Data at ASH, SABCS demonstrate commitment of Novartis R&D in advancing treatments for patients with cancer and rare diseases

- 24-month update on Phase III data comparing Tasigna® to Gleevec® in patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase

- Afinitor® plus hormonal therapy studied in patients with ER+/HER2- metastatic breast cancer with prior exposure to aromatase inhibitors

- Zometa® studies continue to explore anticancer effect in multiple myeloma and breast cancer

- Pipeline advances with presentations on multiple investigational compounds, including pivotal results for LBH589 in relapsed/refractory Hodgkin lymphoma

EAST HANOVER, N.J., Dec. 1, 2010 /PRNewswire/ -- With more than 170 presentations focused on its marketed and pipeline compounds at key oncology medical congresses in December, Novartis continues to demonstrate progress of its innovative research and development efforts, collaboration with the scientific community and commitment to patients with cancer and rare diseases(1,2).

The American Society of Hematology (ASH) annual meeting in Orlando, FL (December 4-7) will feature 30 oral presentations on Novartis Oncology compounds including Tasigna® (nilotinib) 150 mg capsules, Gleevec®  (imatinib mesylate) tablets*, Afinitor® (everolimus) tablets, Exjade® (deferasirox), Zometa® (zoledronic acid) and LBH589 (panobinostat)(1). The San Antonio Breast Cancer Symposium (SABCS), beginning December 8, will feature presentations on everolimus and Zometa(2).

"These data highlight progress of our hematology and oncology research with a focus on developing new treatment approaches based on an understanding of the molecular pathways involved in diseases," said Herve Hoppenot, President of Novartis Oncology. "Our goal is to bring the right treatment to the right patient across a broad range of cancers and rare diseases."

Key presentations at ASH include:

  • Tasigna – ENESTnd 24-month update comparing Tasigna to Gleevec in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (ASH Abstract #207; Dec. 6; 7:30 AM EST) (3).

  • Afinitor Two studies showing activity of everolimus in mantle cell lymphoma (ASH Abstract #2803; Dec. 5; 6:00-8:00 PM EST)(4); (ASH Abstract #3963; Dec. 6; 6:00-8:00 PM EST)(5).

  • Exjade – EPIC sub-studies presenting three-year, end-of-study data on cardiac iron removal (ASH Abstract #4276; Dec. 6; 6:00-8:00 PM EST)(6) and post-hoc analysis from a large study reporting hematologic response in a cohort of MDS patients (ASH Abstract #2912; Dec. 5; 6:00-8:00 PM EST)(7); the first study (109E) to report on long-term safety and efficacy in sickle-cell disease patients up to five years (ASH Abstract #845; Dec. 6; 7:15 PM EST)(8); and the first large study (107E/108E) to assess effect of iron chelation therapy on liver pathology in large cohort of beta-thalassemia patients (ASH Abstract #4274; Dec. 6; 6:00-8:00 PM EST)(9).

  • Zometa – Phase III data evaluating Zometa in the treatment of patients with newly diagnosed multiple myeloma (ASH Abstract #311; Dec. 6; 8:00 AM EST)(10).

  • LBH589 (panobinostat) – Pivotal Phase II data for LBH589 in the treatment of Hodgkin lymphoma patients who relapse or are refractory after autologous stem cell transplant (ASH Abstract #419; Dec. 6; 11:30 AM EST)(11).

  • INC424** – Phase II data showing response rates to INC424 in patients with polycythemia vera (ASH Abstract #313; Dec. 6; 7:00 AM EST)(12); Phase II data of INC424 in patients with refractory leukemias including post-myeloproliferative disorder and acute myeloid leukemia (ASH Abstract #509; Dec. 6; 3:45 PM EST)(13).

  • PKC412 (midostaurin) – Phase II data evaluating midostaurin in the treatment of aggressive systemic mastocytosis (ASH Abstract #316; Dec. 6; 7:45 AM EST)(14).

  • HCD122 (lucatumumab) – Clinical activity evaluated in patients with relapsed/refractory Hodgkin or non-Hodgkin lymphoma treated in a Phase Ia/II trial (ASH Abstract #284; Dec. 6; 7:15 AM EST)(15).

Key presentations at SABCS include:

  • Afinitor – TAMRAD Phase II data on everolimus in the treatment of ER+/HER2- metastatic breast cancer after failure of aromatase inhibitors (SABCS Abstract #S1-6; Dec. 9; 10:30 AM CST)(16).

