Novartis Highlights Advances for Patients With Breast Cancer and Hematological Diseases With Over 160 SABCS and ASH Abstracts

 Updated Phase III data from BOLERO-2 trial studying everolimus in women with ER+HER2- advanced breast cancer

- Tasigna® Phase III trials in Ph+ CML including 36-month follow-up data in newly diagnosed patients

- Exjade® pivotal study results investigating iron chelation in patients with non-transfusion-dependent thalassemia

- Phase III trial further exploring benefit of INC424 (ruxolitinib) in patients with myelofibrosis, a debilitating blood cancer with limited treatment options


EAST HANOVER, N.J., Dec. 2, 2011 /PRNewswire/ -- Novartis Pharmaceuticals Corporation ("Novartis") will showcase more than one hundred and sixty presentations on data from its robust oncology portfolio at two key medical congresses this month, demonstrating significant advances for patients with cancers and hematological diseases.

The CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), held from December 6-10, will feature data presentations from Phase III studies of Afinitor® (everolimus) tablets for investigational uses and Zometa® (zoledronic acid) 4mg/5mL Injection, as well as early-stage studies of the investigational drug BKM120, an inhibitor of PI3K, a key cancer pathway(1).

The American Society of Hematology (ASH) annual meeting in San Diego, held from December 10-13, will showcase key data for Tasigna® (nilotinib), Exjade® (deferasirox) and the investigational drug INC424 (ruxolitinib)(*). Several early-stage studies will also be presented, including everolimus in Hodgkin lymphoma and Waldenstrom's macroglobulinemia and LBH589 (panobinostat) in relapsed and bortezomib (BTZ)-refractory multiple myeloma(2).

"These important data are examples of our research and development strategy to focus on significant unmet medical needs by targeting the fundamental mechanisms of disease," said Herve Hoppenot, President, Novartis Oncology. "Through our collaborations with the scientific and patient communities, we continue to advance our goal of transforming patients' lives."

Highlights at SABCS include:

•Everolimus – Updated data from the BOLERO-2 (Breast cancer trials of OraL EveROlimus) Phase III trial of everolimus in combination with exemestane for postmenopausal women with ER+HER2- advanced breast cancer who recurred or progressed while on or following previous treatment with the hormonal therapies letrozole or anastrozole (SABCS abstract #S3-7; December 8, 9:30 – 11:15AM).
•Zometa – ABCSG-12 (Austrian Breast & Colorectal Cancer Study Group Trial) long-term data will examine possible carry-over anticancer benefits of zoledronic acid three years after treatment completion in premenopausal women with endocrine-responsive early breast cancer receiving adjuvant goserelin and endocrine therapy (SABCS abstract #S1-2; December 7, 9:15 – 11:30AM) and five-year ZO-FAST (ZOmeta-Femara Adjuvant Synergy Trial) follow-up data on long-term overall survival outcomes among postmenopausal women with hormone receptor-positive early breast cancer receiving adjuvant zoledronic acid and letrozole (SABCS abstract #S1-3; December 7, 9:15 – 11:30AM).
•BKM120 – Two studies investigating the activity of BKM120, a pan-PI3K inhibitor, in advanced breast cancer: data from a trial evaluating the safety profile and clinical activity of BKM120 as a single agent for the treatment of patients with metastatic breast cancer (SABCS abstract  #P3−16−01; December 8, 5:00 – 7:00PM) and data from a Phase I/II study evaluating BKM120 in combination with trastuzumab in patients with HER2 overexpressing metastatic breast cancer resistant to trastuzumab-containing therapy (SABCS abstract #PD09−03; December 9, 5:00 – 7:00PM).
Highlights at ASH include:

