But so what? What’s the big deal about pulmonary exacerbations? The trial protocol said little about these as an endpoint, so how do we know that Corbus Pharmaceuticals Holdings Inc (NASDAQ:CRBP) isn’t just massaging the data and pulling something new out of its hat with some clever misdirection?
Because FEV1 is closely correlated to the amount, frequency, and severity of pulmonary exacerbations. If FEV1 decline is the effect, exacerbations are the cause. A 2010 study published in the journal Pediatric Pulmonology for example concluded as much:
THERE IS A STRONG ASSOCIATION BETWEEN THE FREQUENCY OF PULMONARY EXACERBATIONS AND SUBSEQUENT DECLINE IN PULMONARY FUNCTION. IN ADULTS, HAVING 3+ EXACERBATIONS, AND AMONG CHILDREN, HAVING ANY EXACERBATIONS IS ASSOCIATED WITH A GREATER RATE OF DECLINE IN THE ENSUING 3 YEARS. IMPROVED PREVENTION, IDENTIFICATION, AND TREATMENT OF PULMONARY EXACERBATIONS ARE LIKELY TO HAVE LONG-TERM BENEFITS FOR PATIENTS WITH CF, ESPECIALLY CHILDREN.
Many other studies linking exacerbations with FEV1 have been conducted with similar findings. Pulmonary exacerbations happen because of inflammation, the very process that Anabsum targets, so the fact that they were reduced in a dose-dependent manner also makes intuitive sense. During and exacerbation, the immune system flares up, causing severe inflammation in the lungs and patients end up in hospital for 2 to 4 weeks on IV antibiotics at a cost of about $10K to an insurer. According to the Cystic Fibrosis Foundation itself, stopping pulmonary exacerbations is even more important than improving FEV1. FEV1 is just a number, but the exacerbations are the most acute and damaging part of CF.
Most importantly, Corbus Pharmaceuticals Holdings Inc (NASDAQ:CRBP) and the Cystic Fibrosis Foundation believe that a reduction in the annualized rate of these exacerbations is an approvable endpoint for the FDA. In other words, this Phase II trial accomplished exactly what it was supposed to accomplish. It established safety in what is usually a very dangerous inflammation target, and it was able to point Corbus and the CFF in the direction of a measurable endpoint for an upcoming pivotal trial.
Going a bit deeper into the pulmonary exacerbation numbers, annualized pulmonary exacerbations for the Vertex Pharmaceuticals Inc. (NASADAQ:VRTX) Texacaftor/Ivacaftor combination therapy saw a 35% reduction of .64 vs .99 placebo. Anabasum saw a greater pulmonary exacerbation drop of 75%, from 0.89 to 0.22 annualized in the highest-dose cohort. If this number can be replicated in future trials, the chances of approval for this indication are high. Both the CFF and its European counterpart the Cystic Fibrosis Society (ECFS) know this, and both are involved in funding these trials, which is why these two nonprofits view the trial results in a positive light.
