Why The Corbus Pharmaceuticals Holdings Inc (CRBP) Cystic Fibrosis Results Are Very Positive

Importance of Safety in Anti-inflammatories

What is being overlooked here is the importance of safety in this indication. Safety data is not usually as compelling for investors as efficacy, but in this case safety is a big deal. Both for the CF indication itself as well as for the inflammation target, safety is no shoe-in. Going after inflammation usually means messing around systemically with the immune system, which often causes toxicities. This is what happened to Boehringer Ingelheim and Nivalis Therapeutics, Inc. (NASDAQ:NVLS) with their CF drugs targeting inflammation, and the trials were stopped subsequently.

The numbers for Anabasum, however, showed quite clearly that the drug is safe and tolerable. The numbers were as follows. A small number of discontinuations (3) were judged as related to the study drug, but these were mild in class (one was driven by a lack of motivation, one was a lack of cognitive clarity and one was a decrease in focus) and one of the three was in the placebo arm.

Of the treatment adverse events reported, two were considered related to study drug (dry mouth and cognitive impairment) and neither were particularly serious. The number of TEAEs slightly increased in Anabasum-treated subjects compared to placebo, but the increase was seen in mild TEAEs, not moderate or severe.

Basically, there is no concern about the safety implications of dosing, and this is what the trial was set up to show. Primary endpoint hit.

What About Efficacy?

Of course, in these sorts of studies, investors tend to discount safety and are really looking for any obvious indication of clinical benefit. Anabasum saw that, too, but it wasn’t as obvious as a sharp improvement in FEV1, which we cannot expect to see over the course of only 2 months. The Anabasum arm did however see a sharp drop in the annualized rate of pulmonary exacerbations – basically disease flare-ups – compared to placebo, as follows.

In the second stage of the study with the higher dosing cohort at week 5 and beyond, 16.7% of patients in the placebo arm reported acute pulmonary exacerbations. In the two dosing groups of the active arm, this number was 6.5% and 3.3% respectively. This translates to a 75% reduction in the 48-week rate of acute pulmonary exacerbations for Anabasum at the two highest doses, in a dose-dependent manner.

While this is only a small number of patients, the rate of dose-dependent reduction coupled with the fact that inflammation biomarkers were also reduced in a dose-dependent matter in sputum analysis, makes a causal link here seem likely rather than just a statistical fluke.