A setback for the hygiene hypothesis

It’s always interesting when a clinical trial you’ve been watching reads out.  One of the first posts I wrote for this blog was about a clinical trial that Coronado Biosciences was running based on the hygiene hypothesis.  The company was testing the efficacy of T. suis ova (pig whipworm eggs) in treating Crohn’s disease.

Well, Coronado Biosciences just released the results of a phase 2 trial (TRUST-1) and they are not positive.  It was a double-blinded, placebo-controlled trial of 250 patients with moderate to severe Crohn’s disease, so a positive signal would have been pretty convincing evidence of the efficacy of the therapy.  The primary endpoint of the trial measured response using the Crohn’s Disease Activity Index (number of patients who see a >100-point decrease in CDAI) and the secondary endpoint measured induction of remission (number of patients who achieve a CDAI score of less than 150).  For both endpoints, there was no significant difference between the treated patient population and the patients who received a placebo.  This is not a “we almost made it” result, but rather a “this doesn’t work at all” result.

The company did see a small signal in patients with very high CDAI scores (> 290), but unfortunately it was not statistically significant.  Coronado blamed it on a higher than expected placebo response, which may at first glance seem like a cop-out, but is actually quite common in trials for relapsing-remitting inflammatory diseases.

Another European trial is underway (TRUST-2) so Coronado will have a second chance to prove the therapy works, but things don’t look very promising at this point.  Crohn’s disease is a pretty tough market to compete in as several effective therapies already exist.  Even if TRUST-2 has a positive read-out, it’s unlikely the efficacy would be enough to support commercialization.

Coronado is also running trials of T. suis ova in several other indications including ulcerative colitis, multiple sclerosis, autism and psoriasis.  I’ll be following those trials closely as a positive outcome would be an incredible jump forward in our understanding of the immune system and offer new therapies for patients who often have few other options.  I’ll keep you posted.

Follow-up: Only a few days after posting this, Coronado Biosciences halted their TRUST-2 trial due to lack of efficacy.  Not surprising, but certainly a nail in the coffin for T. suis ova in the treatment of Crohn’s disease.  It will be interesting to see how the other indications fare…