NVS » Topics » Basel, November 5, 2009

This excerpt taken from the NVS 6-K filed Dec 29, 2009.
Basel, December 21, 2009 — Novartis announced today that the World Health Organization (WHO) has granted prequalification for all three of its influenza A(H1N1) 2009 monovalent vaccines for supply to United Nations (UN) agencies: the cell culture-based and MF59® adjuvanted vaccine Celtura®, the egg-based and MF59 adjuvanted vaccine Focetria® as well as the egg-based A(H1N1) vaccine manufactured using the seasonal Fluvirin® platform. In addition to granting prequalified status for Novartis’ three influenza A(H1N1) 2009 vaccines, WHO has also granted prequalification for the company’s trivalent seasonal Fluvirin® vaccine.


WHO prequalification facilitates purchasing through UN agencies and thus enhances access for developing world countries to Novartis A(H1N1) 2009 vaccines that meet unified standards of quality and safety. Novartis has worked closely with WHO under WHO’s expedited procedure for evaluating pandemic influenza A(H1N1) 2009 vaccines to ensure rapid prequalification of its A(H1N1) 2009 influenza vaccines.


“With WHO prequalification for all three of our A(H1N1) 2009 vaccines, we have expanded our commitment to contribute to the prevention of A(H1N1) 2009 influenza in all countries around the world,” said Andrin Oswald, CEO of Novartis Vaccines and Diagnostics.


Prequalification of the adjuvanted vaccines is an important milestone to increase vaccine supply due to the proven antigen and dose sparing potential of the MF59 adjuvant. It is the only oil-in-water adjuvant supported by more than 12 years of post-marketing safety data that includes commercial distribution of more than 45 million doses. The adjuvant has also been studied in randomized clinical trials and observational studies involving 124,000 individuals including children, adults, and elderly; and was first licensed in the seasonal influenza vaccine Fluad® in Italy in 1997. Fluad is currently licensed in Europe for use in individuals 65 years of age and older.


Novartis recognizes the public health need for better access to medicines and vaccines in developing countries. Novartis is working closely with developing countries and international health agencies to find sustainable solutions for effective distribution of essential medicines for diseases such as malaria, meningitis, tuberculosis and leprosy.




This excerpt taken from the NVS 6-K filed Dec 29, 2009.
Basel, December 23, 2009 — Novartis will gain exclusive worldwide rights to relaxin, a recombinant version of a naturally occurring human peptide, through the acquisition of the privately held US biopharmaceutical company Corthera Inc. Relaxin is currently in Phase III clinical trials as a potential treatment option for patients with acute decompensated heart failure (ADHF).


Novartis will assume full responsibility for the development and commercialization of relaxin, with regulatory submissions in the US and Europe planned for 2013. The US Food and Drug Administration (FDA) has granted “Fast Track” designation to relaxin as part of its program to expedite the review of new drugs intended to treat serious or life-threatening conditions that can potentially address unmet medical needs.


Relaxin, which is administered to hospitalized patients via a 48-hour infusion, has been shown to cause an increase in cardiac output, systemic and renal vasodilation, which suggests potential benefits for patients with ADHF. In its natural form, this peptide is responsible for relaxing the female reproductive tract as well as mediating the cardiovascular and renal changes during pregnancy, leading to studies showing its potential applications in this cardiovascular disease.


“Despite a range of current treatment options, acute decompensated heart failure is the leading cause of hospitalization in people over age 65 and remains a major clinical challenge with a high and increasing incidence and substantial morbidity and mortality,” said Trevor Mundel, MD, Global Head of Development at Novartis AG. “Relaxin will be an important addition to our expanding pipeline of novel development projects targeting cardiovascular disease.”


Acute decompensated heart failure — estimated to affect millions of people in the US and in Europe — is a condition often associated with chronic heart disease where patients typically suffer from severe shortness of breath (dyspnea) and the heart’s ability to pump blood from the lungs is impaired. As a result, the lungs become overfilled with fluid, which reduces oxygen uptake. Diuretics and vasodilators are the current standard of care, but available agents from these




classes have been associated with renal impairment, low blood pressure (hypotension) and adverse outcomes.


“We are extremely pleased to be entering into this transaction with Novartis, given their world-class capabilities and global leadership position in cardiovascular disease,” said Stan Abel, President and Chief Executive Officer of Corthera. “This transaction highlights relaxin’s potential as an important treatment option for patients suffering from acute heart failure.”


