Linaclotide
An exciting new medication near approval
In mid 2010, linaclotide passed an FDA Phase 3 safety trial with flying colors. Although safety was at issue here, linaclotide also scored marks on reducing abdominal pain, discomfort and bloat. These were so-called secondary measures as the intent of this Phase 3 trial was only safety. However, results from another Phase 3 efficacy trial are expected later this year.
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Linaclotide is a drug aimed at patients who suffer from irritable bowel syndrome with constipation (IBS-C), a subclass of IBS that is characterized by difficulty having bowel movements. Patients with IBS also suffer from abdominal pain. Linaclotide is touted to address both symptoms, simultaneously reducing abdominal pain and also relieving constipation. There is no other drug like this. In late 2009, a phase 2 clinical trial was completed in a small population showing benefits for patients with constipation. Clinical trials are the standard by which medications are approved or not approved under the Federal Drug Administration (FDA). There are 3 phases in order of increasing difficulty from 1 to 3.
A positive Phase II study
The phase 2 study that was completed enrolled 42 adults with chronic constipation. Each adult received either a regular drug or a placebo (a non-active substance) without knowing ahead of time which one was which. The 8 days followng administration of constipation medication, data was collected on patients regarding the frequency and volume of bowel movements. Results showed that patients who had taken linaclotide had a statistically significant increase in number of bowel movements. Moreover, these patients reported less straining and softer stools. The positive effects of the medication seemed to increase with dosage also.
Successful and upcoming Phase III
Linaclotide is a constipation medication that has not only completed several phase 2 studies, but has also been evaluated in a phase 3 trial that was completed in mid 2010, as well as several other phase 2 trials. Since linaclotide has only completed phase 2 trials, it has not yet been approved for general use.
A compound with a novel mode of action
Is there a reason consumers should be very excited about linaclotide? Yes, there is a good scientific reason. Linaclotide is a very novel constipation medication that acts on the gut in a unique way when compared to existing laxatives or even lubiprostone. Any constipation medication has what is called a "mode of action". For example, osmotic agents draw water out by virtue of their physical properties, whereas lubiprostone activates calcium channels in gut cells. Linaclotide is a stimulator of yet another cellular sensor called a guanylate cyclase c receptor. The short story is that stimulation of this sensor causes water to be secreted into the gut, which lubricates and stimulates intestinal movement of stool.
Hope for patients
The reason why physicians and patients are excited is because a drug with a new mode of action means a new way to attack constipation. Perhaps patients who don't respond to traditional laxatives and lubiprostone will response to this entirely new drug. Perhaps the clinical trials will reveal that dosing with two kinds of constipation medications will be even more effective. These are speculative thoughts, but reflect the underlying reason for the kind of excitement many scientists and doctors feel about drugs with novel modes of action.
Sources:
Fox-Orenstein et al, Update on constipation: One treatment does not fit all, Cleveland Clinic Journal of Medicine, 2008; 75(11):813-824
Muller-Lissner, The Pathophysiology, Diagnosis, and Treatment of Constipation, Deutsches Arzteblatt International, 2009; 106(25):424-32