Phase III trial of lower dose Linzess (linaclotide) meets endpoint in chronic idiopathic constipation- Ironwood Pharma

Ironwood Pharmaceuticals announced that the Phase III clinical trial of its 72 µg dose of Linzess/Constella (linaclotide) in adults with chronic idiopathic constipation (CIC) met the primary endpoint. Ironwood and partner Allergan intend to submit a supplemental new drug application to the US Food and Drug Administration (FDA) in the first half of 2016. Top-line data from the Phase III trial indicate that the 72 µg dose of linaclotide demonstrated statistically significant improvement compared to placebo on the 12-week complete spontaneous bowel movements (CSBM) overall responder endpoint, the primary endpoint for the trial. Additionally, in a pre-specified sensitivity analysis, the 72 µg dose of linaclotide demonstrated statistically significant improvement compared to placebo on the durable CSBM overall responder endpoint, which is currently being requested by the FDA for Phase III CIC trials.

Both the 72 µg and 145 µg linaclotide doses were generally well-tolerated in this trial. Consistent with previous Phase III trials of linaclotide, the most common adverse event reported in linaclotide-treated patients was diarrhoea. The majority of diarrhoea cases reported were characterised as mild in severity. The rates of diarrhoea and of discontinuations due to diarrhoea were lower for the 72 µg dose than the 145 µg dose in this trial.

Linaclotide is currently approved by the FDA (as Linzess) as a 145 µg capsule to be taken once per day for the treatment of adults with CIC and as a 290 µg capsule to be taken once per day for the treatment of adults with irritable bowel syndrome with constipation (IBS-C).

Linaclotide is currently approved by the EMA (as Constella) as a 290 µg capsule for symptomatic treatment of severe IBS-C in adults.