Author: Marc Herant

Recon takes an analytical look behind select developments in healthcare

Two steps forward, one step back: an opinionated take on NEJM highlights for January 2018

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

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A golden age for gene therapy: an opinionated take on NEJM highlights for December 2017

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

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Gene therapy, headaches, and tattoos: an opinionated take on NEJM highlights for November 2017

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

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Between the very common and the very rare – An opinionated take on NEJM highlights for October 2017

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

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An opinionated take on NEJM highlights for September 2017

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

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Price, costs, value, and rules: An opinionated take on NEJM highlights for August 2017

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

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An opinionated take on NEJM highlights for July 2017

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

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June was negative-to-ambiguous: an opinionated take on NEJM highlights for June 2017

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

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An opinionated take on NEJM highlights for May 2017

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

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April was a light month: an opinionated take on NEJM highlights for April 2017

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

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A population health approach to value-based drug pricing

Working Paper   Summary Drug companies are naturally incentivized to price their drugs under assumptions of optimal clinical value, i.e. as high as possible.  Payers react to this by setting stringent conditions for patient eligibility for coverage of those therapies. As a consequence, patients who do not meet these conditions do not receive those drugs even though they could derive benefit, albeit not of a magnitude that would justify the cost.  Here we lay out a population health based scheme by which payers and drug companies can design a system

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Regeneration and mitigation: an opinionated take on NEJM highlights for March 2017

Gene therapy for sickle cell disease Typical diseases targeted by gene therapy are those for which there is a defect that prevents the production of a functional protein needed for normal life; remediation is achieved by inserting functioning copies of the gene, and fortunately, it is usually the case that expression at a low level is sufficient to greatly improve outcomes. The situation is different in sickle cell where the defective hemoglobin is actually harmful, and where success of gene therapy requires not only production normal hemoglobin, but replacement of

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It’s in the blood: an opinionated take on NEJM highlights for February 2017

A knock at the door of a monster franchise Adalimumab (Humira, Abbvie) is the best-selling drug on the planet with the bulk of sales coming from patients suffering from rheumatoid arthritis (RA). It is therefore quite a coup for Lilly/Incyte to have shown in a double blind controlled study that baricitinib, an inhibitor of JAK (an important intracellular signaling molecule), performed better in relieving the symptoms of patients with RA than adalimumab. It was all the more surprising given that another JAK inhibitor, tofacitinib (Xeljanz, Pfizer, now also approved for

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Keeping the pipes clean and the wires intact: an opinionated take on NEJM highlights for January 2017

An innovative modality to suppress PCSK9 Antisense technology relies on the concept that it is possible to interfere with the cellular genetic machinery in very specific ways by deploying short RNA sequences that are complementary to the message that one wants to suppress. The idea has been around for a while, but has only achieved limited success in very niche indications (see here for the two latest). This is what makes the publication of phase 1 trial of the antisense agent inclisiran (Alnylam and the Medicines Company) targeting the synthesis

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A strong close to a banner year for progress against cancer: an opinionated take on NEJM highlights for December 2016

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

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We may figure out cancer before we figure out the healthcare system: an opinionated take on NEJM highlights for November 2016

“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

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An ad page in the NEJM and the future of cancer care

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

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An opinionated take on NEJM highlights for October 2016

Continued progress in multiple myeloma About 25,000 patients are diagnosed with multiple myeloma yearly in the US. Despite being initially treatable, typically this disease is ultimately lethal. Following a highly successful phase 1-2 study a monoclonal antibody against a marker of myeloma cells (daratumumab, Janssen) underwent phase 3 studies in combinations with established mainstays of therapy (the proteasome inhibitor bortezomib and the immune modulator lenalinomide) in a patient population several years out from their initial diagnosis.  Results were stellar, with the inclusion of daratumumab decreasing the disease progression rate by

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An opinionated take on NEJM highlights for September 2016

Taking a page from HIV to build a response to opioid abuse A couple of perspectives on the challenges of treating individuals who suffer from opioid dependence. The first highlights the importance of integrating medication assisted treatment (e.g. methadone or buprenorphine) into hospital and post-hospital care – plausibly an ED visit or a hospital stay for an event triggered by opioid abuse (such as an overdose) is a significant opportunity to go beyond treating the acute issue and starting patients on long term treatments. In the second, the author recalls

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An opinionated take on NEJM highlights for August 2016: cleanliness is not next to healthiness, testing before thinking, a long slog for precision medicine

There is such a thing as too much hygiene The prevalence of asthma in children has increased dramatically over the last few decades. Observational studies have shown that children in “dirty” environments such as farms seem to be relatively protected from asthma.  A theory is that the lack of exposure to microbes leads to higher sensitivity to allergens, but this causality has been hard to show. Amish and Hutterite farm communities are genetically similar, but Amish rely on animals instead of machinery, and Amish children have much lower incidence of

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