  • Zometa – Phase III data from the AZURE trial (BIG 01/04) of adjuvant treatment with Zometa in stage II/III breast cancer (SABCS Abstract #S4-5; Dec. 10; 4:15 PM CST)(17); Phase III data analyses from the ABCSG-12 trial evaluating the carry-over effect of Zometa in premenopausal women with early breast cancer after completion of therapy (SABCS Abstract #P5-11-02; Dec. 11; 5:30-7:30 PM CST)(18).

  • BEZ235 – Clinical data from a dose-escalation study with a special drug delivery system of BEZ235 in patients with metastatic/advanced solid tumors (SABCS Abstract #P6-15-07; Dec. 12, 7:00-8:30 PM CST)(19).

About Tasigna

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

Tasigna is indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) in adult patients resistant or intolerant to prior therapy that included imatinib. The effectiveness of Tasigna is based on hematologic and cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.

Tasigna has been approved in more than 80 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. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.

Tasigna important safety information

Tasigna can cause a possible life-threatening heart problem called QTc prolongation. QTc prolongation causes an irregular heartbeat, which may lead to sudden death.

Your doctor should check the electrical activity of your heart with a test called an electrocardiogram (ECG):

  • Before starting Tasigna
  • 7 days after starting Tasigna
  • With any dose changes
  • Regularly during Tasigna treatment

You may lower your chances for having QTc prolongation with Tasigna if you:

  • Take Tasigna:
    • On an empty stomach. Do not take Tasigna with food.
    • At least 2 hours after eating any food, and
    • Wait at least 1 hour before eating any food
  • Avoid grapefruit, grapefruit juice, and any supplement containing grapefruit extract while taking Tasigna.  Food and grapefruit products increase the amount of Tasigna in your body.
  • Avoid taking other medicines or supplements with Tasigna that can also cause QTc prolongation.
  • Tasigna can interact with many medicines and supplements and increase your chance for serious and life-threatening side effects.
  • Do not take any other medicine while taking Tasigna unless your doctor tells you it is okay to do so.

Call your doctor right away if you feel lightheaded, faint or have an irregular heartbeat while taking Tasigna. These can be symptoms of QTc prolongation.

What is Tasigna?

Tasigna is a prescription medicine used to treat a type of leukemia called Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in adults who:

  • Are newly diagnosed, or
  • Are no longer benefiting from previous other treatments, including treatment with imatinib (Gleevec®), or
  • Have taken other treatments, including imatinib (Gleevec®), and cannot tolerate them

It is not known if Tasigna is safe or effective in children.

Who should not take Tasigna?

Do not take if you have:

  • Low levels of potassium or magnesium in your blood
  • Long QTc syndrome

What should I tell my doctor before starting Tasigna?

Tasigna may not be right for you . Before taking Tasigna, tell your doctor about all of your medical conditions, including if you have:

  • Heart problems
  • Irregular heartbeat
  • QTc prolongation or a family history of it
  • Liver problems
  • Had pancreatitis
  • Low blood levels of potassium or magnesium in your blood
  • A severe problem with lactose (milk sugar) or other sugars. The Tasigna capsules contain lactose. Most patients who have mild or moderate lactose intolerance can take Tasigna.
  • Had a surgical procedure involving the removal of the entire stomach (total gastrectomy)
  • Are pregnant or plan to become pregnant. Tasigna may harm your unborn baby. If you are able to become pregnant, you should use effective birth control during treatment with Tasigna. Talk to your doctor about the best birth control methods to prevent pregnancy while you are taking Tasigna.
  • Are breastfeeding or plan to breastfeed. It is not known if Tasigna passes into your breast milk. You and your doctor should decide if you will take Tasigna or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non prescription medicines, vitamins and herbal supplements.

Tasigna can interact with many medicines and supplements and increase your chance for serious and life-threatening side effects. See "What is the most important information I should know about Tasigna?"

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.

How should I take Tasigna?

