16th May 2005 07:01
GlaxoSmithKline PLC15 May 2005 Issued - Sunday 15 May 2005, Orlando, Florida and London, UK - LSE GLAXOSMITHKLINE ISSUES UPDATE ON LAPATINIB: NEW CLINICAL DATA AND REGULATORY FILING PLANS News From The American Society of Clinical Oncology (ASCO) • Lapatinib shows 35% response rate in women with advanced breast cancer in initial trial of the drug as first-line treatment. • Other trials in refractory, previously treated breast-cancer patients report additional data. • GlaxoSmithKline intends to submit regulatory file in late 2006 or early 2007. Thirty-five percent of women (14 of 40) with locally advanced or metastaticbreast cancer have responded to lapatinib as first-line therapy, according tointerim results of a study reported today at the annual meeting of the AmericanSociety of Clinical Oncology (ASCO)1. The data are the first to be reported onthe use of lapatinib as a first-line therapy. Lapatinib is an oral therapy targeting intracellular components of a receptorknown as ErbB2 and a second receptor, ErbB1, which have been implicated in thegrowth of various tumor types. The Phase II trial (EGF 20009) tests lapatinib asfirst-line therapy for breast-cancer patients with tumors that express largeamounts of ErbB2. An already marketed therapy, Herceptin(R) (trastuzumab), alsoworks through its effect on ErbB2, but it is a monoclonal antibody administeredby intravenous infusion. None of the patients in this lapatinib trial have beentreated with Herceptin. "In this trial, we are seeing the strongest demonstration yet of the activity oflapatinib in solid tumors, and the first demonstration of such activity by anoral therapy directed at ErbB2," said Paolo Paoletti, M.D., senior vicepresident, Oncology Medicine Development Center, GlaxoSmithKline (GSK), thedeveloper of lapatinib. "These data further demonstrate the potential oflapatinib in breast cancer, and will help guide the expansion of our Phase IIIprogram to support regulatory filings." The data presented at ASCO were derived from an interim analysis planned at thestart of the trial and have been confirmed through an independent review. In the35 percent of patients who experienced a partial response, tumor size wasreduced by at least 30 percent. An additional 35 percent (an additional 14 ofthe 40 patients) showed stable disease through 12 weeks of therapy. All patientswill continue to be followed for disease progression as part of the plannedefficacy assessment. The trial, sponsored by GSK, will enroll a total of 130patients. The most frequently reported adverse events in this trial have been mild tomoderate itching, rash, diarrhea, acne, and dry skin. No adverse events deemeddrug-related, including cardiotoxicity, have been serious enough to becategorised as Grade 3 or 4 by standard toxicity criteria. "The efficacy and safety data from this trial point to the potential importanceof lapatinib as a treatment option for breast cancer patients," said GeorgeSledge, Jr., M.D., Ballve-Lantero professor of oncology and co-director of theBreast Cancer Program, Indiana University Cancer Center. Trials in previously treated, drug-refractory patients also are being presentedat ASCO. One is a Phase I study (EGF 10023) that has evaluated lapatinib incombination with Herceptin, to evaluate whether two ErbB2-targeted therapiesacting at different sites of the receptor may enhance efficacy.2 At the SanAntonio Breast Cancer Conference last December, it was reported that 6 of 26patients (23 percent) whose cancer progressed during Herceptin treatment laterexperienced partial or complete responses when lapatinib was added to theirstandard Herceptin regimen. Additional data from the now larger patientpopulation in this study will be presented on Tuesday, May 17. Another study, presented on May 14, identified biomarkers from tissue and serumthat may help in predicting drug response as part of a continuing effort toprecisely direct lapatinib therapy to the populations that will most benefitfrom it.3 This study relied on data from two Phase II trials (EGF 20002 and EGF20008) in patients with late-stage disease who were administered lapatinib aftermultiple other treatment options, including Herceptin, had been exhausted. Inthis context, preliminary, overall efficacy results also were noted: Amongpatients overexpressing ErbB2, the response rate ranged from 4.3 percent to 7.7percent, and the stable-disease rate at 16 weeks from 8.6 percent to 14.1percent; in patients not overexpressing ErbB2, there were no responders, and thestable-disease rate was 2.2 percent. The final efficacy and safety analysis fromthese two Phase II studies will be available later this year. In light of all the data presented at ASCO, together with an expanded clinicalprogramme now in progress, GSK intends to revise the regulatory-filing strategyfor