With the US FDA’s controversial recent decision to approve Biogen and Eisai’s aducanumab – the first approval for a new Alzheimer’s disease (AD) drug since 2003 – PharmaBoardroom has raided its archives to bring key industry stakeholders’ takes on the significance of this decision and what it might mean for the future of the field. Questions persist over the drug’s ability to slow the effects of Alzheimer’s, whether enough patients will be willing to join the required follow-up clinical trials and risk receiving a placebo, as well as its hefty US price tag of USD 56,000 per annum.
Even those within Biogen and Eisai admit that the approval is complex and that aducanumab is not a magic bullet for patients suffering from Alzheimer’s. Ivan Cheung, head of Eisai’s US operations, told PharmaBoardroom last year of the “delicate balance” that preparing for an aducanumab launch entailed.
Am I supposed to be excited and proud of the progress we have made in AD, or should I be apologetic about how slow that progress has been?
“Ever since ARICEPT® was launched, the goal was always to advance from simply having a symptomatic treatment to a longer-term disease-modifying therapy for AD. This is an area of serious unmet need. However, at the same time, we are also aware that patients have been waiting for such a long time and have experienced so many disappointing news about failed clinical trials that they are very wary of false hope,” he admitted.
“When I speak to patient groups, I have mixed feelings because, on one hand, I know that we have great science and promising assets, but on the other hand, I know that all these developments have taken a very long time and we have still not crossed the finish line. Am I supposed to be excited and proud of the progress we have made in AD, or should I be apologetic about how slow that progress has been?”
However, other stakeholders have highlighted how an aducanumab approval could open the floodgates for a new era in Alzheimer’s Disease treatment approvals and offer greater hope to patients. Dr Charles Stacey of Cerecin, a clinical-stage CNS company whose Alzheimer’s candidate, unlike aducanumab, does not focus on the amyloid target, sees the approval as an “opportunity.”
What we need to see in Alzheimer’s and across the board in CNS is new drugs gaining approval. This will show that trial endpoints are achievable, studies can be successful, and regulators are engaged
“CNS could be the next oncology,” states Stacey. “The much-discussed “Biogen or aducanumab effect” shows that this has been a tough indication, and what we need to see in Alzheimer’s and across the board in CNS is new drugs gaining approval. This will show that trial endpoints are achievable, studies can be successful, and regulators are engaged.”
He continues “This goes for both the clinical side and the investment side, which is the driving force of this industry – investors need to make money. Investors have lost a lot on CNS, particularly in Alzheimer’s, and now need to recoup their losses. Successful studies and approvals have a positive effect across the board; other CNS/Alzheimer’s companies that are publicly traded have benefited from this surge of interest with some very successful IPOs and fundraisings last year. For example, Athira, a company in relatively early stages of Alzheimer’s drug development, raised almost USD 100 million based on compelling Phase I-II data and then had a very successful IPO in the latter part of 2020, even amidst the COVID pandemic.”
Dr Neil Cashman, a neurodegenerative disease specialist, agrees, noting last year that, while he felt that aducanumab should be approved, “its modest efficacy and safety concerns, however, justify the need for a next-generation therapeutic that selectively targets toxic oligomers.”
[Aducanumab’s] most powerful impact will be on future therapy development
Cashman adds, “Such drugs in development provide a high degree of binding to toxic oligomers without binding to non-toxic forms of amyloid-beta plaque. These highly targeted therapeutics hold great potential to avoid ARIA-E and allow for higher dosing and efficacy. The preclinical data for these drugs are promising compared with therapies like aducanumab that target only amyloid beta plaques. These new drug candidates will benefit from novel blood and cerebrospinal fluid (CSF) biomarkers that measure disease progression, enabling dramatic improvements to the speed and cost-effectiveness of clinical development.”
He concludes that while an aducanumab approval “should be hailed as an important milestone in Alzheimer’s treatment, its most powerful impact will be on future therapy development, specifically second-generation therapies that demonstrate more precise targeting for amyloid-beta toxicity with greater efficacy and safety.”
Even Cheung – whose company’s share price soared on the news of the FDA approval – concurs. “The aducanumab experience has been invaluable for advancing research into AD,” he proffers. “As the many failures in the field have made clear, neuroscience is a very difficult and complex therapeutic area. In my view, it is not a matter of resources. The crux is having a profound and deep understanding of human biology and pathophysiological underpinnings of the neurological condition.”