Biogen began investigations in November 2021 into the untimely demise of a 75-year-old woman from a neurological problem. The woman was on Biogen’s drug Aduhelm (aducanumab) for patients with Alzheimer’s. The women died of the same Amyloid-Related Imaging Abnormalities (ARIAs) that came up during randomized control trials of Aduhelm.
A report from the FDA Adverse Events Reporting System (FAERS) declared the deaths of three more individuals as a result of Aduhelm. One 86-years-old patient suffering from Alzheimer’s, diabetes, and CHD met his end after taking the drug. Another 74-year-old patient with gait disturbances passed away as well. Little is known about the age of the third patient who underwent treatment for seizures and may or may not have ARIAs.
Statement by Biogen
Biogen issued a statement saying “The 3 events of death reported in the FAERS database as of 31 Dec 2021 that were not included in the FAERS database as of September 2021 have not been attributed to treatment with Aduhelm. Alzheimer’s disease is complex, and patients affected by this devastating disease often suffer from other serious medical conditions.”
Biogen directs physicians to keep patients under surveillance for ARIAs but doesn’t ask them to stop drug administration. In the randomized controlled trials of the prescribed dose, around 0.3% of patients presented with extreme side effects like ARIA or death. Indications have been made to monitor patients for ARIA events through MRI before starting infusion and after 7th and 12th doses.
Clinical Trials Arena’s Findings
Clinical Trials Arena stated in August that ARIA is a “known class side effect of antibodies like Aduhelm that target amyloid plaque in the brain.” ARIA includes cerebral edema which is part of ARIA-E, the most common type. Other features include headache, gait disturbances nausea, and confusion.
Aduhelm’s trial results of EMERGE and ENGAGE by Biogen and Eisai, 35% of the patients showed ARIA-E while taking the prescribed dose of Aduhelm. Biogen brushed this off saying that 98% of these cases were sorted out on MRI and 76% did not develop symptoms.
Studies show a relationship between ARIA and APoE4, which forms the genetic basis of Alzheimer’s. Aduhlem’s trial results published by Biogen state that carriers of APoE4 taking Aduhelm were 42% more likely to develop ARIA as compared to 20% in non-carriers.
The controversy between Biogen and FDA:
Concerns over the safety of Aduhelm have been raised since its approval by the FDA in June 2021. Controversy regarding the side effects of Aduhelm and its effectiveness have made the scientific papers multiple times. The drug has proven to destroy beta-amyloid, a protein that accumulates in the brains of patients with Alzheimer’s. The drug has been shown to decelerate the progression of the disease but the claim has been shrouded in mystery and doubt.
Heated debate surrounds the issue of Biogen being questioned by the FDA’s advisory committee about the speedy approval pathway for the drug. FDA believes that Biogen should leverage the accelerated approval pathway as they did not have the required biomarker data or conclusive proof that Aduhelm removes beta-amyloid. The committee advised the agency to wait for post-clinical studies to be conducted before releasing the drug but Biogen refused. The committee withheld approval but Biogen released Aduhelm under an accelerated approval pathway.
Draft National Decision by CMS:
The public commentary by the U.S. Centers for Medicare & Medicaid Services (CMS) on Aduhelm just came to an end and CMS said it would fund Biogen’s Aduhelm “if they are enrolled in qualifying clinical trials.” Research would need to “demonstrate a clinically meaningful benefit in cognition and function.”
Biogen went a step further and considered using this funding offer for any drugs in that class. Two notable stakeholders in Alzheimer’s drugs are Eli Lilly and Roche. Both opposed CMS’s proposal and 47 House Republicans drafted a public letter against the draft coverage determination as they believed that CMS was restricting access to a drug that has “already been approved by the FDA as safe and effective” and that the agency was doubting FDA’s “expertise and authority.”
The safety of Aduhelm is still not clear in light of the recent deaths reported in FAERS. Further studies and research needs to be done by both Biogen and prescribing physicians.