New Data from Biogen Supports Aduhelm's Clinical Effectiveness
Biogen reported new data from a long-term extension phase of the Phase III clinical studies of Aduhelm (aducanumab) for Alzheimer’s disease. The controversial drug was approved by the U.S. Food and Drug Administration in June of 2021, but it has been criticized for its effectiveness and costs. Still, the company continues to collect data that supports its claims for the drug.
The long-term extension data evaluated patients after almost two and a half years of treatment or 128 weeks. Participants received 100 mg/mL of intravenous dosing. The patients demonstrated significant decreases in two key Alzheimer’s pathologies: amyloid beta plaques and plasma p-tau181. In addition, and perhaps most importantly for convincing physicians and insurers of the drug’s benefit, at 78 weeks, patients with decreased plasma p-tau181 levels had less clinical decline than in patients whose plasma p-tau181 levels did not decrease.
The data also showed a significant reduction of amyloid-beta plaque levels out to Week 132. Patients with better amyloid-beta clearance also showed more drops in p-atu181 at week 128. This suggests a likelihood of continued benefit in the longer term.
“These are meaningful findings, which further our understanding of amyloid and downstream biomarkers, such as p-tau181, in Alzheimer’s disease and can help inform how long patients may benefit from treatment to reduce amyloid beta plaque,” said Samantha Budd Haeberlein, head of Neurodegeneration Development at Biogen. “These data demonstrate that long-term treatment with Aduhelm continues to reduce the underlying pathologies of Alzheimer's disease beyond two years.”
The four clinical endpoints evaluated were CDR-SB, MMSE, ADAS-Cog13 and ADCS-ADL-MCI, which are used to evaluate cognition and function. Plasma p-tau181 is an exploratory endpoint, but the data showed that reduction of this biomarker was correlated with slower clinical progression on the four clinical evaluation methods.
The drug has also been associated with a potentially deadly side effect: brain swelling, or ARIA-E. In the placebo-controlled period of the Phase III studies, the incidence of ARIA-E in the 10 mg/kg group was 35.2% but was higher in carriers of the gene variant APOE4 (43.0%) compared to non-carriers (20.3%). They note that most cases of ARIA are asymptomatic, but serious symptoms in ARIA were observed in 0.3% of participants of the 10 mg/kg group, and 98.2% of ARIA-E resolved within 12 to 16 weeks. It’s not clear in the company statement what levels of ARIA-E were seen in the higher doses used for approved treatment.
Biogen presented the data at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2022) in Barcelona, Spain, and virtually.
On Tuesday, Biogen and its partner, Eisai Inc., reported they had amended their existing agreement on Aduhelm and other Alzheimer’s drugs. Essentially, Eisai is backing away from Aduhelm, shifting from sharing global profits and losses to only taking tiered royalties based on the drug’s net sales. The original agreement was signed in 2017.
The two companies will continue to develop and commercialize another Alzheimer’s drug, lecanemab. They initiated a rolling submission to the FDA for it in Sept. 2021. It is an anti-amyloid beta protofibril antibody. Eisai is leading the program for lecanemab, with Biogen splitting commercializing and promotion, and Eisai has final decision-making rights. Biogen is up for 50% of profits and losses on the drug.
Other companies in the Alzheimer’s and Parkinson’s space are also presenting at AD/PD 2022. Dublin-headquartered Prothena presented preclinical data from its dual amyloid beta/tau vaccine for Alzheimer’s and from its tandem C-terminal alpha-synuclein vaccine programs.
Synaptogenix presented clinical results on Bryostatin-1 for Alzheimer’s disease. The data suggests the drug may have applicability for more complicated dementias beyond Alzheimer’s, such as Parkinson’s, multi-infarct dementia, and multiple sclerosis.
INmune Bio announced nine presentations, largely around its XPro program.
“This is the first time many clinician teams in Europe and UK have been exposed to XPro and INmune Bio’s approach to treatment of Alzheimer’s disease,” said RJ Tesi, INmune’s CEO. “These nine presentations show the versatility of XPro and the importance of neuroinflammation in the pathogenesis of neurodegenerative diseases.”