All eyes are on aducanumab, which could become the first disease-modifying therapy (DMT) for Alzheimer’s disease (AD), a landmark achievement following decades of failure in this perennially underserved market.
The most critical need for patients has been a safe, effective DMT that slows cognitive decline. Tools that enable earliest possible diagnosis are also critical.
Aducanumab is the first putative DMT to demonstrate a clinical effect in early AD patients in a Phase III study and the first to undergo regulatory review.
Results from the terminated ENGAGE/EMERGE and completed PRIME trials indicate that aducanumab is biologically active and suggest the potential for efficacy with sufficient exposure to the 10 mg/kg dose.
If approved, it would mark a major clinical, commercial and regulatory milestone.
However, the overall data package is complex and contentious given the limitations associated with the data and its analysis.
Aducanumab could unlock a monumental opportunity to radically change AD patient care and transform the market. If approved, demand for treatment will be enormous, potentially even decreasing willingness to forgo this treatment for an investigational drug in future clinical trials.
It could have a similar effect on companies’ decisions about which drugs to develop, bypassing other sorely needed MOAs to develop next-gen anti-amyloid drugs.
Nevertheless, many questions remain about the drug’s prospects, including, first and foremost, the probability of approval given the questions about its true efficacy, followed by future competition from other DMTs and overall health system preparedness—availability, cost and reimbursement of the drug and requisite diagnostic testing; patient/physician awareness to drive early presentation, specialist referral and diagnosis; and infusion infrastructure.
“I have to say that the data are convincing…there is clear clinical effect. I don’t think it’s a false positive. …aducanumab is, biomarker-wise, the strongest thing possible… from the point of MOA, biomarkers and the effect on the brain amyloid and tau… for how long would you treat patients and what their dosage would be to achieve the clinical effects? If you look closely, the limited data they have sort of parallels the observations they made during Phase I.”