Data from a randomized, double-blind, multicenter, exploratory phase 1b study evaluating the effects of investigational oral GED-0301 ( Mongersen ) 160 mg on both endoscopic response and clinical remission in patients with active Crohn's disease were announced.
Patients with active Crohn's disease [ CDAI score 220-450 ], a total simple endoscopic score for Crohn's disease ( SES-CD ) greater than or equal to 7, or an ileal disease SES-CD greater than or equal to 4, were randomized to three different active treatment regimens of four, eight or 12 weeks of Mongersen 160 mg daily, followed by an observation period off treatment. Endoscopic and clinical assessments were reported through week 12.
A total of 63 patients were enrolled in the study.
The study was designed to further enhance the understanding of Mongersen activity in a difficult-to-treat, moderate to severe patient population. This population was more diverse than prior Mongersen studies and included patients with endoscopically confirmed mucosal damage at entry and those who had previous surgeries. The study also included both biologic-exposed and biologic-naïve patients, as well as patients with a diagnosis of ileitis, ileocolitis or colitis.
Clinical improvement was seen by week 2, and clinical response ( CDAI decrease greater than or equal to 100 ) and remission ( CDAI less than 150 ) rates were highest in the 12-week treatment group at 67 and 48% respectively, at week 12.
The mean CDAI reduction from baseline at week 12 in the 12-week treatment group was 133 points.
Of the patients with evaluable endoscopies at week 12 ( n=52 ), 37% had an endoscopic response ( greater than or equal to 25% reduction in SES-CD score from baseline ), with no meaningful difference across treatment groups.
In addition, of those patients with greater endoscopic disease activity at baseline ( SES-CD score of more than 12; n=16 ), 63% exhibited a reduction greater than or equal to 25% in SES-CD score and 31% had a reduction of greater than or equal to 50%.
The rates of adverse events and serious adverse events were low and similar across treatment groups. There were no new safety signals for oral Mongersen 160 mg daily reported in this study.
In the CD-001 a total of 63 patients were randomized in a 1:1:1 ratio to receive one of three active treatment regimens in a 12-week treatment phase: Mongersen 160 mg once daily for 12 weeks; Mongersen 160 mg once daily for eight weeks followed by four weeks of placebo; or Mongersen 160 mg once daily for four weeks followed by eight weeks of placebo.
This treatment phase was followed by an off-treatment observation phase for up to 52 weeks.
Mongersen is an oligonucleotide designed to target the messenger RNA ( mRNA ) for Smad7, thereby reducing Smad7 protein levels. In patients with Crohn's disease, abnormally high levels of Smad7 interfere with TGF-beta1 anti-inflammatory pathways in the gut, leading to increased inflammation. Mongersen is designed to act locally to reduce Smad7 levels with negligible systemic exposure.
Crohn's disease is an immune-mediated, chronic inflammatory condition of the gastrointestinal tract. Estimated to affect as many as three out of every 1,000 people in Europe and North America, the disease is becoming more common for all ethnic groups. Symptoms of Crohn's disease, including abdominal pain, diarrhea, fatigue, fever, weight loss and malnutrition, most commonly begin to appear between the ages of 13 and 30, although the disease can strike at any age.
The disease may affect any part of the gastrointestinal tract, from the mouth to the anus, but most commonly affects the end of the small bowel ( ileum ) and the beginning of the colon.
The exact cause of Crohn's disease is unknown, and there is no cure. People with Crohn's disease have a slightly reduced life expectancy. ( Xagena )
Source: Celgene, 2016