From the Wires
Novartis highlights key data in patients with hematologic diseases and breast cancer with more than 140 abstracts at ASH and SABCS
-- Long-term follow-up data from Jakavi® Phase III trials in patients with the debilitating blood cancer, myelofibrosis
By: PR Newswire
Nov. 28, 2012 01:20 AM
EAST HANOVER, N.J., Nov. 28, 2012 /PRNewswire/ -- Novartis will highlight more than 140 presentations on key data from its extensive oncology portfolio at the leading year-end scientific meetings devoted to hematology and breast cancer, demonstrating continued innovation in research and development efforts to advance the care of patients with cancer and rare diseases.
The American Society of Hematology (ASH) annual meeting in Atlanta, held December 8-11, will feature significant data across hematologic diseases including two-year follow-up data from Phase III trials of Jakavi® (ruxolitinib) in patients treated with Jakavi for myelofibrosis and data evaluating molecular response following treatment with Tasigna® (nilotinib) in patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) compared with Gleevec® (imatinib mesylate)* tablets therapy. In addition, updated data on Exjade® (deferasirox) in non-transfusion-dependent thalassemia (NTDT), as well as new data on the removal of cardiac iron in β-thalassemia major, will be presented.
Several studies of novel pipeline compounds will also be presented, including additional Phase I/II findings extending proof-of-concept data for the investigational therapy CTL019 (formerly known as CART-19)† in patients with chronic lymphocytic leukemia (CLL) and relapsed refractory acute lymphoblastic leukemia (ALL)1.
"For more than a decade, Novartis Oncology has discovered critical medicines for cancer patients by following the science," said Herve Hoppenot, President, Novartis Oncology. "The presentations at this year's annual meetings show that our research and development pipeline has never been stronger, and we expect new breakthroughs that could lead to even more innovative therapies for patients."
The CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), held December 4-8, will showcase studies exploring therapy with the mTOR inhibitor Afinitor® (everolimus) and the investigational PI3K inhibitors BYL719 and BKM120 in patients with hormone receptor-positive (HR+), HER2/neu-negative (HER2-) advanced breast cancer2.
"Novartis is committed to helping fulfill the large unmet treatment need for patients with advanced breast cancer, and we are continuing to investigate the potential benefits and utility of Afinitor in this population," said Alessandro Riva, Global Head, Oncology Development & Medical Affairs, Novartis Oncology. "The company will also showcase promising results from our pipeline of PI3K/mTOR inhibitors highlighting our commitment to ongoing exploration of compounds that impact key disease pathways."
Highlights at ASH include:
Highlights at SABCS include:
Jakavi® (INC424, ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases3 and was approved by the European Commission in August 2012 for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. Jakavi is available in more than 30 countries including the European Union member states and Canada, with additional global regulatory filings underway.
Novartis licensed INC424 (ruxolitinib) from Incyte Corporation for development and commercialization outside the US. Both the European Commission and the US Food and Drug Administration (FDA) granted INC424 (ruxolitinib) orphan drug status for myelofibrosis. Jakavi is marketed in the United States by Incyte Corporation under the name Jakafi® for the treatment of patients with intermediate or high-risk myelofibrosis.
Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation.
Jakavi® Important Safety Information
Jakavi® can cause serious side effects, including a decrease in blood cell count and infections. Complete blood count monitoring is recommended. Dose reduction or interruption may be required in patients with severe hepatic or renal impairment or in patients developing hematologic adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose reductions are also recommended when Jakavi is co-administered with strong CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not recommended and women should avoid becoming pregnant during Jakavi therapy. Women taking Jakavi should not breast feed.
The most common adverse drug reactions, occurring at any level of severity, (incidence >10%) are urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolaemia, dizziness, headache, alanine aminotransaminase increased, asparte aminotransferase increased, bruising, bleeding and increased blood pressure. Other common adverse drug reactions (incidence 1 to 10%) are herpes zoster, weight gain, flatulence and tuberculosis (1%).
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):
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.
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 can cause fetal harm when administered to a pregnant woman. Women should not become pregnant, and should be advised of the potential risk to the unborn child.
GLEEVEC is often associated with edema (swelling) and serious fluid retention. Studies have shown that edema (swelling) tended to occur more often among patients who are 65 and older or those taking higher doses of GLEEVEC.
