9th Apr 2007 21:38
GlaxoSmithKline (LSE and NYSE:GSK) and Adolor Corporation(Nasdaq:ADLR) today announced data from Study 767905/014 and providedan update on the clinical development program for alvimopan(Entereg/Entrareg(R)). £ Study 014, a Phase 3, double blind, placebo-controlled (12 month)study, was designed to evaluate the long-term safety and tolerabilityof alvimopan 0.5 mg twice daily in patients taking opioids for chronicnon-cancer pain and experiencing opioid-induced bowel dysfunction(OBD). A total of 805 patients were enrolled into the study andrandomized 2:1; a total of 538 patients received alvimopan and 267received placebo. £ Consistent with findings from previous studies the most commonadverse events observed in Study 014 were those affecting thegastrointestinal (GI) tract, including abdominal pain and diarrhea.The incidence of GI adverse events observed was similar betweenpatients treated with alvimopan (40%) and placebo (35%). £ While the proportion of patients experiencing serious adverseevents was similar between those treated with alvimopan (13%) andplacebo (11%), a numerical imbalance was observed in the number ofcardiovascular (CV) and neoplasm cases categorized as serious adverseevents among alvimopan-treated patients. £ Preliminary findings from Study 014 are outlined below, togetherwith information regarding actions taken by GSK and Adolor regardingthe two ongoing alvimopan studies. £ Cardiovascular Adverse Events £ Results from a six-month interim analysis of Study 014, previouslyannounced in November 2006, showed an increase which was notstatistically significant in the reported incidence of serious CVadverse events in patients receiving alvimopan relative to placebo.Results from completed Study 014 showed an increase in myocardialinfarctions and all CV SAEs reported by patients treated withalvimopan compared to placebo. These are outlined in the table below,together with aggregate data from other non-cancer OBD studies. The CVdata from Study 014 are currently under review by an Independent DrugMonitoring Committee (IDMC). \* T Non-Cancer Non-Cancer OBD Studies* OBD Studies* Study 014 (w/o Study 014) (w/Study 014)---------------------------------------------------------------------- Placebo Alvimopan Placebo Alvimopan Placebo Alvimopan (N=267) (N=538) (N=523) (N=1190) (N=790) (N=1728)----------------------------------------------------------------------Myocardial Infarction - (0) 7 (1.30%)2 (0.38%) 1 (0.08%)2 (0.25%) 8 (0.46%)----------------------------------------------------------------------All Cardio - vascular SAEs 3 (1.12%)14 (2.60%)5 (0.96%)14 (1.18%)8 (1.01%)28 (1.62%)---------------------------------------------------------------------- *Includes Studies 011, 012, 013, 217, and 304 \* T £ The CV SAEs reported in Study 014 occurred in patients withestablished or at high risk for CV disease. Five of seven myocardialinfarctions occurred at two investigational sites. Additionally, theincidence of myocardial infarctions does not appear to be linked tothe duration of dosing, with the majority of reported events in Study014 occurring within the first 12 weeks of treatment. £ Neoplasm Events £ Study 014 showed an imbalance in the incidence of neoplasms(benign, malignant, skin cancers and unspecified, including polyps),with 15 neoplasms reported in patients receiving alvimopan (2.8%) and2 in patients receiving placebo (0.7%). Of these, 4 alvimopan (0.7%)and 1 placebo (0.4%) neoplasms were categorized as serious adverseevents. £ Fracture Events £ An increase in the incidence of fractures was also observed inpatients receiving alvimopan. This data is in contrast to previouslyconducted studies that showed a similar or lower incidence offractures in patients receiving alvimopan relative to placebo. £ Preliminary Conclusions and Next Steps £ As the findings outlined were observed during the preliminaryevaluation of data from Study 014, and a full analysis has not yetbeen completed, further details are not yet available. Additional dataare being collected and further analyses, which will include allalvimopan OBD studies, will be undertaken as soon as possible tobetter understand these findings. £ Pending completion of these analyses, the protocol for anadditional Phase 3 safety and efficacy study in patients with OBD(Study 015), which had been submitted to regulatory authorities, isbeing withdrawn by GSK. £ As a precautionary measure, GSK has taken the decision to stopStudy 101684, an extension of Study 008 in a cancer pain population,which currently has 15 patients receiving treatment. Clinicalinvestigators involved in this study have been informed. £ "Patient well-being is always our primary concern. Theseunexpected findings are not yet fully understood and require furtheranalyses to ascertain the significance of the data. We are working togain a better understanding of these findings, which will help guideour future development," said Yvonne Greenstreet, Senior VicePresident, Research and Development, GlaxoSmithKline. £ Adolor has also suspended enrollment in Study 228 in rotator cuffsurgery patients, a co-administration study being conducted as part ofAdolor's Combination Product Development Program, until a morecomplete understanding of these data are available. Clinicalinvestigators involved in these studies are being informed. GSK andAdolor currently have no other ongoing studies with alvimopan. £ "We continue to believe in the clinical benefit of Entereg andlook forward to the further analyses of these preliminary Study 014results," said Michael R. Dougherty, President and Chief ExecutiveOfficer of Adolor. "We are committed to working with GSK to provide anupdate on further clinical development plans in the opioid-inducedbowel dysfunction program as soon as is possible. With regard to thePOI program, we continue to target the second quarter of 2007 tosubmit to the FDA a Complete Response to the November 2006 approvableletter." £ Conference Call Information £ Adolor will be hosting a conference call and webcast on April 9,2007 at 5:00 p.m. Eastern Time 2:00 p.m. Pacific Time to discuss theseresults. To participate in the audio portion and have the