A memory clinic consultant who read NICE's final draft guidance on lecanemab and donanemab in June 2025 knew what it meant for the person across the desk. Two licensed drugs had been shown to slow cognitive decline, and neither would be available on the NHS, because the committee judged the benefit too small for the cost and for the resources needed to deliver them. That consultant can be forgiven some reserve on reading this week's announcement from the Medicines and Healthcare products Regulatory Agency. Three investigational medicines have been granted Innovation Passports, the entry point to the Innovative Licensing and Access Pathway, one for early Alzheimer's disease, one for non-small cell lung cancer and one for Huntington's disease. The award is welcome. It addresses the front of the pipeline, and the harder problems sit further along.

Diranersen, from Biogen and Ionis, is an antisense therapy aimed at the tau protein in Alzheimer's. Brezosiran, from Alnylam and Regeneron, targets the huntingtin gene. BGB-58067, from BeOne Medicines, is a PRMT5 inhibitor intended for lung tumours that have lost the MTAP gene. None is close to a licence. Brezosiran is in a phase 1b trial, with a pivotal study planned for 2027. A passport gives a developer a target development profile and joint early advice from the MHRA, NICE and the appraisal bodies in Scotland and Wales. It signals promise and commits the agencies to coordinate. It is not evidence of benefit.

That coordination has real value at present. Industry confidence in the UK frayed through 2025 over rebate rates under the branded medicines pricing scheme, and the agreement with Washington in December capped the rebate at 15 per cent until 2028 and raised NICE's threshold to £25,000 to £35,000 per quality-adjusted life year from April 2026. Ministers want Britain to be read as a place where medicines are developed and then used, and an early alignment scheme is a visible part of that offer. Visible offers invite scrutiny of what follows, and what follows is the NHS.

Alzheimer's shows the pressure point most clearly. Around 982,000 people in the UK live with dementia and more than a third have no diagnosis. Any disease-modifying therapy will need patients identified early and the disease confirmed with biomarker testing, in a diagnostic pathway where capacity is already stretched. NHS England estimated in 2024 that the amyloid antibodies could cost between £500m and £1bn a year, and NICE concluded that managed access would consume resources the NHS could not justify. A tau-targeting drug with a better profile would still have to pass through the same queue for assessment. If it arrives to find that queue unchanged, the appraisal committee will be asked the same question again, and the answer may be the same.

Lung cancer offers the clearest test of whether the NHS can deliver a targeted drug. About 50,200 people are diagnosed with the disease in the UK each year, and up to 85 per cent of cases are non-small cell. Published estimates put MTAP loss at roughly 13 to 15 per cent of those tumours, which implies several thousand patients a year who could one day be candidates. Finding them requires that MTAP status is established at diagnosis, quickly and in every region. That depends on genomic testing capacity, laboratory turnaround and pathology workflow. A targeted drug that reaches a patient after the treatment window has closed has not been accessed in any sense a patient would recognise.

Huntington's disease is the rarest of the three and carries the sharpest moral weight, since there is currently no treatment that slows its progression. Care sits in a limited number of specialist centres, and a gene-silencing therapy would raise questions about delivery, monitoring and long-term follow-up for a small population that existing commissioning arrangements handle awkwardly. Rare disease populations rarely produce the large trials that appraisal committees prefer, which makes early agreement on acceptable evidence more valuable here than anywhere.

Value remains the unresolved matter. Early dialogue with NICE can clarify what a developer must demonstrate, and that is a useful discipline. It cannot settle the price at which a clinical gain becomes affordable to a service with fixed budgets and long waiting lists. Health economists have argued that the higher threshold lacks an empirical basis and carries opportunity costs for other care, and that argument will return with force when expensive therapies reach committee. Public expectations are a further risk. A headline that says fast-track will be heard by patient groups as a promise of access, which no regulator has made.

For NHS leaders and integrated care boards, the passports are an early warning. Commissioners can begin asking what diagnostic and genomic capacity each of these therapies would demand if the trials succeed, and can raise it in planning while there is time to act. Policymakers should resist describing designations as breakthroughs, because the gap between a process milestone and a treatment on the ward is measured in years. Developers should read early NHS engagement as a requirement to plan for deployment alongside their trials, since a licence without a route into practice has limited commercial value in the UK.

The UK has built a good front door. A passport costs a regulator little to award and costs the NHS a great deal to honour. Whether that bill is met depends on decisions about diagnostics, genomics and specialist services that have to be taken while the trials are still running.