•Tasigna – ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials) 36-month update of the ENESTnd study comparing Tasigna to Gleevec® (imatinib mesylate) tablets(**) in patients with newly diagnosed chronic phase Ph+ chronic myeloid leukemia (ASH abstract #452; December 12, 10:30AM – 12:00PM) and results from ENESTcmr trial assessing the efficacy and safety of switching patients with residual molecular disease on Gleevec treatment to Tasigna (ASH abstract #606; December 12, 2:45 – 4:15PM).
•Exjade – Data from the first randomized, placebo-controlled study evaluating the reduction of liver iron concentration and serum ferritin in patients with non-transfusion-dependent thalassemia after one year of treatment with Exjade oral iron chelation therapy (ASH abstract #902; December 13, 7:30 – 9:00AM) and data from a retrospective analysis of hematological response during iron chelation therapy in patients with myelodysplastic syndrome (MDS) and aplastic anemia with transfusional iron overload (ASH abstract #611; December 12, 2:45 – 4:15PM).
•INC424 – Data from multiple research programs will be presented, including two pivotal Phase III studies evaluating INC424 benefit versus placebo (COMFORT-I [COntrolled MyeloFibrosis study with ORal JAK inhibitor Therapy]) (ASH abstract #278; December 12, 7:00 – 8:30AM) and versus best available therapy (COMFORT-II) (ASH abstract #795; December 12, 4:30 – 6:00PM). These data will assess measures of spleen reduction, symptom improvement, health-related quality of life and overall survival.
•Everolimus – Results from a Phase II study evaluating everolimus as a monotherapy in relapsed/refractory Hodgkin lymphoma (ASH abstract #2717; December 11, 6:00 – 8:00PM) and data from a Phase I trial of everolimus in combination with rituximab or in combination with BTZ and rituximab in relapsed/refractory Waldenstrom's macroglobulinemia (ASH abstract #2705; December 11, 6:00 – 8:00PM).
•LBH589 – Results from PANORAMA-2 (PANobinostat ORAl in Multiple myelomA), a Phase II study of LBH589 in combination with BTZ and dexamethasone in patients with relapsed and BTZ-refractory multiple myeloma (ASH abstract #814; December 12, 4:30 – 6:00PM). Data from two trials in myelofibrosis: final results from a Phase I trial of prolonged low dose therapy with LBH589 in myelofibrosis patients (ASH abstract #794; December 12, 4:30 – 6:00PM) and a preclinical study of LBH589 in combination with INC424 in JAK2V617F-driven disease (ASH abstract #798; December 12, 4:30 – 6:00PM).
About everolimus
In the US, Afinitor® (everolimus) tablets is approved for the treatment of progressive neuroendocrine tumors of pancreatic origin (pNET) in patients with unresectable, locally advanced or metastatic disease and for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. The US Food and Drug Administration (FDA) determined that the safety and effectiveness of Afinitor in the treatment of patients with carcinoid tumors have not been established.

Afinitor is also approved in the US to treat patients with SEGA associated with TS who require therapeutic intervention but are not candidates for curative surgical resection. The effectiveness of everolimus is based on an analysis of change in SEGA volume. Clinical benefit such as improvement in disease-related symptoms or increase in overall survival has not been shown.

In the US, everolimus is available from Novartis in different dosage strengths and for different uses in non-oncology patient populations under the trade name Zortress®. Everolimus is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Not all indications are available in every country. Access to everolimus outside of the approved indications has been carefully controlled and monitored in clinical trials designed to better understand the potential benefits and risks of the compound. As an investigational compound, the safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.

Afinitor (everolimus) tablets Important Safety Information
Patients should not take Afinitor if they are allergic to Afinitor or to any of its ingredients. Patients should tell their healthcare provider before taking Afinitor if they are allergic to sirolimus (Rapamune®#) or temsirolimus (Torisel®#).

Afinitor can cause serious side effects including lung or breathing problems, infections and kidney failure, which can lead to death. If patients experience these serious side effects, they may need to stop taking Afinitor for a while or use a lower dose. Patients should tell their healthcare provider right away if they have any of these symptoms: new or worsening cough, shortness of breath, chest pain, difficulty breathing or wheezing.

Afinitor may make patients more likely to develop an infection, such as pneumonia, or a bacterial, fungal or viral infection. Viral infections may include reactivation of hepatitis B in people who have had hepatitis B in the past. In some people these infections may be severe, and can even lead to death. Patients may need to be treated as soon as possible. Patients should tell their healthcare provider right away if they have a temperature of 100.5?F or above, chills or do not feel well. Symptoms of hepatitis B or infection may include the following: fever, skin rash, joint pain and inflammation, tiredness, loss of appetite, nausea, pale stool or dark urine, yellowing of the skin or pain in the upper right side.

Afinitor can cause mouth ulcers and sores, which are the most frequently occurring side effects occurring in approximately 44%-70% advanced kidney cancer and advanced pancreatic NET patients taking Afinitor. Eighty-six percent of patients taking Afinitor for SEGA developed mouth ulcers/sores. Patients should tell their healthcare provider if they have pain, discomfort or open sores in their mouth. Their healthcare provider may tell them to use a special mouthwash or mouth gel that does not contain alcohol or peroxide.

