Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

It’s been looking for some time as if these coronavirus infections need a biphasic approach to therapy – an antiviral approach earlier on, and for those in serious trouble, perhaps a shift to immune modulation as the body’s reaction to the virus starts doing even more harm. That post goes into some detail on possible therapies targeting IL-6 for this purpose, and today we finally have some clinical data on the idea. Prepare yourself, if you are one of the many people who haven’t had experience with investigational therapies but are watching to see how things play out with the pandemic. Because this is another one of those cases that will make you wonder what’s going on.

There’s an antibody against the IL-6 receptor from Roche/Genentech, tocilizumab (brand name Actemra), and this morning came preliminary word from France that the CORIMUNO-TOCI trial had produced positive results. This was in patients who had “moderate to severe” disease but were not in the ICU: 65 got standard of care, and 64 got standard of care plus tocilizumab (but note: the trial, although it has a control group, was open-label). The press release says that both deaths and the need for later ventilator support were “significantly reduced” in the treatment group, with no more adverse effects than in the control group.

The French team is also studying tocilizumab in patients in intensive care, and they’re looking at another approved antibody to the IL-6 receptor as well, sarilumab (brand name Kevzara) from Sanofi and Regeneron. These two drug are both given for rheumatoid arthritis, with the same mechanism of action, but every antibody is a different beast. For example, tocilizumab is given i.v. and sarilumab is subcutaneous, so they have different pharmacokinetics right from the start.

And those results are certainly going to be interesting, because we have the results of a separate study on sarilumab this morning where it was shown to be almost completely ineffective. There had been an earlier report from China of efficacy for the drug, albeit in a small trial without a control group – and if there’s one thing that people should take away about drug discovery from this whole pandemic experience, it’s that small uncontrolled trials cannot prove anything. All they can do is to point to something that might be interesting to study for real, and you should be ready for most such signals to turn out to be noise.

In the Sanofi-Regeneron trial, patients got either standard of care, standard of care plus 200 mg of sarilumab, or standard of care plus a 400 mg dose. The patients were classified as either “severe” or “critical”, and the severe patients were not helped at all by either dose. In fact, there was some worry that they had done even worse on the drug than in the control group, but as more data came in it appears that sarilumab was merely useless. For the critical patients, though, there was a slight trend towards better outcomes in the treatment groups, especially in the higher-dose group, but the results weren’t statistically significant (and thus could be more noise).

We’re going to get more data to resolve this: Roche is running its own controlled trial of tocilizumab in coronavirus patients, and as mentioned, the French study is also looking at sarilumab. Is there such a dramatic discrepancy in the two drugs? And if so, is due to different sorts of patients being recruited in each trial or is it just that there is some weird split in activity between the two different antibodies? How good are the tocilizumab data from the open-label French study in general? And so on.

Welcome to the clinic, folks. This kind of stuff happens all the time; it’s not just with the coronavirus. What we do have is a lot more data, of widely varying quality, hitting with greater frequency with (understandably!) a lot more attention being paid to it. But this is how it goes, even when it’s just us biopharma people scratching our heads.