Martha Deja and Marc Herant, Martha Deja, Marc Herant, Author at Recon Strategy

Working paper: Incentivizing progress, even if small and incremental, in therapies for Alzheimer’s disease should be a priority

Marc Herant October 22, 2024

Summary: Over the coming decades, Alzheimer’s disease threatens to become a huge drag on national well-being. To put things in perspective, by 2040, the US may be allocating more resources to the care of Alzheimer’s patients than care and education of children. Unfortunately, we are not likely to find a therapeutic “silver bullet”; progress will most probably take place in incremental steps as is the case with the latest A-beta directed therapies. Because of the potential modest benefit of new individual therapies, one could reasonably argue to place stringent limits

An opinionated take on NEJM highlights for the third quarter of 2024

Marc Herant October 2, 2024

The new Humira? It’s not that often that you see industry-sponsored head-to-head studies of one biologic vs. another, but Abbvie took the plunge comparing risankizumab (Skyrizi) to ustekinumab (Stelara, J&J) a leading therapeutic for Crohn’s disease, a notoriously hard indication because of its unpredictable manifestations. The risk paid off for Abbvie: a significant advantage was seen for risankizumab which provided clinical remission in 60.8% of patients. Abbvie probably had no choice: ustekinumab biosimilars are expected on the market by 2025; absent a clinical advantage, most payers would have demanded patients

A Kaplan-Meier view of oncology development

Marc Herant August 8, 2024

We refresh a prior analysis of two cohorts of oncology development programs: one with first-in-human (FIH) in 2012, and the other with FIH in 2017H2. We use a Kaplan-Meier approach to track whether programs have reached either of two final outcomes: a first approval from FDA, or a discontinuation of development. We find again that programs from commercial pharma reach final outcomes much faster than those from early-stage biotechs, which likely reflects a mix of a higher operational resourcing and efficiency, and more portfolio prioritization rigor. Beyond other specific findings,

An opinionated take on NEJM highlights for the second quarter of 2024

Marc Herant July 1, 2024

The quest for solid tumor CAR-T For all their success in hematological cancers, the track record of CAR-Ts against solid tumors has been disappointing (though see here for an exception). One key obstacle has been access by CAR-Ts to the tumor site. Here, a Mass General team reports on their experience treating 3 patients afflicted with glioblastoma multiforme (GBM, a nearly always fatal brain malignancy) positive for a variant of the EGFR receptor. In each case they prepared (autologous) CAR-Ts against the EGFR variant, and delivered them directly into the

An opinionated take on NEJM highlights for the first quarter of 2024

Marc Herant April 2, 2024

Hitting reset for the immune system Every time I get into a new issue of the NEJM, I have a sense of anticipation as in “will this one have an article that blows my mind?” It doesn’t happen very often, perhaps once or twice a year, but when it does, it’s an awesome feeling. From Germany, an application of CAR-T (CD19 directed) therapy to severe autoimmune disease reporting on 15 patients, 8 with severe SLE with renal involvement, 3 with myositis, and 4 with scleroderma, all progressing despite treatments with

Trends in biotech deals in 2022 and 2023: oncology vs. the rest

Marc Herant February 7, 2024

Summary After challenging conditions in 2022, deal-driven biotech spending appears to have picked up in 2023. To quantify this trend we have systematically reviewed deals announced during this period and examined differences based on therapeutic areas and stage of development. We find that (1) deal counts shrank in oncology compensated by growth in other TAs; (2) the decrease in number of oncology deals was largely driven by less appetite for earlier phase assets, whereas compensated growth in other TAs came from the same earlier stages of development, (3) across the

An opinionated take on NEJM highlights for the fourth quarter of 2023

Marc Herant January 3, 2024

A Chinese study uncovers a new use for an old drug Bleeding in the small intestine is often due to vascular malformations and is difficult to diagnose and manage because 1) the area is hard to reach with a scope and 2) bleeding tends to be intermittent. Existing approaches are cumbersome and far from satisfactory, which makes a recent blinded RCT study conducted in China exploring thalidomide use in those patients valuable – not only did it show a significant decrease in bleeding episodes after a course of 4 months

