Background
The CLN2 gene, which is found on chromosome 11, produces an enzyme called tripeptidyl peptidase 1 the purpose of which is to break down proteins. The enzyme is insufficiently active in CLN2 disease and as a result those unbroken down proteins settle in the brain tissues. Developmental delay begins around the end of age 2. Children develop seizures and begin to gradually lose the ability to walk and speak. Brief, involuntary jerks in a muscle or muscle group (called myoclonic jerks) typically begin around age 4-5. By age 6 most children are completely dependent on their caregivers, and many will require a feeding tube. Most children with CLN2 disease die between the ages of 8–12 years. Until recently, the only treatment options for children with CLN2 were treatments that relieved symptoms of the condition, or palliative care in the final stages of the disease.
BioMarin
BioMarin undertook research and developed an enzyme replacement therapy trademarked as Brineura®.
Brineura®
The drug, which is called cerliponase alfa or Brineura®, has been approved by the MHRA following successful clinical trials at Great Ormond Street Hospital in collaboration with other centres around the world.
The therapy, which is infused directly into the brain via an implanted device, has been shown to restore enzyme activity and slows the onset of disability. In the trial, patients given cerliponase alfa showed a slower progression of the disease when compared to the natural progression of the disease. The new therapy also reduced loss of brain tissue.
Professor Paul Gissen, NIHR GOSH BRC deputy theme lead for Novel Therapies and lead investigator at GOSH, said at the time of launch of the drug:
“The research shows that this cutting-edge therapy can make a huge difference for patients with this devastating condition. Until now there have been no drugs to treat Battens Disease so we are delighted that the treatment has been made available”.
The Managed Access Agreement and BDFA involvement
After a National Institute for Health and Care Excellence (NICE) Highly Specialised Technology (HST) appraisal, in November 2019, NICE recommended that a five-year Managed Access Agreement (MAA) be put in place to enable access to Cerliponase Alfa and collect more information on its benefits, before deciding whether it should be routinely available through the NHS for patients with CLN2.
The original end date for the five-year period was November 2024. Since January 2024 NICE has been considering all the existing evidence and new information gathered during the MAA in order to make a decision about whether or not to recommend Brineura® for routine availability through the NHS.
The BDFA are an important part of this process. They have been involved by:
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Generating and providing information needed to support NICE’s re-evaluation and decision making
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Involving the CLN2 community in the generation of evidence and the re-evaluation process
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Ensuring that the CLN2 community are well informed for the remainder of the MAA of progress and the next steps in the process
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Being the representative voice for the community with all key stakeholders
Timeline of Updates
- Following two committee meetings, NICE have announced that the MAA was extended for 6 months, then scheduled to finish on 27th May 2025. This will allow NHS England and BioMarin to enter into commercial negotiations we hope will result in Brineura® becoming available for everyone through the NHS.
- Update March 2025- NICE held a third Committee meeting on Thursday 3rd April and they have also announced an additional 3-month extension to the current MAA, which will run until 27th August 2025. This ensures continued access to Brineura® for current and new patients whilst the evaluation concludes.
- Update May 16th 2025- NICE has released draft guidance, read the update here- https://www.bdfa-uk.org.uk/news/bdfa-statement-response-nice-publication-draft-guidance-treatment-cln2
- Update August 14th 2025 – NICE held a fourth Committee meeting on Thursday 10th July following a public Consultation on the draft guidance. They also announced an extension to the current MAA to 31st December 2025. On 14th August NICE issued final draft guidance not recommending Brineura® for children diagnosed after the MAA ends. Read the BDFA’s response here - https://bdfa-uk.org.uk/news/bdfa-response-nice-final-draft-guidance-not-recommending-cerliponase-alfa-treating-neuronal
- Update 6th October 2025 – BDFA were informed that our appeal against the final draft guidance would be heard at an appeal hearing on Tuesday 25th November 2025 - https://bdfa-uk.org.uk/news/update-nice-re-evaluation-brineura-nice-appeal-hearing-25-november-2025
- Update 26th November 2025 – BDFA attended the NICE appeal hearing on 25th November and our six appeal points, alongside the company’s 4 points were discussed with the appeal panel and NICE Committee representatives. We are currently awaiting the outcome of our appeal and in the meantime, NICE have announced an extension to the current MAA. This extension will run until the end of June 2026, or the publication of final NICE guidance if earlier.
- Update 18th February 2026 – Sadly BDFA’s appeal has been rejected, and NICE have published Final Guidance which does not recommend Brineura for newly-diagnosed children. NICE cited a lack of evidence about Brineura’ s long-term benefits and its costs as the reason for not recommending the drug. Although the NICE appraisal process has now concluded, the BDFA will continue to fight relentlessly for access to Brineura and we are urging all key stakeholders to come together and find a way forward that enables every child diagnosed with CLN2 to access treatment. You can read BDFA’s full statement here- https://bdfa-uk.org.uk/news/important-update-bdfa-statement-nice-final-decision-reject-brineura-newly-diagnosed-children