Novartis drug Tasigna® meets primary endpoint in pivotal trial
against Glivec® as first-line treatme
(Thomson Reuters ONE) - Corporate news announcement processed and transmitted by Hugin AS.The issuer is solely responsible for the content of this announcement. ------------------------------------------------------------------------------------ * Tasigna produced faster and deeper responses compared to Glivec as first-line treatment in Philadelphia chromosome-positive chronic myeloid leukemia * First registration study using molecular response as key indicator of patient outcomes; Bcr-Abl biomarker test measures very low levels of residual disease[1],[2] * Tasigna is a potent and selective inhibitor of the Bcr-Abl protein that causes production of cancer cells[3],[4] * Complete results to be submitted for presentation at the American Society of Hematology (ASH) meeting in DecemberBasel, October 20, 2009 - Novartis announced today that Tasigna®(nilotinib) met its primary endpoint in the first head-to-headcomparison with the company's groundbreaking drug Glivec®(imatinib).* Tasigna produced faster and deeper responses than Glivecwhen given as first-line therapy for adult patients with newlydiagnosed Philadelphia chromosome-positive chronic myeloid leukemia(Ph+ CML) in chronic phase. Tasigna was well tolerated in thestudy[5],[6].The Phase III clinical trial, Evaluating Nilotinib Efficacy andSafety in Clinical Trials of Newly Diagnosed Ph+ CML Patients(ENESTnd), is the largest global randomized comparison of two oraltherapies ever conducted in newly diagnosed Ph+ CML patients.Designed to detect a difference in major molecular response (MMR)between Tasigna and Glivec after 12 months of treatment, it is alsothe first registration study in which molecular traces of a keybiomarker specific to Ph+ CML have been used as a primary endpointfor regulatory review. The comparison study also met its secondaryendpoint, a difference in complete cytogenetic response (CCyR) infavor of Tasigna[5],[6]."We developed Tasigna to be a potent and selective inhibitor ofBcr-Abl, with the goal of eliminating the underlying cause of Ph+CML. We now know that Tasigna reduces the level of Bcr-Abl faster andto a lower level than Glivec, with profound implications forimproving patients' outcomes," said David Epstein, President and CEOof Novartis Oncology and Novartis Molecular Diagnostics. "Molecularmonitoring enables us to evaluate whether patients have achieved thisdeep level of CML residual disease, reducing the fundamentalbiomarker of leukemia to nearly undetectable levels."The blood test used to determine molecular response can detect asingle cell containing traces of Bcr-Abl in up to one million normalblood cells[7]. In addition to being simpler and less invasive forpatients, the test has a much greater sensitivity than standardcytogenetic tests, which require a sample of bone marrow to be drawnfor visual detection of cells containing the Ph chromosome[1].Molecular monitoring measures the deepest level of CML residualdisease[13].In earlier clinical trials, molecular responses were found to bepredictive of better patient outcomes: 100% of Ph+ CML patients whoachieved MMR (defined as a thousand-fold or greater reduction inBcr-Abl relative to standardized baseline level) in the first 12months of treatment survived without disease progression for at leastfive years[8]. Follow up of patients in these studies is ongoing.Details of the ENESTnd findings will be submitted as a late-breakingabstract to the 51st annual meeting of the American Society ofHematology (ASH), to take place in December, in New Orleans,Louisiana, USA.Previous studies of Tasigna as first-line therapy for patients withnewly diagnosed Ph+ CML include the Gruppo Italiano MalattieEmatologiche dell'Adulto (GIMEMA) study, an ongoing, open-label,single-stage, multicenter Phase II clinical trial; and NCT00129740,an ongoing, open-label, single-center Phase II clinical trialundertaken at M.D. Anderson Cancer Center in Houston, Texas, USA. Newdata from the GIMEMA study presented earlier this year at theEuropean Hematology Association (EHA) congress show that at 12months, 85% of patients taking Tasigna achieved MMR. These dataindicate a more rapid reduction in disease burden compared to thatseen in previous studies with Glivec[9].Study detailsENESTnd is a Phase