New data presented at the United European Gastroenterology
Week (UEGW) confirm the efficacy and safety of prucalopride, a novel
enterokinetic compound, in patients with chronic constipation for whom
laxatives do not provide adequate relief.
Prucalopride was evaluated in a large double-blind (n=231),
placebo-controlled, phase II dose-finding trial (USA-3) that supports the
choice of 2 mg as the lowest effective dose. Both the 2 mg and 4 mg dosing of
prucalopride were superior to the 0.5 mg and 1 mg dosing with 4 mg showing a
marginal benefit over 2 mg but a less favourable AE profile. There was no
rebound effect during the run-out phase. Prucalopride was well tolerated at
all doses tested.
In a phase III trial (USA-28) aimed at studying the effects of
retreatment with prucalopride, the product demonstrated rapid and sustained
symptom relief in patients with chronic constipation. The efficacy findings
during 4 weeks of treatment were comparable to those during 4 weeks of
re-treatment. It was also shown that episodic use of 4 mg prucalopride was
well tolerated.
From a safety perspective, prucalopride is well tolerated at
repeated doses up to 5 times the anticipated therapeutic dose for treatment
of chronic constipation. In a randomized, double-blind, placebo-controlled,
cross-over trial (GBR-9) focusing on cardiovascular safety of prucalopride in
healthy subjects, no significant difference versus placebo was noted on a
variety of CV parameters including BP, QT and HR.
Furthermore, at UEGW, data from a small double-blind,
placebo-controlled, cross-over trial (GBR-7) to evaluate the effects of
prucalopride in patients with chronic intestinal pseudo-obstruction (CIP) due
to visceral myopathy or neuropathy, were presented that demonstrated the
favourable effect prucalopride had a on pain, nausea, vomiting, bloating and
analgesic intake.
The pharmacokinetic (PK) profile of prucalopride was
documented in a trial involving male and female subjects. The product has a
predictable PK profile and can be taken with or without meals. Its half-life
allows for once daily (o.d.) dosing. Prucalopride has a low potential for
metabolic drug-drug interactions, including CYP 450 iso-systems. This further
confirms the wide safety margin of the product.
. Dirk Reyn, CEO of Movetis, commented: “We are pleased with
the presentation of these data at UEGW because it reinforces the strength of
our dataset after recent publications in peer reviewed journals like the New
England Journal of Medicine (NEJM).” Lieve Vandeplassche, VP late clinical
development for Resolor at Movetis continues: “There is a serious unmet need
for a well tolerated, efficacious treatment for chronic constipation. For
years, the impact of chronic constipation has been underestimated and
research relating to this condition has been much less than in other medical
areas. In Europe alone, approximately 10 million patients visit their doctors
seeking help after unsatisfactory results with over-the-counter medications.
We hope that prucalopride will help to improve the lives of these patients
both in Europe and worldwide.”
About prucalopride
Prucalopride is a novel enterokinetic treatment, and the first
compound in a new generation of selective, high-affinity 5-HT4 receptor
agonists, specifically designed to restore impaired bowel motility and help
patients with chronic constipation for whom laxatives do not provide adequate
relief. By direct action on the wall of the gut, prucalopride offers a novel
approach to a debilitating disease. Prucalopride has completed three
identically designed Phase III studies and has been tested in more than 3,000
patients. Movetis filed for marketing approval in May 2008 in Europe and is
currently under review by the EMEA and Swissmedic.
About chronic constipation
Chronic constipation is a general disorder of the
gastrointestinal tract that affects an estimated 80 million people worldwide
and at least 37 million in Europe(1). It is a prevalent and debilitating
condition with a clear impact on quality of life. The ROME III guidelines
define chronic constipation as two or more of the following symptoms at least
a quarter of the time for at least six months: straining, lumpy or hard
stools, a sensation of incomplete evacuation, a sensation of anorectal
obstruction or blockage, and/or less than 3 defecations per week(2). In many
cases available prescription or over the counter drugs, offer inadequate
treatment. There is need for an alternative and novel approach to help
chronic constipation patients.
About Movetis
Through a clear focus on gastroenterology (GI), Movetis seeks
to improve the lives of millions of patients – both adults and children – by
discovering, developing and ultimately commercializing innovative treatments
targeting GI conditions with a high unmet medical need. Movetis NV – founded
in Belgium in December 2006 – aims to become a leading European specialty
pharmaceutical organization focused on GI diseases. Movetis has a broad GI
portfolio with one product for which the marketing application was filed, two
products in clinical development, one product ready to move into clinical
development and four in preclinical, all addressing important GI areas
including chronic constipation, ascites, paediatric reflux in infants,
diabetic gastroparesis, specific subgroups of patients with severe forms of
irritable bowel syndrome or dyspepsia. In addition, Movetis has rights to a
large library of qualified lead compounds with potential for development in
different GI indications and access to know how for compounds in secretory
diarrhoea. The current portfolio has been licensed from Janssen Pharmaceutica
NV, Belgium and Ortho-McNeil Pharmaceutical Inc., two Johnson & Johnson (J&J)
companies.
The current portfolio includes:
– Prucalopride, which has completed clinical development for
chronic constipation and has been filed with the EMEA and Swiss health
authorities.
– M0002 is in Phase II clinical development for ascites
– M0003 is in clinical development for gastroparesis and
paediatric reflux.
– M0004 is ready to go into clinical development for refractory GORD
and/or non erosive reflux disease (NERD);
– four compounds in preclinical development;
– two compound libraries, each with more than 600 ligands.
(1) Reyn. D. Opportunities in gastroenterology. Drug Discovery World -
Winter 2007/8.
(2) Drossman (2006) Rome III: The new criteria. Chinese Journal of
Digestive Diseases 7 (4) , 181-185
Source
Ingrid Jansen
Movetis NV