Novartis highlights key data in patients with hematologic diseases and breast cancer with more than 140 abstracts at ASH and SABCS

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 Glivec® (imatinib)* 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 Beta-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 Hervé 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 cancer[2].

“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:

• Jakavi (ruxolitinib) – Long-term safety, efficacy and survival findings from COMFORT-II (COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment), a Phase III study comparing ruxolitinib with best available therapy for the treatment of myelofibrosis (ASH abstract #801; December 10, 6:45 PM EST). Long-term outcome of ruxolitinib treatment in patients with myelofibrosis: durable reductions in spleen volume, improvements in quality of life and overall survival advantage in COMFORT-I (ASH abstract #800; December 10, 6:30 PM EST).
• Tasigna (nilotinib) – Two-year follow-up results from Evaluating Nilotinib Efficacy and Safety in Clinical Trials – Complete Molecular Response (ENESTcmr), evaluating sustained deeper molecular response following a switch to Tasigna in patients with Ph+ CML in chronic phase who still had evidence of residual disease after two or more years of Glivec therapy (ASH abstract #694; December 10, 5:15 PM EST). Long-term landmark data from Evaluating Nilotinib Efficacy and Safety in Clinical Trials – Newly Diagnosed Patients (ENESTnd), correlating early molecular response and outcome of patients with Ph+ CML in chronic phase (ASH abstract #167; December 9, 5:30 PM EST). Four-year update from ENESTnd evaluating superiority of Tasigna vs. Glivec in patients with newly diagnosed Ph+ CML in chronic phase (ASH abstract #1676; December 8, 5:30 PM EST).
• Exjade (deferasirox) – Two-year update to THALASSA, the first randomized, placebo-controlled study evaluating reduction of liver iron concentration and serum ferritin in patients with NTDT syndromes after treatment with deferasirox oral iron chelation therapy (ASH abstract #3258; December 10, 6:00 PM EST). First data from CORDELIA, the first head-to-head multicenter, randomized, open-label trial evaluating deferasirox compared with deferoxamine for the removal of cardiac iron in patients with Beta-thalassemia major and iron overload (ASH abstract #2124; December 9, 6:00 PM EST).
• CTL019 (CART-19) – Outcomes and extended follow-up from a Phase I/II study in patients with advanced, refractory and high-risk CLL and relapsed refractory ALL treated with CART-19 cells (ASH abstract #717; December 10, 5:00 PM EST).
• PKC412 (midostaurin) – First presentation from the pivotal Phase II study of PKC412 in patients with advanced systemic mastocytosis and mast cell leukemia (ASH abstract #799; December 10, 6:15 PM EST).
• LBH589 (panobinostat) – Updated results from PANORAMA-2 (PANobinostat ORAl in Multiple myelomA) Phase II study of LBH589 in combination with bortezomib (BTZ) and dexamethasone in patients with relapsed and BTZ-refractory multiple myeloma (ASH abstract #1852; December 8, 5:30 PM EST).

Highlights at SABCS include:

• Afinitor (everolimus) – New data from a Phase II clinical trial evaluating Afinitor (everolimus) in combination with fulvestrant in postmenopausal women with HR+ advanced breast cancer who progressed on a previous endocrine therapy (SABCS abstract #P2-14-05; December 6, 7:00 AM CST) and an additional Phase II study evaluating the potential efficacy of Afinitor in combination with letrozole (SABCS abstract #P5-20-06; December 7, 5:00 PM CST). Final progression-free survival analysis of BOLERO-2 Phase III trial of Afinitor plus exemestane for postmenopausal women with HR+/HER2- advanced breast cancer after failure of letrozole or anastrazole (SABCS abstract #P6-04-02; December 8, 7:00 AM CST).
• BYL719 – Preliminary results from a Phase I study of BYL719 in patients with PIK3CA mutant ER+ metastatic breast cancer (SABCS abstract #P6-10-07; December 8, 7:00 AM CST).
• BKM120 – Abstract highlighting trial in progress BELLE-3 Phase III randomized study of PI3K inhibitor BKM120 in combination with fulvestrant in postmenopausal women with HR+/HER2- advanced breast cancer whose disease has progressed after treatment with an aromatase inhibitor and on or after an mTOR inhibitor (SABCS abstract #OT2-3-08; December 6, 5:00 PM CST).
• LBH589 (panobinostat) – Pre-clinical data explores the potential utility of HDAC inhibition in triple-negative breast cancer alone and in combination with other agents (SABCS abstract #S3-7; December 6, 9:30 AM CST).