III randomized, open-label, multicenter studycomparing the efficacy and safety of Tasigna versus Glivec in adultpatients with newly diagnosed Ph+ CML in chronic phase[5],[6].ENESTnd is being conducted at 220 global sites, with 846 patientsenrolled. Patients were randomized to receive Tasigna 400 mg twicedaily (n = 281), Tasigna 300 mg twice daily (n = 282) or Glivec 400mg daily (n = 283). The primary endpoint was MMR at 12 months; thesecondary endpoint was complete cytogenetic response (CCyR) by 12months. Planned follow-up is for five years[5],[6].About Ph+ CMLCML is a disease in which the body produces cancerous white bloodcells. Almost all patients with CML have an abnormality known as thePhiladelphia chromosome, which produces a protein called Bcr-Abl.Bcr-Abl causes malignant white blood cells to proliferate[3].Worldwide, CML is responsible for approximately 10 to 15% of alladult cases of leukemia[10], with an incidence of one to two casesper 100,000 people per year[11].About Tasigna[4]Tasigna has been approved in 73 countries for the treatment ofchronic phase and accelerated phase Ph+ CML in adult patientsresistant or intolerant to at least one prior therapy, includingGlivec. The effectiveness of Tasigna for this indication is based onconfirmed hematologic and unconfirmed cytogenetic response rates.There are no controlled trials demonstrating a clinical benefit, suchas improvement in disease-related symptoms or increased survival.Tasigna important safety informationBecause taking Tasigna with food may increase the amount of drug inthe blood, Tasigna should not be taken with food and patients shouldwait at least two hours after a meal before taking Tasigna. Inaddition, no food should be consumed for at least one hour after thedose is taken.The most frequent Grade 3 or 4 adverse events for Tasigna wereprimarily hematological in nature and included neutropenia andthrombocytopenia. Elevations seen in bilirubin, liver function tests,lipase enzymes and blood sugar, were mostly transient and resolvedover time. These cases were easily managed and rarely led todiscontinuation of treatment. Pancreatitis was reported in less than1% of cases. The most frequent non-hematologic drug-related adverseevents were rash, pruritus, nausea, fatigue, headache, constipationand diarrhea. Most of these adverse events were mild to moderate inseverity.Tasigna should be used with caution in patients with uncontrolled orsignificant cardiac disease (e.g., recent heart attack, congestiveheart failure, unstable angina or clinically significantbradycardia), as well as in patients who have or may developprolongation of QTc. These include patients with abnormally lowpotassium or magnesium levels, patients with congenital long QTsyndrome, patients taking anti-arrhythmic medicines or other drugsthat may lead to QT prolongation. Low levels of potassium ormagnesium must be corrected prior to Tasigna administration. Closemonitoring for an effect on the QTc interval is advisable and abaseline echocardiogram is recommended prior to initiating therapywith Tasigna and as clinically indicated.About Glivec[12]Glivec is approved in more than 90 countries including the US, EU andJapan, for the treatment of all phases of Ph+ CML. Glivec is alsoapproved in the US, EU and other countries for the treatment ofpatients with Kit (CD117)-positive gastrointestinal tumors (GIST),which cannot be surgically removed and/or have already spread toother parts of the body (metastasized). In the US and EU, Glivec isnow approved for the post-surgery treatment of adult patientsfollowing complete surgical removal of Kit (CD117)-positivegastrointestinal stromal tumors. In the EU, Glivec is also approvedfor the treatment of adult patients with newly diagnosed Ph+ acutelymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy andas a single agent for patients with relapsed or refractory Ph+ ALL.Glivec is also approved for the treatment of adult patients withunresectable, recurrent and/or metastatic dermatofibrosarcomaprotuberans (DFSP) who are not eligible for surgery. Glivec is alsoapproved for the treatment of patients withmyelodysplastic/myeloproliferative diseases (MDS/MPD). Glivec is alsoapproved for hypereosinophilic syndrome and/or chronic eosinophilicleukemia (HES/CEL).The effectiveness of Glivec is based on overall hematological andcytogenetic