The Centers for Medicare and Medicaid Services (CMS) issued its closely awaited final national coverage decision (NCD)for FDA-approved monoclonal antibodies (mAbs) directed against amyloid for the treatment of Alzheimer’s disease (AD).  

The NCD places controversial restrictions on the Medicare coverage of FDA-approved treatments. While some will debate whether this is an overreach of CMS authority, the end result is that the decision introduces greater uncertainty around attaining CMS coverage of new therapies despite FDA stamp of approval, particularly those therapies approved through the accelerated approval pathway.     

So, what are the restrictions for the mABs for the treatment of AD? 

  • For these FDA-approved treatments approved through the accelerated approval program, Medicare coverage will be provided only when the therapy is administered in FDA drug application trials or studies conducted by the National Institutes of Health. 

  • For those approved through traditional FDA approval, treatments are eligible to be used on-label, for FDA-approved indications, in clinical studies or other prospective comparative studies to answer the “coverage with evidence development” (CED) questions specified in the NCD. 

This is a significant decision for many reasons.

Medicare has  traditionally paid for FDA-approved therapies – including those approved through the accelerated pathway – for on-label indications. For manufacturers invested or interested in the AD space, CED presents sharp limitations for commercialization and market access. The recent CMS NCD sets important precedent that could have approval and access implications for other FDA-approved therapies and the accelerated approval program. 

Environmental considerations and ‘how we got here’:  

  • While the CED determination was anticipated by some observers, the requirement to cover mAb therapy only in the context of randomized controlled trials (RCT) is impactful. 

  • RCTs for mAB therapies for the treatment of Alzheimer’s disease will not be limited to hospital-based outpatient settings – as proposed in the initial draft decision – but still must include a study population whose diversity of patients are representative of the national population with mild cognitive impairment (MCI) due to AD or mild AD dementia. 

  • The mobilization and convergence of stakeholder influence was swift and constant.  

  • While patient advocacy groups criticized the proposed requirements and launched public pressure campaigns in favor of access, many policymakers cited questions of clinical efficacy and cost impacts when they commended the CMS’ draft decision in a nine-page letter.  

  • In the weeks leading up to the final NCD, nine of 17 scientific advisory board members to an advocacy organization resigned to show support for CMS’ decision for the need of evidence development.   

  • The lessons from the FDA’s approval of Biogen’s Aduhelm and the increased scrutiny over the past year led to the perfect storm.   

Why this matters: 

The final NCD further restricts access to Aduhelm.  

  • For the few Medicare offices that have covered the treatment, reimbursement will be halted outside of clinical trials. While State Medicaid programs are obligated to cover any FDA-approved drug, Medicaid Administrators may seek to impose usage restrictions to limit cost.  

  • Private insurers tend to follow CMS coverage decisions and may seek to adopt Medicare’s approach – coverage with evidence development – by requiring specific improved outcomes in the form of a risk-based agreement. 

The decision highlights the implications that arise when the FDA and CMS arrive at two different judgements with the same evidence.  

  • Manufacturers will need to consider – and prepare for – scenarios in which ‘reasonable and necessary’ (CMS coverage standard) and ‘safe and effective’ (FDA approval standard) are in conflict.   

  • For manufacturers developing monoclonal antibodies based on their own amyloid data, evidence of cognitive function will be needed for payer reimbursement.  

The potential impact to the accelerated approval pathway.  

  • The accelerated approval pathway remains under intense scrutiny and the NCD for monoclonal antibodies (mAbs) directed against amyloid may intensify calls for reform by leading stakeholders.  

  • The recently introduced Accelerated Approval Integrity Act would increase the FDA’s authority to ensure that drugs that receive accelerated approval provide a proven clinical benefit to patients. If passed, the bill would mandate codified requirements for post-market trials, detailed procedures to revoke a drug’s approval if post-marketing trials fail or not completed after five years. 

  • Thecommitments by FDA Commissioner Califf that confirmatory studies “must be done in a timely manner” will seek to hold manufacturers accountable for trial data.  

What can life science companies do:  

Develop value communications that account for the current risk environment: The NCD demonstrates the importance of contextualizing value for new and existing therapies to a host of stakeholders. This should also include updated messaging on R&D, innovation and health equity.  

Engage the appropriate stakeholders early: Identify the right stakeholders and systematically engage 12-18 months ahead of launch to ensure that partners and surrogates are prepared to advocate for the product and answer tough questions on price and data points.  

Define your product’s value before stakeholders do it for you: Drug pricing debates will continue to generate media headlines about a drug’s price point. Companies need to be prepared with messages that convey the value of their products and drive a targeted media narrative.  

The Syneos Health Reputation & Risk Management and Corporate Communications teams will continue to monitor the policy landscape, provide insights and recommendations for clients with stakeholder engagement and value communications strategies. If you have questions, please reach out to [email protected] or [email protected].    

About the Author:

Patrick Rigby joined Syneos from the private sector where he specialized in corporate communication, government relations, and public affairs across the healthcare industry. Patrick served as Director of Communications and later as Chief of Staff for the New Jersey Office of Homeland Security and Preparedness under two administrations. He also served as an Advisor to the Chairman of the U.S. Senate Foreign Relations Committee. Prior to government service, Patrick held positions with Bloomberg L.P., the Council on Foreign Relations, U.S. House of Representatives, and in the financial services industry. Patrick brings with him over 15 years of managing large teams and directing complex communications and reputation management programs for businesses and government.