About Jakavi (ruxolitinib)

Jakavi (INC424, ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases[3] 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, hypercholesterolemia, 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%).

Please see full Prescribing Information for Jakavi available at www.jakavi.com.

About Tasigna (nilotinib)

Tasigna (nilotinib) is approved in more than 90 countries for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) in adult patients resistant or intolerant to at least one prior therapy, including imatinib, and/or for the treatment of adult patients with newly diagnosed Ph+ CML in chronic phase. Take twice daily 12 hours apart. Do not take with food. No food to be consumed for 2 hours before or one hour after dosing. Avoid grapefruit juice and CYP3A4 inhibitors.

Tasigna Important Safety Information

Use with caution in patients with uncontrolled or significant cardiac disease and in patients who have or may develop prolongation of QTc. Low levels of potassium or magnesium must be corrected prior to Tasigna administration. Monitor closely for an effect on the QTc interval. Baseline ECG is recommended prior to initiating therapy and as clinically indicated. Uncommon cases (0.1 to 1%) of sudden death have been reported in clinical studies in patients with significant risk factors.

Use with caution in patients with liver impairment, with a history of pancreatitis and with total gastrectomy. Patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption should not use Tasigna. Tasigna may cause fetal harm in pregnant women. Women taking Tasigna should not breastfeed.

The most frequent Grade 3 or 4 adverse events are hematological (neutropenia and thrombocytopenia) which are generally reversible and usually managed by withholding Tasigna temporarily or dose reduction. Monitor blood counts regularly. Pancreatitis has been reported. The most frequent non-hematologic adverse events were rash, pruritus, nausea, fatigue, headache, alopecia, myalgia, constipation and diarrhea. Most of these adverse events were mild to moderate in severity.

Please see full Prescribing Information.

About Glivec (imatinib)

Glivec (imatinib) is approved in more than 110 countries for the treatment of all phases of Ph+ CML, for the treatment of adult patients with KIT (CD117)-positive gastrointestinal stromal tumors (GIST) which cannot be surgically removed and/or have metastasized, and for the treatment of adult patients following complete surgical removal of KIT+ GIST. Take with food and a large glass of water.

Glivec Important Safety Information

Glivec can cause fetal harm in pregnant woman. Glivec has been associated with severe edema (swelling) and serious fluid retention. Cytopenias (anemia, neutropenia, thrombocytopenia) are common, generally reversible and usually managed by withholding Glivec or dose reduction. Monitor blood counts regularly. Severe congestive heart failure and left ventricle dysfunction, severe liver problems including cases of fatal liver failure and severe liver injury requiring liver transplants have been reported. Use caution in patients with cardiac dysfunction and hepatic dysfunction. Monitor carefully.

Bleeding may occur. Severe gastrointestinal (GI) bleeding has been reported in patients with KIT+ GIST. Skin reactions, hypothyroidism in patients taking levothyroxine replacement, GI perforation, in some cases fatal and tumor lysis syndrome, which can be life threatening, have also been reported with Glivec. Correct dehydration and high uric acid levels prior to treatment. Long-term use may result in potential liver, kidney, and/or heart toxicities; immune system suppression may also result from long-term use. In patients with hypereosinophilic syndrome and heart involvement, cases of heart disease have been associated with the initiation of Glivec therapy. Growth retardation has been reported in children taking Glivec. The long-term effects of extended treatment with Glivec on growth in children are unknown.