response rates and progression-free survival in CML, onhematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, onhematological response rates in systemic mastocytosis (SM), HES/CEL,on objective response rates and progression-free survival inunresectable and/or metastatic GIST, on recurrence free survival inadjuvant GIST and on objective response rates in DFSP. Increasedsurvival in controlled trials has been demonstrated only in newlydiagnosed chronic phase CML and GIST.Not all indications are available in every country.Glivec important safety informationThe majority of patients treated with Glivec in clinical trialsexperienced adverse events at some time. Most events were of mild tomoderate grade and treatment discontinuation was not necessary in themajority of cases.The safety profile of Glivec was similar in all indications. The mostcommon side effects included nausea, superficial edema, musclecramps, skin rash, vomiting, diarrhea, abdominal pain, myalgia,arthralgia, hemorrhage, fatigue, headache, joint pain, cough,dizziness, dyspepsia and dyspnea, dermatitis, eczema and fluidretention, as well as neutropenia, thrombocytopenia and anemia.Glivec was generally well tolerated in all of the studies that wereperformed, either as monotherapy or in combination with chemotherapy,with the exception of a transient liver toxicity in the form oftransaminase elevation and hyperbilirubinemia observed when Glivecwas combined with high dose chemotherapy.Rare/serious adverse reactions include: sepsis, pneumonia,depression, convulsions, cardiac failure, thrombosis/embolism, ileus,pancreatitis, hepatic failure, exfoliative dermatitis, angioedema,Stevens-Johnson syndrome, renal failure, fluid retention, edema(including brain, eye, pericardium, abdomen and lung), hemorrhage(including brain, eye, kidney and gastrointestinal tract),diverticulitis, gastrointestinal perforation, tumorhemorrhage/necrosis and hip osteonecrosis/avascular necrosis.Patients with cardiac disease or risk factors for cardiac failureshould be monitored carefully and any patient with signs or symptomsconsistent with cardiac failure should be evaluated and treated.Cardiac screening should be considered in patients with HES/CEL, andpatients with MDS/MPD with high level of eosinophils (echocardiogram,serum troponin level).Glivec is contraindicated in patients with known hypersensitivity toimatinib or any of its excipients. Women of childbearing potentialshould be advised to avoid becoming pregnant while taking Glivec.DisclaimerThe foregoing release contains forward-looking statements that can beidentified by terminology such as "to be submitted," "implications,""predictive," "will," "to take place," or similar expressions, or byexpress or implied discussions regarding potential new indications orlabeling for Tasigna or regarding potential future revenues fromTasigna or Glivec. You should not place undue reliance on thesestatements. Such forward-looking statements reflect the currentviews of management regarding future events, and involve known andunknown risks, uncertainties and other factors that may cause actualresults with Tasigna or Glivec to be materially different from anyfuture results, performance or achievements expressed or implied bysuch statements. There can be no guarantee that Tasigna will beapproved for any additional indications or labeling in any market.Nor can there be any guarantee that Tasigna or Glivec will achieveany particular levels of revenue in the future. In particular,management's expectations regarding Tasigna and Glivec could beaffected by, among other things, unexpected clinical trial results,including unexpected new clinical data and unexpected additionalanalysis of existing clinical data; unexpected regulatory actions ordelays or government regulation generally; the company's ability toobtain or maintain patent or other proprietary intellectual propertyprotection; competition in general; government, industry and generalpublic pricing pressures; the impact that the foregoing factors couldhave on the values attributed to the Novartis Group's assets andliabilities as recorded in the Group's consolidated balance sheet,and other risks and factors referred to in Novartis AG's current Form20-F on file with the US Securities and Exchange Commission. Shouldone or more of these risks or uncertainties