Tag: oncology

Recon takes an analytical look behind select developments in healthcare

Some very disappointing failures: An opinionated take on NEJM highlights for August and September 2022

Is Parkinson’s α-synuclein going to be as elusive a target as β-amyloid has been for Alzheimer’s? Alpha-synuclein aggregates are characteristic of Parkinson’s disease and genetic variants of this protein clearly lead to familial forms of Parkinson’s; it was therefore reasonable to target alpha-synuclein with antibodies in the hope of modifying disease progression. Sadly, two well designed placebo-controlled studies have now crushed this hope. Both showed absolutely no impact on the progression of patients with early Parkinson’s over times that extended to 1.5 year of follow-up. If there is silver lining,

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Trends in oncolytic virus therapeutics: then and now

PDF: Trends in oncolytic virus therapeutics: then and now The idea of using pathogens to treat disease is not new; ranging from phage therapy to malariotherapy (resulting in the only Nobel in medicine to a psychiatrist – in 1927), but it was really only with the onset of the biotech revolution in the 1990s that an old concept of using viruses as tumor killing agents started to come into its own.  As the ability to characterize viruses at the genetic level grew, it was followed by the techniques to genetically modify

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An excellent July vintage: an opinionated take on NEJM highlights for July 2022

Tirzepatide in pole position As previously described in this blog, GLP-1 agonists initially designed to treat glycemia in Type-2 diabetes are emerging as powerful weight loss agents in obesity independent of diabetic status. Recently, tirzepatide (Mounjaro, Lilly, approved May 2022) which combines GLP-1 and GIP activity has shown potential to be best in class, and this is supported by a 72-week study that randomized 2539 obese individuals to 3 different tirzepatide doses or placebo. The results are nothing short of spectacular with ~-21% mean change in weight at the optimal

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An opinionated take on NEJM highlights for June 2022

A cell therapy success against a solid tumor In CAR-T therapies, T-cells are transformed to express an antibody on their surface that allows them to home in on cancer cells and effect killing. This approach has seen remarkable successes in hematological tumors but not so much in solid tumors. However, efforts have been underway to use the intrinsic killing mechanism by T-cells which relies on the native T-cell receptor. The idea is that instead of inserting an antibody construct (i.e., the CAR-T approach), the T-cell receptor is modified to be

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An opinionated take on NEJM highlights for March-April 2022

The opioid crisis and patient abandonment A perspective from a February issue that I originally missed highlighting the plight of patients who have been on a long-term opioid regimen for chronic pain. They are often stable, but it is when their physician retires or leaves that all hell breaks loose because, in this day and age, they cannot find another physician to continue the regimen. For someone who has been taking large doses of opioid for many years, going cold-turkey, or even tapering, is just not an option. These folks

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The coming site-of-care shock for infusions

There’s a major disruption looming in how the site-of-care for infusions is managed which will have repercussions for plan competition, delivery system economics, PE hunting for healthcare opportunity and biopharma commercialization strategy. Plans have long been frustrated by the growth of infusion care in expensive hospital outpatient department (HOPD) settings. HOPD infusion services can cost health plans on average 70% more than a physician office for the same infusion. But because patients on infusion therapy are often very sick and the therapies hard to tolerate, plans have historically been reluctant

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Summer catch-up: an opinionated take on NEJM highlights for May-July 2021

Cancer and mutational complexity Probably the biggest news in cancer treatment this year is the approval of sotorasib (Lumkras, Amgen) which received accelerated approval in lung cancer with mutated KRAS (G12C) and has potential for use in other cancers (see here). Mirati is hot on the trail with adagrasib, but unusually for a drug in the approval process, their paper in the NEJM is a deep dive into the mechanisms of resistance to KRAS G12C inhibition that lead to treatment failure. They present very detailed in vitro studies in which

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All immunity: an opinionated take on NEJM highlights for February 2021

We can cure Hep C but not immunize against it Sovaldi and other drugs have made curing chronic Hepatitis C a routine, if expensive, proposition. Still, given how common Hep C infection is, and how it can irreversibly damage the liver without overt signs, a vaccine would be highly valuable. Unfortunately, an NIH sponsored trial with a GSK vaccine in 548 IV drug users at high risk of contracting the disease failed to show any protection: 28 participants developed chronic Hep C evenly divided between the placebo and treatment groups. 

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We are back and catching-up: An opinionated take on NEJM highlights for Sep, Oct, and Nov 2020

Small but real progress in ALS: Despite enormous public attention and significant effort, ALS remains a disease for which the development of new therapies has been challenging. Animal models showed potential activity against ALS by sodium phenylbutyrate and taurursodiol, both old (generic) molecules. Now, their effect in combination therapy has been confirmed in a randomized controlled trial.  What’s especially interesting is that the effect at 24 weeks (the original duration of the trial) was a modest though statistically significant improvement in functional scores. However, the trial was extended with all

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An ADC renaissance: a resurgence of antibody drug conjugates for cancer

PDF:  An ADC renaissance: a resurgence of antibody drug conjugates for cancer Summary: Antibody-drug conjugates (ADCs) have seen a record number of approvals in 2020. This comes after a first era of intense activity in the early 2000s followed by a period of relative quiescence from the late 2000s to mid-2010s. To understand how the nature of the ADC pipeline has changed over time, we have reviewed all 88 ADC oncology programs that have reached phase 2 development and beyond from 1997 onward. We found that, currently, the main contributor

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Covid, iPSCs, and ADCs: An opinionated take on NEJM highlights for May 2020

Remdesivir works… but not enough to change the public health perspective The eagerly awaited results of the remdesivir NIH trial are out, and it’s solid but not smashing, although this is a partial read since the study was interrupted before completion because of evidence of benefit (and we should get more data in the coming months).  Overall, the primary end-point of faster improvement in the treatment group was met while mortality showed a benefit that was just short of statistical significance. Also important is that remdesivir is clearly safe. But

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An opinionated take on NEJM highlights for October 2019

Genomic applications and scalability Two very different papers about applications of genomics, one for a very common clinical scenario, the other for an ultra-rare disease. It is well known that while clopidogrel (now available as a generic but branded as Plavix) is an excellent antiplatelet agent for a majority of patients, it works poorly in some due to individual genetic idiosyncrasies of cytochrome driven drug metabolism. Since then, other agents (tigracrelor AKA Brilinta, prasugrel AKA Effient) with a similar mechanism of action but more consistent metabolism have come on market,

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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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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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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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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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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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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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