing pricing and reimbursement framework, or at the very least show greater flexibility. Otherwise, it is unlikely that Isa-Pd will be the last instance that patient access via routine NHS commissioning to a much-needed treatment option will be at threat of being denied or, worse still, not even submitted to NICE for consideration.
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