‘Exploitation in the name of biomedical innovation cannot be tolerated’ was the heading of an article this week featuring the Alzheimer’s drug Aduhlem as an example of ‘drug development gone bad.’[i]
Produced by American company Biogen and Japanese firm Eisai, Aduhelm was marketed as improving patients’ cognition and delaying progress of the disease. It failed to do this in clinical trials, so the company changed the end point from improving cognition to the surrogate of removing plaques in the brain, thought by some scientists to be the cause of the disease. On this basis it obtained FDA approval through the ‘back door’ known as accelerated approval, despite strong objections from its panel of independent experts who said the science didn’t support it. Aduhelm also had significant side effects: a pooled analysis of two phase 3 studies showed that 41% of patients who took it had swelling or bleeding on the brain, and since the launch one patient has died.
Rejection by major health providers
Aduhelm has been rejected by several health providers and insurance companies, among them the European Medicines Agency which said it could cause harm and the benefits did not outweigh the risks. The American Academy of Neurology referred to the principle of beneficence, stating that ‘neurologists should inform patients that aducanumab will not cure Alzheimer’s disease or restore cognitive function and they should be aware of potential conflicts of interest that may compromise beneficence.’ [v] The Academy also said that there are insufficient grounds to warrant offering Aduhelm to patients with moderate or advanced Alzheimer’s dementia or to patients without biomarker evidence of brain β-amyloid.’
In April this year, the Centers for Medicaid and Medicare Services (CMS) that covers medical costs for over 65s, the main market for Aduhelm, said it would cover only patients enrolled in clinical trials supported by the CMS, FDA, and the National Institutes of Health. ‘That decision was scientifically based and politically courageous,’ said analyst Anand Kumar,[ii] ‘the drug is clinically ineffective, unsafe, and expensive.’ He added that interested biotech and pharmaceutical companies considering obtaining approval through the FDA’s accelerated approval pathway were disappointed with the requirement that drugs approved under this mechanism will need to show real benefit to patients in placebo-controlled studies – the international gold standard in randomized clinical trials.
He admired the CMS for putting patients first despite facing intense lobbying from the pharmaceutical industry and advocacy groups, including Alzheimers’ Societies, with campaigns that failed to mention the risks or that the drug hasn’t been shown to work.
Now Biogen has shelved Aduhelm, ‘substantially limiting’ all expenditure on it and firing the entire commercial team involved. Biogen’s CEO also resigned. But the company isn’t finished with plaque-clearing drugs and is beginning a ‘rolling submission’ to the FDA of its latest, Lecanamab. It may be beaten to the post by Eli Lilly, which is developing donanemab – another monoclonal antibody.
The good news coming out of all of this is that neuroscientists and doctors ‘on the ground’, with patients who are desperate for a cure, are taking a stand that protects them from a drug that doesn’t work and could cause harm. One neurologist took it for four months and describes how he ended up in intensive care, with brain swelling and bleeds. (See website below – *2)
It also begs a number of questions. One is , even knowing that it didn’t work and has significant risks, why have many researchers welcomed the approval of Aduhelm? (Some experts’ comments have been rounded up on the website below*). What happened to the centuries’ old principle of ‘do no harm?’
Also, why continue with trials aimed at removing plaque deposits when, as this trial shows, even when removed there is no improvement in cognition, and many older people’s brains have plaques but do not develop Alzheimer’s? The plaques are part of an ‘amyloid hypothesis’ that has never been universally accepted, and critics point to the numerous failed drug trials on this basis over the last 20 years. [ii]
The focus on removing the plaques is preventing research into other possible cures many scientists believe, with influential researchers believing so dogmatically in one theory of Alzheimer’s that they have systematically thwarted alternative approaches. In more than two dozen interviews for Stat, a leading biotech journal, scientists whose ideas fell outside the dogma recounted how, for decades, believers in the dominant hypothesis suppressed research on alternative ideas. They influenced what studies got published in top journals, which scientists got funded, who got tenure, and who got speaking slots at reputation-buffing scientific conferences.(See *3)
Or could it be that pharmaceutical companies are working towards a ‘moonshot vision’ of a pill that could be taken to prevent Alzheimers, rather like a Statin to prevent cholesterol build-up?
One thing is sure: after the approbrium heaped on the FDA after the ‘back door’ approval of Aduhelm, other plaque removing drugs put forward are going to be closely inspected.
- 3 https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/
- 2 https://louisemorse.com/aduhelm-the-new-drug-to-beat-alzheimers-or-the-bomb-that-blows-the-amyloid-b-hypothesis-out-of-the-water-once-and-for-all/)
[i] https://www.statnews.com/2022/05/05/exploitation-in-the-name-of-biomedical-innovation-cannot-be-tolerated/? utm_source=STAT+Newsletters&utm_campaign=b587e642b9-First_Opinion&utm_medium=email&utm_term=0_8cab1d7961-b587e642b9-153685150