Afinitor may cause kidney failure. In some people this may be severe and can even lead to death. Patients should have tests to check their kidney function before and during their treatment with Afinitor.

Patients will have regular blood tests before they start and as needed during their treatment with Afinitor. These tests will include tests to check the patient's blood cell count, kidney and liver function and blood sugar levels. Patients who receive Afinitor for the treatment of SEGA will need regular blood tests to measure how much Afinitor is in their blood since this will help their doctor decide how much Afinitor they need to take.

Afinitor may affect the way other medicines work, and other medicines can affect how Afinitor works. Using Afinitor with other medicines can cause serious side effects. Patients should tell their healthcare provider about all of the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements such as: St. John's Wort, and medicine for fungal infections, bacterial infections, tuberculosis, seizures, HIV-AIDS, heart conditions or high blood pressure and medicines that suppress their immune system. Patients should not drink grapefruit juice or eat grapefruit during their treatment with Afinitor as it may make the amount of Afinitor in their blood increase to a harmful level.

Patients should not take Afinitor tablets which are broken or crushed. Patients should not chew or crush the tablets.

The amount of Afinitor in the blood was increased in patients who had liver problems.  Patients should tell their healthcare provider about all their medical conditions, including if they have or have had liver problems, diabetes or high blood sugar, high cholesterol levels, infections, hepatitis B or other medical conditions.

Patients should tell their healthcare provider if they are scheduled to receive any vaccinations. Patients should not receive a live vaccine or be around people who have recently received a live vaccine during treatment with Afinitor.

It is not known if Afinitor will harm an unborn baby. Women should use effective birth control while using Afinitor and for eight weeks after stopping treatment.

Common side effects of Afinitor in patients with advanced pancreatic neuroendocrine tumors include mouth ulcers, rash, diarrhea, swelling of arms, hands, feet, ankles, face or other parts of the body, abdominal pain, nausea, fever and headache. Common side effects of Afinitor in patients with advanced kidney cancer include mouth ulcers, infections, feeling weak or tired, cough and diarrhea. Common side effects of Afinitor in patients with SEGA include mouth ulcers, infections of the respiratory tract, sinuses and ears and fever.

Please see full Prescribing Information for Afinitor.

About ZOMETA
ZOMETA (zoledronic acid) 4 mg/5 mL Injection is a treatment for hypercalcemia of malignancy (HCM; a condition resulting in high calcium blood levels due to cancer). ZOMETA is also used to reduce and delay bone complications due to multiple myeloma and bone metastases from solid tumors; used with anti-cancer medicines. ZOMETA is not an anti-cancer therapy. If you have prostate cancer, you should have failed treatment with at least one hormonal therapy prior to taking ZOMETA.

ZOMETA Important Safety Information 
Do not use ZOMETA if you have had a severe allergic reaction to zoledronic acid or any components of ZOMETA. These reactions, including rare cases of hives and angioedema (swelling often near your eyes and lips), and very rare cases of life-threatening allergic reactions, have been reported. ZOMETA is in a class of drugs called bisphosphonates, and contains the same active ingredient as that found in Reclast®(***) (zoledronic acid). If you are treated with ZOMETA, you should not be treated with Reclast.

If you have HCM, you should drink plenty of clear fluids before using ZOMETA. If you have kidney problems, tell your doctor. The risk of adverse reactions (especially related to the kidney) may be greater for you. ZOMETA treatment is not for patients with severe kidney problems. Patients with kidney problems on multiple cycles of ZOMETA or other bisphosphonates are at greater risk for further kidney problems. It is important to get your blood tests while you are receiving ZOMETA. Your doctor will monitor your kidney function before each dose. Tell your doctor if you are on other drugs, including aminoglycosides, loop diuretics, and drugs which may be harmful to the kidney.

