The CHMP positive opinion is a recommendation to the European Commission (EC) and one of the final steps in the review of a marketing authorization application. The EC usually follows the recommendations of the CHMP. Once approved, it will be marketed under the brand name Constella®.
"Patients with IBS-C suffer from several very uncomfortable gastrointestinal symptoms for which there are currently very few available therapies", said Bertil Lindmark, Chief Scientific Officer at Almirall. "With linaclotide physicians will have one of the first specifically designed therapies with proven efficacy and tolerability over time. Therefore, we are very pleased at Almirall with this first IBS-C treatment recommended for approval by CHMP and are confident in linaclotide's benefits".
This positive recommendation is based on the efficacy and safety of linaclotide evaluated in two double-blind, placebo-controlled Phase III clinical studies. The clinical trials involved approximately 1,600 adult patients, of which more than 800 were treated with linaclotide 290 mcg. In both trials, treatment with linaclotide resulted in statistically significant improvements in both abdominal pain/discomfort and degree of relief of IBS-C symptoms (co-primary endpoints), as well as complete spontaneous bowel movement frequency, stool consistency and severity of straining and bloating (secondary endpoints). These improvements were maintained over the entire treatment period (12 and 26 weeks). The incidence of adverse events was similar in both studies, with diarrhoea being the most common adverse event in linaclotide-treated patients1,2.
"This positive opinion is a significant step toward helping these highly symptomatic adult patients; many of whom are searching for new treatment options," said Mark Currie, PhD, Senior Vice President, R&D and Chief Scientific Officer of Ironwood. "The discovery of linaclotide by Ironwood scientists and the work we have done to reach patients in Europe with our partner, Almirall, has been a collaborative effort with the goal of helping this underserved patient population."
Almirall holds exclusive marketing rights for linaclotide in Europe.
About linaclotide (Constella®)
Linaclotide is a guanylate cyclase-C (GCCA) agonist that is provided as an oral capsule intended for once-daily administration for the treatment of irritable bowel syndrome with constipation.
It binds to guanylate cyclase C locally in the intestine, with no measurable blood plasma concentrations, resulting in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevations in intracellular cGMP are believed to stimulate secretion of intestinal fluid and accelerate gastrointestinal transit resulting in increased frequency of bowel movements. Elevations in extracellular cGMP are believed to decrease activity of pain-sensing nerves, which is thought to be responsible for a reduction in intestinal pain, according to nonclinical models.
Constella® is a trademark owned by Ironwood Pharmaceuticals, Inc. and its use in Europe is pending marketing approval from the European Commission.
About Irritable Bowel Syndrome with Constipation (IBS-C)
IBS is defined as a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit and with features of disordered defecation.[i] IBS-C is one of four clinically different subtypes of IBS. One-third of patients with IBS are thought to have IBS-C[ii] and suffer chronically from both abdominal pain and constipation.
The Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders includes criterion for the diagnosis of IBS3 as:
- Recurrent abdominal pain or discomfort at least three days/month, in the last three months with symptom onset at least 6 months prior to diagnosis, associated with two or more of the following:
- improvement with defecation
- onset associated with a change of frequency of stool
- onset associated with a change in form (or appearance) of stool