  • Take Tasigna exactly as your doctor tells you to take it. Do not change your dose or stop taking Tasigna unless your doctor tells you.
  • Tasigna is a long-term treatment.
  • Your doctor will tell you how many Tasigna capsules to take and when to take them.
  • Do not take Tasigna with food. Take Tasigna at least 2 hours after you eat and at least 1 hour before you eat.
  • Swallow Tasigna capsules whole with water. If you cannot swallow Tasigna capsules whole, tell your doctor.
  • Do not drink grapefruit juice, eat grapefruit, or take supplements containing grapefruit extract at any time during treatment. See "What is the most important information I should know about Tasigna?"
  • If you miss a dose, just take your next dose as scheduled. Do not make up for a missed dose.
  • If you take too much Tasigna, call your doctor or poison control center right away. Symptoms may include vomiting and drowsiness. During treatment with Tasigna your doctor will do tests to check for side effects and to see how well Tasigna is working for you. The tests will check your:
    • Heart
    • Blood cells (white blood cells, red blood cells, and platelets). Your blood cells should be checked every two weeks for the first two months and then monthly.
    • Electrolytes (potassium, magnesium)
    • Pancreas and liver function
    • Bone marrow samples
  • Your doctor may change your dose. Your doctor may have you stop Tasigna for some time or lower your dose if you have side effects with it.

What are the possible side effects of Tasigna?

Tasigna may cause serious side effects including:

  • See "What is the most important information I should know about Tasigna?"
  • Low blood counts. Low blood counts are common with Tasigna. Your doctor will check your blood counts regularly during treatment with Tasigna. Symptoms of low blood counts include:
    • Unexplained bleeding or bruising
    • Blood in urine or stool
    • Unexplained weakness
  • Liver damage. Symptoms include yellow skin and eyes.
  • Pancreas inflammation (pancreatitis). Symptoms include sudden stomach area pain with nausea and vomiting.
  • Bleeding in the brain: Symptoms include sudden headache, changes in your eyesight, not being aware of what is going on around you and becoming unconscious.

The most common side effects of Tasigna include:

  • Low blood count
  • Rash
  • Nausea
  • Fever
  • Headache
  • Itching
  • Tiredness
  • Stomach (abdominal) pain
  • Diarrhea
  • Constipation
  • Muscle and joint pain
  • Back pain
  • Muscle spasms
  • Weakness
  • Hair loss
  • Runny or stuffy nose, sneezing, sore throat
  • Cough

About Gleevec

Gleevec® (imatinib mesylate) tablets are indicated for the treatment of 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 severe fluid retention. Patients should be weighed and monitored regularly for signs and symptoms of fluid retention, which can be serious or life-threatening.

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 adjustments may be necessary due to hepatotoxicity, other nonhematologic adverse reactions, or hematologic adverse reactions.

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 reactions (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.

Severe congestive heart failure and left ventricular dysfunction have occasionally been reported. Most of the 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. 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.

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/day 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/day are not recommended. Gleevec should be used with caution in patients with severe renal impairment.

In the newly diagnosed CML trial, 2% of patients had (NCI Grades 3/4) hemorrhage.

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

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.

Gleevec is metabolized by the CYP3A4 isoenzyme and is an inhibitor of CYP3A4, CYP2D6, and CYP2C9. Dosage of Gleevec should increase by at least 50%, and clinical response should be carefully monitored, in patients receiving Gleevec with a potent CYP3A4 inducer such as rifampin or phenytoin. Examples of commonly used drugs that may significantly interact with Gleevec include ketoconazole, acetaminophen, warfarin, erythromycin, and phenytoin. (Please see full Prescribing Information for other potential drug interactions.)

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

Common side effects of Gleevec tablets

The majority of adult patients with Ph+ CML 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.

Gleevec tablets should be taken with food and a large glass of water to minimize GI irritation. Gleevec tablets should not be taken with grapefruit juice and other foods known to inhibit CYP3A4.

Patients should be informed to take Gleevec exactly as prescribed, 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.

About Afinitor (everolimus)

Afinitor® (everolimus) tablets is approved in the US for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib and in the European Union (EU) for the treatment of patients with advanced RCC whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy.

Afinitor is also approved in the US to treat patients with SEGA associated with tuberous sclerosis who require therapeutic intervention but are not candidates for curative surgical resection. The effectiveness of Afinitor is based on an analysis of change in SEGA volume. Improvement in disease-related symptoms or increase in survival has not been shown. Novartis has submitted marketing applications for everolimus to the European Medicines Agency (EMA) and the Swiss Agency for Therapeutic Products (Swissmedic), and additional regulatory submissions are underway worldwide.

Afinitor is available in the US in 2.5 mg, 5 mg and 10 mg tablet strengths.

In the US, everolimus is available in different dosage strengths under the trade name Zortress® for the prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant. In the EU, everolimus is available in different dosage strengths under the trade name Certican® for the prevention of organ rejection in heart and kidney transplant recipients.