materialize, or shouldunderlying assumptions prove incorrect, actual results may varymaterially from those anticipated, believed, estimated or expected.Novartis is providing the information in this press release as ofthis date and does not undertake any obligation to update anyforward-looking statements contained in this press release as aresult of new information, future events or otherwise.About NovartisNovartis provides healthcare solutions that address the evolvingneeds of patients and societies. Focused solely on healthcare,Novartis offers a diversified portfolio to best meet these needs:innovative medicines, cost-saving generic pharmaceuticals, preventivevaccines, diagnostic tools and consumer health products. Novartis isthe only company with leading positions in each of these areas. In2008, the Group's continuing operations achieved net sales of USD41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2billion was invested in R&D activities throughout the Group.Headquartered in Basel, Switzerland, Novartis Group companies employapproximately 99,000 full-time-equivalent associates and operate inmore than 140 countries around the world. For more information,please visit http://www.novartis.com.References[1] NCCN Practice Guidelines in Oncology - v.1.2010. ChronicMyelogenous Leukemia.[2] Sessions J. Chronic Myeloid Leukemia in 2007.http://www.amcp.org/data/jmcp/pages%204-7.pdf. Accessed September2009.[3] National Cancer Institute. General Information About ChronicMyelogenous Leukemia (PDQ).http://www.cancer.gov/cancertopics/pdq/treatment/CML/patient/.Accessed March 2009.[4] Tasigna (nilotinib) European Summary of Characteristics. NovartisAG. http://www.tasigna.com/en/tasigna-product-information.jsp#.[5] Novartis data on file[6] A Study of Imatinib Versus Nilotinib in Adult Patients With NewlyDiagnosed Philadelphia Chromosome Positive (Ph+) Chronic MyelogenousLeukemia in Chronic Phase (CML-CP).http://clinicaltrials.gov/ct2/show?term=ENEST&rank=3. AccessedOctober 2009.[7] Kurzrock R, Talpaz M. The molecular pathology of chronicmyelogenous leukaemia. Br J Haematol. 1991 Oct; 79 Suppl 1:34-7.[8] Druker BJ, Guilhot F, O'Brien SG, et al. Five-Year Follow-up ofPatients Receiving Imatinib for Chronic Myeloid Leukemia. N Engl JMed. 2006; 355(23):2408-2517.[9] Rosti, G et al. Nilotinib for the Frontline Treatment of Ph+Chronic Myeloid Leukemia. Blood. Published online October 12, 2009.http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2009-07-232595v1[10] American Cancer Society. Detailed Guide: CML. What are the keystatistics about CML? (Sept 2008 revision) Available at:http://www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Are_the_Key_Statistics_About_Chronic_Myeloid_Leukemia_CML.asp?rnav=cri.Accessed April 2009.[11] Central European Leukemia Study Group. About CML. [Cited 2009Jan 13] Available from:http://www.cml-info.com/de/healthcare-professionals/about-cml.html.[12] Glivec® (imatinib) prescribing information. Basel, Switzerland:Novartis International AG; March 2009.[13] Jabbour E, Cortes J, Kantarjian H, et al. Molecular Monitoringin Chronic Myeloid Leukemia Response to Tyrosine Kinase Inhibitorsand Prognostic Implications. Cancer. DOI10.1002/cncr.23427. Publishedonline 17 March 2008.* Known as Gleevec® (imatinib mesylate) tablets in the US, Canada andIsrael. # # #Novartis Media RelationsCentral media line : +41 61 324 2200Eric Althoff Sabrina OeiNovartis Global Media Relations Novartis Oncology+41 61 324 7999 (direct) +1 862 778 6387)+41 79 593 4202 (mobile) sabrina.oei(at)novartis.comeric.althoff(at)novartis.come-mail: media.relations(at)novartis.comNovartis Investor RelationsCentral phone: +41 61 324 7944Ruth Metzler-Arnold +41 61 324 North America: 9980Pierre-Michel Bringer +41 61 324 Richard Jarvis +1 212 830 1065 2433John Gilardi +41 61 324 Jill Pozarek +1 212 830 3018 2445Thomas Hungerbuehler +41 61 324 Edwin Valeriano +1 212 830 8425 2456Isabella Zinck +41 61 324 7188e-mail: e-mail:investor.relations(at)novartis.com investor.relations(at)novartis.comhttp://hugin.info/134323/R/1348449/324525.pdf --- End of Message ---Novartis International AGPosfach Basel WKN: 904278; ISIN: CH0012005267; Index: SLCI, SMI, SPI, SLIFE;Listed: Main Market in SIX Swiss Exchange, ZLS in BX Berne eXchange;
Datum: 20.10.2009 - 07:00 Uhr
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