For those of you interested in the brouhaha about the widely reported remdesivir (RDV) positive results, my amateur take is that it’s maybe a “bunt base hit,” certainly not a home run. In some of the sicker patients it reportedly did shorten the hospital stay, from an interim analysis of a trial still on-going with ~ 1000 pts, not published yet. Anyway, here’s the NIH press release Apr 29, from the Nat’l Inst Allergy/Inf Disease (click on the highlighted text to get to the webpage). As the trial sponsor, they chose to release results from their independent data and safety monitoring board.
The NEJM did publish, Apr 10, 53 patients who were analyzed on the “compassionate use” program, i.e. not on a clinical trial, and no control group. There were no endpoints, as one expects in a clinical trial study, but they did log a lot of measurements. Interesting to me was this figure, 3C above, which does show “clinical improvement” (decreased O2 requirement, etc) by age, but that it takes awhile (maybe weeks) to really see clinical improvement. These are very small numbers, but to get to 50% of patients improved in those <age 50 was about 11 days, but for those >age 70, more like 28 days.
In contrast, The Lancet did publish (Apr 29) a double blind randomized control study of remdesivir, 237 patients in the Wuhan area of China, drug supplied by the company but the study funded through the Chinese health system, with a non-statistical advantage for the drug (I think they used a similar improvement score, and they mention improvement); the trial was stopped because people were not getting as sick in Wuhan! [the best reason ever to stop a trial!?!] Technically, it’s “underpowered” for not meeting study accrual goals, but still a negative study:
[Wang Y et al, The Lancet, Fig 2. https://doi.org/10.1016/S0140-6736(20)31022-9, Open Access]
The Lancet also published a commentary on how to interpret this study: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31023-0/fulltext
FDA has now (May 1) approved emergency usage of RDV for COVID-19, along with a fact sheet, which is a “package insert” type of document.
COVID-19’s severity happens so fast that it may allow faster evaluation cycle, and perhaps RDV could be a component for combination trials. Just to put a cancer spin on it, the advent of chemotherapy (Farber, Diamond et al in childhood leukemia , 1948) increased survival, but only by a few months. We now think we durably cure >90% of kids with childhood ALL, but it takes multiple drugs, over a few years, proven in combination trials.
The devastating speed of the infection is a contrast to the slower pace of deterioration in most dementias, especially Alzheimer’s. But the approach to the clinical problem also seems different: the infection was just given a name about six months ago, yet clinicaltrials.gov lists 289 recruiting interventional clinical trials for COVID-19, while there are only 276 listed for Alzheimer’s or dementia.
The COVID trials list things from estrogen patches to monoclonal antibodies with “play-the-winner” trial design. The point is, Alzheimer’s / dementia has been called a multi-national “pandemic” in the past, but the COVID-19 pandemic has brought on a whirlwind of all sorts of creativity and broadly based outside the box thinking.
The most immediate concern for dementia patients, of course, is prevention from infection. If the pandemic plateaus or even diminishes, are there clinical trial or creative intervention lessons to be learned, to move dementia therapeutics forward, or will the field remain status quo for even more years?