I’ve been meaning to write about what has to be called a regulatory mystery. Eli Lilly obtained an Emergency Use Authorization for its monoclonal antibody (bamlanivimab) against SARS-Cov-2, but (as detailed in this post) the dosage that they applied for was 700mg. Which is one-quarter of the dose that showed any efficacy against the primary endpoint in the actual clinical trial. The approved 700mg dose did not reach statistical significance (nor, it should be said, did the even-higher 8g dose) in lowering viral loads at day 11 vs. placebo.
Here’s BioCentury on this, which has to be the only EUA ever granted for a dose that failed in the clinic. To be sure, the company has said that there was no difference between the three doses on various secondary endpoints, and in fact says that they’re not sure that they’ve found the lowest effective dose yet. The FDA’s Janet Woodcock has said the same thing. That’s definitely looking on the bright side, but it suggests that the original endpoint in the trial was either too optimistic or aimed in the wrong direction, doesn’t it?
The best spin I can put on this is that perhaps the viral loads (the primary endpoint that failed) are not well correlated with later hospitalizations (where there was a significant difference). In that case, it may be that those hospitalizations have more to do with the immune over-response to the virus than they do with the virus itself, although that’s sheer speculation on my part. But it seems clear that the mAb treatment needs to be aimed at people who are at high risk, particularly those who don’t seem to be mounting a good antibody response on their own. In that population, I think Lilly’s therapy (and Regeneron’s two-mAb cocktail) could do some real good, but that’s definitely a smaller subset of the total coronavirus population,
Not that we have enough of the mAbs to treat the total coronavirus population, anyway! The government has contracted to buy 300,000 doses of bamlanivimab this year, and Lilly is supposed to be shipping 80,000 doses this week. We just had 163,000 cases reported yesterday, to put that in perspective. Now, it’s for sure that not all of these people would be getting a monoclonal antibody, even if we had barrels of it sitting around, but there’s clearly a need for targeting the supplies we do have. I’m not sure how that’s to be done, though: you want to catch people early in the infection who are having trouble mounting a vigorous antibody response, but how many people are being tested in a manner (that early on) to pick that up? I really don’t know, and so far I haven’t seen any information addressing this issue. But it’s surely something that’s being worked on now that the mAb is starting to appear – I’ll update as the situation becomes clearer.