Novartis Tasigna® trial shows superior results to Glivec® in patients
with early-stage chronic myelo
(Thomson Reuters ONE) - Corporate news announcement processed and transmitted by Hugin AS.The issuer is solely responsible for the content of this announcement. ------------------------------------------------------------------------------------ * Tasigna surpassed Glivec in every measure of treatment efficacy designated in the trial including prevention of disease progression at 12 months[1] * At 12-month milestone, significantly fewer patients progressed to accelerated or blastic phase on Tasigna 300 mg twice daily than on Glivec 400 mg once daily[1] * Tasigna was well tolerated; few patients receiving 300 mg twice daily discontinued because of adverse events[1] * Results support Tasigna as treatment in newly diagnosed patients with Ph+ CML; Novartis to file worldwide applicationsBasel, December 8, 2009 - In a large Phase III clinical trial,Tasigna?® (nilotinib) demonstrated greater efficacy over Glivec®(imatinib)* in the treatment of adult patients with newly diagnosedPhiladelphia chromosome-positive chronic myeloid leukemia (Ph+ CML)in chronic phase[1].In the first head-to-head comparison of these two oral therapies asinitial treatment for this life-threatening blood cancer, Tasignaresults showed statistically significant improvement over Glivec inevery measure of efficacy, including major molecular response (MMR),complete cytogenetic response (CCyR) and prevention of progression toaccelerated or blastic phase[1]. The new data were presented as alate breaker abstract at the 51st annual meeting of the AmericanSociety of Hematology (ASH), held in December, in New Orleans, USA.At 12 months, significantly fewer patients progressed to acceleratedor blastic phase on Tasigna 300 mg twice daily than on Glivec 400 mgonce daily (2 patients vs. 11 patients)[1], demonstrating astatistically significant improvement in disease control. In thestudy, Tasigna was well tolerated. Fewer patients discontinued due toadverse events from the Tasigna 300 mg twice daily arm of the studycompared to the Glivec 400 mg once daily arm. No patients in thestudy had prolongation of QT interval >500 milliseconds1. No suddendeaths occurred with either treatment[2]."The outstanding rates of response observed with Tasigna, combinedwith the very low rate of disease progression, strongly indicate thatpatients who begin their treatment with Tasigna may have long-termimprovement of progression-free survival," said Giuseppe Saglio,University of Turin, San Luigi Hospital, Orbassano-Torino, Italy, amember of the study management committee. "The efficacy results andtolerability of Tasigna should support its use in newly diagnosed Ph+CML patients."With Tasigna 300 mg twice daily, the rate of MMR at 12 months wastwice that of patients receiving Glivec 400 mg once daily (44% vs.22%, p < 0.0001)[1]. In addition, 80% of patients achieved CCyR withTasigna versus 65% with Glivec 400 mg once daily (p < 0.0001)[1].Responses were achieved faster in the Tasigna group than in theGlivec group[1].MMR was defined in the study as reduction in the level of theabnormal Bcr-Abl protein to less than or equal to 0.1% of thepre-treatment level based on an internationally agreed standard[1].This can be interpreted to mean that for every 1,000 cells containingBcr-Abl that were present in the blood at the start of therapy, onlyone cell was present at the 12-month follow-up. CCyR indicates thatno CML cells containing the diagnostic Ph chromosome can be seen in asample of bone marrow taken from the patient."Novartis is pioneering research targeting the molecular origin ofPh+ CML, which has led to treatments of unprecedented effectivenessand safety," said David Epstein, President and CEO of NovartisOncology and Novartis Molecular Diagnostics. "Considering the alreadylow rates of progression to advanced disease and the excellentlong-term survival of patients on Glivec, the efficacy and safetyprofile of Tasigna at 12 months is fantastic news and brings promisefor further improving the outcomes of patients with Ph+ CML."Tasigna is a potent and selective inhibitor of the Bcr-Abl proteinthat causes production of cancer cells in Ph+ CML[2],[3]. Uponinitial reports of resistance in the Glivec registration trials,Novartis scientists created a new molecule, Tasigna, just a yearafter the launch of Glivec. The first clinical trials began just 21months after discovery. The drug received its first regulatoryapproval in the second-line indication in 2007.Novartis plans to file worldwide applications for approval of Tasignaas a treatment for adult patients with newly diagnosed Ph+ CML.Tasigna is currently approved in more than 80 countries including theEuropean Union, United States and other countries for the treatmentof adult patients with Ph+ CML in chronic phase or accelerated phasewho are resistant or intolerant to prior treatment including Glivec.Study detailsThe clinical trial, Evaluating Nilotinib Efficacy and Safety inClinical Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd), is aPhase III randomized, open-label, multicenter trial comparing theefficacy and safety of Tasigna versus Glivec in adult patients withnewly diagnosed Ph+ CML in chronic phase[1]. It is the largest globalrandomized comparison of two oral therapies ever conducted in newlydiagnosed Ph+ CML patients. Designed to detect a difference in MMRbetween 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 trial's secondary endpoints included CCyR,as well as progression to accelerated or blastic phase, and overallsurvival.