Data at ASH, SABCS demonstrate commitment of Novartis R&D in advancing treatments for patients with cancer and rare diseases
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].
- (1888PressRelease) December 01, 2010 - 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), Glivec® (imatinib)*, Afinitor® (everolimus), 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].
* 24-month update on Phase III data comparing Tasigna® to Glivec® 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
"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 Hervé 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 Glivec 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[i] - 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 has also been approved in more than 80 countries for the treatment of chronic phase (CP) and accelerated phase Ph+ CML in adult patients resistant or intolerant to at least one prior therapy, including Glivec. The effectiveness of Tasigna for this indication is based on confirmed hematologic and unconfirmed cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.
Tasigna is not approved in the EU for the treatment of newly diagnosed Ph+ CML-CP.
Tasigna important safety information
Tasigna should be taken twice daily at an interval of approximately 12 hours apart and must not be taken with food. No food should be consumed for two hours before the dose and for at least one hour after the dose. Avoid grapefruit juice and other foods that are known to inhibit CYP3A4.
Tasigna should not be used in patients who are hypersensitive to nilotinib or any of the excipients.
Treatment with Tasigna has been associated with hematological side effects such as thrombocytopenia, neutropenia and anemia which was generally reversible and usually managed by withholding Tasigna temporarily or dose reduction. Complete blood counts should be performed every two weeks for the first two months and then monthly thereafter as clinically indicated.
Tasigna should be used with caution in patients with uncontrolled or significant cardiac disease (e.g., recent heart attack, congestive heart failure, unstable angina or clinically significant bradycardia), as well as in patients who have or may develop prolongation of QTc. These include patients with abnormally low potassium or magnesium levels, patients with congenital long QT syndrome, patients taking anti-arrhythmic medicines or other drugs that may lead to QT prolongation. Low levels of potassium or magnesium must be corrected prior to Tasigna administration. Close monitoring for an effect on the QTc interval is advisable and a baseline electrocardiography is recommended prior to initiating therapy with Tasigna 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.
Tasigna should be used with caution in patients with liver impairment, in patients with a history of pancreatitis and in patients with total gastrectomy. Patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption should not use Tasigna. Tasigna should not be used during pregnancy unless clearly necessary and breast feeding is not recommended during treatment.
The most frequent Grade 3 or 4 adverse events for Tasigna were primarily hematological in nature and included neutropenia and thrombocytopenia. Elevations seen in bilirubin, liver function tests, lipase enzymes and blood sugar were mostly transient and resolved over time. These cases were easily managed and rarely led to discontinuation of treatment. Pancreatitis was reported in less than 1% of cases. The most frequent non-hematologic drug-related adverse events were rash, pruritus, nausea, fatigue, headache, alopecia, myalgia, constipation and diarrhea. Most of these adverse events were mild to moderate in severity.
About Glivec
Glivec is approved in more than 90 countries, including the US, EU and Japan, for the treatment of all phases of Ph+ CML. Glivec is also approved in the US, EU and other countries for the treatment of patients with Kit (CD117)-positive gastrointestinal tumors (GIST), which cannot be surgically removed and/or have already spread to other parts of the body (metastasized). In the US and EU, Glivec is now approved for the post-surgery treatment of adult patients following complete surgical removal of Kit (CD117)-positive GIST. In the EU, Glivec is also approved for the treatment of adult patients with newly diagnosed Ph+ acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy and as a single agent for patients with relapsed or refractory Ph+ ALL. Glivec is also approved for the treatment of adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) who are not eligible for surgery. Glivec is also approved for the treatment of patients with myelodysplastic/myeloproliferative diseases (MDS/MPD). Glivec is also approved for hypereosinophilic syndrome and/or chronic eosinophilic leukemia (HES/CEL).
The effectiveness of Glivec is based on overall hematological and cytogenetic response rates and progression-free survival in CML, on hematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, on hematological response rates in systemic mastocytosis (SM), HES/CEL, on objective response rates and progression-free survival in unresectable and/or metastatic GIST, on recurrence free survival in adjuvant GIST and on objective response rates in DFSP. Increased survival in controlled trials has been demonstrated only in newly diagnosed chronic phase CML and GIST.
Not all indications are available in every country.
Glivec important safety information
The majority of patients treated with Glivec in clinical trials experienced adverse events at some time. Most events were of mild to moderate grade and treatment discontinuation was not necessary in the majority of cases.
The safety profile of Glivec was similar in all indications. The most common side effects included nausea, superficial edema, muscle cramps, skin rash, vomiting, diarrhea, abdominal pain, myalgia, arthralgia, hemorrhage, fatigue, headache, joint pain, cough, dizziness, dyspepsia and dyspnea, dermatitis, eczema and fluid retention, as well as neutropenia, thrombocytopenia and anemia. Glivec was generally well tolerated in all of the studies that were performed, either as monotherapy or in combination with chemotherapy, with the exception of a transient liver toxicity in the form of transaminase elevation and hyperbilirubinemia observed when Glivec was combined with high dose chemotherapy.
Rare/serious adverse reactions include: sepsis, pneumonia, depression, convulsions, cardiac failure, thrombosis/embolism, ileus, pancreatitis, hepatic failure, exfoliative dermatitis, angioedema, Stevens-Johnson syndrome, renal failure, fluid retention, edema (including brain, eye, pericardium, abdomen and lung), hemorrhage (including brain, eye, kidney and gastrointestinal tract), diverticulitis, gastrointestinal perforation, tumor hemorrhage/necrosis and hip osteonecrosis/avascular necrosis.
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. Cardiac screening should be considered in patients with HES/CEL, and patients with MDS/MPD with high level of eosinophils (echocardiogram, serum troponin level).
Glivec is contraindicated in patients with known hypersensitivity to imatinib or any of its excipients. Women of childbearing potential should be advised to avoid becoming pregnant while taking Glivec.
About Afinitor (everolimus)
Afinitor tablets is approved in the European Union (EU) for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy and also in the US for the treatment of patients with advanced RCC after failure of treatment with sunitinib or sorafenib.
Afinitor is also approved in the US to treat patients with subependymal giant cell astrocytomas (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.
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. 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.
Everolimus is exclusively licensed for use in drug-eluting stents to Abbott for the XIENCE V® and XIENCE PRIME(TM)[ii] Everolimus Eluting Coronary Stent System, and sublicensed to Boston Scientific for the PROMUS(TM) and PROMUS(TM) Element(TM)** 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 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.
Hypersensitivity reactions have been observed.
Mouth ulcers, stomatitis and oral mucositis have been seen. Topical treatments are recommended; alcohol- or peroxide-containing mouthwashes should be avoided.
Monitoring of renal function, blood glucose and complete blood counts is recommended prior to initiation and periodically during treatment. Cases of renal failure, some fatal, have been observed.
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. Male fertility may be compromised by Afinitor.
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 (≥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 (≥1 to
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