Larazotide

The verdict

Our read at a glance.

Whether tightening intestinal tight junctions reduces symptoms in people with celiac disease who still have symptoms on a gluten-free diet.

The signal

The phase 2b randomized controlled trial met its primary endpoint at the 0.5 mg dose, with fewer symptoms than placebo in patients with persistent symptoms despite a gluten-free diet. A later systematic review and meta-analysis pooled the randomized evidence across trials. On mid-stage evidence alone this looked like a drug that worked.

The unknown

Whether any subgroup genuinely benefits. The sponsor said it would analyse the data further to see whether a responsive subgroup existed, and no approved product resulted. Whether the zonulin and tight-junction model itself is the right target for symptom relief remains open.

Our read

Keep this memo next to any compound whose case rests on phase 2 data. Larazotide met its mid-stage endpoint, went into a properly powered phase 3, and stopped because the effect was not big enough to find. That sequence is common, it is not a scandal, and it is exactly why this Watchlist grades by trial stage rather than by promise.