Everolimus is exclusively licensed for use in drug-eluting stents to Abbott for the XIENCE V® and XIENCE PRIME™**** Everolimus Eluting Coronary Stent System, and sublicensed to Boston Scientific for the PROMUS™ and PROMUS™ Element™*****  Everolimus Eluting Coronary Stent System.

Not all indications are available in every country. As an investigational compound the safety and efficacy profile of everolimus has not yet been established in additional indications or disease areas. 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. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere in the world.

Afinitor (everolimus) tablets important safety information

Afinitor is contraindicated in patients with hypersensitivity to everolimus, to other rapamycin derivatives or to any of the excipients.

Cases of non-infectious pneumonitis have been described; some of these have been severe and occasionally fatal. Management of pneumonitis may require dose adjustment and/or interruption, or discontinuation of treatment and/or addition of corticosteroid therapy.

Afinitor is immunosuppressive. Localized and systemic bacterial, fungal, viral or protozoal infections (e.g., pneumonia, aspergillosis, candidiasis, hepatitis B reactivation) have been described; some of these have been severe and occasionally fatal. Pre-existing infections should be treated prior to starting treatment. Patients and physicians should be vigilant for symptoms and signs of infection; in case of emergent infections, appropriate treatment should be promptly instituted and interruption or discontinuation of Afinitor should be considered. Patients with systemic invasive fungal infections should not receive Afinitor.

Mouth ulcers, stomatitis and oral mucositis have been seen in patients treated with Afinitor. Monitoring of renal function, blood glucose and complete blood counts is recommended prior to initiation and periodically during treatment.

Afinitor is not recommended in patients with severe hepatic impairment. Use of live vaccines should be avoided. Afinitor is not recommended during pregnancy or for women of childbearing potential not using contraception. Afinitor may cause fetal harm in pregnant women. Women taking Afinitor should not breast feed.

Patients should avoid concurrent treatment with strong CYP3A4 and PgP inhibitors and use caution with moderate inhibitors. Avoid concurrent treatment with strong CYP3A4 or PgP inducers.

In advanced RCC, the most common adverse reactions (greater than or equal to 10%) include stomatitis, rash, fatigue, asthenia, diarrhea, anorexia, nausea, mucosal inflammation, vomiting, cough, infections, peripheral edema, dry skin, epistaxis, pneumonitis, pruritus and dyspnea. Common adverse reactions (greater than or equal to 1 to <10%) include headache, dysgeusia, dry mouth, pyrexia, weight loss, hand-foot syndrome, abdominal pain, erythema, insomnia, dyspepsia, dysphagia, hypertension, increased daytime urination, dehydration, chest pain, hemoptysis and exacerbation of diabetes mellitus. Uncommon adverse reactions (<1%) include ageusia, congestive cardiac failure, new-onset diabetes mellitus, impaired wound healing, grade 1 hemorrhage and hepatitis B reactivation.

In the SEGA study, the most common adverse reactions (greater than or equal to 10%, all grades) irrespective of relationship to the drug reported among the 28 patients with evidence of established SEGA growth included: stomatitis or mouth sores, upper respiratory tract infection, sinusitis, middle ear infection, fever, convulsion, acne-like skin inflammation, diarrhea, cellulitis or acute infection of the deep tissues of skin or muscle, vomiting, cough, body tinea or fungal infection, headache, personality change, rash, skin infection, dry skin, gastroenteritis or inflammation of the gastrointestinal tract, contact dermatitis, dizziness, external ear infection, allergic rhinitis or inflammation of nasal passages, gastric infection, nasal congestion, excoriation or skin abrasion, acne, constipation, abdominal pain and pharyngitis or inflammation of the pharynx.

Grade three adverse reactions irrespective of relationship to the study drug included convulsion, infections (single cases of sinusitis, pneumonia, tooth infection and viral bronchitis) and single cases of stomatitis, aspiration, cyclic neutropenia, sleep apnea syndrome, vomiting, dizziness, white blood cell count decreased and neutrophil count decreased. A grade four convulsion was reported.

About Exjade

Exjade is approved in more than 100 countries, including the US, Switzerland, Japan and the European Union. Exjade is indicated for chronic iron overload due to blood transfusions in patients aged 2 years and older. Exjade is approved for use at doses up to 40 mg/kg in the vast majority of countries.

Disclaimer: The results seen in the EPIC study were achieved with a starting dose of 30 mg/kg, which is approved in most but not all countries and with a dose range of up to 45 mg/kg which is not approved in any country.

