Author: Marc Herant

Recon takes an analytical look behind select developments in healthcare

An opinionated take on NEJM highlights for September 2019

Best care vs. good care In wealthy countries, the recommended standard of care can often lead to complex medication regimens requiring frequent follow-ups: this can be very challenging for people who though they live in wealthy countries but are poor themselves. In developing countries, efforts have been made to prioritize simplicity and population level impact through one-size fits all polypill interventions, but that has not been tested in the US. Here the authors report on a randomized study including 303 individuals living in poverty and at risk for cardiovascular disease.

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Busy summer: An opinionated take on NEJM highlights for July/August 2019

Is the lack of new (non-viral) antibiotics a market failure? A lament about the lack of success in getting the biopharma industry to invest sustainably in the development of new antibiotics against highly-resistant organisms, and a recommendation “it is time to seriously consider the establishment of nonprofit organizations for developing these lifesavings drugs”.  Let’s be clear; the reason economic viability of this therapeutic area is problematic is due to three confluent factors: (1) treatment is curative – i.e. does not provide recurrent revenues (2) the targeted population is small (3)

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Fishing for nucleic acids: An opinionated take on NEJM highlights for June 2019

Huntington’s disease: light at the end of the tunnel? The awful thing about Huntington’s is that in most cases, people know they are going progressively lose their mind at an early age, but there is absolutely nothing they can do about it.  Recently there has been tremendous excitement around suppressing toxic huntingtin production in the brain by using antisense oligonucleotides (ASOs) administered intrathecally (i.e. in the cerebrospinal fluid through the spine). Two ASOs are in full blown clinical testing: HTTRx (Ionis and Roche) which does not discriminate between mutant and

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Full-service vs. self-service: an emerging bifurcation in healthcare

A clinical vignette: the cases of Jane and Joe Imagine if you will two individuals both at age 50. Jane is a project manager whose recent health care has focused on managing menopausal symptoms, a knee injury sustained while skiing, and moderate episodic depression, with a medication list of one chronic medication, and one medication as needed.  Joe is a bus driver whose recent health care has focused on managing Type II diabetes, hypertension, and low back pain, with a regimen of 4 chronic medications, and 2 medications as needed.

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An opinionated take on NEJM highlights for May 2019

TAVR for all? TAVR has become the standard of care for patients who need an aortic value replacement but are at high/medium surgical risk.  But what about those at low-risk? Two studies answer that question, one with the Edwards device and the other with Medtronics. Both show that TAVR is superior along a number of end-points (stroke, hospitalization duration, atrial fibrillation) both at 30 days and at 1-2 year. Long-term outcomes remain a question though. Low-risk patients are younger (mean age 73-74) and will live with their valves longer, which

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It’s in the brain: An opinionated take on NEJM highlights for April 2019

He’s dead, Jim As previously widely advertised, the BACE-1 inhibitor verubecestat (Merck) (and in journal correspondence atabecestat, Janssen) has now failed in a population with very early signs of cognitive impairment (this after a failure of those agents in mild-moderate Alzheimer’s). Target engagement clearly occurred with a decline of the amyloid detected through PET imaging in the treatment arms and an increase in the placebo arm. However, if anything, cognition declined more in the treatment arm than in the placebo arm after 2 years on study. A silver lining is

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An opinionated take on NEJM highlights for March 2019

Target assessment with genetic polymorphisms Please bear with me for a long (but interesting!) story. Bempedoic acid (Esperion) is an inhibitor of ATP citrate lyase (ACLY), an enzyme in the cholesterol synthesis pathway (upstream of HMG-CoA reductase, the target of statins). In a study of 2,230 patients at high risk for cardiovascular events, on maximum statin therapy, and LDL > 70 (basically the PCSK9 target population), bempedoic acid was well tolerated and lowered the LDL by around 16% – a substantial effect. This would potentially position bempedoic acid, an oral

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February was short and cold: An opinionated take on NEJM highlights for February 2019

Targeted conjugated cancer therapeutics – so few, but may be more soon The idea that one could combine the precision of a targeted biologic with the potency of a traditional cytotoxic to demolish a tumor has been around for decades, but with very rare exceptions, has not had the level of traction one would have expected.  But this month, the journal has two studies reporting on these types of therapies, both in breast cancer. One shows that in a group of heavily pre-treated triple-negative breast cancer patients, sacituzumab govitecan-hziy (Immunomedics)