Osteonecrosis of the jaw (ONJ) has been reported mainly in cancer patients treated with intravenous bisphosphonates, including ZOMETA. Many of these patients were also receiving anti-cancer drugs and corticosteroids, which may make it more likely to get ONJ. If you have advanced breast cancer or a type of cancer called multiple myeloma, or if you have had dental extraction, periodontal disease, local trauma, including poorly fitting dentures, you may be at greater risk of getting ONJ. Many reports of ONJ involved patients with signs of local infection, including bone/bone marrow inflammation. You should maintain good oral hygiene and have a dental examination with preventive dentistry prior to beginning ZOMETA. While on treatment, avoid invasive dental procedures, if possible, as recovery may take longer. If you develop ONJ while on bisphosphonate therapy, dental surgery may worsen the condition. If you require dental procedures, there are no data available to suggest whether stopping ZOMETA treatment reduces the risk of ONJ. A causal relationship between bisphosphonate use and ONJ has not been established. Based on your condition, your doctor will determine the treatment plan you will receive.

Do not use ZOMETA if you are pregnant or plan to become pregnant, or if you are breast-feeding.

Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates, including ZOMETA. Do not continue using ZOMETA if severe symptoms develop, as some patients had the symptoms reappear after taking ZOMETA or another bisphosphonate again. In aspirin sensitive patients, bronchoconstriction (tightening of the airways in the lungs) has been observed while taking bisphosphonates.

If you are an HCM patient with liver problems, talk to your doctor about whether ZOMETA is appropriate for you.

HCM patients may experience flu-like symptoms (fever, chills, flushing, bone pain and/or joint or muscle pain). Common side effects in HCM patients include fever, nausea, constipation, anemia, shortness of breath, diarrhea, abdominal pain, worsening of cancer, insomnia, vomiting, anxiety, urinary tract infection, low phosphate levels, confusion, agitation, a fungal infection called moniliasis, low potassium levels, coughing, skeletal pain, low blood pressure, and low magnesium levels.  Redness and swelling may occur at the site that you are injected.

Common side effects for patients with multiple myeloma and bone metastases due to solid tumors include bone pain, nausea, fatigue, anemia, fever, vomiting, constipation, shortness of breath, diarrhea, weakness, muscle pain, anorexia, cough, joint pain, lower-limb swelling, worsening of your cancer, headache, dizziness (excluding vertigo), insomnia, decreased weight, back pain, numbness/tingling, and abdominal pain. These side effects are listed regardless of any potential association with the medications used in registration studies of ZOMETA in bone metastases patients.

Eye-related side effects may occur with bisphosphonates, including ZOMETA. Cases of swelling related to fluid build-up in the eye, as well as inflammation of the uvea, sclera, episclera, conjunctiva, and iris of the eye have been reported.

Patients with multiple myeloma and bone metastases from solid tumors should be taking an oral calcium supplement of 500 mg and a multiple vitamin containing 400 IU of vitamin D daily.

Please see full Prescribing Information and talk to your doctor for more information.

About BKM120 and LBH589 (panobinostat)
Because these are investigational compounds, the safety and efficacy profile of BKM120 and LBH589 have not yet been established. Access to these investigational compounds is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Because of uncertainty of clinical trials, there is no guarantee that BKM120 and LBH589 will ever be commercially available anywhere in the world.

About Tasigna
TASIGNA® (nilotinib) is approved for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The effectiveness of TASIGNA for this indication is based on major molecular response and cytogenetic response rates at 12 months. The study is ongoing and further data will be required to determine long-term outcome.

TASIGNA is also approved in more than 90 countries for the treatment of chronic phase and accelerated phase Ph+ CML in adult patients resistant or intolerant to at least one prior therapy, including Gleevec. The effectiveness of TASIGNA for this indication is based on hematologic and cytogenetic response rates.

BOXED WARNING and Important Safety Information for TASIGNA (nilotinib)

WARNING: QT PROLONGATION AND SUDDEN DEATHS

 

- TASIGNA prolongs the QT interval. Prior to TASIGNA administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and follow any dose adjustments.

- Sudden deaths have been reported in patients receiving nilotinib. Do not administer TASIGNA to patients with hypokalemia, hypomagnesemia, or long QT syndrome.

- Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors.

- Patients should avoid food 2 hours before and 1 hour after taking dose.
 
