Pamela Spicer, principal analyst at Informa Pharma Intelligence looks at Biogen's recently approved Alzheimer's drug and questions its rollout in countries outside of the US.
Earlier this month, the FDA approved Biogen’s Alzheimer’s drug, Aduhelm, in a decision which many in the industry are calling somewhat controversial. Aduhelm has been labelled by Biogen as the first drug of its kind to target the underlying cause of Alzheimer’s disease. The drug – which was approved through the FDA’s accelerated approval pathway – looks to reduce the build-up of amyloid- beta plaque in the brain in the hope of reducing cognitive decline.
The nature of the FDA’s approval of Aduhelm and the data Biogen has gathered through clinical trials has brought with it many questions from the industry. One of the major concerns many people have is with the cost of Aduhelm – some $56,000 per year depending on the patient’s insurance. This is for a treatment that is still yet to be proven effective and is based on data that indicates a clinical benefit but does not prove it.
Moving on, the landmark approval of Biogen’s anti-amyloid antibody in the US raises questions about potential approvals and access to the drug in other countries. If proven effective, the product may become critical in combating the progressive disease as, globally, the number of prevalent cases of Alzheimer’s disease is expected to increase over the coming years. Biogen has already started conversations with regulators around the globe and has filed aducanumab (Aduhelm) in the EU, Switzerland, Canada, Japan, Australia, and Brazil.
With a total prevalence of Alzheimer’s disease predicted to be around 10 million in the five major European markets, France, Germany, Italy, Spain, and the UK, bringing a successful treatment to these countries is important. Indeed, the early Alzheimer’s disease segment of patients tested during the Phase III program for aducanumab comprise the majority of these patients, though treatment rates in prodromal Alzheimer’s disease have remained low as the mainstay therapies are indicated for dementia due to Alzheimer’s disease. As such, there are few options for individuals with biomarkers for the underlying disease pathophysiology and only mild cognitive impairment.
Biogen has not yet filed aducanumab in the UK, a necessary first step before anything else can happen, though approval decisions in the UK are typically expected within a year of filing. As we’ve seen post-Brexit, the UK regulator MHRA has shown some flexibility in speeding up access to COVID-19 vaccines, ahead of European timelines, but this is only one of the hurdles before patients could receive this drug on the NHS, the UK’s public healthcare system.
Reimbursement will be a major hurdle in markets like the UK, especially as there is not yet definitive data on cognition and there remain questions about how well the biomarkers that the FDA used - amyloid plaque reduction - correspond to cognitive benefit. The UK’s cost-effectiveness regulator, NICE, is one of the strictest bodies globally and is unlikely to recommend that aducanumab is reimbursed at the pricing levels indicated in the US ($56k annually). Notably, though, the average price per patient for psoriasis biologics in Europe can be less than a quarter of the US annual price.
Aducanumab was filed for regulatory approval with the European Medicines Agency in October 2020, so the earliest potential availability may be towards the end of 2021 but more likely into 2022. There is no guarantee that European regulators will view the drug application in a similar positive way, especially considering the use of accelerated approval in order to access the US market. The highly anticipated FDA decision is controversial in that it goes against the prior recommendation of an advisory panel, whose judgement was that the current data were insufficient. In recognition of the mixed Phase III clinical trial data, with one positive and one negative study, the FDA opted to use the accelerated approval pathway, requiring Biogen to perform a confirmatory trial to fully establish aducanumab’s clinical benefit. These precedent-setting decisions showcase the extent of the need for a treatment that might help slow the progress of this devastating disease.
If approved in Europe with favourable reimbursement decisions, a few questions surrounding access will remain. Discussions around requirements for amyloid positivity for drug eligibility are ongoing, despite the broad label and, though CSF biomarkers may be more receptive by Europeans than PET scans, even lumbar puncture services may not be available at scale. Additionally, it may be important to take into context the delivery of the drug and facilities to administer repeated infusions in elderly patients. In some areas, mental health services may be community-based and not necessarily set up basically to administer biologics.
Based on this, realistically, we are still some way from UK patients potentially benefitting from the drug.
Additional reporting by Reece Armstrong