An opinionated take on NEJM highlights for August 2018

Transthyretin heats up

Last month saw a couple landmark papers about the use of parenteral RNA drugs (from Alnylam and Ionis) in hereditary transthyretin amyloidosis with a focus mainly on mitigating the progression of polyneuropathy. But what matters most for the survival of these patients is cardiomyopathy and although the Alnylam paper did show some impact on that pathology, this was based on exploratory analyses of biomarkers, not pre-specified hard outcomes.  A few weeks later, Pfizer comes out with their oral Tafamidis with clear improved cardiac outcomes including survival, in a placebo-controlled RCT that included not only patients with hereditary disease, but also patients with wild type disease which is thought to be a much larger group. Aside from patients who now have new options, who wins, and who loses? Pfizer has made a case where it matters most (survival), simultaneously expanded the addressable population, and has the commercial organization to run with it. However given the completely different mechanism of action one can very well imagine combination therapy between an RNA drug and Tafamidis. If I were the patient – I’d go for Onpattro (the Anylam drug that has some data on cardiac effect) and if my insurance would not pay to add Tafamidis, I would layer on diflusenal, an old generic NSAID with similar mechanism of action.  Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy; Stabilizing Transthyretin to Treat ATTR Cardiomyopathy (free access)


Why Jimmy Carter is alive today

Metastasis to the brain is common in melanoma and until recently had a dismal prognosis (few weeks to months survival). Immuno-oncology has changed that, and in this last installment of progress, a single arm study of 94 patients with previously untreated brain metastases receiving nivolumab and ipilimumab (Opdivo and Yervoy, BMS) shows a median survival that will likely surpass 18 months once the study has fully run its course. Jimmy Carter received pembrolizumab (Keyrtruda, Merck), but same principle.  Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain; Immunotherapy for Melanoma Metastatic to the Brain (subscriber access)


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.

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