RNA drugs coming of age
Hereditary Transthyretin Amyloidosis (ATTR) is a genetic disease in which one of the alleles of Transthyretin (TTR), a protein produced by the liver and with a role in thyroid hormone metabolism, is mutated resulting in amyloid fiber deposits mainly in nerve and cardiac tissues. Patisiran (Alnylam) and inotersen (Ionis) are both oligonucleotides designed to knock down translation of TTR mRNA, the first through the silencing mechanism, the second through an antisense effect. Phase 3 placebo-controlled studies published back-to-back in the journal show clear efficacy for both in reducing progression of neuropathy (and sometime improving it). In the background of fairly similar profiles, a few differentiating factors jumped out at me: patisiran is IV, while inotersen is SQ allowing for self-management; exploratory analyses in the patisiran showed potential impact on the cardiac manifestations of ATTR (which cause much morbidity and mortality) while such analyses were absent from the inotersen trial (and one might read something into that). How Alnylam and Ionis price and promote their respective products will be interesting to see. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis; Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis; Oligonucleotide Drugs for Transthyretin Amyloidosis (subscriber access)
The long road to VBC: new results from the bundled payments initiative (BPCI)
The Medicare-sponsored BPCI offers hospitals the opportunity to take financial accountability for a full 90-day episode of care from index admission to subsequent post-acute care, readmissions etc. for specific diagnoses chosen by them. It has shown some promise in reducing costs for joint replacement, but this study looks at 5 medical conditions (acute MI, CHF, pneumonia, sepsis, COPD) by comparing participant hospitals to a carefully selected control group which did not participate. The findings are sobering, indicating minimal difference between the two. The authors offer a variety of explanations for this including a much frailer patient substrate than for joint replacement (55% over 80, mortality at 90 days was 17%), lack of control of post-acute management etc. But underneath all this, I believe the explanation is time – for all hospitals, the before-after comparison spanned 18 months or less. Changing ingrained systems and attitudes for the management of patients that are complex takes much longer than a year. Evaluation of Medicare’s Bundled Payments Initiative for Medical Conditions (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.