Cytopenias (reduction or lack of certain cell elements in blood circulation), such as anemia, have occurred. If the cytopenia is severe, your doctor may reduce your dose or temporarily stop your treatment with GLEEVEC.
Severe congestive heart failure and left ventricle dysfunction have been reported, particularly in patients with other health issues and risk factors. Patients with heart disease or risk factors or history of renal failure will be monitored and treated for the condition.
Severe liver problems (hepatotoxicity) 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.
Bleeding may occur. Severe gastrointestinal (GI) bleeding has been reported in patients with KIT+ GIST. GI tumor sites may be the cause of this bleeding; therefore, GI symptoms should be monitored at the start of treatment.
In patients with hypereosinophilic syndrome (a condition with increased eosinophils, which are a type of white blood cell) and heart involvement, cases of heart disease (cardiogenic shock/left ventricular dysfunction) have been associated with the initiation of GLEEVEC therapy.
Skin reactions, such as fluid-filled blisters, have been reported with the use of GLEEVEC.
Clinical cases of hypothyroidism (reduction in thyroid hormones) have been reported in patients taking levothyroxine replacement with GLEEVEC.
Long-term use may result in potential liver, kidney, and/or heart toxicities; immune system suppression may also result from long-term use.
GI perforation (small holes or tears in the walls of the stomach or intestine), in some cases fatal, has been reported.
Growth retardation has been reported in children taking GLEEVEC. The long-term effects of extended treatment with GLEEVEC on growth in children are unknown.
Cases of tumor lysis syndrome (TLS), which refers to a metabolic and electrolyte disturbance caused by the breakdown of tumor cells, have been reported and can be life-threatening in some cases. Correction of clinically significant dehydration and treatment of high uric acid levels are recommended prior to initiation of GLEEVEC.
Reports of motor vehicle accidents have been received in patients receiving GLEEVEC. Caution patients about driving a car or operating machinery.
Almost all patients treated with GLEEVEC experience side effects at some time. Some common side effects you may experience are fluid retention, muscle cramps or pain and bone pain, abdominal pain, loss of appetite, vomiting, diarrhea, decreased hemoglobin, abnormal bleeding, nausea, fatigue and rash.
GLEEVEC is sometimes associated with stomach or intestinal irritation. GLEEVEC should be taken with food and a large glass of water to minimize this problem. There have been rare reports, including deaths, of stomach or intestinal perforation (a small hole or tear).
If you are experiencing any of the mentioned side effects, please be sure to speak with your doctor immediately.
Do not take any other medications without talking to your doctor or pharmacist first, including Tylenol® (acetaminophen); herbal products (St. John's wort, Hypericum perforatum); Coumadin® (warfarin sodium); rifampin; erythromycin; metoprolol; ketoconazole; and Dilantin® (phenytoin). Taking these with GLEEVEC may affect how they work, or affect how GLEEVEC works.
You should also tell your doctor if you are taking or plan to take iron supplements. Patients should also avoid grapefruit juice and other foods that may affect how GLEEVEC works.
Please see full Prescribing Information.
Exjade® is an oral iron chelation therapy indicated for the treatment of chronic iron overload due to blood transfusions in adult and pediatric patients (aged 2 years and over). It is approved in more than 100 countries including the US, Switzerland, Japan and the countries comprising the EU. The approved indication may vary depending upon the individual country.
Exjade® Important Safety Information
Exjade is contraindicated in patients with creatinine clearance <40 mL/min or serum creatinine >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/L; known hypersensitivity to deferasirox or any component of Exjade.
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. The full prescribing information including the Boxed Warning for Exjade is available at http://www.pharma.us.novartis.com/product/pi/pdf/exjade.pdf.
About Afinitor (everolimus)
Afinitor® (everolimus) is approved in the United States for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole.
For more information visit www.AFINITOR.com or call 1-888-4-AFINITOR. US patients who may be eligible for financial assistance can learn about the Novartis Patient Assistance Now Oncology (PANO) reimbursement support program by contacting 1-800-282-7630 or visiting the Afinitor website.
