The US Food and Drug Administration has approved a new treatment, aducanumab for Alzheimer’s Disease. The Chief Executive of Alzheimers NZ was quoted by TVNZ
“What I’d say is, cautious optimism,” Alzheimer’s New Zealand chief executive Catherine Hall told 1 NEWS when asked about her reaction to the drug’s approval overseas.
“They get told there’s a brand new cure and then very quickly afterwards their hopes are dashed. It’s really important to recognise this is early days and there’s still a lot of data to be collected.”
It’s a very sensible attitude, in the abstract: if the drug turns out to be effective it could be valuable, but it’s too early to know if that will be the case. What’s surprising is that this is the situation we’re in after the drug has been approved, and when its manufacturer is planning to charge US$56000/year for it.
The drug (or, technically, the ‘biologic’ since it’s an antibody) has been through a lot of ups and downs in its clinical trial history. There were two main trials that were supposed to show it was effective. They failed. A re-analysis of one of them suggested that it might actually work, at least for some patients. Normally, this would be the cue to do a confirmatory trial to see if it does actually help an identifiable group of people. And the FDA did mandate this trial — but they will let the manufacturer sell and promote the medication for nine years while the trial goes on. Given that the the market for aducanumab is conservatively estimated at tens of millions of dollars per day, and there’s only a possible downside to getting trial results, the trial is unlikely to end a day sooner than it has to; it’s not unheard of for these post-approval trials to just never recruit enough participants and drag on longer than ‘allowed’.
The FDA takes external expert advice on drug approvals. In this case, there were 11 people on the panel. Exactly none of them thought there was good enough evidence for approval; one was uncertain, ten were against. Three of the panel members have since resigned. It’s not unprecedented for the FDA to disagree with the panel when the panel vote is split, but it’s pretty bloody unusual for them to disagree with a unanimous panel. It’s notable that the FDA approval does not say they think there’s evidence drug improves memory or cognition or ability to live independently or anything like that — the FDA thinks it reduces the amount of amyloid plaque in patients’ brains and hopes this will translate to (currently unobserved) improvements in how they live.
TVNZ goes on to say
It’s only suitable for those with mild Alzheimer’s when the damage to brain function is still limited.
This is what the trials would say, under the optimistic interpretation that they say it’s suitable for anyone. The FDA, however, says it is an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease. No restriction. Since most people who’d want the drug are over 65, it will predominantly be funded by Medicare, the US government health program. Medicare tends to pay for anything the FDA approves, but they might not have the option this time. Presumably in NZ we won’t get Pharmac subsidy for aducanumab at least until it’s shown to work; an incautiously optimistic date would be 2030.
Something like the aducanumab approval is what many of us were afraid of for Covid vaccines — an product with weak evidence of modest effectiveness being given the green light because demand was high: “something must be done; this is something; therefore we must do it”. We were lucky with Covid that the temptation didn’t arise for the FDA: the vaccines it has been asked to approve are more effective than anyone could have hoped. Aducanumab won’t be that sort of disaster, but it will put a lot of pressure on a US health cover system for older people where the government is expected to pay but not to count the cost, let alone balance it against effectiveness.