Exjade important safety information


 
 

WARNING: RENAL, HEPATIC FAILURE AND/OR GASTROINTESTINAL HEMORRHAGE

 

 
 

Exjade may cause:

 
  • renal impairment, including failure
 
  • hepatic impairment, including failure
 
  • gastrointestinal hemorrhage
 

 
 

In some reported cases, these reactions were fatal. These reactions were more frequently observed in patients with advanced age, high risk myelodysplastic syndromes (MDS), underlying renal or hepatic impairment or low platelet counts (<50 x 10(9)>

 

Exajde therapy requires close patient monitoring, including measurement of:

 
  • serum creatinine and/or creatinine clearance prior to initiation of therapy and monthly thereafter; in patients with underlying renal impairment or risk factors for renal impairment, monitor creatinine and/or creatinine clearance weekly for the first month, then monthly thereafter;
 
  • serum transaminases and bilirubin prior to initiation of therapy, every two weeks during the first month and monthly thereafter.
 
 


 

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 10(9)>
  • known hypersensitivity to deferasirox or to any component of Exjade.

Renal

Acute renal failure, fatal in some patients and requiring dialysis in others, has been reported following the postmarketing use of Exjade. Most of the fatalities occurred in patients with multiple comorbidities and who were in advanced stages of their hematologic disorders. Monitor serum creatinine and/or creatinine clearance in patients who: are at increased risk of complications, have pre-existing renal conditions, are elderly, have comorbid conditions, or are receiving medicinal products that depress renal function. Closely monitor the renal function of patients with creatinine clearances between 40 and less than 60 mL/min, particularly in situations where patients have additional risk factors that may further impair renal function such as concomitant medications, dehydration, or severe infections.

Assess serum creatinine and/or creatinine clearance in duplicate before initiating therapy to establish a reliable pretreatment baseline, due to variations in measurements. Monitor serum creatinine and/or creatinine clearance monthly thereafter. In patients with additional renal risk factors (see above), monitor serum creatinine and/or creatinine clearance weekly during the first month after initiation or modification of therapy and monthly thereafter.

Consider dose reduction, interruption, or discontinuation for increases in serum creatinine. In clinical studies, Exjade -treated patients experienced dose-dependent increases in serum creatinine at a greater frequency compared to deferoxamine-treated patients (38% vs. 14%, respectively, in Study 1 and 36% vs. 22%, respectively, in Study 3). Most of the creatinine elevations remained within the normal range. For adult patients, reduce the daily dose of Exjade by 10 mg/kg if a rise in serum creatinine to >33% above the average of the pretreatment measurements is seen at 2 consecutive visits, and cannot be attributed to other causes. For pediatric patients, reduce the dose by 10 mg/kg if serum creatinine levels rise above the age-appropriate upper limit of normal at 2 consecutive visits. If there is a progressive increase in serum creatinine beyond the age-appropriate upper limit of normal, interrupt Exjade use. Once the creatinine has returned to within the normal range, therapy with Exjade may be reinitiated at a lower dose followed by gradual dose escalation, if the clinical benefit is expected to outweigh potential risks. There have also been reports of renal tubulopathy in patients treated with Exjade. The majority of these patients were children and adolescents with Beta-thalassemia and serum ferritin levels <1500 mcg>

Hepatic

There have been postmarketing reports of hepatic failure, some with a fatal outcome, in patients treated with Exjade. Most of these events occurred in patients greater than 55 years of age. Most reports of hepatic failure involved patients with significant comorbidities, including liver cirrhosis and multi-organ failure. Serum transaminases and bilirubin should be monitored before the initiation of treatment, every 2 weeks during the first month and monthly thereafter. Consider dose modifications or interruption of treatment for severe or persistent elevations.

Gastrointestinal

Fatal gastrointestinal (GI) hemorrhages, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts, have been reported. Non-fatal upper GI irritation, ulceration, and hemorrhage have been reported in patients, including children and adolescents, receiving Exjade. Physicians and patients should remain alert for signs and symptoms of GI ulceration and hemorrhage during Exjade therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. Use caution when administering Exjade in combination with drugs that have ulcerogenic or hemorrhagic potential, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, oral bisphosphonates, or anticoagulants.

Cytopenias

There have been postmarketing reports of cytopenias, including agranulocytosis, neutropenia and thrombocytopenia, in patients treated with Exjade. Some of these patients died. The relationship of these episodes to treatment with Exjade is uncertain. Most of these patients had pre-existing hematologic disorders that are frequently associated with bone marrow failure. Monitor blood counts regularly. Consider interrupting treatment with Exjade in patients who develop unexplained cytopenia. Reintroduction of therapy with Exjade may be considered once the cause of the cytopenia has been elucidated.