opportunityto pose questions, dial 1-866-383-7989 for domestic callers, and1-617-597-5328 for international callers, and provide the Passcode76912495. Slides accompanying the call, as well as a webcast of theaudio portion of the call, will be available on the Investor Relationssection of the Company's website, www.adolor.com. £ A replay of the conference call will be available beginning at7:00 PM Eastern Time on April 9, 2007. To listen to a replay of theconference call, dial 1-888-286-8010 (domestic callers) or1-617-801-6888 (international callers) with a Passcode of 78747273 orlisten via the website. The replay will be available for one week. £ About Adolor Corporation £ Adolor Corporation (Nasdaq:ADLR) is a biopharmaceutical companyspecializing in the discovery, development and commercialization ofnovel prescription pain management products. Entereg(R) (alvimopan) isAdolor's lead product candidate under development for the managementof the gastrointestinal side effects associated with opioid use.Adolor and GlaxoSmithKline (GSK) are collaborating in the worldwidedevelopment and commercialization of Entereg(R) in multipleindications. Adolor also has a number of discovery research programsfocused on the identification of novel compounds for the treatment ofpain. By applying its knowledge and expertise in pain management,along with ingenuity, Adolor is seeking to make a positive differencefor patients, caregivers and the medical community. For moreinformation, visit www.adolor.com. £ About GlaxoSmithKline £ GlaxoSmithKline is one of the world's leading research-basedpharmaceutical and healthcare companies and is committed to improvingthe quality of human life by enabling people to do more, feel betterand live longer. For more information, visit GlaxoSmithKline on theWorld Wide Web at www.gsk.com. £ Adolor Forward-Looking Statements £ This release, and oral statements made with respect to informationcontained in this release, may constitute forward-looking statementswithin the meaning of the Private Securities Litigation Reform Act of1995. Such forward-looking statements include those which expressplan, anticipation, intent, contingency, goals, targets or futuredevelopment and/or otherwise are not statements of historical fact.These statements are based upon management's current expectations andare subject to risks and uncertainties, known and unknown, which couldcause actual results and developments to differ materially from thoseexpressed or implied in such statements. Such known risks anduncertainties relate to, among other factors: the risk that the OBDdevelopment program remains on hold indefinitely; the risk that Adolormay not receive regulatory approval of Entereg (R) (alvimopan) forPOI, OBD, or any other indication; the risk that Adolor may not beable to adequately address the deficiencies in the November 2006 FDAapprovable letter; the risk that a risk management plan couldmaterially adversely affect the commercial prospects for Entereg, ifregulatory approval is achieved; the risk that Adolor may not obtainFDA approval for Entereg in POI, whether due to Adolor's inability toprovide additional data satisfactory to the FDA to obtain approval forthe NDA, the adequacy of the safety and efficacy data from all of theEntereg studies, changing regulatory requirements, the risk that theFDA may not agree with Adolor's and GSK's analyses of the Enteregstudies (including Study 014) and may evaluate the results of thesestudies by different methods or conclude that the results from thestudies, whether or not statistically significant, do not supportsafety, efficacy, a favorable risk/benefit profile, or there werehuman errors in the conduct of the studies, or otherwise; adversesafety findings in any Entereg studies; the risk that regulatoryapprovals for the use of Entereg in OBD are not achieved; the riskthat filing targets for regulatory submissions or user fee goal datesare not met; the risk that the results of other clinical trials ofAdolor's drug product candidates, including Entereg, are not positive;the risk of product liability claims; reliance on third partymanufacturers; the costs, delays and uncertainties inherent inscientific research, drug development, clinical trials and theregulatory approval process; Adolor's history of operating lossessince inception and its need for additional funds to operate itsbusiness; Adolor's reliance on its collaborators, including GSK, inconnection with the development and commercialization of Entereg;market acceptance of Adolor's products, if regulatory approval isachieved; competition; and securities litigation. £ Further information about these and other relevant risks anduncertainties may be found in Adolor's Reports on Form 8-K, 10-Q and10-K filed with the U.S. Securities and Exchange Commission. Adolorurges you to carefully review and consider the disclosures found inits filings which are available in the SEC EDGAR database athttp://www.sec.gov and from Adolor at http://www.adolor.com. Given theuncertainties affecting pharmaceutical companies in the developmentstage, you are cautioned not to place undue reliance on any suchforward-looking statements, any of which may turn out to be wrong dueto inaccurate assumptions, unknown risks, uncertainties or otherfactors. Adolor undertakes no obligation to (and expressly disclaimsany such obligation to) publicly update or revise the statements madeherein or the risk factors that may relate thereto whether as a resultof new information, future events, or otherwise. £ GlaxoSmithKline Forward-Looking Statements £ Under the safe harbor provisions of the US Private SecuritiesLitigation Reform Act of 1995, the company cautions investors that anyforward-looking statements or projections made by the company,including those made in this announcement, are subject to risks anduncertainties that may cause actual results to differ materially fromthose projected. Factors that may affect the Group's operations aredescribed under 'Risk Factors' in the Business and Prospects in thecompany's Annual Report on Form 20-F for 2006. Copyright Business Wire 2007Related Shares:
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