NICE defers decision on CAB-LA as PrEP needing more information

27 September 2024. Related: Treatment access, HIV prevention and transmission.

Simon Collins, HIV i-Base

On 26 September, NICE posted a draft recommendation not to approve the use of long-acting cabotegravir injections as PrEP in the UK, even in people who are recognised to be at a high risk of becoming HIV positive. [1]

This decision was based on needing additional analyses from the manufacturer. If these are returned by 17 October, the submission can be reassessed at a second appraisal meeting on 5 November, with a new decision available by 29 January 2025. Further stakeholder and individual comments about the draft recommendation can also be submitted by 17 October.

The draft recommendation acknowledges evidence from large international randomised studies that found injectable PrEP to be more effective than oral PrEP with superiority driven by low adherence to oral PrEP. Importantly, with good adherence oral PrEP is just as effective as injectable PrEP, where some early infections were missed in screening. It also recognises that injectable PrEP can be more effective than oral PrEP or no PrEP and that some people are not able to take oral PrEP.

The small number of people who are already using CAB-LA PrEP under an early access or named-patient programme are not affected by this decision.

The online explanation for the decision is that the submitted evidence from ViiV does not cover everyone who could have access to cabotegravir in clinical practice… “so cabotegravir is not recommended.”

However, a more detailed report, explains that the decision is based on needing cost-effectiveness analyses for the population covered in the approved MHRA licence for PrEP, rather than just for those who are defined as having an unmet need. [3]

The MHRA indication for PrEP is for use “in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in high-risk adults and adolescents, weighing at least 35 kg”. [4, 5]

The original cost-effectiveness submission was based on meeting the unmet need for the sub-group of people who couldn’t use oral PrEP, rather than the full licence population. ViiV Healthcare who developed and market cabotegravir-LA are committed to working with NICE to submit the additional data requested.

The full NICE report includes important details and although marked confidential, is openly available online. This includes a discussion on the difficulties of trying to define a population of unmet need, including people with low adherence and other reasons that oral PrEP is not appropriate, and the lack of clinical data in such populations.

It is unfortunate that only limited information is available in the report due to commercial sensitivity, including the price, because of the secrecy of drug pricing in the UK.

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Although the initial decision is disappointing this might just be a short term delay that could change with the additional information and analyses. The longer report is broadly very positive but communications from NICE are not always easy to follow or predict.

Much of the full report includes the forensic approach that NICE takes to evaluating evidence and modelling, and the related assumptions behind this work. Even to a lay reader, the approach is both intriguing and questionable. For example, cost effectiveness will assume median age of people using injectable PrEP as 33, when intuitively, much younger people at high risk are probably less likely to want daily pills.

Cost-effectiveness of CAB-LA PrEP still has to be proven in a setting where oral generic TD/FTC will be used by the majority of people on PrEP.

When NICE recommended oral PrEP in December 2021, based on remarkable efficacy results from the UK PROUD study, the press announcement failed to include that results from PROUD were reported in October 2014.

During the seven years that NICE took to evaluate the evidence for oral PrEP, more than 20,000 people were likely to have become HIV positive.

Hopefully, the second appraisal for cabotegravir-LA will lead to approval for injectable PrEP in the UK early in 2025.

HIV still disproportionally affects communities that are already socially marginalised and disconnected from optimum care and in whom long-acting PrEP is more likely to have advantages over oral PrEP.

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