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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… Read More

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It’s hard to quit (and E-cigs don’t help) A large trial (6000 participants) comparing free cessation support, e-cigarettes, and a $600 cash incentive for sustained abstinence shows that none of these approaches are particularly effective with 1-3% overall success rates depending on the arm.  Prevention is where it’s at. A Pragmatic Trial of E-Cigarettes, Incentives, and Drugs for Smoking Cessation (free access)   NPs and PAs numbers are growing fast A look back at the last 15 years and forward to the next 15 shows that the physician workforce is growing at about ~1% per year while mid-level… Read More

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Are we nearing an asymptote with implantable cardiac pumps? Severe heart failure is common, and spare hearts for transplant are rare, which has led to the development of implantable mechanical alternatives. In the last few decades, progress has been immense, and in the latest installment of a 3rd (4th?) generation pump, outcomes have reached a level where survival of several years is the rule. Still, at every iteration incremental improvement is less, and performance remains well behind what happens with transplant in terms of complications such as infection, stroke, or bleeding. One is left with the impression that perhaps, there… Read More

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A-fib in heart failure – time to be aggressive Over the last 15 years, there has been a growing body of evidence for the effectiveness of catheter ablation to treat atrial fibrillation (a-fib), a condition for which the standard of care has been anti-arrhythmic medications. A-fib commonly coexists with heart failure but until now it has not been clear whether medication or catheter ablation would be the preferred treatment – we now have the answer, at least for patients with a substantially reduced ejection fraction. In a randomized trial of ~350 patients, the medication arm’s death rate was about 25%… Read More

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Playing chess against cancer Tumors are not intelligent, but, because they have escaped mutational control, they constantly probe for mutations that will allow them to escape chemotherapeutic suppression. The epidermal growth factor receptor (EGFR) is a frequent driver of malignancy in the lung and as such, a target for EGFR inhibitors such as erlotinib (Tarceva, Roche) or gefitinib (Iressa, Astra Zeneca); unfortunately, tumors initially responsive to these agents quickly develop mutations which make them resistant. Osimertinib (Tagrisso, Astra Zeneca) was designed to overcome the most common resistance mutations and has been approved as rescue therapy for cancers that progress under… Read More

Posted by on in Biopharma, NEJM Highlights

Successes in gene therapy for hemophilia B and A Hemophilia A and B are X-linked genetic diseases which prevents the formation of functional coagulant factors VII and IX respectively and cause a propensity to bleeding in about 20,000 people in just the US. The standard of care of intravenous administration of recombinant factors is effective but also burdensome, expensive, and does not fully prevent the disabling sequellae of the disease caused by repeated bleeding in the joints. A possible cure is to deliver a functional copy of the defective gene piggy-backed on a viral vector. The proof of concept for… Read More

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Taking stock: two decades of progress in heart failure: Here comes a clever study using existing clinical trial data to assess progress in standard of care over time for heart failure. For each trial, the authors assessed the rate of sudden cardiac death during the early part of the study (excluding patients with ICDs), and it appears that between 1995 and 2014, it decreased by nearly half.  As always, in observational retrospective studies, one has to worry about systematic biases around the population that are included (i.e. are they really the same over time?), but there is a likely a… Read More

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Successful use of CAR-T therapy in a solid tumor Chimeric Antigen Reception T-cells (CAR-T) are immune cells molecularly engineered to seek out and destroy cancer cells; the push to develop them into a scalable generally usable treatment is likely the most exciting challenge in cancer right now.  Successful CAR-T use has so far been generally confined to hematological tumors.  In a brief report, a group from City of Hope reports on the use of CAR-T in a patient who was dying from an advanced, aggressive form of brain cancer, which led to a regression of the tumors for several months. Read More

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“My name is T-Cell…, James T-Cell” Immune T-cells are licensed to kill other cells through a quick molecular kiss of death, and as such are potentially powerful allies in controlling a tumor. For obvious reasons this killing power is under strict regulatory control and in particular T-cells display PD-1 proteins on their surface, which when engaged by the ligand PD-L1 on another cell, protects that cell from being killed. Tumors often display high levels of PD-L1 so that disrupting the interaction between PD-L1 and PD-1 can enhance the effectiveness of immune killing of tumor cells. Amplifying results from last year… Read More

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I am not sure how many docs continue to do this, but I still read the actual hard copy of my NEJM, and that means I flip past ad pages with smiling grandfathers playing with grandchildren thanks to supercalifragilistic products on my way to scholarly papers with tables and figures.  But this time, I stopped in puzzlement when I came across exhibit 1; Intermountain is a health system based in Utah, very highly respected for its sound approach to quality and cost control[1], but not broadly well known for cancer care in the way of centers like Dana Farber… Read More