Novartis showcases ongoing research at ASCO to help patients fight various cancers, including updated data in advanced breast cancer

EAST HANOVER, N.J., May 31, 2012 /PRNewswire/ -- Novartis Pharmaceuticals Corporation ("Novartis") will showcase the clinical progress of multiple marketed and pipeline compounds with 160 abstracts at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO; June 1-5, Chicago)(4). These studies demonstrate key findings for Novartis compounds to address unmet treatment needs of patients with cancer and rare diseases.

"Among the data we will share at this year's ASCO are results from our key products, Afinitor and Tasigna, which demonstrate the magnitude of benefit these treatments may provide for patients with some types of advanced breast cancer and chronic myeloid leukemia," said Herve Hoppenot, President, Novartis Oncology. "In addition, we are seeing promising data from our early pipeline across multiple disease areas, including non-small cell lung cancer, multiple myeloma, NRAS-mutated melanoma and other solid tumors."

Updated data from BOLERO-2

An 18-month analysis from the Phase III BOLERO-2 study (Breast cancer trials of OraL EveROlimus) (abstract #559; June 2, 8:00AM – 12:00PM) confirm that Afinitor^® (everolimus) plus exemestane, an aromatase inhibitor, more than doubled the time postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer lived without tumor growth (progression-free survival; PFS).

The updated results show median PFS for everolimus plus exemestane was 7.8 months compared to 3.2 months with hormonal therapy alone (hazard ratio=0.45 [95% confidence interval (CI): 0.36 to 0.54]; p<0.0001) by local investigator assessment and significantly reduced the risk of cancer progression by 55% versus exemestane alone(1). In addition, 32.2% of patients in the exemestane-only arm and 25.4% in the everolimus plus exemestane arm died(1). The overall survival data is not yet mature.

The most common adverse events in the everolimus arm (incidence greater than or equal to 30%) were stomatitis, rash, fatigue, nausea, diarrhea and decreased appetite. The most common grade 3/4 adverse reactions (incidence greater than or equal to 2%) were stomatitis, hyperglycemia, non-infectious pneumonitis, fatigue and diarrhea(1).

These results are supportive of previously presented data from BOLERO-2. Regulatory submissions for Afinitor in HR+ advanced breast cancer are currently under consideration with the US Food and Drug Administration and other health authorities worldwide.

Tasigna in Philadelphia chromosome-positive CML in chronic phase

Also featured at ASCO will be two Phase III studies from the ENEST (Evaluating Nilotinib Efficacy and Safety in Clinical Trials) clinical research program, which demonstrate that twice as many adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase treated with Tasigna^® (nilotinib) achieved deeper levels of response compared to those treated with imatinib mesylate(2,3). These findings were first presented at the 2011 American Society of Hematology Annual Meeting and include:

• ENESTnd 36-month update showed the superiority of Tasigna vs. imatinib mesylate for the treatment of patients with newly diagnosed chronic phase Ph+ CML, with 32% of patients reaching the deepest levels of response on Tasigna compared to 15% on imatinib mesylate (abstract #6509; June 1, 1:00PM – 5:00PM)(2).
• ENESTcmr 12-month analysis demonstrated that switching patients with detectable Bcr-Abl transcripts from imatinib mesylate to Tasigna resulted in deeper molecular responses compared to those patients who remained on imatinib mesylate, with 23% of patients switched to Tasigna achieving undetectable levels of Bcr-Abl compared to 11% who continued on imatinib mesylate (abstract #6505; June 4, 9:30AM – 9:45AM)(3).

These data will also be presented at 17th Congress of the European Hematology Association (EHA), June 14-17 in Amsterdam.

Notable data on Novartis pipeline compounds

Early data on several Novartis pipeline compounds show promise for further research and development in areas of unmet medical needs and for targeted treatment approaches(5).

"Our strong pipeline data demonstrate the progress we are making to target new signaling pathways, including MEK, ALK, Hh and PI3K, that play a critical role in many types of cancers where there remain significant unmet medical needs," said Alessandro Riva, Global Head, Oncology Development & Medical Affairs, Novartis Oncology. "This is representative of our ongoing research using multiple strategies across a broad range of cancers and rare diseases."

