Almirall, SA, an international pharmaceutical company, and an entrepreneurial pharmaceutical company, Ironwood Pharmaceuticals, Inc. have announced that the Committee for Medicinal Products for Human Use ( CHMP) has issued a positive opinion recommending approval of the sale of Constella (linaclotide 290 mcg) for the symptomatic treatment of irritable bowel syndrome with constipation (IBS-C) moderate to severe in adults.
The CHMP positive opinion is a recommendation to the European Commission (EC) and one of the last steps in the review of an application for marketing authorization. The European Commission generally follows the recommendations of the CHMP. Once approved, will be marketed under the trademark Constella.
Linaclotide is an agonist of guanylate cyclase C (SCFA) which is in the form of capsules for oral administration once daily in the treatment of irritable bowel syndrome and constipation.
It binds to the guanylate cyclase C in the intestine, without reaching substantial plasma concentrations, resulting in an increase in intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). It is believed that the increases in intracellular cGMP stimulate intestinal fluid secretion and intestinal transit speed, which results in an increased frequency of bowel movements. It is believed that increases in extracellular cGMP reduces the activity of pain-sensitive nerve, which is thought to cause a reduction in intestinal pain, according to non-clinical models.
"Patients with IBS-C have various gastrointestinal symptoms very uncomfortable, for which today there are very few treatments available," said Bertil Lindmark, chief scientific officer of Almirall. "With linaclotide, physicians will have one of the first treatments designed specifically for this disease, with proven efficacy and tolerability over time. In Almirall, we are very pleased with this first treatment for IBS-C whose CHMP recommends approval and trust benefits linaclotide may bring. "
This positive recommendation is based on the efficacy and safety of linaclotide, evaluated in two phase III clinical trials, double blind and placebo controlled. In these trials have involved approximately 1,600 adult patients, of which more than 800 have been treated with 290 mcg linaclotide. In both trials, linaclotide treatment resulted in an improvement of the symptoms in both statistically significant pain and abdominal discomfort, and the degree of relief of the symptoms of IBS (endpoints co-primary), and the frequency of spontaneous bowel movements, consistency of stools and the seriousness of the efforts of defecation and swelling (secondary endpoints). These improvements were maintained throughout the 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 patients.
"This positive opinion is a significant step to help adults with high symptoms, many of which are looking for new treatment options," said Dr. Mark Currie, senior vice president and chief scientific officer of Ironwood. "Discovering linaclotide by Ironwood scientists and the work we have done to reach patients in Europe with our partner Almirall have been the result of a joint effort with the goal of helping this patient population with unmet needs " .
Almirall holds the exclusive commercial rights to linaclotide in Europe.