As the SMA community is aware, due to the high unmet need, Biogen opened one of the largest pre-approval global expanded access programmes (EAP) for eligible patients in infantile-onset SMA (consistent with Type 1) in Autumn 2016, before filing with the regulatory agencies.
Despite a number of EAP sites having been opened since then, individual hospital trusts have struggled to enroll all eligible children onto the EAP due to ongoing infrastructure and capacity challenges within the NHS.
This has been a difficult and challenging time for families, carers, treating physicians, the community and Biogen, understandably resulting in anxiety and concern.
To attempt to address this continued challenge, Biogen has been involved in a number of discussions with NHS England (NHSE) and members of the clinical and patient advocacy community. These discussions have focused on the possibility of NHSE being able to provide funding to support the additional aspects of care (ancillary costs) required to administer nusinersen above and beyond the provision of the drug, at no charge, by Biogen.
At the request of NHSE, documentation was provided to support the business case for this approach. This involved the provision of publically available data outlining the clinical evidence base for nusinersen as well as estimates of additional funding that might be required by the NHS to support children receiving the drug.
The outcome of these discussions has now been made public by SMA Support UK who has published the minutes of the meeting where the conclusion of this assessment by NHSE was made known to Biogen, to clinicians and representatives of the patient community.
Biogen is disappointed with the outcome. The request by NHSE to view the clinical data in a peer-reviewed journal is something we are actively pursuing and plans to publish the full results of the Phase III studies are in development. In the interim, Phase III data has been presented at international scientific congresses as is normal prior to full publication. However it is important to note that the Phase II data has already been published in a peer-reviewed journal, The Lancet.
The preparation of data for submission to a peer-reviewed journal requires a number of months for consolidation, analysis and preparation. Biogen’s timelines for this are in line with the standard process for publication of pivotal clinical trial data. Under usual embargo conditions, a manuscript submitted to a medical journal for publication must not be disclosed until the publication date. Biogen is optimistic that publication can be confirmed in the summer.
NHSE has requested that Biogen considers supporting the ancillary costs in addition to provision of drug under the EAP programme. It is fundamental that in partnership with the NHS, Biogen understands specifically how any additional funding would be applied at each existing and potential EAP site to resolve its infrastructure challenges. Biogen has offered to work with individual hospitals to assess this. Biogen remains committed to continue these discussions and to review what is possible.
The EAP in Europe will remain open for new patients for a period of time following marketing authorisation. The actual date of closure will be discussed and agreed country by country. As such, Biogen continues to receive and assess EAP applications from individual hospitals within the process already established. As of May 12th 2017, the EAP is active in 5 sites in England, 1 in Scotland and 1 in Northern Ireland. Additional sites have been approved but are not yet active. The intention is these sites will eventually form a small number of regional hubs.
Importantly, children enrolled in the EAP will remain in the free of charge programme until local reimbursement and access is established. At this point, the NHS would then take on responsibility for funding nusinersen for all patients that are defined in any criteria for reimbursement (ie, a specific group of patients for whom the NHS is willing to pay for the drug). In the event of an overall negative reimbursement decision, or for those patients already established on the EAP but who fall outside of any reimbursement criteria, Biogen has committed to continue to provide nusinersen.
Update on regulatory and Health Technology Appraisal processes
As well as the continuation of the EAP, the regulatory process is now nearing completion.
The recent positive CHMP opinion has been referred to the European Commission (EC) which grants marketing authorisations in Europe. A decision from the EC is expected imminently (within 67 days following CHMP opinion).
In the UK, once a medicine has been granted a marketing authorisation, the NHS will ordinarily ask for an assessment to be made to determine whether the medicine offers value for money for the NHS. The NHS funding decision will be made on the outcome of this assessment. This is a cost-effectiveness analysis (an appraisal) and is undertaken by a Health Technology Assessment body; in England this body is NICE (National Institute for Health and Care Excellence – Wales and Northern Ireland usually follow NICE guidance) and in Scotland, it is the SMC (Scottish Medicines Consortium).
In January 2017, a ‘scoping workshop’ took place for NICE to assess which appraisal route nusinersen will be considered under – a Single Technology Appraisal (the majority of medicines referred for technology appraisal go through this route) or the Highly Specialised Technology (HST) route (which is reserved for medicines that fall under the rare or ultra rare disease category). Biogen believes the most appropriate route for assessment of nusinersen is the HST route which allows for a more flexible approach and offers the greatest potential for reimbursement and subsequent access within this particular patient population.
Biogen is still waiting to hear from NICE on the appraisal route for nusinersen– this should be known around the end of June/beginning of July, and it is at this point that NICE will formally invite Biogen to make a submission.
Biogen remains committed to working with all stakeholders to enable a viable funding pathway following EC approval. We believe this is the best way to provide broad and sustainable access to nusinersen for the SMA community. We will continue to address your requests for more information.