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 both in reducing progression of neuropathy (and sometime improving it). Read More
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 growing at about ~1% per year while mid-level… Read More
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 population, although described as “mild-to-moderate”, clearly has sustained substantial brain… Read More
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 bleeding. One is left with the impression that perhaps, there… Read More
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 – either routine or after injury… Read More
WMT is in talks with HUM about a relationship enhancement, possibly an acquisition. The two already know how to work together in alliances (narrow pharmacy network, marketing collaborations, points programs). If a new structure is needed, WMT and HUM must be considering a major expansion of scope or a set of operating models where contributions are difficult to attribute and reward (e.g. joint asset builds). What is on their minds? Beyond any interim incremental moves, what could be the endgame? Catching convergence fever Horizontal combinations among the top five health plans have arguably reached the regulatory “permissible envelope.” But provider… Read More
United’s Medicare Advantage footprint and OptumCare network do not overlap much (so far)
United’s OptumCare promises a lot of value for health plans. An integrated system supported by Optum technology should be able to deliver consistent, analytically sophisticated care. Its ambulatory-focused configuration (clinics plus urgent care plus ambulatory surgical centers or ASCs) should keep patients out of high-cost settings through mutually reinforcing referral loops (where it has density[1]). One obvious question is whether United can use OptumCare to materially advantage its own health plans. Is a new, nationally-scaled Kaiser in the offing? If that is its endgame, United has a lot of work to do — at least as far as… Read More
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 PSCK9. It’s as good as one can imagine in defining… Read More
Google’s health insurance apprenticeship: some unicorns (maybe) but no masterpieces
Last month, word got out that Verily is in talks with health plans to “jointly bid” on care management contracts. Medicaid populations might be a reasonable surmised as the target given that (1) managed Medicaid requires bidding, (2) Medicaid contracts typically come in packets of hundreds of thousands of lives (which was the scale mentioned in the press reports) and (3) Verily had been considering (but decided against) bidding on Medicaid contracts using Oscar Health as a partner. It is curious, however, to see an organization seek collaboration with health plan incumbents when its partnered venture arms have invested in… Read More
What precisely lies behind UPMC’s $2B investment in three new specialty hospitals?
Last December, UPMC announced plans to spend $2B on three new specialty hospitals in downtown Pittsburgh. Each will abut an existing UPMC hospital currently serving as system center of excellence for the particular specialty: cancer will be located near Shadyside; cardiac and transplant near Presbyterian; eye and rehab near Mercy. Given inpatient’s declining share in care delivery, any new hospital construction in an over-bedded market with slow-moving demographics is a curiosity. Even if, as UPMC has promised, no net new beds will be added to the market, the new hospitals will still add fixed cost and reimbursement uncertainty (acceptance of… Read More