Hypersensitivity

Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving Exjade, with the onset of the reaction occurring in the majority of cases within the first month of treatment. If reactions are severe, discontinue Exjade and institute appropriate medical intervention.

Rash

Rashes may occur during treatment with Exjade. For rashes of mild to moderate severity, Exjade may be continued without dose adjustment, since the rash often resolves spontaneously.  In severe cases, Exjade may be interrupted. Reintroduction at a lower dose with escalation may be considered in combination with a short period of oral steroid administration. Erythema multiforme has been reported during Exjade treatment.

Comorbidities

Clinical trials to demonstrate increased survival or to confirm clinical benefit have not been completed.  Exjade has been shown to decrease serum ferritin and liver iron concentration in clinical trials. Consider the importance of these factors as well as individual patient factors and the prognosis associated with any underlying conditions before initiation of Exjade therapy.

In postmarketing experience, there have been reports of serious adverse reactions, some with a fatal outcome, in patients taking Exjade therapy, predominantly when the drug was administered to patients with advanced age, complications from underlying conditions or very advanced disease. Most of these deaths occurred within six months of Exjade initiation and generally involved worsening of the underlying condition. The reports do not rule out the possibility that Exjade may have contributed to the deaths.    

Special Senses

Auditory (high-frequency hearing loss, decreased hearing) and ocular (lens opacities, cataracts, elevations in intraocular pressure, and retinal disorders) disturbances have been reported with Exjade therapy in less than 1% of patients in clinical trials. Auditory and ophthalmic testing (including slit lamp examinations and dilated fundoscopy) are recommended before the start of Exjade treatment and thereafter at regular intervals (every 12 months). If disturbances are noted, consider dose reduction or interruption.

Adverse Reactions

The most frequently occurring adverse reactions with a suspected relationship to Exjade were diarrhea, vomiting, nausea, abdominal pain, skin rash, and increases in serum creatinine. Maintenance of adequate hydration for patients experiencing diarrhea or vomiting is recommended. Gastrointestinal symptoms, increases in serum creatinine, and skin rash were dose related. These commonly reported adverse events were predominantly mild to moderate in severity, with serious adverse events reported in 9.1% of patients in the Exjade arm and 8.6% of patients in the deferoxamine arm. Intermittent proteinuria (urine protein/creatinine ratio >0.6 mg/mg) occurred in 18.6% of Exjade -treated patients compared to 7.2% of deferoxamine-treated patients in Study 1. Although no patients were discontinued from Exjade in clinical studies up to 1 year due to proteinuria, monthly monitoring is recommended.

About Zometa

Zometa is indicated for the prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumor-induced hypercalcemia) in patients with multiple myeloma and advanced malignancies involving bone. An intravenous bisphosphonate, Zometa is the only therapy to demonstrate efficacy in reducing or delaying bone complications across a broad range of tumor types such as breast, prostate, lung and renal cell cancers, in patients with metastatic disease when administered monthly. Zometa offers patients, nurses and clinicians a 4 mg, 15-minute infusion.

Zometa is the world's leading treatment for the prevention or delay of skeletal-related events (SREs) in patients with advanced malignancies involving bone across a broad range of tumors. Laboratory research has suggested that Zometa may also help protect patients from the spread of cancer to other parts of the body (distant metastatic sites) and help keep patients recurrence-free.

Zometa important safety information

Zometa has been associated with reports of renal insufficiency. Patients should be adequately rehydrated and have their serum creatinine assessed prior to receiving each dose of Zometa. Due to the risk of clinically significant deterioration in renal function, single doses of Zometa should not exceed 4 mg and the duration of infusion should be no less than 15 minutes in 100 ml of dilutent. The risk of renal adverse events may be greater in patients with renal insufficiency. Zometa is not recommended for treatment of patients with severe renal impairment. Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates including Zometa. Caution is advised when Zometa is used in aspirin-sensitive patients, or with aminoglycosides, loop diuretics and other potentially nephrotoxic drugs. Zometa contains the same active ingredient (zoledronic acid) as found in Aclasta. Patients being treated with Zometa should not be treated with Aclasta concomitantly. Zometa should not be used in patients who are pregnant, or plan to become pregnant, or who are breast-feeding.

