{"id":4402,"date":"2022-01-29T18:36:40","date_gmt":"2022-01-30T00:36:40","guid":{"rendered":"https:\/\/blogs.luc.edu\/compliance\/?p=4402"},"modified":"2022-01-29T18:36:40","modified_gmt":"2022-01-30T00:36:40","slug":"compliance-and-aducanumab-how-should-providers-balance-fda-and-cms-guidance","status":"publish","type":"post","link":"https:\/\/blogs.luc.edu\/compliance\/?p=4402","title":{"rendered":"Compliance and Aducanumab \u2013 How Should Providers Balance FDA and CMS Guidance?"},"content":{"rendered":"

Andrew Thompson<\/em><\/p>\n

Associate Editor<\/em><\/p>\n

Loyola University Chicago School of Law, JD 2023<\/em><\/p>\n

As my colleague at Inside Compliance discussed here<\/a> in September, the FDA approved Aducanumab<\/a> for the treatment of Alzheimer\u2019s Disease on June 7, 2021. Aducanumab, marketed as Aduhelm, is intended to reduce beta-amyloid levels. This compound is responsible for forming a \u201cplaque\u201d which inhibits neuron function and eventually triggers neuronal apoptosis<\/a> (death of neurons). Now, a recent decision by CMS on insurance reimbursement for aducanumab has increased the compliance responsibilities of providers.<\/p>\n

<\/p>\n

FDA approval and surrogate endpoints<\/strong><\/p>\n

In recognition of aducanumab\u2019s potential to treat the approximately 6.2 million American\u2019s living with Alzheimer\u2019s Disease (AD) the FDA reviewed aducanumab through its Accelerated Approval Program<\/a>. The Accelerated Approval Program uses a \u201csurrogate endpoint\u201d in lieu of confirmatory trials, where a surrogate endpoint is some biological or clinical marker correlated to disease pathology. Since increased levels of beta-amyloid<\/a> are correlated with AD pathology and are present in later stages of AD<\/a>, reduced levels of beta-amyloid were able serve a surrogate endpoint in the accelerated approval of Aducanumab. However, as the FDA provides, a surrogate endpoint is not the same as proving a drug is safe, effective, and potent. In turn, after receiving accelerated approval, a drug must undergo additional trials known as phase 4 confirmatory trials<\/a> which validate the surrogate endpoint and confirm the drug offers patients a clinical benefit. As part of the accelerated approval process, the FDA is requiring Biogen, aducanumab\u2019s manufacturer, to conduct a post-approval clinical trial to confirm the anticipated clinical benefit of aducanumab.<\/p>\n

CMS\u2019s Decision on Aducanumab <\/strong><\/p>\n

On January 11, 2022 the Centers for Medicare and Medicaid Services (CMS) released its coverage decision<\/a> on aducanumab. CMS\u2019s decision to offer Coverage with Evidence Development<\/a> (CED) means a patient must be in a CMS approved trial in order to receive insurance reimbursement. Additionally, CMS mandates that all trials be conducted in a hospital-based outpatient setting, which may present barriers to access for patients who cannot access hospital based services due to financial or travel related needs. CMS\u2019s CED decision in turn imposes a clinical compliance requirement on providers, where providers must ensure a patient is properly enrolled in a CMS approved trial in order to prescribe aducanumab with subsequent reimbursement. The National Institute on Aging<\/a> (NIA) also released a statement regarding CMS\u2019s decision on January 11, 2022 which reiterated the role of beta-amyloid in AD, FDA approval, and CMS\u2019s CED decision.<\/p>\n

The Alzheimer\u2019s Association\u2019s statement on Aducanumab<\/strong><\/p>\n

The Alzheimer\u2019s Association<\/a>, a leading organization dedicated to supporting patients, providers, and caregivers, released a formal statement<\/a> on CMS\u2019s decision by Alzheimer\u2019s Association CEO Harry Johns. While further evidence of aducanumab\u2019s clinical benefit is both anticipated and required by the FDA, the Alzheimer\u2019s Association raises a compelling point, that \u201caccess to treatment would not only be available to a privileged few, those with access to research institutions, exacerbating and creating further health inequities.\u201d The Association\u2019s reference to access to research institutions connects to CMS requiring patients to be enrolled in a trial conducted in a hospital-based outpatient setting. Access to this may be challenging for patients in advanced disease stages who are unable to travel and enroll and who would otherwise stand to benefit from aducanumab. The Alzheimer\u2019s Association points out that despite CMS citing to the Alzheimer\u2019s Association 2021 Alzheimer\u2019s Disease Facts and Figures<\/a> report covering barriers faced by underrepresented communities when attempting to enroll in clinical trials, the CED requirement imposes an additional barrier to access.<\/p>\n

The Alzheimer\u2019s Association\u2019s position on CMS\u2019s CED requirement for aducanumab may also be motivated by the infrequent use of CED requirements for coverage, as described by Dr. Caleb Alexander<\/a>, co-director of the Center for Drug Safety and Effectiveness at Johns Hopkins Medicine. Regarding CED, Dr. Alexander states \u201cI\u2019m not aware that they\u2019ve [CMS] ever required coverage with evidence development for a prescription drug before.\u201d Turning to the need for validation of the clinical benefit suggested by the surrogated endpoint of beta-amyloid reduction, Dr. Alexander noted \u201cto some degree, their hand [CMS] is forced by the absence of evidence whether or not this product even works.\u201d<\/p>\n

What Steps Ought Providers and Patients Take?<\/strong><\/p>\n

Due to CMS\u2019s decision and the trend of hospitals and universities to decline prescribing aducanumab<\/a>, patients and providers should consider what steps will best align with compliance requirements and treatment goals. To ensure compliance with CMS\u2019s coverage decision, providers must prescribe only if the patient is enrolled in a CMS approved trial. Additionally, patients and providers might choose to advocate for CMS allowing expanded enrollment where CMS will offer reimbursement for patients receiving treatment who are not enrolled in a CMS approved trial. Data from patients who are prescribed aducanumab could in turn be reported to the FDA, NIA, and CMS to support the phase 4 confirmatory trials required by the FDA. With more robust data, the clinical benefit of aducanumab can be validated or rejected, allowing patients easier access to this drug should it prove to offer the clinical benefit anticipated.<\/p>\n","protected":false},"excerpt":{"rendered":"

As my colleague at Inside Compliance discussed here in September, the FDA approved Aducanumab for the treatment of Alzheimer\u2019s Disease on June 7, 2021. Aducanumab, marketed as Aduhelm, is intended to reduce beta-amyloid levels. This compound is responsible for forming a \u201cplaque\u201d which inhibits neuron function and eventually triggers neuronal apoptosis (death of neurons). Now, a recent decision by CMS on insurance reimbursement for aducanumab has increased the compliance responsibilities of providers.<\/p>\n","protected":false},"author":80,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55],"tags":[60,61,62,432,810,1696],"class_list":["post-4402","post","type-post","status-publish","format-standard","hentry","category-pharma-industry","tag-aducanumab","tag-aduhelm","tag-alzheimers-disease","tag-cms","tag-fda","tag-regulatory-compliance"],"_links":{"self":[{"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=\/wp\/v2\/posts\/4402","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=\/wp\/v2\/users\/80"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=4402"}],"version-history":[{"count":0,"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=\/wp\/v2\/posts\/4402\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4402"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=4402"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.luc.edu\/compliance\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=4402"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}