Development of ADX10059 ended for long-term use
(Thomson Reuters ONE) - Corporate news announcement processed and transmitted by Hugin AS.The issuer is solely responsible for the content of this announcement. ------------------------------------------------------------------------------------ Conference call and webcast at 2pm CET / 8am ETGeneva, Switzerland, 15 December 2009 - Addex Pharmaceuticals(SIX:ADXN) announced today that based on preliminary review of theunblinded data from study 206, it has terminated development ofADX10059 for chronic indications, including long term treatment ofgastroesophageal reflux disease and migraine prophylaxis.In study 206 the incidence of alanine transaminase (ALT) levelsgreater than five times the upper limit of normal (>5xULN) levels was6% (16 of 257 patients); however, bilirubin remained normal in allbut one patient. The elevation of ALT occurred in all dose groups andappears to be related to the duration of dosing. The incidence was3.9% (10 patients) in the 100 mg group; 0.8% (2 patients) in the 50mg group; 1.6% (4 patients) in the 25 mg group. No abnormalities ofliver function were observed in the placebo group.A rise in transaminases to >5x ULN is considered to be predictive ofa potential for drug induced liver injury. As these significantelevations in ALT have been observed in all the dose groups, Addexconsiders that future development of ADX10059 for long term useappears unlikely. The company will evaluate potential developmentoptions based on the complete analysis of the data from study 205, a4-week study in GERD patients, which will report top-line data inearly January.Study 205 is still blinded however, a review of blinded safety datashow an incidence of ALT >5x ULN of 0.6% (2 of 295 patients). This isin-line with expectations for this type of study."The occurrence of liver function abnormalities in patients receivingthe lowest dose, makes future development of this compound difficult,especially for long term use," said Charlotte Keywood, chief medicalofficer."We have cash for operations until the end of 2011 and plan to focusour efforts on development of ADX48621, which has completed Phase Itesting and is scheduled to start Phase II testing for the treatmentof Parkinson's disease levodopa induced dyskinesia in the fourthquarter of 2010," said Vincent Mutel, chief executive officer. "Wealso will accelerate development of selected programs in discoveryand preclinical development and continue to leverage our uniquediscovery and development platform for allosteric modulator drugs."No liver function abnormalities have been seen in any of thepreviously reported clinical trials, several of which explored higherdoses, including the recently reported study ADX10059-204, a 2-weekstudy of monotherapy in 103 GERD patients. Study 205 a 4-week studyof ADX10059 as an add-on therapy to PPIs in GERD patients, is due toun-blind around the end of the year and data will be reported inJanuary.A webcast and conference call will be held at 2pm CET (8am ET) today,December 15. Please see www.addexpharma.com or use the followingdial-in numbers:+41 91 610 56 00 (Europe)+44 207 107 06 11 (UK)+1 866 291 41 66 (USA)Study ADX10059-206 is a double-blind, placebo-controlled, dose rangefinding, multi-center European Phase IIb trial in 240 patients whosuffer from three or more migraine attacks per month. Following aone-month baseline period, patients take study medication for 3months. The primary endpoint compares migraine frequency and severityin the last month of treatment with the baseline. The data are beingun-blinded and will be analyzed and any indications of efficacy willbe reported in early January.Study ADX10059-205 is a double-blind, placebo-controlled,multi-center U.S. and European Phase IIb trial in 280 GERD patientswho are partial responders to proton pump inhibitors (PPIs). In Study205 ADX10059 is being used as an add-on therapy to the patients'existing PPI treatment. There was a baseline symptom evaluationperiod followed by four weeks of administration of twice-dailyADX10059 (50mg, 100mg or 150mg). The primary endpoint is patientreported symptom control compared to baseline. Data are expected tobe communicated in early January.Study ADX10059-204 was a double-blind, placebo-controlled,multi-center European Phase IIb trial in 103 GERD patients known torespond well to PPIs. There was a two-week baseline symptomevaluation period followed by two weeks of administration of ADX10059120 mg twice daily. ADX10059 achieved the co-primary endpoints ofpatient reported symptom control compared to baseline and the effectsof ADX10059 on lower esophageal sphincter (LES) function as well asmultiple secondary endpoints. There were no serious adverse events inthe study and safety monitoring parameters were within normal limits.Mild or moderate adverse events included dizziness, vertigo and sleepdisturbance.Migraine is a condition distinguished by recurrent episodes of acharacteristic headache, which can be accompanied by a variety ofother symptoms such as nausea, and sensitivity to light and sound.The average migraine patient suffers 12 attacks a year. TheInternational Headache Society estimates that about 25% of migrainepatients have