As evidenced by the recent approvals in the Alzheimer's space and coverage issues for gene therapies, any approval other than full traditional FDA approval will lead to access barriers for patients. This must be a key consideration in the commercialization strategy when circumstances align for early approvals.

The pace of innovation in the pharmaceutical pipeline is incredible with novel drug approvals on track to mirror similar annual number of approvals as was seen prior to the pandemic.  While the pace of innovation continues to show strength, the implications on patients’ ability to access the drug based on how the FDA approves a drug is a key consideration.  The recent full approval of LEQEMBI® highlights potential patient access barriers related to the way in which a drug is approved.  From an historical perspective, the plight of treatments in the Alzheimer’s space has been challenging.  The first drug approved in the treatment of Alzheimer’s disease, COGNEX®, a cholinesterase inhibitor, was approved in 1993 but removed from the market in 2013 due to concerns over liver toxicity.  ARICEPT®, approved in 1996 also a cholinesterase inhibitor, however, concerns over questionable Alzheimer’s disease effectiveness clouded the view of stakeholders for its use.  The body of thought around causation of disease shifted research from cholinesterase inhibition to amyloid beta reduction and Biogen’s Aduhelm®, an amyloid beta-directed antibody, was approved in 2021 under conditional approval with much controversy over effectiveness.  This concern over effectiveness resulted in CMS stating that it would decline coverage until the FDA granted full and traditional FDA approval.    LEQEMBI, also an amyloid beta-directed antibody, was approved in January of 2023 however the challenge of CMS remained due to the drug being approved through the FDA’s accelerated pathway.  After further consideration, the FDA granted full traditional approval for LEQEMBI® on July 6, 2023, opening the opportunity for CMS coverage for Medicare patients.  But this is just the beginning, many other barriers to access exist including: 

  • Label indication:  the limitation to early disease with the labeled to treat Alzheimer’s disease in patients with mild cognitive impairment or mild dementia
  • Black box warning: amyloid related imaging abnormalities (ARIA).  This ARIA occurs more frequently in people with two copies of the APOE gene, which is the gene associated with increased risk of development Alzheimer’s disease discovered through genetic testing.  Genetic testing is a recommendation, not a requirement as treatment and monitoring would not change  (Genetic testing opens up an entirely different conundrum with downstream implications for entire families – we will address this in an additional blog)
  • Patient registry:   CMS-facilitated portal requirement to collect real world evidence to study the usefulness of the drug(s) as all drugs in the same class with full and traditional FDA approval will be required to use
  • Cost:  with projected cost of ~$26,000 annually, Medicare patients would be responsible for 20% coinsurance as on out-of-pocket cost

 Whether in the amyloid beta space or in the broader gene therapy realm, any approval other than full traditional FDA approval will lead to access barriers for patients.  This must be a key consideration in the commercialization strategy when circumstances align for early approvals.  

References: 

Novel Drug Approvals for 2023 FDA

LEQEMBI Now Approved

https://www.cms.gov/newsroom/press-releases/cms-announces-plan-ensure-availability-new-alzheimers-drugs