Posted by on in NEJM Highlights

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

Posted by on in NEJM Highlights

Two new therapies against a horrible congenital disease – but trouble ahead on pricing… Spinal Muscular Atrophy (SMA) is a genetic disease that declares itself at a few months of age, and typically leads to death before the second birthday. Two studies for two different therapies are reported in the Journal. First, the final results for a phase 3 placebo-controlled trial studying nusinersen (Spinraza, Sarepta, approved by FDA Dec 2016) therapy which involves monthly injections into the infant’s spine of an RNA-based drug. These show a clear beneficial effect over placebo (good enough for FDA approval), but still a high… Read More

Posted by on in NEJM Highlights

Between the very common and the very rare – An opinionated take on NEJM highlights for October 2017   Another tool for prevention in cardiovascular disease Taking aspirin daily has been standard of care for cardiovascular disease for decades, but attempts to demonstrate the additive usefulness of other agents to prevent clot formation have not been successful. Now things have changed: in a large study of patients with established cardiovascular disease, those who took rivaroxaban (Xarelto, Bayer) daily on top of aspirin did markedly better than with aspirin alone, although with increased risk of bleeding (mostly gastrointestinal, but very rarely… Read More

Posted by on in Uncategorized

A new drug to address hard-to-treat severe asthma In ~10% of people with asthma, traditional therapies do not work well and they have recurrent exacerbations leading them to the ED. Over the past few years, a number of biologics (mAbs) have been developed to treat such patients, but each of these agents is targeted to a small subgroup with specific biomarker characteristics for which it has been shown to be effective, resulting in ultra-niche therapies with limited uptake.  For broader penetration of those modalities, what is needed is a drug that has more general applicability to the non-responders with severe… Read More

Posted by on in NEJM Highlights

At last, drug prices influence physician usage patterns Association of Reference Pricing with Drug Selection and Spending (subscriber access); Nitroprusside and Isoproterenol Use after Major Price Increases (free access) Not that long ago, the share of mind US physicians devoted to the cost of the drugs they prescribe was essentially zilch. Thankfully, times have changed as demonstrated in two interesting papers that describe natural experiments. The first compared trends in prescribing patterns at a payer that instituted reference pricing in 2013 vs. one that did not (reference pricing means that for each drug class, the payer will limit… Read More

Posted by on in NEJM Highlights

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

Posted by on in Uncategorized

Stent news First there was angioplasty, then bare stents, then drug-eluting stents, and now the next generation: bioresorbable stents: each generation commanding a significant price premium for the manufacturers (but only for a few years). But, while bare stents and drug eluting stents were clear improvements on the previous standard of care, the case is not at all obvious for bioresorbable stents.  Now the latest news is that the Absorb stent (Abbott), instead of showing a benefit over the previous standard of care, appears to lead to a higher rate of device thrombosis.  A reminder that it’s hard to… Read More

Posted by on in NEJM Highlights

A hammer finds new nails (which happen to be eyeballs) The insulin growth factor receptor 1 (IGF-1R) was once upon a time a popular cancer target pursued by multiple biopharmas each with their own humanized antibody, and each without much success. In 2013, River Vision licensed the Roche compound teprotumumab, to treat Graves’ ophthalmopathy, a condition in which hyperactivity of the thyroid gland causes (among many other issues) bulging eyeballs with esthetic, comfort, and sometimes severe visual implications for which treatment options are limited. Nobody quite knows why the ocular issues occur, but hyperactivity of fibroblasts which are cells that… Read More

Posted by on in NEJM Highlights

Calendaring care The length of our sidereal year is an accident – we happen to be circling a G2 star from which the habitable zone where free surface liquid water can exist lies at around 150,000,000 km; by Newton’s laws this in turn corresponds to an orbital period that is our year.  Even if it is not particularly strongly connected to the underlying human biology, a lot of healthcare cycles are aligned to the Earth Year for convenience but is it effective and efficient? Individuals with diabetes are at risk for diabetic retinopathy which can cause blindness and for which… Read More