• BEZ235 – Phase I/Ib dose-escalation study of BEZ235 plus trastuzumab in patients with trastuzumab-resistant HER2+ metastatic breast cancer demonstrated an acceptable safety profile and established maximum tolerated dose (abstract #508; June 2, 1:30PM – 1:45PM)(5).
• BKM120 – Phase Ib study of BKM120 with letrozole in patients with metastatic ER+/HER2- breast cancer (abstract #510; June 2, 2:15PM – 2:30PM)(6) and a Phase Ib study of BKM120 in combination with the MEK inhibitor GSK1120212 in patients with advanced solid tumors showed positive safety results for these combinations. Signs of clinical activity were seen in patients with RAS/RAF-mutated tumors treated with BKM120 and GSK1120212 (abstract #3003; June 3, 10:45AM – 11:00AM)(7).
• LBH589 – Updated data from the Phase II PANORAMA-2 (PANobinostat ORAl in Multiple myelomA) study showed promise of LBH589 in combination with bortezomib and dexamethasone to achieve overall responses and clinical benefit in patients with relapsed and bortezomib-refractory multiple myeloma (abstract #8012; June 3, 9:00AM – 9:15AM)(8).
• LDE225 – A Phase I/II study demonstrated promising efficacy of LDE225 in pediatric patients with recurrent medulloblastoma and correlative analysis supports the use of the 5-gene hedgehog (Hh) assay as a pre-selection tool in future trials (abstract #9519; June 4, 12:00PM – 12:15PM)(9).
• LDK378 – First-in-human Phase I study of LDK378 showed preliminary clinical response in patients with ALK-positive advanced non-small cell lung cancer (abstract #3007; June 3, 12:00PM – 12:15PM)(10).
• MEK162 – Phase II study of MEK162 showed clinical activity in patients with BRAF and NRAS-mutated advanced melanoma. This is the first targeted therapy to show activity in patients with NRAS-mutated melanoma (abstract #8511; June 4, 3:45PM – 4:00PM)(11).

About Afinitor^® (everolimus)

In the US, Afinitor tablets is approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib and for the treatment of progressive neuroendocrine tumors of pancreatic origin (pNET) 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 in the US to treat 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. Afinitor is also approved in the US to treat adult and pediatric patients, three years of age or older, with SEGA associated with TSC, who require therapeutic intervention but are not candidates for surgical resection. The effectiveness of Afinitor is based on an analysis of change in SEGA volume. Clinical benefit such as improvement in disease-related symptoms or increase in overall survival has not been shown.

In the US, 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 if they are allergic to AFINITOR or to any of its ingredients. Patients should tell their healthcare provider before taking AFINITOR if they are allergic to sirolimus (Rapamune^®) or temsirolimus (Torisel^®).

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

AFINITOR 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.

Common side effects include mouth ulcers. AFINITOR can cause mouth ulcers and sores.  Other common side effects include nausea and vomiting, skin problems, headache, cough, diarrhea, fever, swelling of the hands, arms, legs, feet, face or other parts of the body, stomach-area (abdomen) pain, nose bleeds, respiratory tract infection, 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 available at afinitor.com.

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

About Tasigna

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

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

BOXED WARNING and Important Safety Information for TASIGNA (nilotinib):

Treatment with TASIGNA can cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. Complete blood counts should be performed every 2 weeks for the first 2 months and then monthly thereafter.

Caution is recommended in patients with a history of pancreatitis.

The use of TASIGNA may result in elevations in bilirubin, AST/ALT, and alkaline phosphatase.

TASIGNA can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia (see Boxed WARNING).

The concomitant use of strong CYP3A4 inhibitors or anti-arrhythmic drugs (including, but not limited to, amiodarone, disopyramide, procainamide, quinidine, and sotalol) and other drugs that may prolong the QT interval (including, but not limited to, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, and pimozide) should be avoided. Grapefruit products should also be avoided. 

The concomitant use of strong CYP3A4 inducers should be avoided (including, but not limited to, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's wort).

TASIGNA must not be taken with food.

TASIGNA exposure is increased in patients with impaired hepatic function.

Cases of tumor lysis syndrome have been reported in TASIGNA treated patients with resistant or intolerant CML. Due to potential for tumor lysis syndrome, maintain adequate hydration and correct uric acid levels prior to initiating therapy with TASIGNA.

The exposure of TASIGNA is reduced in patients with total gastrectomy.

