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Novartis, new products portfolio

Novartis has a comprehensive portfolio of cardiovascular products both in the market ( Diovan and Lotrel ) as well as in development ( such as LAF237 and SPP100 ), for the treatment of hypertension, dyslipidemia and diabetes.

Other compounds in development include APP018 ( D-4F ), an oral Apo A-1 mimetic in trials for atherosclerosis disease, as well as compounds interacting with the SCD-1 target as an anti-obesity treatment to complement the development focus on hypertension, diabetes, athero-dyslipidemia and metabolic syndrome/obesity.

Expanding the potential of Diovan ( Valsartan ), Novartis plans to submit in 2006 for regulatory approval a fixed-dose combination of Valsartan with Amlodipine, a calcium channel blocker. This would mark the first combination of a channel blocker with an ARB ( angiotensin receptor blocker ), offering a once-daily treatment with a dual mechanism of action that combines the benefits of both drugs in one pill.
The use of combinations of therapies is becoming more common in the treatment of hypertension.
Novartis has many compounds in development that have the potential to become a new standard of care and the first to market in their respective classes.

The priority development projects include:

Aclasta ( Zoledronic Acid 5 mg ) was recently shown in a head-to-head Phase III study published in the New England Journal of Medicine to offer superior efficacy, faster onset of action and a longer period of remission compared to Risedronate, the current oral standard of care in Paget's disease.
Aclasta was first launched in Germany in May 2005, and other launches are expected during 2005 and 2006.
The FDA issued an approvable letter for this product for the treatment of Paget's disease in March 2005, and a complete response was submitted in August. Phase III trials are underway to demonstrate the benefits of Aclasta as a once-yearly treatment for various forms of osteoporosis, with submissions to US and EU regulatory authorities planned for 2007.

AMN107, a novel investigational oral compound being developed as a new treatment for advanced chronic myeloid leukemia ( CML ) patients, is planned to be submitted for regulatory approval in 2007. Enrollment in a pivotal Phase II study of patients with CML resistant to Gleevec/Glivec began in April 2005, with a Phase III study in chronic phase CML patients initiating treatment planned to begin in the first quarter of 2006. AMN107 further expands the Novartis franchise for helping patients with CML and GIST ( gastrointestinal stromal tumors ).

Exjade ( Deferasirox ) ( ICL670 ) is awaiting US regulatory approval after being granted a six-month priority review in June 2005. It was shown in clinical studies ( 20-30 mg/kg/day ) to be effective in removing excess iron from repeated blood transfusions and was submitted for regulatory approval in the US, EU and Switzerland in April 2005. It has orphan drug status in the US and EU. As a once-daily oral formulation, Exjade offers the potential to improve treatment compliance and quality of life of patients with chronic transfusional iron overload - a potentially life-threatening condition - compared to Deferoxamine, the current cumbersome infusion therapy standard of care.

Femara ( Letrozole ), a leading therapy for early and advanced breast cancer in postmenopausal women, was submitted for US and EU regulatory approval for use immediately after surgery ( adjuvant setting ).
The FDA has granted priority review for this new indication, with a decision expected by the end of 2005. Femara was also recently submitted for approval in Japan for treatment of postmenopausal women with breast cancer, and a decision is expected by the end of 2005 or in early 2006.

FTY720 has demonstrated sustained benefits and good tolerability as an oral treatment for patients with relapsing multiple sclerosis ( MS ), in the extension of a Phase II trial to 12 months. Six-month data from the Phase II trial showed that FTY720 significantly reduced the rate of clinical relapses by more than 50% in people with multiple sclerosis compared to placebo.
FTY720 also reduced inflammatory disease activity, as measured by magnetic resonance imaging ( MRI ), by up to 80% over six months compared to placebo.
Novartis is discussing its Phase III program with regulatory authorities, which is expected to be launched by the end of 2005.
Currently approved therapies have limited clinical effect and require frequent injections ranging from daily to weekly.
If confirmed in larger-scale Phase III studies, FTY720 could represent a major and long-awaited breakthrough for MS patients.