Relaxin is expected to further strengthen the position of Novartis and its extensive range of cardiovascular medicines and development portfolio:


·                  Diovan

This excerpt taken from the NVS 6-K filed Dec 18, 2009.
Basel, December 18, 2009 — Novartis Vaccines announced today that Menveo® (Meningococcal Group A, C, W-135 and Y-CRM Conjugate Vaccine) has received a Positive Opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA). The investigational conjugate vaccine is recommended for active immunization of adolescents (from 11 years of age) and adults at risk of exposure to Neisseria meningitidis groups A, C, W135 and Y, to prevent invasive disease. Menveo is designed to help protect against four of the five major groups of meningococcal bacteria, which are leading causes of bacterial meningitis — an infection of the membrane around the brain and spinal cord — and sepsis — a bloodstream infection1a, 2.


The CHMP recommendation serves as the basis for a European Commission licensing Decision. The CHMP is recommending that the European Commission grant Marketing Authorization for Menveo in all 27 European Union (EU) countries, which is expected during the first quarter of 2010. Regulatory review for Menveo by the US Food and Drug Administration is ongoing.


Upon licensure, Menveo is expected to be the first conjugate vaccine to be commercially available in Europe to help protect against four major groups of meningococcal bacteria.  Meningococcal disease is a sudden, life-threatening illness that can lead to death within 24 to 48 hours of the first symptoms3a, 4a, 5a. Of those who survive, as many as one in five will suffer life-long after effects, such as brain damage, learning disabilities, hearing loss and limb loss 1b.


“The Committee’s positive recommendation of Menveo is a significant advance in the fight against meningococcal disease,” said Professor Ray Borrow who heads the Health Protection Agency’s Vaccine Evaluation Unit in the UK. “Five groups of meningococcal bacteria cause the majority of meningococcal disease cases around the world3b. Since it is impossible to predict which meningococcal bacterial group one might come into contact with, a vaccine that offers effective protection against four of the groups should be extremely effective in preventing and controlling the disease. It is a welcome development.”


“This is an important milestone toward our vision to eradicate this devastating, deadly and unpredictable disease,” said Andrin Oswald, CEO of Novartis Vaccines and Diagnostics. “We are confident that broad coverage with Menveo will eventually be available to all age groups.”




Menveo was developed using conjugate technology, which was also used to develop Novartis Vaccines’ meningococcal group C conjugate vaccine, Menjugate®. A conjugate vaccine is developed by attaching a polysaccharide antigen — the key component of a vaccine that prompts the body to respond to infection — to a carrier protein. When utilized in a national immunization program, conjugate vaccines (such as those designed to help protect against Hib, pneumococcal and meningococcal group C disease) have reduced the number of people (both vaccinated and unvaccinated) who carry the bacteria that cause the disease.


Adolescents are particularly susceptible to meningococcal disease and are more likely to carry the bacteria than other age groups3c. In addition, adolescents and young adults have relatively high death rates from meningococcal infection. A study in the United States found that nearly a quarter of meningococcal infections in 15- through 24-year-olds were fatal8.


Menveo has been administered to more than 18,500 people and is currently in multiple Phase III clinical studies in infants and toddlers worldwide.


This excerpt taken from the NVS 6-K filed Dec 10, 2009.
Basel, December 9, 2009 — Novartis is set to sustain its leading global position in oncology by expanding the range of indications for several marketed therapies and developing its competitive development pipeline with 16 new molecular entities focused on various life-threatening diseases, senior executives told investors at a meeting today.


Plans include regulatory submissions by the end of 2009 to expand the use of the marketed products Tasigna and Zometa for treatment of various cancers. Up to five other regulatory submissions are possible in 2010 involving Afinitor and other development compounds based on the outcome of ongoing clinical trials in various tumor types.


Novartis has been leading the pharmaceuticals industry in delivering growth in 2009 from recently launched products, according to IMS Health. Contributions from products launched in the last two years rose to 18% of net sales in the 2009 third quarter from 8% in the 2008 first quarter. Oncology will play a key role in this transformation ahead of the end of market exclusivity for Diovan (hypertension) in Europe (2011) and the US (2012).


“We have a productive and innovative pipeline that holds promise for many patients,” said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division. “The benefits of our sustained R&D investments are reflected in the nearly 30 major regulatory approvals achieved so far in 2009 in




the US, Europe, Japan and China. A further 27 projects are currently in late-stage clinical trials, while eight more projects are awaiting regulatory decisions.”