•Treatment with TASIGNA can cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. Complete blood counts should be performed every 2 weeks for the first 2 months and then monthly thereafter.
•Caution is recommended in patients with a history of pancreatitis.
•The use of TASIGNA may result in elevations in bilirubin, AST/ALT, and alkaline phosphatase.
•TASIGNA can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia (see Boxed WARNING).
•The concomitant use of strong CYP3A4 inhibitors or anti-arrhythmic drugs (including, but not limited to, amiodarone, disopyramide, procainamide, quinidine, and sotalol) and other drugs that may prolong the QT interval (including, but not limited to, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, and pimozide) should be avoided. Grapefruit products should also be avoided. 
•The concomitant use of strong CYP3A4 inducers should be avoided (including, but not limited to, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's wort).
•TASIGNA must not be taken with food.
•TASIGNA exposure is increased in patients with impaired hepatic function.
•Cases of tumor lysis syndrome have been reported in TASIGNA treated patients with resistant or intolerant CML. Due to potential for tumor lysis syndrome, maintain adequate hydration and correct uric acid levels prior to initiating therapy with TASIGNA.
•The exposure of TASIGNA is reduced in patients with total gastrectomy.
•Since the capsules contain lactose, TASIGNA is not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency with a severe degree of intolerance to lactose-containing products, or of glucose-galactose malabsorption.
•Women of childbearing potential should avoid becoming pregnant while taking TASIGNA and should be advised of the potential hazard to the fetus if they do. The safety and effectiveness of TASIGNA in pediatric patients have not been established.
•In newly diagnosed Ph+ CML-chronic phase, the most commonly reported nonhematologic adverse drug reactions (>10%) were rash, pruritus, headache, nausea, fatigue, and myalgia.
•In resistant or intolerant Ph+ CML-chronic phase, the most commonly reported nonhematologic adverse drug reactions (greater than or equal to 10%) were rash, pruritus, nausea, fatigue, headache, constipation, diarrhea, vomiting, and myalgia.
•In resistant or intolerant Ph+ CML-accelerated phase, the most commonly reported nonhematologic adverse drug reactions (greater than or equal to 10%) were rash, pruritus, and fatigue.
•TASIGNA may need to be temporarily withheld and/or dose reduced for QT prolongation, hematologic toxicities that are not related to underlying leukemia, clinically significant moderate or severe nonhematologic toxicities, laboratory abnormalities, or concomitant use of strong CYP3A4 inhibitors.
Please see full Prescribing Information including Boxed Warning.

About Gleevec
Gleevec® (imatinib mesylate) tablets are indicated for newly diagnosed adult patients with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in the chronic phase (CP). Gleevec is also indicated for the treatment of patients with Ph+ CML in blast crisis (BC), accelerated phase (AP), or in CP after failure of interferon-alpha therapy.

GLEEVEC Important Safety Information
GLEEVEC is often associated with edema and occasionally serious fluid retention. Patients should be weighed and monitored regularly for signs and symptoms of fluid retention, which can be serious or life-threatening. Be advised to carefully investigate and provide appropriate management for unexpected weight gain. The probability of edema tended to be increased among older patients (>65 years) or those taking higher doses of GLEEVEC. If severe fluid retention occurs, GLEEVEC should be withheld until the event has resolved and then resumed depending on the initial severity of the event.

Cytopenias have been reported. Complete blood counts should be performed weekly for the first month, biweekly for the second month, and periodically thereafter as clinically indicated (for example, every 2-3 months). Dose reduction or treatment interruption may be required for severe neutropenia or thrombocytopenia (see full Prescribing Information for dose adjustment recommendations).

Severe congestive heart failure and left ventricular dysfunction have occasionally been reported. Most patients with reported cardiac events have had other comorbidities and risk factors, including advanced age and previous medical history of cardiac disease. Patients with cardiac disease or risk factors for cardiac failure should be monitored carefully, and any patient with signs or symptoms consistent with cardiac failure should be evaluated and treated.

Hepatotoxicity, occasionally severe, may occur. Cases of fatal liver failure and severe liver injury requiring liver transplants have been reported with both short-term and long-term use of GLEEVEC. Assess liver function before initiation of treatment and monthly thereafter or as clinically indicated. Monitor liver function when combined with chemotherapy known to be associated with liver dysfunction. A 25% decrease in the recommended dose should be used for patients with severe hepatic impairment. If severe hepatotoxicity occurs, GLEEVEC should be withheld until the event has resolved and then resumed depending on the initial severity of the event.

In the newly diagnosed CML trial, 1.8% of patients had (NCI Grades 3/4) hemorrhage. 

In patients with hypereosinophilic syndrome and cardiac involvement, cardiogenic shock and left ventricular dysfunction have been associated with initiation of GLEEVEC. The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures, and temporarily withholding GLEEVEC.