An opinionated take on NEJM highlights for the third quarter of 2023

Marc Herant October 2, 2023

How the US taxpayer saved 25M+ people A short piece celebrating the 20th anniversary of PEPFAR, a program that few outside of the field of Global Health are aware of. The world is not always nasty and brutish – it’s a shame it’s not said a bit more often. PEPFAR at 20 — A Game-Changing Impact on HIV in Africa A hypertension trend? A second study of an investigational antihypertensive drug in the Journal this year; are we back in the 80s or something? Joking aside, cardiac and vascular

An opinionated take on NEJM highlights for the second quarter of 2023

Marc Herant July 3, 2023

Preparing for the next pandemic: don’t waste the value of waste During the Covid-19 pandemic, I got in the habit of checking weekly the Boston sewage report, as a reliable, unbiased way of monitoring trends of infectious activity. There is clearly much more information to extract from waste monitoring and a recent report from the National Academies of Sciences, Engineering, and Medicine makes a number or recommendations. The CDC is implementing some of them, but in the end, exploiting this source of information will depend on 100s of local actors

Trends and strategy in oncology development

Marc Herant May 15, 2023

PDF: Trends and strategy in oncology development Summary We review a sample of oncology programs from the past decade and arrive at the following key findings: The use of expansion cohorts in first-in-human (FIH) studies has grown significantly in the last decade, with an accompanying decrease in separate phase 2 studies Commercial-stage sponsors and early-stage companies backed by established VCs are much more aggressive in discontinuing programs quickly compared to other early-stage companies For drugs that achieve approval, the time from FIH to approval is much shorter for big pharma

An opinionated take on NEJM highlights for the first quarter of 2023

Marc Herant April 20, 2023

Hypertension?! Antihypertensive drugs are so 80s and 90s (well, except for pulmonary hypertension) to the point that I cannot recall when I last read research in the NEJM about a new blood pressure drug. One of the reason is that we have so many existing drugs (most of them cheap generics) but despite this, a fraction of hypertensive patients are refractory and cannot get to their blood pressure goal despite using multiple agents. This is where baxdrostat (CinCor Pharma) comes in; it is an oral drug blocking the synthesis of

An opinionated take on NEJM highlights for December 2022

Marc Herant January 4, 2023

An unusual article on road safety Motor vehicle accidents are a major share of morbidity and mortality in the young, and as such prevention has long been considered a medically adjacent area (e.g. with pediatricians asking about infant car seats etc.). Still it was a surprise to see an article on an intervention specifically designed to improve road safety in the NEJM, but it applies specifically to teens with an ADHD diagnosis, for whom distraction while driving is a significant risk factor. In the study, 152 teen drivers with ADHD

Hearts and souls: An opinionated take on NEJM highlights for October and November 2022

Marc Herant December 4, 2022

A psychedelic for refractory depression While major depression is awful, treatment-resistant depression (as defined not responding to at least two different courses of therapy) is worse with sufferers stuck in a long dark tunnel of anguish without a light at the end of it. Since psilocybin (the psychedelic agent in so-called magic mushrooms) has shown some effectiveness in depression, it seemed reasonable to test its differentiated mechanism of action in this high need patient population. In this study that was mostly Europe-based but included sites in the US (finally), patients

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

Marc Herant October 2, 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,

Trends in oncolytic virus therapeutics: then and now

Marc Herant September 26, 2022

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

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

Marc Herant August 1, 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

An opinionated take on NEJM highlights for June 2022

Marc Herant July 1, 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

An opinionated take on NEJM highlights for May 2022

Marc Herant June 2, 2022

A step forward for kidney xenotransplantation A report on the recent, well-publicized, temporary transplantation of kidneys from genetically modified pigs in two deceased individuals at NYU. The kidneys functioned well and there was no sign of acute rejection, but because these experiments took place over only 54 hours, this is not indicative of longer term compatibility of the transplant of kidneys from this particular strain of pigs. A question in my mind is why there have not been kidney xenotransplants in live patients yet – especially given a recent porcine

An opinionated take on NEJM highlights for March-April 2022

Marc Herant May 1, 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

The growth of small molecule drug classes over time

Marc Herant April 8, 2022

Modern drug discovery is largely based on the identification and validation of a biochemical target, and then screening and optimizing molecules that engage that target. Over time, this has given rise to an extensive set of small molecule drugs approved for human use with activity at specific biological targets. We wanted to answer the question of how many different targets are addressed by existing agents, and how the rate of addition of newly addressed-target has varied over time. To do this, we reviewed every small molecule drug approved since 1970

Author: Marc Herant

Recon takes an analytical look behind select developments in healthcare