lapatinib. Previously, the company had considered an initial file in late2005 on the basis of the two Phase II studies (EGF 20002 and EGF 20008) inpatients with late-stage disease, as noted above. Given the results of thesestudies and the promising new data on lapatinib efficacy in breast cancer, GSKnow plans to submit a New Drug Application for lapatinib with the U.S. Food andDrug Administration in late 2006 or early 2007 on the basis of data from PhaseIII trials in progress. Lapatinib has been granted fast-track status by the FDA for the treatment ofrefractory advanced or metastatic breast cancer who have documented ErbB2overexpression and who have failed previous therapy, including Herceptin. S M BicknellCompany Secretary15th May 2005 About Lapatinib Lapatinib, a small molecule that can be administered orally, inhibits thetyrosine kinase components of ErbB1 and ErbB2 receptors. Stimulation of ErbB1and ErbB2 is associated with cell proliferation, and with multiple processesinvolved in tumor progression, invasion, and metastasis. Overexpression ofthese receptors has been reported in a variety of human tumors and is associatedwith poor prognosis and reduced overall survival. GSK is using advancedtechnologies including pharmacogenetics to better define patient populationsthat may respond to lapatinib. Lapatinib is an experimental drug that does not have regulatory approval in anycountry for any use outside of clinical trials. It is being developed by GSK asan orally administered therapy for breast cancer and other solid tumors. About Lapatinib Trials Information about ongoing clinical trials of lapatinib in breast cancer can beobtained by visiting http://www.4BreastCancerTrials.com or calling 800-563-7137.Information is also available at http://www.clinicaltrials.gov (keyword:GW572016), a website maintained by the US government, or at a toll-free numberof the National Cancer Institute's Cancer Information Service, 800-4-CANCER. About Metastatic Breast Cancer The World Health Organization reports that just over one million cases of breastcancer are diagnosed annually. Breast cancer is the most common malignancy inwomen and one of the leading causes of cancer death. Approximately 10 percent of newly diagnosed breast-cancer patients have locallyadvanced and/or metastatic disease; 20 to 85 percent of patients (depending oninitial stage, tumor biology, and treatment strategy) diagnosed with earlybreast cancer will develop recurrent and/or metastatic disease.4 The mediansurvival time for women treated for metastatic breast cancer is two years.5 About GlaxoSmithKline GlaxoSmithKline -- one of the world's leading research-based pharmaceutical andhealthcare companies -- is committed to improving the quality of human life byenabling people to do more, feel better, and live longer. For companyinformation, visit GlaxoSmithKline at http://www.gsk.com. # # # Notes to editors: Lapatinib is also designated as GW572016. Herceptin(R) is a registered trademark of Genentech, Inc. References: 1 H.L. Gomez et al. A phase II, randomized trial using the smallmolecule tyrosine kinase inhibitor lapatinib as a first-line treatment inpatients with FISH positive advanced or metastatic breast cancer. 2 A.M. Storniolo et al. A Phase I, open-label study of lapatinib(GW572016) plus trastuzumab; a clinically active regimen. 3 K.L. Blackwell et al. Determining relevant biomarkers from tissue andserum that may predict response to single agent lapatinib in trastuzumabrefractory metastatic breast cancer. 4 C. Bernard-Marty et al. Facts and Controversies in Treatment ofMetastatic Breast Cancer. The Oncologist. 2004:9:617-632. 5 ibid. Cautionary statement regarding forward-looking statements Under the safe harbor provisions of the US Private Securities Litigation ReformAct of 1995, the company cautions investors that any forward-looking statementsor projections made by the company, including those made in this announcement,are subject to risks and uncertainties that may cause actual results to differmaterially from those projected. Factors that may affect the Group's operationsare described under 'Risk Factors' in the Operating and Financial Review andProspects in the company's Annual Report on Form 20-F for 2004. Enquiries: UK Media enquiries: Philip Thomson (020) 8047 5502 David Mawdsley (020) 8047 5502 Chris Hunter-Ward (020) 8047 5502 Alice Hunt (020) 8047 5502 US Media enquiries: Nancy Pekarek (215) 751 7709 Mary Anne Rhyne (919) 483 2839 Patricia Seif (215) 751 7709 European Analyst/Investor enquiries: Duncan Learmouth (020) 8047 5540 Anita Kidgell (020) 8047 5542 Jen Hill (020) 8047 5543 US Analyst/ Investor enquiries: Frank Murdolo (215) 751 7002 Tom Curry (215) 751 5419 This information is provided by RNS The company news service from the London Stock ExchangeRelated Shares:
Glaxosmithkline