This excerpt taken from the NVS 6-K filed Dec 10, 2009.
Basel, December 8, 2009 — In a large Phase III clinical trial, Tasigna® (nilotinib) demonstrated greater efficacy over Glivec® (imatinib)* in the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase(1).


In the first head-to-head comparison of these two oral therapies as initial treatment for this life-threatening blood cancer, Tasigna results showed statistically significant improvement over Glivec in every measure of efficacy, including major molecular response (MMR), complete cytogenetic response (CCyR) and prevention of progression to accelerated or blastic phase(1). The new data were presented as a late breaker abstract at the 51st annual meeting of the American Society of Hematology (ASH), held in December, in New Orleans, USA.


At 12 months, significantly fewer patients progressed to accelerated or blastic phase on Tasigna 300 mg twice daily than on Glivec 400 mg once daily (2 patients vs. 11 patients)(1), demonstrating a statistically significant improvement in disease control. In the study, Tasigna was well tolerated. Fewer patients discontinued due to adverse events from the Tasigna 300 mg twice daily arm of the study compared to the Glivec 400 mg once daily arm. No patients in the study had prolongation of QT interval >500 milliseconds(1). No sudden deaths occurred with either treatment(2).


“The outstanding rates of response observed with Tasigna, combined with the very low rate of disease progression, strongly indicate that patients who begin their treatment with Tasigna may have long-term improvement of progression-free survival,” said Giuseppe Saglio, University of Turin, San Luigi Hospital, Orbassano-Torino, Italy, a member of the study management committee. “The efficacy results and tolerability of Tasigna should support its use in newly diagnosed Ph+ CML patients.”


With Tasigna 300 mg twice daily, the rate of MMR at 12 months was twice that of patients receiving Glivec 400 mg once daily (44% vs. 22%, p < 0.0001)(1). In addition, 80% of patients




achieved CCyR with Tasigna versus 65% with Glivec 400 mg once daily (p < 0.0001)(1). Responses were achieved faster in the Tasigna group than in the Glivec group(1).


MMR was defined in the study as reduction in the level of the abnormal Bcr-Abl protein to less than or equal to 0.1% of the pre-treatment level based on an internationally agreed standard(1). This can be interpreted to mean that for every 1,000 cells containing Bcr-Abl that were present in the blood at the start of therapy, only one cell was present at the 12-month follow-up. CCyR indicates that no CML cells containing the diagnostic Ph chromosome can be seen in a sample of bone marrow taken from the patient.


“Novartis is pioneering research targeting the molecular origin of Ph+ CML, which has led to treatments of unprecedented effectiveness and safety,” said David Epstein, President and CEO of Novartis Oncology and Novartis Molecular Diagnostics. “Considering the already low rates of progression to advanced disease and the excellent long-term survival of patients on Glivec, the efficacy and safety profile of Tasigna at 12 months is fantastic news and brings promise for further improving the outcomes of patients with Ph+ CML.”


Tasigna is a potent and selective inhibitor of the Bcr-Abl protein that causes production of cancer cells in Ph+ CML(2),(3). Upon initial reports of resistance in the Glivec registration trials, Novartis scientists created a new molecule, Tasigna, just a year after the launch of Glivec. The first clinical trials began just 21 months after discovery. The drug received its first regulatory approval in the second-line indication in 2007.


Novartis plans to file worldwide applications for approval of Tasigna as a treatment for adult patients with newly diagnosed Ph+ CML. Tasigna is currently approved in more than 80 countries including the European Union, United States and other countries for the treatment of adult patients with Ph+ CML in chronic phase or accelerated phase who are resistant or intolerant to prior treatment including Glivec.


This excerpt taken from the NVS 6-K filed Dec 4, 2009.
Basel, December 3, 2009 — Novartis announced today that the European Commission (EC) has approved Onbrez Breezhaler (QAB149 or indacaterol) in both 150 mcg and 300 mcg doses as a new once-daily maintenance bronchodilator treatment of airflow obstruction in adult patients with chronic obstructive pulmonary disease (COPD).


“Onbrez Breezhaler has demonstrated greater improvements in lung function, breathlessness and quality of life compared to current therapies,” said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division. “The EC approval of Onbrez Breezhaler means this new and effective therapy will soon be available to people in the EU with COPD and, through better symptom control, will help them to live more active and productive lives despite their condition.”


