Licensing lecanemab by the MHRA in the UK: pharmacovigilance comments

Saad Shakir writes:

Humanised monoclonal antibodies for dementia are very complex products with a narrow benefit risk balance at the time of launch. The MHRA seems to have given the benefit of doubt to the licensing of lecanemab in contrast to the National Institute of Clinical Excellence (NICE) and the European Medicines Agency (EMA).

These products are the first new therapeutic advance for dementia for a long time. As everyone knows, dementia is an increasing global public health burden with the ageing population.
On the favourable side, these products have an innovative anti-amyloid pharmacological effect.
On the negative side, their efficacy was demonstrated in the artificial setting of clinical trials. It is yet to be demonstrated that their efficacy in RCTs will be mirrored in real-world clinical use.

These products have been associated with unusual adverse drug reactions (ADRs). Amyloid Related Imaging Abnormalities (ARIAs) are in two categories: micro cerebral oedema or haemorrhage. The somewhat unusual name aims to emphasise the reversibility of these ADRs. However, vigilance must be exercised for any possible long term sequalae of these ADRs. In addition, and possibly related, there has been a small number of serious and fatal ADRs, such as large cerebral haemorrhages with these products.

The use of these products is very complex for any patient, let alone those with dementia. It requires genetic testing, PET scans, regular MRI scans and fortnightly intravenous infusions. All these are expected to be done or initiated in dementia care settings with their limited access to advanced medical technology.

The MHRA made a decision to licence lecanemab with safeguards including prior genetic testing for ApoE4 gene and inclusion of patients in a post-authorisation safety study. The details of the study is not available in the public domain yet, it must be published. Testing for ApoE4 reduces the incidence of ARIAs, but has no impact on the efficacy of the product. Without NICE approval the product can only be used by private patients in England.

Even with the company’s PASS study, independent on-going pharmacovigilance evaluation of the benefit risk of this product is mandatory.