Aducanumab Phase 4 Real-World Observational Study Announced

Biogen and Eisai have announced the design of the first real-world observational phase 4 study, dubbed ICARE AD-US (NTC pending), to evaluate long-term effectiveness and safety of aducanumab (Aduhelm; Biogen) injection 100 mg/mL solution, which received approval to treat Alzheimer disease (AD) last month.¹ The study intents to enroll patients with AD over 4 years from approximately 200 sites in the US, with ongoing monitoring for up to 5 years.

The announcement was made during a late-breaking presentation at the 2021 Alzheimer’s Association International Conference (AAIC), July 26-30. Aducanumab, the first disease-modifying therapy approved to treat AD since 2003, was approved under the Accelerated Approval pathway, which required the company to conduct phase 4 studies to confirm the benefit of the drug.

ICARE AD-US, a prospective, single-arm, multicenter, noninterventional real-world study, will primarily aim to characterize and evaluate real-world, long-term changes in cognition, function, and neuropsychiatric status among patients treated with the anti-amyloid agent. Secondary objectives are related to gaining a better understanding of the drug’s safety in real-world clinical practice. At least 16% of the estimated 6000 participants in the study are expected to be Black/African American and Latinx, as part of Biogen’s commitment to increase participation from traditionally underrepresented communities.

"Biogen is committed to both generating new data about ADUHELM and supporting steps to bring adequate representation to this trial and other clinical trials from traditionally underrepresented groups,” Ivana Rubino, PhD, US and Global Head of Medical, Alzheimer Disease, Biogen, said in a statement.¹ "We believe this can help us better understand the safety and effectiveness of treatment in patients with Alzheimer’s disease across ethnicities, something that has challenged researchers in this field for decades. The ICARE AD-US study, designed in collaboration with Alzheimer’s disease experts, underscores both of these commitments.”

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There have been several notable events since the agent’s approval. Earlier this month, the FDA announced it had approved an updated label for aducanumab, which included an addition to the Indications and Usage section of the label.² The new language stated that the treatment should be initiated in patients with mild cognitive impairment or mild dementia stages of the disease, the population in which the treatment was initiated in clinical trials.

A week later, the acting commissioner of the FDA, Janet Woodcock, MD, announced that she was requesting an independent review and assessment of the interactions between representatives of Biogen and the agency during the process that led to the approval of the drug.³ She noted that the review and assessment will help ensure continued confidence in the integrity of the FDA’s regulatory processes and decision-making. Amidst the ongoing discussion and controversy, Biogen’s head of research and development, Alfred Sandrock, MD, Phd, penned an open letter to the AD community, claiming that the approval has been subject to extensive misinformation and misunderstanding.⁴ The letter’s main points of clarification were centered around the FDA’s Accelerated Approval pathway, the agency’s decision to approve based on the available supporting data, and the potential impact on “innovation and competition” that the approval may have on the clinical development of therapies in Alzheimer.

Biogen still has 2 other clinical programs, aside from ICARE AD-US, that are designed to generate new data about aducanumab. The others include EMBARK, an ongoing, phase 3b re-dosing study for eligible patients previously enrolled in aducanumab clinical trials, including the PRIME long-term extension, EMERGE and ENGAGE, and the confirmatory phase 4 trial that is in the process of being designed.

"The ICARE AD-US study will provide important information on the safety, effectiveness and management of Alzheimer’s disease with ADUHELM, the first approved treatment for Alzheimer’s disease that targets the amyloid pathway, in the real-world setting across diverse populations," Harald Hampel, MD, PhD, vice president, chief medical officer, Neurology Business Group, Eisai, said in a statement.¹ “It is important for Eisai and the larger scientific community to recruit patients of diverse ethnicities for clinical trials to help address health disparities.”

For more coverage of AAIC 2021, click here.

REFERENCES

1. Biogen and Eisai announce design of Aduhelm ICARE AD-US study, the first real-world observational phase 4 study in Alzheimer’s Disease at AAIC 2021. News release. Biogen. July 29, 2021. https://www.globenewswire.com/news-release/2021/07/29/2271775/0/en/Biogen-and-Eisai-Announce-Design-of-ADUHELM-ICARE-AD-US-Study-the-First-Real-World-Observational-Phase-4-Study-in-Alzheimer-s-Disease-at-AAIC-2021.html

2. FDA approves updated Aduhelm prescribing information to emphasize population studied in clinical trials. News release. Biogen. July 8, 2021. Accessed July 29, 2021. https://www.eisai.com/news/2021/pdf/enews202156pdf.pdf

3. Woodcock J. @DrJanetWoodcock. Twitter website. Published July 9, 2021. Accessed July 29, 2021. https://twitter.com/DrWoodcockFDA/status/1413540801934774283?s=20

4. An open letter to the Alzheimer’s disease community from our Head of Research and Development, Alfred Sandrock, MD, PhD. News release. Biogen. July 22, 2021. Accessed July 29, 2021. https://investors.biogen.com/news-releases/news-release-details/open-letter-alzheimers-disease-community-our-head-research-and