Since the capsules contain lactose, TASIGNA is not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency with a severe degree of intolerance to lactose-containing products, or of glucose-galactose malabsorption.

Women of childbearing potential should avoid becoming pregnant while taking TASIGNA and should be advised of the potential hazard to the fetus if they do. The safety and effectiveness of TASIGNA in pediatric patients have not been established.

In newly diagnosed Ph+ CML-chronic phase, the most commonly reported nonhematologic adverse drug reactions (>10%) were rash, pruritus, headache, nausea, fatigue, and myalgia.

In resistant or intolerant Ph+ CML-chronic phase, the most commonly reported nonhematologic adverse drug reactions (greater than or equal to 10%) were rash, pruritus, nausea, fatigue, headache, constipation, diarrhea, vomiting, and myalgia.

In resistant or intolerant Ph+ CML-accelerated phase, the most commonly reported nonhematologic adverse drug reactions (greater than or equal to 10%) were rash, pruritus, and fatigue.

TASIGNA may need to be temporarily withheld and/or dose reduced for QT prolongation, hematologic toxicities that are not related to underlying leukemia, clinically significant moderate or severe nonhematologic toxicities, laboratory abnormalities, or concomitant use of strong CYP3A4 inhibitors.

Please see full Prescribing Information including Boxed Warning.

About Gleevec[*]

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

GLEEVEC Important Safety Information

GLEEVEC 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.

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

About LBH589, MEK162, BEZ235, BKM120, LDK378, LDE225

Because these are investigational compounds, the safety and efficacy profile of LBH589, MEK162, BEZ235, BKM120, LDK378 and LDE225 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, MEK162, BEZ235, BKM120, LDK378 and LDE225 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 "ongoing," "pipeline," "potential," "will," "may," "promising," "under consideration," "promise," "expected," or similar expressions, or by express or implied discussions regarding potential new submissions or marketing approvals for the Novartis Oncology products referred to in this release, potential new indications or labeling for such Novartis Oncology products, or regarding potential future revenues from such Novartis Oncology 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 with to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that the Novartis Oncology products referred to in this release will be submitted or approved for sale, or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Novartis Oncology products will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Novartis Oncology 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; unexpected manufacturing issues; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 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 124,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.

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References

1.     Piccart M et al. Everolimus for Postmenopausal Women with Advanced Breast Cancer: Updated Results of the BOLERO-2 Phase III Trial. Abstract #559. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

2.     Kantarjian H et al. Nilotinib vs. imatinib in patients with newly diagnosed CML in chronic phase: ENESTnd 3-year follow-up. Abstract #6509. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.  

3.     Lipton J et al. Switch to nilotinib vs. continued imatinib in patients with CML in chronic phase with detectable Bcr-Abl after greater than or equal to 2 years on imatinib; ENESTcmr 12-month follow-up. Abstract #6505. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

4.     American Society of Clinical Oncology. ASCO Annual 2012 Meeting Program. Available at: http://chicago2012.asco.org/MeetingProgram.aspx. Accessed May 2012.

5.     Krop I et al. A phase I/Ib dose-escalation study of BEZ235 in combination with trastuzumab in patients with Pl3-kinase or PTEN altered HER+ metastatic breast cancer. Abstract #508. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

6.     Mayer et al. SU2C phase Ib study of pan-Pl3K inhibitor BKM120 with letrozole in ER+/HER2- metastatic breast cancer. Abstract #510.  American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

7.     Bedard P et al. A phase Ib, open-label, multi-center, dose-escalation study of the oral pan-Pl3K inhibitor BKM120 in combination with the oral MEK1/2 inhibitor GSK1120212 in patients with selected advanced solid tumors. Abstract #3003.  American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

8.     Alsina M et al. PANORAMA 2: A phase II study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma. Abstract #8012. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

9.     Geoerger B et al. A Phase I/II study of LDE225, a Smoothened (Smo) antagonist, in pediatric patients with recurrent medulloblastoma (MB) or other solid tumors. Abstract #9519. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

10.   Mehra R et al. First-in-human Phase I study of the ALK inhibitor LDK378 in advanced solid tumors. Abstract #3007. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

11.   Ascierto P et al. Efficacy and safety of oral MEK162 in patients with locally advanced and unresectable or metastatic cutaneous melanoma harboring BRAFV600 or NRAS mutations. Abstract #8511. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

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