Addex ADX10059 Monotherapy is Effective on GERD Symptoms in Phase IIb
Clinical Trial
(Thomson Reuters ONE) - Corporate news announcement processed and transmitted by Hugin AS.The issuer is solely responsible for the content of this announcement. ------------------------------------------------------------------------------------ Primary and Secondary Endpoints AchievedWebcast Today at 4pm CET (10am ET)Geneva, Switzerland, 16 November 2009 - Addex Pharmaceuticals(SWX:ADXN), the allosteric modulation company, announced that itachieved statistically significant efficacy on the primary endpoint,increasing the number of symptom free days in the Phase IIb trial ofADX10059 as a monotherapy in patients with gastroesophageal refluxdisease (GERD), the cause of heartburn and other symptoms. ADX10059is a first-in-class reflux inhibitor that works by reducingactivation of the metabotropic glutamate receptor 5 (mGluR5) throughnegative allosteric modulation (NAM). This approach may lead to a newclass of drugs that addresses the causes of GERD rather than just thesymptoms.Chief Medical Officer Charlotte Keywood said: "We saw the number ofsymptom free days increase by five-fold, an exciting and clinicallymeaningful effect for ADX10059 monotherapy. The magnitude of theeffect, along with the tolerability profile, indicate thatADX10059 has potential to be a useful therapy for GERD management.""Based on its marked efficacy in both reducing reflux and controllingsymptoms in this study, I would be pleased to see ADX10059 tested inlater stage trials as a monotherapy for GERD patients," saidprofessor Frank Zerbib, head of gastroenterology at the UniversityHospital of Bordeaux and a leading expert on GERD. "Furthermore, thegood tolerability seen with this modified-release formulation ofADX10059 was also a crucial part of these results, since GERD is achronic disease where long-term therapy is needed in the majority ofpatients."Vincent Mutel, CEO of Addex said, "These data confirm our belief inusing this mechanism of action, mGluR5 inhibition, to treat GERD.Furthermore, we believe that the market potential for a product withthe profile of ADX10059 is very significant. We look forward tofurther development of this molecule in GERD."Study ADX10059-204 was a double-blind, placebo-controlled,multi-center European Phase IIb trial in 103 GERD patients known torespond well to proton pump inhibitors (PPIs). There was a two-weekbaseline symptom evaluation period followed by two weeks ofadministration of ADX10059 120 mg twice daily. ADX10059 was used as amonotherapy so patients in the study did not use PPIs or other acidsuppressant therapy during the baseline and study treatment periods.The primary clinical endpoint was the patient reported number of GERDsymptom free days in week 2 of treatment compared to the last 7 daysof baseline. Objective measures of the effects of ADX10059 onesophageal function and reflux events were made in a subset of 24patients on the day before starting treatment and on the last day oftreatment using impedance pH monitoring and esophageal manometry.Reflux events on impedance pH monitoring were the mechanistic primaryvariables.ADX10059 significantly increased the mean number of GERD symptom freedays in week 2 of treatment. At baseline the mean number of symptomfree days was 0.46 in the ADX10059 group and 0.72 days in the placebogroup. During treatment week 2 this increased to 2.5 days in theADX10059 group and to 1.71 days in the placebo group (p = 0.0452)In the subset of 24 patients who underwent mechanistic monitoringADX10059 also achieved statistical significance in two mechanisticprimary endpoints. ADX10059 significantly reduced total impedancemeasured reflux events and also acidic reflux events over the 24 hourmonitoring period. In the ADX10059 treated group the mean number oftotal reflux events decreased by 26% from 64.9 at baseline to 47.9 ontreatment compared to no change in the placebo group with a mean of77.0 reflux episodes at baseline and 78.4 on treatment (p = 0.0342).In the ADX10059 group the mean number of acidic reflux events in 24hours decreased by 29% from 52.1 at baseline to 37.0 at end oftreatment compared to a small increase in the placebo group with 55.7episodes at baseline, and 59.7 at end of treatment (p = 0.0032).In addition to the primary efficacy endpoints, ADX10059 showedstatistical superiority over placebo for a variety of secondaryvariables including an increase in heartburn free days, a reductionin sleep disturbance, a reduction in the requirement for antacidmedication, an improvement in a GERD symptom patient reported outcomequestionnaire (p<0.05 for all measures). Finally patients alsoexpressed a significant preference for ADX10059 treatment compared toplacebo (p<0.05).ADX10059 120 mg twice-daily given for two weeks was well toleratedand the tolerability profile seen is compatible with use in thetreatment of GERD. Adverse events were reported more frequently forADX10059 than placebo but in both treatment groups the vast majoritywas mild and none was described as severe. There were no significantchanges in safety monitoring parameters.Addex also announced today that enrolment has been completed in thesecond trial of ADX10059 in GERD patients. In the study ADX10059-205,the product is being used as an add-on therapy in patients who arepartial responders to Proton Pump Inhibitors (PPIs), the standardtherapy for GERD. Results are expected in January 2010. A thirdtrial, where ADX10059 is being studied as a migraine prophylaxis inpatients with frequent migraines is progressing as expected and datawill be reported in the second quarter of 2010.GERD is a chronic condition caused by stomach contents flowing backinto the esophagus on a regular basis. The underlying cause of thisis an abnormally functioning lower esophageal sphincter (LES) musclethat allows stomach contents to pass back into the esophagus tooeasily. GERD