Gleevec/Glivec ( Imatinib mesylate ), indicated for all stages of Philadelphia chromosome positive ( Ph+ ) chronic myeloic leukemia ( CML ) and certain forms of gastro-intestinal stromal tumors ( GIST ), has recently received approval from the EMEA for increasing the average daily dose to 600 mg or 800 mg from 400 mg in patients with chronic phase CML and GIST.
Gleevec is on track to be submitted by the end of 2005 in the US, EU and Japan as a treatment for Ph+ acute lymphoid leukemia ( ALL ) and other rare diseases.
A registration program in glioblastoma multiforme, the most common and aggressive of the primary brain tumors, has been initiated.

LDT600 ( Telbivudine ) successfully reached its primary composite efficacy endpoint of therapeutic response in the Phase III GLOBE registration trial in chronic hepatitis B.
All key filings for LDT600 are planned to be completed by the end of the 2006 first quarter. This once-daily treatment for hepatitis B infections, estimated to affect about 350 million people worldwide, is being developed in collaboration with Idenix Pharmaceuticals.

Lucentis ( ranibizumab ), the potential new "gold standard" treatment for wet age-related macular degeneration ( AMD ), the leading cause of blindness in people over age 50, has shown strong efficacy and a good safety profile in recent clinical trials.
The Phase III MARINA study reported unprecedented results in maintaining and/or improving vision in patients with either the minimally classic or the occult form of wet AMD, FOCUS, a Phase I/II clinical study investigating the safety and efficacy of Lucentis in combination with Visudyne compared to Visudyne alone in patients with predominantly classic wet AMD, met its primary efficacy endpoint of maintaining or improving vision.
Data from the second Phase III study, ANCHOR, which is assessing Lucentis versus photodynamic therapy in the treatment of the predominantly classic form of wet AMD, are expected in the fourth quarter of 2005. Lucentis is being developed with Genentech, which retains the right to develop and market the product in North America. Regulatory submission is expected in 2006 in the EU.

Prexige ( Lumiracoxib ) was launched in Brazil in August 2005 for the treatment of osteoarthritis and acute pain. Additional launches of this new COX-2 selective inhibitor are anticipated for other markets, including the United Kingdom, by the end of the year. The application for EU regulatory approval is planned for early 2006, while re-submission in the US is planned for 2007. Prexige is already approved in 22 countries.

QAB149 ( Indacaterol ), a long-acting beta-agonist, may provide a new standard of care in patients with asthma and chronic obstructive pulmonary disease ( COPD ) based on Phase II data showing a rapid onset of action and 24-hour control.
QAB149 has the potential to become the first once-daily beta agonist by offering significant therapeutic potential for patients with asthma and COPD, either as a single agent or in combination with other Novartis respiratory compounds, such as the long-acting anti-muscarinic agent NVA237. Phase III trials are planned to start in early 2006, with regulatory submissions expected in 2007. Several options for combination products are currently being evaluated in parallel.

Xolair ( Omalizumab ), a first-in-class therapy for the treatment of severe persistent allergic asthma, is awaiting EU regulatory approval after the Committee for Medicinal Products for Human Use ( CHMP ) issued a positive opinion in July 2005. First approved in the US in 2003 with partner Genentech, Xolair is set to become the first humanized antibody to be approved for the treatment of asthma in Europe, representing a highly innovative approach to controlling this disease.

Zelnorm/Zelmac ( Tegaserod ), is currently under review by the EMEA for approval in the EU for the treatment of irritable bowel syndrome with constipation ( IBS-C ). Two Phase III clinical trials with Zelnorm, which was approved in the US in 2004, are currently ongoing for the treatment of dyspepsia, and both are planned to be completed in 2006. Data from a proof-of-concept study in GERD ( gastroesophageal reflux disease ) is being analyzed following the recent completion of the study.

Source: Novartis, 2005