Mitigating the harm of influenza pandemic is certainly an important endeavor. Despite the clinical importance, however, we’ve simply been kicking the oseltamivir can down the road for over a decade. Given the ongoing controversy over its usefulness, this is suboptimal – and winter, of course, is coming.
The newest agent to the scene is baloxavir marboxil, being developed in Japan. Baloxavir is a selective inhibitor of influenza endonuclease, rather than a neuraminidase inhibitor like oseltamivir. This recent article details the phase 2 dose-ranging study and subsequent phase 3 placebo and oseltamivir-controlled trial, CAPSTONE-1.
There were 1,436 patients enrolled in CAPSTONE-1, 1,064 of whom were ultimately confirmed to have influenza A or B. Most of the patients (~85%) had influenza A. The results are – well, “favorable”, by which I mean most likely “profitable”. Symptom duration in the infected population was attenuated by the the same length of time as oseltamivir, which in turn was about a day shorter than placebo. Various measures of viral expression were improved by baloxavir, which seemed to virtually eliminate detectable infective activity within the first 24 hours. There were a small number of extra treatment-related adverse events in the baloxavir cohort, but there were only a handful in each cohort overall, and it remains to be seen in further surveillance the true incidence.
As anyone who has been afflicted by influenza can tell you, a day’s shorter illness is no small feat. of course, this is just a single, sponsored trial, with all the advantages to the “home team”, as it were. Whether treatment with baloxavir can be demonstrated to decrease clinically important deterioration remains to be seen – as has been a persistent struggle for other antivirals, given the low rate of complications, overall. Then, even with rigorous screening, a third of those treated did not have influenza. Real-world use would almost certainly include a greater proportion of patients without influenza. Lastly, baloxavir-treated patients were observed to develop resistance mutations in substantial numbers, leading to questions whether this medication will provide durable efficacy in widespread use.
“Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents”
https://www.nejm.org/doi/full/10.1056/NEJMoa1716197