leads to painful symptoms like heartburn and can alsodamage the lining of the esophagus. It is a common disorder withprevalence at about 15% in the United States and between 10% and 25%in EU. Marketed GERD products work by reducing the acidity of thestomach contents but do nothing to reduce reflux events, so that inmany patients symptoms of GERD persist.mGluR5 inhibition in GERD aims to restore normal function and improvethe tone of the LES muscle, thereby preventing reflux and addressingthe cause of the disease. Indeed, ADX10059 has been shown by Addex toreduce reflux and reduce esophageal acid exposure in three separateclinical trials(1,2). Research has shown that mGluR5 inhibitionimproves LES function in animals. Reflux inhibitors are beingrecognized as potentially the next generation of GERD therapy becausethey address the cause of the disease and are complementary tomarketed acid suppression therapies.Inhibition of mGluR5 has therapeutic potential in multiple otherindications because, as with other glutamate receptors, mGluR5 isinvolved in a variety of functions in the central and peripheralnervous systems(3). In addition to GERD, mGluR5 inhibitors haveachieved clinical proof of concept in separate studies in patientswith migraine headache(4), Parkinson's disease levodopa induceddyskinesia (PD-LID) and generalized anxiety disorder (GAD).Inhibition of mGluR5 also has potential in Fragile X syndrome,neuropathic pain and depression.(1) Keywood, C., et al., GUT online May 20, 2009 (free download:http://bit.ly/2Rcu0k)(2) Zerbib, F., et al., Digestive Disease Week (DDW) 2009 (freedownload: http://bit.ly/HjehE)(3) Gasparini, F. et al., Current Opinion in Drug Discovery &Development 2008 11(5):655-665(4) Goadsby, P. et al., American Academy of Neurology (AAN) 2009(free download: http://bit.ly/13aBkw)Webcast and conference call today at 4pm CET (10am ET). Visit theAddex website for more information.Addex Pharmaceuticals (www.addexpharma.com) discovers and developsallosteric modulators for human health. Allosteric modulators are adifferent kind of orally available small molecule therapeutic agent,which we believe will offer a competitive advantage over classicaldrugs. Our lead allosteric modulator product, ADX10059, has achievedclinical proof of concept and is in Phase IIb testing for thetreatment of GERD and, separately, migraine headache. ADX10059 is afirst-in-class mGluR5 inhibitor, a therapeutic strategy that also isbeing pursued in multiple indications by large pharma competitors.Addex products and technology already have proven their value throughour relationships with four of the top 10 pharmaceutical companies inthe world. Specifically, under an agreement with Ortho-McNeil-JanssenInc., a Johnson & Johnson company, ADX71149, a positive allostericmodulator (PAM) of mGluR2, is undergoing Phase I clinical testing andhas potential for treatment of schizophrenia and anxiety. Under twoseparate agreements with Merck & Co., Inc., we are developing PAMs ofmGluR4 and mGluR5 as drugs to treat Parkinson's disease andschizophrenia, respectively. In addition, GlaxoSmithKline and Rochehave made equity investments in Addex.Chris MaggosHead of IR & CommunicationsAddex Pharmaceuticals+41 22 884 15 11chris.maggos(at)addexpharma.comDisclaimerThe foregoing release contains forward-looking statements that can beidentified by terminology such as "not approvable", "continue","believes", "believe", "will", "remained open to exploring", "would","could", or similar expressions, or by express or implied discussionsregarding Addex Pharmaceuticals Ltd, its business, the potentialapproval of its products by regulatory authorities, or regardingpotential future revenues from such products. Such forward-lookingstatements reflect the current views of Addex Pharmaceuticals Ltdregarding future events, and involve known and unknown risks,uncertainties and other factors that may cause actual results withallosteric modulators of mGluR4, mGluR2, mGluR5 or other therapeutictargets to be materially different from any future results,performance or achievements expressed or implied by such statements.There can be no guarantee that allosteric modulators of mGluR4,mGluR2 or mGluR5 will be approved for sale in any market or by anyregulatory authority. Nor can there be any guarantee that allostericmodulators of mGluR4, mGluR2, mGluR5 or other therapeutic targetswill achieve any particular levels of revenue (if any) in the future.In particular, management's expectations regarding allostericmodulators of mGluR4, mGluR2, mGluR5 or other therapeutic targetscould be affected by, among other things, unexpected actions by ourpartners, unexpected regulatory actions or delays or governmentregulation generally; unexpected clinical trial results, includingunexpected new clinical data and unexpected additional analysis ofexisting clinical data; competition in general; government, industryand general public pricing pressures; the company's ability to obtainor maintain patent or other proprietary intellectual propertyprotection. Should one or more of these risks or uncertaintiesmaterialize, or should underlying assumptions prove incorrect, actualresults may vary materially from those anticipated, believed,estimated or expected. Addex Pharmaceuticals is providing theinformation in this press release as of this date and does notundertake any obligation to update any forward-looking statementscontained in this press release as a result of new information,future events or otherwise.http://hugin.info/138017/R/1355124/328815.pdfhttp://hugin.info/138017/R/1355124/328816.pdfhttp://hugin.info/138017/R/1355124/328829.pdf --- End of Message ---Addex Pharmaceuticals12, chemin des Aulx Plan-les-Ouates, Geneva SwitzerlandISIN: CH0029850754; Index: SLIFE, SPI, SPIEX, SSCI;Listed: Main Market in SIX Swiss Exchange;
Datum: 16.11.2009 - 07:00 Uhr
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