Onbrez Breezhaler, containing the active ingredient indacaterol maleate, is the first new inhaled compound for the treatment of COPD to be made available for EU patients in seven years. Additionally, it is the first and only treatment to demonstrate in clinical studies both 24-hour bronchodilation1,2,3 and a rapid onset of action within five minutes of inhalation4,5.


COPD is a progressive, life-threatening respiratory disease10 that affects 210 million people worldwide6, up to 82 million in Europe7,8, the majority of whom are under the age of 6511. COPD impairs lung function resulting in chronic breathlessness. This leads to a profound, negative impact on patients’ ability to work and support families. COPD currently ranks tenth in overall disease burden, ahead of asthma and diabetes12.


The EC based its approval of Onbrez Breezhaler on data from over 6,000 patients. This data included pivotal Phase III results showing Onbrez Breezhaler significantly improved lung function1 and provided clinically relevant improvement in symptoms of breathlessness compared to tiotropium13. Recent data presented at the American College of Chest Physicians (ACCP) Chest Conference showed once-daily Onbrez Breezhaler also achieved significant improvements in lung function compared to twice-daily salmeterol, another current treatment option3. In addition, Onbrez Breezhaler provided better health status* and improved breathlessness compared with salmeterol3.




Onbrez Breezhaler has shown good overall safety and tolerability, which is comparable to other current treatments3,14,15. The most common adverse drug reactions were nasopharyngitis, cough, upper respiratory tract infection, and headache16. These were in the vast majority mild or moderate and became less frequent as treatment was continued16.


QAB149 was filed with the United States Food and Drug Administration (FDA) in late 2008. In October 2009, Novartis received a Complete Response letter from the US. The FDA requested additional information on the dosing proposed, which Novartis is working to address.


Improving the management of COPD is a priority focus for Novartis and Onbrez Breezhaler is the lead compound in an expected once-daily portfolio for the treatment of this growing public health issue. Novartis has three additional investigational treatments in its late-stage COPD portfolio, NVA237, QVA149 and QMF149. Novartis is also exploring new pathways in the treatment of COPD as part of an innovative, early-stage pipeline with disease modifying potential.


This excerpt taken from the NVS 6-K filed Nov 27, 2009.
Basel, November 25, 2009 — Novartis has gained exclusive rights to two oral targeted investigational therapies for patients with a range of life-threatening blood disorders and cancers that currently do not have effective treatment options.


Under a licensing agreement with Incyte Corporation, Novartis will have responsibility for the future development of Incyte’s investigational JAK inhibitor outside the US and for future development of an early-stage cMET inhibitor globally.


·                  The lead compound is a Janus kinase (JAK) inhibitor with the investigational name INCB18424. This oral targeted therapy is in Phase III clinical trials for the treatment of myelofibrosis, a life-threatening neoplastic condition with no effective medical treatment(1) that is characterized by varying degrees of bone marrow failure, splenomegaly (enlarged spleen) and debilitating symptoms. INCB18424 has the potential of becoming a first-in-class therapeutic agent for the treatment of this and other hematologic diseases.


·                  The second compound covered in the licensing agreement, a mesenchymal-epithelial transition factor kinase (cMET) inhibitor with the investigational name INCB28060, is entering Phase I development. Compounds in this class are envisioned to become effective cancer therapies through their ability to block molecular signals leading to tumor cell angiogenesis, proliferation, survival, invasion and metastasis. Multiple cancers have shown to be dependent on activation of molecular signals by genetic alterations of the cMET gene(2).  Emerging evidence indicates that cMET inhibition may be useful in the treatment of certain cancers, including gastric and kidney cancer(2), and may help to overcome resistance to some targeted therapies, such as gefitinib in non-small cell lung cancer(3).


“A key Novartis priority is to bring innovative medicines to patients as quickly as possible,” said David Epstein, President and CEO, Novartis Oncology and Novartis Molecular Diagnostics. “This agreement leverages these two promising investigational drugs with Novartis Oncology’s global development and commercialization expertise and our wide range of multi-targeted approaches to cancer treatment.”




This excerpt taken from the NVS 6-K filed Nov 24, 2009.
Basel, November 24, 2009 — Today, Novartis officially inaugurated the US’s first ever large-scale flu cell culture vaccine and adjuvant manufacturing facility in Holly Springs, North Carolina. The facility is a result of a partnership between Novartis and the US Department of Health and Human Services (HHS). It is the first of its kind in the United States and highlights an important milestone in efforts to improve influenza vaccine manufacturing technology in the US and enhance domestic pandemic preparedness.


