In Canada, an active 66-year-old man with no signs or symptoms of heart failure is diagnosed with atrial fibrillation after experiencing several weeks of intermittent palpitations. He is referred for an echocardiogram, which demonstrates severely increased concentric left ventricular wall thickness with preserved ejection fraction, suspicious for cardiac amyloidosis. Further evaluation with laboratory testing and technetium-99m-pyrophosphate scintigraphy confirms a diagnosis of wild-type transthyretin amyloid cardiomyopathy (ATTR-CM). His cardiologist explains to him that although there is an approved therapy for attenuating disease progression named tafamidis, public reimbursement is only available to patients with a history of heart failure in compliance with provincial eligibility criteria based on recommendations from the Canada Drug Agency; in the absence of private health insurance that would cover the cost, his only other option is to pay out of pocket in order to get treatment. Without private insurance or the means to pay for the medication himself, he is told that he will have to wait until he develops symptoms of heart failure before he can access treatment.
Patient 2
In the United States, a 68-year-old man has NYHA functional class 2 heart failure, 3 years after being diagnosed with ATTR-CM. Despite being treated with tafamidis from the time of diagnosis, his disease has inexorably progressed. He is excited to participate in a phase 3 clinical trial of a new therapy, mechanistically distinct from the only currently approved therapy, and already approved for an indication in what is essentially the same disease, just manifesting in another organ system. The makers of the therapy cleared all the hurdles to bring it to a phase 3 clinical trial, and aligned with the Food and Drug Administration (FDA) on the primary endpoint before the trial began. The trial is a clear success: the primary endpoint and multiple prespecified secondary endpoints are achieved.1 Though the trial was not powered for mortality or hospitalizations, the trends there also point in the right direction. There are no safety issues. With this clean result, FDA approval seems a formality. However, the FDA surprisingly takes the unusual step of convening a formal advisory committee to provide a recommendation. The advisory committee votes 9 to 3 in favor, which by precedent nearly always leads to formal approval.2 The patient is therefore dismayed when the FDA overrules the advisory committee, cutting off access for a new therapy to him and thousands of other patients diagnosed with the disease.
How did we get here? Does any of this make sense? We believe it is time for a reassessment to aid patients with this devastating disease.