Last week the Alzheimer’s Association appealed to the FDA to approve Biogen’s anti-amyloid immunotherapy drug aducanumab after the FDA heard appeals from patients and families affected by this Alzheimer’s disease. The statement from the Alzheimer’s Association read in part: “The Alzheimer’s Association worked directly with the FDA to arrange this session as part of our advocacy for new treatments. We were deeply concerned that the voices of those diagnosed with Alzheimer’s and their caregivers had not been heard during a recent advisory committee meeting on aducanumab. … The Alzheimer’s Association, as a science-driven organization, continues to believe that aducanumab should be approved.”
This advocacy position from the Alzheimer’s Association stands in stark contrast to a critical review from the scientific advisory committee which raised serious concerns about the safety and inadequately demonstrated efficacy of aducanumab. Two Phase 3 trials were stopped prematurely for futility. Only on later re-evaluation was a positive result observed in one of studies, while the second trial did not meet primary efficacy endpoints. The inconsistent results from these studies is concerning. Importantly, however, premature approval of this drug is not just a matter of potentially exposing patients to a drug that may not work, a remarkable 35% of treated patients developed swelling of the brain called ARIA-E and nearly 20% had bleeding associated with the swelling. The concerns around this side-effect have been widely downplayed, but the long-term risk of vascular cognitive impairment and/or intracerebral hemorrhage in patients who experience ARIA-E is not well understood and could be substantial.
The Alzheimer’s Association’s statement argued that “If approved, it would be the first treatment to potentially change the progression of Alzheimer’s. We believe the accumulated science, the publicly released data on aducanumab and the absence of other treatment justifies FDA approval, accompanied by a Phase 4 post marketing surveillance study.” This greatly concerns me. When they say, “it would potentially change the progression of Alzheimer’s,” it betrays that efficacy has not been adequately proven. Proving the efficacy and safety of aducanumab is Biogen’s responsibility – trying to accomplish this in a Phase 4 post marketing surveillance study would transfer the risk and the cost of developing this drug to our patients. This is aligned with corporate interests, but not the health and well-being of our patients.
Alzheimer’s disease is a bad disease and the need for an effective treatment is clear and urgent, but I remember the famous saying that says “There is no problem so bad that you can’t make it worse by doing the wrong things.” Responsible advocacy should lead us to insist that treatments meet a high standard of safety and efficacy before they are distributed to potentially millions of our most-vulnerable patients.