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Methods towards better care: An opinionated take on NEJM highlights for January 2019

The bundle Unlike many other CMMI experiments, the Comprehensive Care for Joint Replacement (CJR) program was a true randomized control trial in that participation was mandatory in a selection of metropolitan areas and not allowed anywhere else, which allows for an analysis untainted by self-selection bias. In brief the question to be answered was does a 90-day bundled payment for a joint replacement (knee/hip) get better value (improved care and/or lower costs) than the traditional FFS approach? A differences of differences analysis comparing the bundled vs. control arms before and

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On the uses of genetic information in disease: An opinionated take on NEJM highlights for December 2018

Genetic trade secrets In 2012, the US Supreme Court decided a case known as “Prometheus” establishing that therapeutic methods based on biomarkers were not patentable – this essentially blocked one of the two main avenues to monetizing intellectual property from the very hard clinical work of figuring out personalized medicine, i.e. what works for whom. The other avenue that would remain is that of trade secrets, and I for one, have been waiting for the other shoe to drop.  A hint comes from a study on ovarian cancer just published

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Eating your way out of disease: An opinionated take on NEJM highlights for November 2018

Peanut medicine that won’t cost peanuts Allergy to peanuts is a major issue and though prevention is now possible in infants there is a huge population for whom actual survival is connected to vigilance in what they consume and availability of epi-pens. Desensitization to allergens is a well-established method to overcome an allergy, but it is typically done through injections, and it requires well calibrated micro-doses of the allergen.  Aimmune has been pursuing an oral approach with progressive dosing with peanut protein (AR101) and in a phase 3 trial, two

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T-cells are everywhere: An opinionated take on NEJM highlights for October 2018

One century after the use of convalescent serum, convalescent T-cells The use of tailored T-cells (e.g. CAR-T) is transforming our approach to (blood) cancers, but what about using T-cells against their raison d’être, intracellular pathogens such as viruses?  JC virus is the cause of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease of the brain triggered by immunosuppression commonly occurring during cancer or auto-immune disease therapy. In a series of three consecutive patients with PML, scientists from MD Anderson infused in the spinal fluid T-cells that had been selected and expanded

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An opinionated take on NEJM highlights for September 2018

Primary care organizations are better ACOs when it comes to achieving savings Initial results from the Medicare Shared Savings Program ACO have been disappointing pointing to small to negligible net effects on net spending, but a clever analysis digging into the details shows that there is a silver lining. The key insight is to distinguish between ACOs that are health systems and those that are physician practice groups: health systems show no net savings (after bonus incentive payments) while physician group ACOs do. In the physician group ACOs, the savings

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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

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What’s harder, making new drugs or improving care delivery at scale? An opinionated take on NEJM highlights for July 2018

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

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An opinionated take on NEJM highlights for June 2018

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

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Struggling: An opinionated take on NEJM highlights for May 2018

One more on the chin for Alzheimer’s A report of a large phase 3 study of the highly potent oral BACE inhibitor verubecestat (Merck) with yet again a lack of therapeutic effect, despite a dramatic reduction of the cerebrospinal fluid content of beta amyloid in various forms.  With a string of prior failures, this may be the near final blow for amyloid as a treatment target for Alzheimer’s disease (and Biogen’s adacanumab would be the end of the line if it also comes up tails). But note that the study

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An opinionated take on NEJM highlights for April 2018

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

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Disease as an information defect

One way to think about disease[1] is as a loss of information[2] from the operating blueprint for human physiology.  Broadly speaking, there are three main possible types of informational defects depending on the nature of the informational encoding that is compromised. The first is genetic through loss of information due to corruption of the genetic (and sometime epigenetic) code, for instance in congenital disease or in cancer. The second is spatial through loss of architectural information due to cumulative changes away from a structural template. This prevents turnover of tissue

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EHRs + Genomics = Drugs? – An opinionated take on NEJM highlights for March 2018

GWAS, Regeneron and Geisinger, and liver disease Genome wide association studies (GWAS) look at broad populations for gene variants associated with a particular phenotype. Often, like in Type II diabetes, one finds hundreds of genes correlated with disease, and that’s obviously not very helpful. In lucky cases there are only a few variants, and that gives clues on potential underlying mechanisms of disease. But for the very lucky, there is a jackpot which is finding a variant that is actually protective against the disease – this is what happened with

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