three or more attacks per month and could benefit frommigraine prevention treatment. A migraine attack, which typicallylasts about 24 hours but can range from 4-72 hours, has threedistinct phases: the prodrome phase, when an array of individualwarning signs - like blurred vision or tingling of the skin - maybegin to appear; the headache phase; and the postdrome phase, whenmany patients report fatigue or other "hangover-like" symptoms. Asmigraine attacks are prolonged, many patients and especially thosewith frequent attacks, lose a significant amount of work and familytime to suffering caused by the disease. Indeed, migraine iscurrently estimated to cost employers $13 billion annually in lostproductivity in the United States. Prevalence of migraine isestimated at 12% in the United States, where about 30 million peoplesuffer from migraine.GERD (gastroesophageal reflux disease) is a chronic condition causedby stomach contents flowing back into the esophagus on a regularbasis. The underlying cause of this is an abnormally functioninglower esophageal sphincter (LES) muscle that allows stomach contentsto pass back into the esophagus too easily. GERD leads to painfulsymptoms like heartburn and can also damage the lining of theesophagus. It is a common disorder with prevalence at about 15% inthe United States and between 10% and 25% in EU. Marketed GERDproducts work by reducing the acidity of the stomach contents but donothing to reduce reflux events, so that in many patients symptoms ofGERD persist.ADX10059 is a metabotropic glutamate receptor 5 (mGluR5) negativeallosteric modulator (NAM). Glutamate overstimulation is thought tocontribute via different mechanisms to pathology in both migraine andGERD. ADX10059 has been shown in clinical studies to reduce symptomsof acute migraine and, separately, to reduce reflux and GERDsymptoms.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, an mGluR5negative allosteric modulator (NAM), has achieved clinical proof ofconcept and is in Phase IIb testing for the treatment of GERD and,separately, migraine prevention. ADX48621, our next-stage mGluR5 NAM,has completed Phase I testing and will enter Phase II for Parkinson'sdisease levodopa-induced dyskinesia (PD-LID) in 2010.Our 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, an mGluR2 positiveallosteric modulator (PAM), is undergoing Phase I clinical testingand has potential for treatment of schizophrenia and anxiety. Undertwo separate agreements with Merck & Co., Inc., we are developingPAMs of mGluR4 and mGluR5 as drugs to treat Parkinson's disease andschizophrenia, respectively. In addition, SR-One, the corporateventure arm of GlaxoSmithKline, and Roche Venture Fund have madeequity investments in Addex.Chris MaggosInvestor Relations & CommunicationsAddex Pharmaceuticals+41 22 884 15 11chris.maggos(at)addexpharma.comDisclaimer: The foregoing release contains forward-looking statementsthat can be identified by terminology such as "not approvable","continue", "believes", "believe", "will", "remained open toexploring", "would", "could", or similar expressions, or by expressor implied discussions regarding Addex Pharmaceuticals Ltd, itsbusiness, the potential approval of its products by regulatoryauthorities, or regarding potential future revenues from suchproducts. Such forward-looking statements reflect the current viewsof Addex Pharmaceuticals Ltd regarding future events, and involveknown and unknown risks, uncertainties and other factors that maycause actual results with allosteric modulators of mGluR4, mGluR2,mGluR5 or other therapeutic targets to be materially different fromany future results, performance or achievements expressed or impliedby such statements. There can be no guarantee that allostericmodulators of mGluR4, mGluR2 or mGluR5 will be approved for sale inany market or by any regulatory authority. Nor can there be anyguarantee that allosteric modulators of mGluR4, mGluR2, mGluR5 orother therapeutic targets will achieve any particular levels ofrevenue (if any) in the future. In particular, management'sexpectations regarding allosteric modulators of mGluR4, mGluR2,mGluR5 or other therapeutic targets could be affected by, among otherthings, unexpected actions by our partners, unexpected regulatoryactions or delays or government regulation generally; unexpectedclinical trial results, including unexpected new clinical data andunexpected additional analysis of existing clinical data; competitionin general; government, industry and general public pricingpressures; the company's ability to obtain or maintain patent orother proprietary intellectual property protection. Should one ormore of these risks or uncertainties materialize, or shouldunderlying assumptions prove incorrect, actual results may varymaterially from those anticipated, believed, estimated or expected.Addex Pharmaceuticals is providing the information in this pressrelease as of this date and does not undertake any obligation toupdate any forward-looking statements contained in this press releaseas a result of new information, future events or otherwise. --- 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: 15.12.2009 - 13:39 Uhr
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