Bullous dermatologic reactions (eg, erythema multiforme and Stevens-Johnson syndrome) have also been reported. In some cases, the reaction recurred upon rechallenge. Several postmarketing reports describe patients able to tolerate the reintroduction of GLEEVEC at a lower dose with or without concomitant corticosteroids or antihistamines following resolution or improvement of the bullous reaction.

Clinical cases of hypothyroidism have been reported in thyroidectomy patients undergoing levothyroxine replacement during treatment with GLEEVEC. TSH levels should be closely monitored in such patients.

Consider potential toxicities—specifically liver, kidney, and cardiac toxicity—and immunosuppression from long-term use.

Fetal harm can occur when administered to a pregnant woman; therefore, women of childbearing potential should be advised to not become pregnant while taking GLEEVEC tablets and to avoid breast-feeding while taking GLEEVEC tablets because of the potential for serious adverse reactions in nursing infants. Sexually active female patients taking GLEEVEC should use adequate contraception. If the patient does become pregnant while taking GLEEVEC, the patient should be advised of the potential hazard to the fetus.

Growth retardation has been reported in children and pre-adolescents receiving GLEEVEC. The long-term effects of prolonged treatment with GLEEVEC on growth in children are unknown; therefore, monitoring of growth in children taking GLEEVEC is recommended.

Cases of tumor lysis syndrome (TLS), including fatal cases, have been reported. The patients at risk of TLS are those with tumors having a high proliferative rate or high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

In Ph+ CML trials(****), severe (NCI Grades 3/4) lab abnormalities—including neutropenia (3.6%-48%), anemia (1%-42%), thrombocytopenia (<1%-33%), and hepatotoxicity (approx 5%)—and severe adverse experiences (NCI Grades 3/4), including hemorrhage (1.8%-19%), fluid retention (eg, pleural effusion, pulmonary edema, and ascites) (2.5%-11%) and superficial edema (1.5%-6%), and musculoskeletal pain (2%-9%), were reported among patients receiving GLEEVEC. Severe fluid retention appears to be dose-related, was more common in the advanced phase studies (where the dosage was 600 mg/day), and is more common in the elderly.

There have also been reports, including fatalities, of cardiac tamponade, cerebral edema, acute respiratory failure, and gastrointestinal (GI) perforation.

GLEEVEC is metabolized by the CYP3A4 isoenzyme and is an inhibitor of CYP3A4, CYP2D6, and CYP2C9. Significant reductions in imatinib concentrations may occur when GLEEVEC is administered concomitantly with agents that are strong CYP3A4 inducers such as rifampin, St. John's wort, and enzyme-inducing anti-epileptic drugs, eg, phenytoin. The use of concomitant strong CYP3A4 inducers should be avoided. If patients must be administered a strong CYP3A4 inducer, the dosage of GLEEVEC should be increased by at least 50% and clinical response should be carefully monitored. Caution is recommended when GLEEVEC is administered with CYP3A4 inhibitors such as ketoconazole, with CYP2D6 substrates that have a narrow therapeutic window, or with CYP3A4 substrates that have a narrow therapeutic window. Other examples of commonly used drugs that may significantly interact with GLEEVEC include acetaminophen, warfarin, erythromycin, and metoprolol.  Grapefruit juice should also be avoided in patients taking GLEEVEC. (Please see full Prescribing Information for other potential drug interactions).

Patients with moderate renal impairment (CrCL = 20-39 mL/min) should receive a 50% decrease in the recommended starting dose and future doses can be increased as tolerated. Doses greater than 600 mg are not recommended in patients with mild renal impairment (CrCL = 40-59 mL/min). For patients with moderate renal impairment, doses greater than 400 mg are not recommended. GLEEVEC should be used with caution in patients with severe renal impairment.

Common Side Effects of GLEEVEC Tablets

Almost all adult Ph+ CML patients who received GLEEVEC in clinical studies experienced adverse reactions at some time, but most were mild to moderate in severity. The most frequently reported adverse reactions (all Grades) were superficial edema (60%-74%), nausea (50%-73%), diarrhea (43%-57%), musculoskeletal pain (38%-49%), rash and related terms (36%-47%), muscle cramps (28%-62%), and vomiting (23%-58%)(+).

