The UK's National Institute for Health and Care Excellence (NICE) has issued a draft guidance rejecting NHS coverage of Johnson & Johnson's antidepressant nasal spray Spravato (esketamine) for treatment-resistant depression, citing both financial and clinical concerns.
The decision impacts a potentially significant patient population, with approximately 1.45 million adults with depression in England alone, of whom up to 30% may have treatment-resistant disease. Spravato, which received EMA approval in December, is indicated as an add-on therapy for patients who have failed at least two conventional oral antidepressants.
Cost and Clinical Evidence Concerns
NICE's primary concerns center around the treatment's substantial cost of approximately £10,500 per course, before any potential discounts. Beyond pricing, the agency identified several gaps in the clinical evidence package, including:
- Lack of comparative data against other adjunctive oral antidepressants
- No direct comparisons with electroconvulsive therapy (ECT)
- Absence of comparative studies versus psychological therapies
- Uncertainty about maintenance of therapeutic benefits after treatment completion
Implementation Challenges
Meindert Boysen, director of the centre for health technology evaluation at NICE, emphasized the practical challenges of implementing Spravato in clinical practice: "Introduction of esketamine into clinical practice in the NHS will be complex because the structure and delivery of services would need to be changed."
The agency also expressed concerns about the unclear costs associated with potential repeat treatments and overall service delivery modifications required to support the therapy's administration.
Industry Response and Innovation Concerns
Janssen-Cilag has responded forcefully to the draft guidance, with executive Jennifer Lee arguing that "current NICE technology appraisal processes are not fit for purpose in terms of evaluating innovative technologies for complex mental health conditions."
The company emphasizes Spravato's significance as the first antidepressant with a novel mechanism of action in three decades, noting its particularly rapid onset of action - showing effects within days rather than the weeks typically required for conventional antidepressants.
Next Steps
The draft guidance has opened a consultation period extending to February 18, with a follow-up appraisal committee meeting scheduled for March or April to review submitted comments. Additionally, J&J is pursuing expanded approval in both US and European markets for Spravato's use in major depression patients at suicide risk, leveraging the drug's rapid onset of action.
The final decision could have significant implications for treatment-resistant depression patients in the UK, particularly given the substantial number of individuals who fail to respond adequately to currently available therapeutic options.
