Active Crohn's disease: Mongersen shows endoscopic improvement and clinical response and remission at week 12
Interim topline data from a randomized, double-blind, multicenter, exploratory phase 1b study evaluating the effects of oral Mongersen ( GED-0301 ) on both endoscopic and clinical outcomes in patients with active Crohn's disease, were presented.
The trial, CD-001, is an ongoing study evaluating three different treatment regimens of Mongersen in a 12-week treatment phase, followed by an observation phase up to 52 weeks ( off treatment ).
The trial enrolled a total of 63 patients across multiple countries.
The primary objective of the study is to explore the effect of Mongersen on endoscopic outcomes.
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.
Topline data from CD-001 show that in a proportion of patients treated with oral Mongersen there was endoscopic improvement ( defined as a 25% improvement from baseline ) and clinical response and remission across all treatment groups at week 12.
Findings to date reveal no new safety signals and tolerability is consistent with earlier studies.
CD-001 is a phase 1b randomized, double-blind, multicenter, exploratory study evaluating the effects of oral Mongersen on endoscopic and clinical outcomes in patients with active Crohn's disease. A total of 63 patients were randomized in a 1:1:1 ratio to receive one of three 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. Eligible patients can also enter an extension phase ( on treatment ) for an additional 24 weeks.
The investigational oral antisense therapy Mongersen is an oligonucleotide that is 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 and is thought 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 ( GI ) 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
Amyotrophic lateral sclerosis: therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice
Amyotrophic lateral sclerosis ( ALS ) is a rapidly progressing neurodegenerative disease that is characterized by motor neuron loss and...
Duchenne muscular dystrophy is caused by dystrophin deficiency and muscle deterioration and preferentially affects boys. Antisense-oligonucleotide-induced exon skipping allows synthesis...
Multiple sclerosis: ATL1102, an antisense inhibitor of CD49d, reduces by 54.4% the cumulative number of new active brain lesions
Phase IIa clinical trial data on ATL1102 were published in the medical journal Neurology. The article highlights the successful outcomes...
Crohn’s disease-related inflammation is characterized by defective activity of the immunosuppressive cytokine transforming growth factor ( TGF )-beta1, due to...
EMA refused the marketing authorisation for Kynamro, a drug for treatment of patients with certain forms of familial hypercholesterolaemia
On 13 December 2012, the Committee for Medicinal Products for Human Use ( CHMP ) has adopted a negative opinion,...
The stability and propagation of hepatitis C virus ( HCV ) is dependent on a functional interaction between the HCV...
De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome
Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations...
A new type of treatment significantly reduces the severity of muscle weakness in myasthenia gravis, giving hope for a new...
Researchers have developed a successful strategy for interfering with Ebola virus infection that protected 75 percent of nonhuman primates exposed...