In clinical trials, the most commonly reported adverse events included flu-like syndrome (fever, arthralgias, myalgias, skeletal pain), fatigue, gastrointestinal reactions, anemia, weakness, cough, dyspnea and edema. Zometa should not be used during pregnancy. Zometa is contraindicated in patients with clinically significant hypersensitivity to zoledronic acid or other bisphosphonates, or any of the excipients in the formulation of Zometa.

Osteonecrosis of the Jaw (ONJ): ONJ has been reported in patients with cancer receiving treatment including bisphosphonates, chemotherapy, and/or corticosteroids. The majority of reported cases have been associated with dental procedures such as tooth extraction. A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors. While on treatment, these patients should avoid invasive dental procedures if possible. No data are available to suggest whether discontinuation of bisphosphonate therapy reduces the risk of ONJ in patients requiring dental procedures. A causal relationship between bisphosphonate use and ONJ has not been established.

Please see full Prescribing Information.

About the compounds LBH589, INC424, PKC412, HCD122, BEZ235

Because these are investigational compounds, the safety and efficacy profile of LBH589, INC424, PKC412, HCD122 and BEZ235 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 LBH589, INC424, PKC412, HCD122 and BEZ235 will ever be commercially available anywhere in the world.

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as "commitment," "continue to explore," "pipeline," "will," "goal," "potential," or similar expressions, or by express or implied discussions regarding potential new products, potential new indications for existing products, or regarding potential future revenues from any 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 new products will be submitted or approved for sale in any market, or that any new indications will be submitted or approved for existing products in any market, or that such products will achieve any particular revenue levels. 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; 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 healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, the Novartis Group offers a diversified portfolio to best meet these needs: innovative medicines, preventive vaccines, diagnostic tools, cost-saving generic pharmaceuticals and consumer health products. The Novartis Group is the only company with leading positions in each of these areas. In 2009, the Group's continuing operations achieved net sales of USD 44.3 billion, while approximately USD 7.5 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.us.novartis.com.