In the United States, Afinitor tablets is approved for the treatment of adult patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib and for the treatment of progressive neuroendocrine tumors of pancreatic origin in adult patients with unresectable, locally advanced or metastatic disease. 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 approved for the treatment of adult patients with renal angiomyolipomas and tuberous sclerosis complex (TSC), who do not require immediate surgery. The effectiveness of Afinitor in treatment of renal angiomyolipoma is based on an analysis of durable objective responses in patients treated for a median of 8.3 months. Further follow-up of patients is required to determine long-term outcomes. In addition, Afinitor and Afinitor Disperz™ are approved in the United States in pediatric and adult patients with TSC for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. Effectiveness is based on demonstration of durable objective response, as evidenced by reduction in SEGA tumor volume. Improvement in disease-related symptoms and overall survival in patients with SEGA and TSC have not been demonstrated.
In the United States, Afinitor 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 Afinitor 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 Afinitor has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that Afinitor will become commercially available for additional indications anywhere else in the world.
Afinitor® Important Safety Information
Patients should not take Afinitor or Afinitor Disperz if they are allergic to Afinitor or Afinitor Disperz or to any of its ingredients. Patients should tell their healthcare provider before taking Afinitor or Afinitor Disperz if they are allergic to sirolimus (Rapamune®) or temsirolimus (Torisel®).
Afinitor or Afinitor Disperz can cause serious side effects, including lung or breathing problems, infections, and kidney failure, which can even lead to death. If patients experience these side effects, they may need to stop taking Afinitor or Afinitor Disperz for a while or use a lower dose. Patients should follow their healthcare provider's instructions.
In some patients, lung or breathing problems may be severe and can even lead to death. 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 or Afinitor Disperz 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, chills, skin rash, joint pain and inflammation, tiredness, loss of appetite, nausea, pale stools or dark urine, yellowing of the skin, or pain in the upper right side of the stomach.
Afinitor or Afinitor Disperz 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 or Afinitor Disperz.
Common side effects include mouth ulcers. Afinitor or Afinitor Disperz can cause mouth ulcers and sores. Other common side effects include infections, feeling weak or tired, nausea and vomiting, skin problems, headache, weight loss, loss of appetite, cough, diarrhea, fever, swelling of the hands, arms, legs, feet, face, or other parts of the body, joint pain, abnormal taste, stomach-area (abdomen) pain, nose bleeds, seizure, increased blood cholesterol and sugar levels, decreased blood phosphate levels, low red and white blood cells, and the absence of menstrual periods (menstruation).
Please see full Prescribing Information for AFINITOR and AFINITOR DISPERZ available at AFINITOR.com.
About CTL019, PKC412, LBH589 and BKM120
Because these are investigational compounds, the safety and efficacy profile of CTL019, PKC412, LBH589 and BKM120 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 CTL019, PKC412, LBH589 and BKM120 will ever be commercially available anywhere in the world.
The foregoing release contains forward-looking statements that can be identified by terminology such as "pipeline," "ongoing," "commitment," "will," "expects," "could," "committed," "potential," "exploration," "explores," or similar expressions, or by express or implied discussions regarding potential marketing submissions or approvals for investigational compounds, or potential new indications or labeling for existing 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 of the investigational compounds referred to in this release will be submitted or approved for sale in any market, or at any particular time. Nor can there be any guarantee that any of the approved products referred to in this release will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that any of the investigational compounds or products referred to in this release will achieve any particular levels of revenue in the future. In particular, management's expectations regarding such products 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; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; 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.
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets innovative prescription drugs used to treat a number of diseases and conditions, including cardiovascular, dermatological, central nervous system, bone disease, cancer, organ transplantation, psychiatry, infectious disease and respiratory. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
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 2011, the Group's continuing operations achieved net sales of USD 58.6 billion, while approximately USD 9.6 billion (USD 9.2 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Novartis Group companies employ approximately 127,000 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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* Known as Glivec® (imatinib) outside the US, Canada and Israel.
1. American Society of Hematology. ASH Annual 2012 Meeting Program. Available at https://ash.confex.com/ash/2012/webprogram/start.html. Accessed November 2012.
2. San Antonio Breast Cancer Symposium. SABCS Annual 2012 Meeting Program. Available at http://www.sabcs.org/ProgramSchedule/index.asp. Accessed November 2012.
3. JAKAVI [Summary of Product Characteristics]. Basel, Switzerland: Novartis Pharma AG; 2012.
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