Commitment of Novartis in advancing treatments for patients with cancer and rare diseases

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].

"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.

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.

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.

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.

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 number one prescribed treatment for the prevention or delay of skeletal-related events (SREs) in patients with advanced malignancies involving bone across a broad range of tumors.

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.

About Novartis
Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in 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.novartis.com.

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 β-­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 Gleevec® (imatinib mesylate) tablets in the US, Canada and Israel.
** PROMUS(TM) AND PROMUS(TM) ELEMENT are registered trademarks of Boston Scientific.

i. 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.
ii. XIENCE V® AND XIENCE PRIME(TM) are registered trademarks of Abbott.