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 once daily (n = 283). The primary endpoint was MMR at 12 months; asecondary endpoint was CCyR by 12 months[1]. Planned follow-up is forfive years[2]. Patients on the Glivec treatment arm who hadsuboptimal response or treatment failure will be able to escalatedose and/or switch to Tasigna via a protocol extension.Samples for molecular response were evaluated by a single referencelaboratory. The blood test used to determine molecular response candetect a single cell containing traces of Bcr-Abl in up to onemillion normal blood cells[4]. In addition to being simpler and lessinvasive for patients, the test has a much greater sensitivity thanstandard cytogenetic tests, which require a sample of bone marrow tobe drawn for visual detection of cells containing the Phchromosome[5].All patients had a minimum of 12 months of treatment or discontinuedearly; the median follow-up was 14 months. Overall, 84%, 82% and 79%of patients remained in the study on Tasigna 300 mg twice daily,Tasigna 400 mg twice daily and Glivec 400 mg once daily,respectively.Rates of MMR at 12 months were statistically higher for patients inthe Tasigna 300 mg twice daily group compared with Glivec 400 mg oncedaily (44% vs. 22%, p < 0.0001) and also for Tasigna 400 mg twicedaily compared with Glivec 400 mg once daily (43% vs. 22%, p <0.0001). Among patients who achieved MMR, median time to MMR wasfaster for Tasigna 300 mg twice daily (5.7 months) and Tasigna 400 mgtwice daily (5.8 months) compared with Glivec 400 mg once daily (8.3months). Molecular response was assessed by polymerase chain reaction(PCR) at baseline, monthly for three months, and every three monthsthereafter.Rates of CCyR by 12 months were significantly higher for Tasigna at300 mg twice daily compared with Glivec 400 mg once daily (80% vs.65%, p < 0.0001) and for Tasigna 400 mg twice daily compared withGlivec 400 mg once daily (78% vs. 65%, p = 0.0005). Overall,progression to advanced disease was lower for Tasigna 300 mg twicedaily (2 patients) and Tasigna 400 mg twice daily (1 patient)compared with Glivec 400 mg once daily (11 patients).Both Tasigna and Glivec were well tolerated overall. Rates ofdiscontinuation due to adverse events or laboratory abnormalitieswere 7% for Tasigna 300 mg twice daily, 11% for Tasigna 400 mg twicedaily, and 9% for Glivec 400 mg once daily.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[6].Worldwide, CML is responsible for approximately 10% to 15% of alladult cases of leukemia[7], with an incidence of one to two cases per100,000 people per year[8].About Tasigna[3]Tasigna has been approved in more than 80 countries for the treatmentof chronic 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[9]Glivec is approved in more than 90 countries, including the US, EUand Japan, 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 file," "may," "should,""potential," "promise," "plans," "will," or similar expressions, orby express or implied discussions regarding potential new indicationsor labeling 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 besubmitted or approved for any additional indications or labeling inany market. Nor can there be any guarantee that Tasigna or Glivecwill achieve any particular levels of revenue in the future. Inparticular, management's expectations regarding Tasigna and Gliveccould be affected by, among other things, unexpected clinical trialresults, including unexpected new clinical data and unexpectedadditional analysis of existing clinical data; unexpected regulatoryactions or delays or government regulation generally; the company'sability to obtain or maintain patent or other proprietaryintellectual property protection; competition in general; government,industry and general public pricing pressures; the impact that theforegoing factors could have on the values attributed to the NovartisGroup's assets and liabilities as recorded in the Group'sconsolidated balance sheet, and other risks and factors referred toin Novartis AG's current Form 20-F on file with the US Securities andExchange Commission. Should one or more of these risks oruncertainties materialize, or should underlying assumptions proveincorrect, actual results may vary materially from those anticipated,believed, estimated or expected. Novartis 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.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] Saglio G, Kim DW, Issaragrisil S, Philipp le Coutre, et al.Nilotinib Demonstrates Superior Efficacy Compared with Imatinib inPatients with Newly Diagnosed Chronic Myeloid Leukemia in ChronicPhase: Results from the International Randomized Phase III ENESTndTrial. Abstract #LBA-1. American Society of Hematology 2009 AnnualMeeting.[2] Novartis data on file.[3] Tasigna (nilotinib) European Summary of Characteristics. NovartisAG. http://www.tasigna.com/en/tasigna-product-information.jsp#.[4] Kurzrock R, Talpaz M. The Molecular Pathology of ChronicMyelogenous Leukaemia. Br J Haematol. 1991 Oct; 79 Suppl 1:34-7.l 1:definition of PCR. Here'[5] NCCN Practice Guidelines in Oncology - v.1.2010. ChronicMyelogenous Leukemia.[6] National Cancer Institute. General Information About ChronicMyelogenous Leukemia (PDQ).http://www.cancer.gov/cancertopics/pdq/treatment/CML/patient/.l 1:definition of PCR. Here'[7] 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.[8] Central European Leukemia Study Group. About CML. [Cited 2009 Jan13] Available from:http://www.cml-info.com/de/healthcare-professionals/about-cml.html.[9] Glivec® (imatinib) prescribing information. Basel, Switzerland:Novartis International AG; March 2009.*Known as Gleevec® (imatinib mesylate) tablets in the US, Canada andIsrael. # # #Novartis Media RelationsCentral media line : +41 61 324 2200Eric Althoff Kim FoxNovartis Global Media Relations Novartis Oncology+41 61 324 7999 (direct) +1 862 778 7692 (direct)+41 79 593 4202 (mobile) kim.fox(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 +41 61 324 Richard Jarvis +1 212 830Bringer 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.comMedia materials can be accessed at:http://www.novartisoncology.com/media/index.jsp or for mobile deviceshttp://www.novartisoncology.com/mobile/index.html.http://hugin.info/134323/R/1359764/331519.pdf --- End of Message ---Novartis International AGPostfach Basel WKN: 904278; ISIN: CH0012005267; Index: SLCI, SMI, SPI, SLIFE;Listed: Main Market in SIX Swiss Exchange, ZLS in BX Berne eXchange;
Datum: 08.12.2009 - 14:30 Uhr
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