References

  1. American Society of Hematology. 52nd Annual Meeting of the American Society of Hematology Final Program, 2010.
  2. San Antonio Breast Cancer Symposium. 33rd Annual Meeting of the San Antonio Breast Cancer Symposium Final Program, 2010.
  3. Hughes T, et al. ENESTnd Update: Continued Superiority of Nilotinib Versus Imatinib In Patients with Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP). 52nd Annual Meeting of the American Society of Hematology. Abstract #207. December 6, 2010.
  4. Renner C, et al. A Multi-Center Phase II Study (SAKK 36/06) of Single Agent Everolimus (RAD001) In Patients with Relapsed or Refractory Mantle Cell Lymphoma. 52nd Annual Meeting of the American Society of Hematology. Abstract #2803. December 5, 2010.
  5. O'Connor O, et al. PILLAR-1: Preliminary Results of a Phase II Study of mTOR Inhibitor Everolimus In Patients with Mantle Cell Lymphoma (MCL) Who Are Refractory or Intolerant to Bortezomib. 52nd Annual Meeting of the American Society of Hematology. Abstract #3963. December 6, 2010.
  6. Pennell D, et al. Continued Improvement and Normalization of Myocardial T2* In Patients with β?thalassemia Major Treated with Deferasirox (Exjade®) for up to 3 Years. 52nd Annual Meeting of the American Society of Hematology. Abstract #4276. December 6, 2010.
  7. Gattermann N, et al. Hematologic Responses In Myelodysplastic Syndromes (MDS) Patients Treated with Deferasirox: An EPIC Post-Hoc Analysis Using International Working Group (IWG) 2006 Criteria. 52nd Annual Meeting of the American Society of Hematology. Abstract #2912. December 5, 2010.
  8. Vichinsky E, et al. Long-Term Safety and Efficacy of Deferasirox (Exjade®) In Transfused Patients with Sickle Cell Disease Treated for up to 5 Years. 52nd Annual Meeting of the American Society of Hematology. Abstract #845. December 6, 2010.
  9. Deugnier Y, et al. Deferasirox Improves Liver Pathology In Beta-­Thalassemia Patients with Transfusional Iron Overload. 52nd Annual Meeting of the American Society of Hematology. Abstract #4274. December 6, 2010.
  10. Morgan G, et al. Optimising Bone Disease In Myeloma; Zoledronic Acid Plus Thalidomide Combinations Improves Survival and Bone Endpoints: Results of the MRC Myeloma IX Trial. 52nd Annual Meeting of the American Society of Hematology. Abstract #311. December 6, 2010.
  11. Sureda A, et al. Final Analysis: Phase II Study of Oral Panobinostat In Relapsed/Refractory Hodgkin Lymphoma Patients Following Autologous Hematopoietic Stem Cell Transplant. 52nd Annual Meeting of the American Society of Hematology. Abstract #419. December 6, 2010.
  12. Verstovsek S, et al. Durable Responses with the JAK1/JAK2 Inhibitor, INCB018424, In Patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Refractory or Intolerant to Hydroxyurea (HU). 52nd Annual Meeting of the American Society of Hematology. Abstract #313. December 6, 2010.
  13. Eghtedar A, et al. Phase II Study of the JAK2 Inhibitor, INCB018424, In Patients with Refractory Leukemias Including Post-Myeloproliferative Disorder (MPD) Acute Myeloid Leukemia (sAML). 52nd Annual Meeting of the American Society of Hematology. Abstract #509. December 6, 2010.
  14. Gotlib J, et al. KIT Inhibitor Midostaurin Exhibits a High Rate of Clinically Meaningful and Durable Responses in Advanced Systemic Mastocytosis: Report of a Fully Accrued Phase II Trial. 52nd Annual Meeting of the American Society of Hematology. Abstract #316. December 6, 2010.
  15. Freedman AS, et al. Clinical Activity of Lucatumumab (HCD122) In Patients (pts) with Relapsed/Refractory Hodgkin or Non-Hodgkin Lymphoma Treated In a Phase Ia/II Clinical Trial (NCT00670592). 52nd Annual Meeting of the American Society of Hematology. Abstract #284. December 6, 2010.
  16. Bachelot T, et al. TAMRAD: A GINECO Randomized Phase II Trial of Everolimus In Combination with Tamoxifen Versus Tamoxifen Alone In Patients (pts) with Hormone-Receptor Positive, HER2 Negative Metastatic Breast Cancer (MBC) with Prior Exposure to Aromatase Inhibitors (AI). 33rd Annual Meeting of the San Antonio Breast Cancer Symposium. Abstract #S1-6. December 9, 2010.
  17. Coleman R. Adjuvant Treatment with Zoledronic Acid In Stage II/III Breast Cancer. The AZURE Trial (BIG 01/04). 33rd Annual Meeting of the San Antonio Breast Cancer Symposium. Abstract #S4-5. December 10, 2010.
  18. Gnant, M. The Carry-Over Effect of Adjuvant Zoledronic Acid: Comparison of 48- and 62-Month Analyses of ABCSG-12 Suggests That the Benefits of Combining Zoledronic Acid With Adjuvant Endocrine Therapy Persist Long After Completion of Therapy. 33rd Annual Meeting of the San Antonio Breast Cancer Symposium. Abstract #P5-11-02. December 11, 2010.
  19. Rodon J. A Dose-Escalation Study with a Special Drug Delivery System (SDS) of BEZ235, a Novel Dual PI3K/mTOR Inhibitor, in Patients with Metastatic/Advanced Solid Tumors. 33rd Annual Meeting of the San Antonio Breast Cancer Symposium. Abstract #P6-15-07. December 12, 2010.

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

** INC424, also known as INCB018424, is being developed collaboratively by Incyte and Novartis. Novartis has licensed the rights to INC424 outside the United States. Incyte maintains the rights within the United States.

*** Numbers indicate the range of percentages in 4 studies among adult patients with newly diagnosed Ph+ CML and patients in BC, AP, and CP after failure of interferon-alpha therapy.

**** XIENCE V® AND XIENCE PRIME™ are registered trademarks of Abbott.

***** PROMUS™ AND PROMUS™ ELEMENT are registered trademarks of Boston Scientific

Novartis Media Relations


 
 

 

 
 

Media only:

Investors only:

 

Denise Brashear

Richard Jarvis

 

Novartis Oncology

Novartis Corporation

 

P: +1 862 778 7336

(direct) P: +1 212 830 2433

 

 

 
 

Dana Kahn Cooper


 
 

P: +1 732 817 1800


 
 
   


 

SOURCE Novartis

CONTACT: Media, Denise Brashear, Novartis Oncology, +1-862-778-7336, or Dana Kahn Cooper, +1-732-817-1800; or Investors, Richard Jarvis, Novartis Corporation, (direct) +1-212-830-2433
 

Web Site: http://www.us.novartis.com
 

 

 
 

Posted: December 2010

View comments

Hide
(web5)