Supportive care may help reduce the severity of some mild-to-moderate adverse reactions. However, in some cases, either a dose reduction or interruption of treatment with GLEEVEC may be necessary.

For daily dosing of 800 mg and above, dosing should be accomplished using the 400-mg tablet to reduce exposure to iron.

GLEEVEC tablets should be taken with food and a large glass of water to minimize GI irritation.

Patients should be informed to take GLEEVEC exactly as prescribed, and not to change their dose or stop taking GLEEVEC unless they are told to do so by their doctor. If patients miss a dose, they should be advised to take their dose as soon as possible unless it is almost time for their next dose, in which case the missed dose should not be taken. A double dose should not be taken to make up for any missed dose.

****For more detailed study information, please see full Prescribing Information.

(+)Numbers indicate the range of percentages in 4 studies among adult patients, with newly diagnosed Ph+ CML, patients in blast crisis, accelerated phase, and in the chronic phase after failure of interferon-alpha therapy.

About Exjade
Exjade is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in adult and pediatric patients (aged 2 years and over). It is approved in over 100 countries including the U.S., Switzerland, Japan, and the countries comprising the European Union. The approved indication may vary depending upon the individual country.

Exjade important safety information
Exjade is contraindicated in patients with creatinine clearance <40 ml>2 times the age-appropriate upper limit of normal; poor performance status and high-risk myelodysplastic syndromes or advanced malignancies: platelet counts <50 x 109>

There have been postmarketing reports of acute renal failure, hepatic failure, and cytopenias. Renal failure requiring temporary or permanent dialysis, renal tubulopathy, and interstitial nephritis have been reported. Upper gastrointestinal ulceration and hemorrhage, sometimes fatal, have been reported. Caution should be used in elderly patients due to a higher frequency of adverse reactions. Exjade is not recommended in patients with a short life expectancy (e.g., high-risk myelodysplastic syndromes), especially when co-morbidities could increase the risk of adverse events.

Skin rashes, serious hypersensitivity reactions, decreased hearing, and lens opacities have been reported. The most common adverse reactions are nausea, vomiting, diarrhea, abdominal pain, rash, non?progressive increases in serum creatinine, increased transaminases, abdominal distension, constipation, dyspepsia, proteinuria, and headache. 

Please visit www.exjade.com for more information.

About INC424 (ruxolitinib)
INC424 (ruxolitinib) is an oral inhibitor of the JAK1 and JAK2 tyrosine kinases. INC424 is being investigated in primary myelofibrosis as well as post-polycythemia vera  myelofibrosis (PPV-MF) and post-essential thrombocythemia myelofibrosis (PET-MF). INC424 is also being investigated in clinical trials for the treatment of polycythemia vera (PV).

Novartis licensed INC424 from Incyte for development and potential commercialization outside the US. Incyte has retained rights for the development and potential commercialization of INC424 in the US. Both the US Food and Drug Administration and the European Medicines Agency have granted INC424 orphan drug status for myelofibrosis.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "will," "goal," "potential," or similar expressions, or by express or implied discussions regarding potential new indications or labeling, or potential marketing approvals for Novartis Oncology products, or regarding potential future revenues from such products. You should not place undue reliance on these statements.  Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that any additional indications or labeling will be approved for any existing Novartis Oncology products, or that any new Novartis Oncology products will be approved for sale in any market, or at any particular time. Nor can there be any guarantee that any such products will achieve any particular levels of revenue in the future. In particular, management's expectations could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; unexpected manufacturing issues; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Novartis Group companies employ approximately 121,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.

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References
(1)  San Antonio Breast Cancer Symposium. SABCS Annual '11 Meeting Program. Available at http://www.sabcs.org/ProgramSchedule/index.asp. Accessed November 2011.

(2)  American Society of Hematology. ASH Annual '11 Meeting Program. Available at http://ash.confex.com/ash/2011/webprogram/start.html. Accessed November 2011.

(*) Novartis and Incyte Corporation have a worldwide collaboration and licensing agreement for INC424.

(**)Known as Glivec® (imatinib) outside the US, Canada and Israel.

(#) Rapamune® (sirolimus) and Torisel® (temsirolimus) are registered trademarks of Wyeth Pharmaceuticals Inc.

(***) Known as Aclasta outside the US.

 
 
 
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Novartis Oncology    
 Novartis Corporation
 
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SOURCE Novartis Pharmaceuticals Corporation


 

Posted: December 2011

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