The most common side effects include fluid retention, muscle cramps or pain and bone pain, abdominal pain, loss of appetite, vomiting, diarrhea, decreased hemoglobin, abnormal bleeding, nausea, fatigue and rash.

Please see full Prescribing Information.

About Exjade (deferasirox)

Exjade (deferasirox) is an oral iron chelation therapy indicated for the treatment of chronic iron overload due to frequent blood transfusions (>=7 ml/kg/month of packed red blood cells) in patients with beta thalassemia aged 6 years and older). It is also indicated for the treatment of chronic iron overload due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient groups: patients with beta thalassemia major with iron overload due to frequent blood transfusions (>=7 ml/kg/month of packed red blood cells) aged 2 to 5 years; patients with beta thalassemia major with iron overload due to infrequent blood transfusions (<7 ml/kg/month of packed red blood cells) aged 2 years and older; and patients with other anemias aged 2 years and older[4].

It is approved in more than 100 countries including the US, Switzerland, Japan and countries comprising the EU. The approved indication may vary depending upon the individual country.

Exjade Important Safety Information

Exjade is contraindicated in patients with an estimated creatinine clearance <60 mL/min, with hypersensitivity to the active substance or any of the excipients, or in combination with other iron chelator therapies. Exjade is not recommended in patients with severe hepatic impairment.

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 Afinitor (everolimus)

Afinitor (everolimus) is approved in the European Union for the treatment of hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor. In the United States, Afinitor is approved 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.

Afinitor (everolimus) tablets is approved in more than 80 countries including the United States and throughout the European Union in the oncology settings of advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy, and in the United States and European Union for locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin.

Everolimus is also approved as Votubia® (everolimus) tablets in the European Union for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC) who are at risk of complications (based on factors such as tumor size or presence of aneurysm, or presence of multiple or bilateral tumors) but who do not require immediate surgery. The evidence is based on analysis of change in sum of angiomyolipoma volume. Votubia is also approved in the EU for the treatment of patients aged 3 years and older with subependymal giant cell astrocytoma (SEGA) associated with TSC, who require therapeutic intervention but are not amenable to surgery. The evidence is based on analysis of change in SEGA volume. Further clinical benefit, such as improvement in disease-related symptoms, has not been demonstrated.

Everolimus is also available from Novartis for use in non-oncology patient populations under the brand names Certican® and Zortress® and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country. 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 Important Safety Information

Afinitor/Votubia can cause serious side effects including lung or breathing problems, infections and renal failure, which can lead to death. Mouth ulcers and mouth sores are common side effects. Afinitor/Votubia can affect blood cell counts, kidney and liver function, and blood sugar and cholesterol levels. Afinitor/Votubia may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Afinitor/Votubia and for up to eight weeks after ending treatment. Women taking Afinitor/Votubia should not breast feed.

The most common adverse drug reactions (incidence >=15%) are mouth ulcers, diarrhea, feeling weak or tired, skin problems (such as rash or acne), infections, nausea, swelling of extremities or other parts of the body, loss of appetite, headache, inflammation of lung tissue, abnormal taste, nose bleeds, inflammation of the lining of the digestive system, weight decreased and vomiting. The most common grade 3-4 adverse drug reactions (incidence >=2%) are mouth ulcers, feeling tired, low white blood cells (a type of blood cell that fights infection), diarrhea, infections, inflammation of lung tissue, diabetes and amenorrhea. Cases of hepatitis B reactivation and blood clots in the lung and leg have been reported.

Please see full Prescribing Information.

About CTL019, PKC412, LBH589, BYL719 and BKM120

Because these are investigational compounds, the safety and efficacy profile of CTL019, PKC412, LBH589, BYL719 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, BYL719 and BKM120 will ever be commercially available anywhere in the world.

References

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.
4. EMC. Summary of product characteristics: EXJADE 125 mg, 250mg, 500mg dispersible tablets. Last updated January 13, 2012. Accessed at http://www.medicines.org.uk/emc/medicine/18805.