“We are proud to be one of the first companies to bring influenza cell culture as well as adjuvant technology to the United States,” said Daniel Vasella, CEO and Chairman of Novartis. “We have seen a great need to invest into new technologies for flu vaccines that will allow for quicker and more reliable production capacity. We are pleased to be working closely with the US government to build a world-class, state of the art manufacturing facility in the US that will change the way we manufacture influenza vaccines in the future.”


The total investment in the facility is nearly USD 1 billion, through a partnership between Novartis and HHS to support the design, construction, validation and licensing of the manufacturing facility in Holly Springs.


The operations at this facility will use modern, cell culture-based manufacturing technology. Cell culture-based production operations are cleaner, can be scaled up more quickly to respond to a pandemic and do not rely on eggs for rapid response to a pandemic. Cell culture technology for influenza vaccines is not yet approved in the US, however part of the HHS contract support for Holly Springs includes funding for the development of a flu cell culture vaccine. If licensed in an emergency, the facility will be ready to respond to a pandemic as early as 2011. The plant is planned to be running at full scale commercial production in 2013.


Novartis already operates a cell culture-based manufacturing plant in Marburg, Germany. It is licensed to produce a seasonal cell culture-based influenza vaccine, Optaflu®, which is approved in all 27 member states of the European Union as well as in Iceland and Norway. It currently produces Celtura®, a H1N1 pandemic vaccine licensed in Germany and Switzerland.




The Novartis Holly Springs facility can also start producing MF59®, the Novartis proprietary adjuvant, as early as December 2009. Although not yet approved in the US, studies with adjuvants are currently underway in the US. Results of the most recent clinical trials conducted with the Novartis MF59 adjuvanted cell culture-based vaccine have shown that it is possible to induce protective antibody levels against A(H1N1) infection within two weeks of administration of a single low-dose adjuvanted vaccine. MF59 has also been shown to provide cross-protection across similar strains of a H5N1 virus, which is an additional important element for a pre-pandemic vaccine given that mutations are a common feature of emerging influenza strains.


As part of its partnership with HHS, Novartis is responsible for, among other things, pre-construction document development, land use and zoning, construction, commissioning, validation and licensing of the facilities with the goals of regulatory licensure, manufacture and release of seasonal and pre-pandemic vaccine, as well as provision for pandemic vaccine supply in the event of a pandemic or other vaccines or biologicals in the event of an emergency for an emerging infectious disease. The partnership also requires Novartis to provide two commercial-scale annual lots of pre-pandemic vaccine for a minimum of three years. In addition, HHS has the right to exercise options to purchase additional influenza vaccine over 17 years.


This excerpt taken from the NVS 6-K filed Nov 17, 2009.
Basel, November 17, 2009 — Novartis announced today new interim data from ongoing clinical trials demonstrating that a single 7.5µg dose of the company’s influenza A(H1N1) 2009 unadjuvanted vaccine, half of the currently-approved US dose, fulfilled immune response criteria associated with protection in adults and the elderly (>65 years of age).


The data also showed a single 3.75µg dose of MF59-adjuvanted A(H1N1) 2009 vaccine met serologic protection criteria against influenza A(H1N1) in children ages 3 to 8, adults ages 18 to 64, and the elderly. All A(H1N1) 2009 influenza study vaccines were manufactured using the Novartis established seasonal Fluvirin® manufacturing platform. Novartis has discussed these new data with the US Food and Drug Administration (FDA) and is performing additional statistical analysis suggested by the agency. It is still under evaluation whether the antigen content per dose can be reduced in the US.


Current US guidelines for A(H1N1) 2009 vaccine use state that adolescents, adults and the elderly are required to receive one 15µg dose to achieve adequate protective antibody levels against the A(H1N1) virus, and children 9 years of age and under are required to receive two 15µg doses four weeks apart.


“These promising data suggest that many more people could potentially be vaccinated with our current vaccines supply, protecting more people earlier against the current pandemic,” said Andrin Oswald, CEO of Novartis Vaccines and Diagnostics. “The data also confirms the antigen sparing potential of our proprietary adjuvant, MF59®. The vaccines output of our Liverpool, U.K., based flu manufacturing facility, fully dedicated to the US since the emergence of the pandemic, could be quadrupled if vaccines are adjuvanted.”


These interim data were generated from pivotal clinical studies designed to evaluate the immunogenicity, safety and reactogenicity of both MF59-adjuvanted and unadjuvanted, inactivated novel swine origin A(H1N1) 2009 monovalent subunit influenza virus vaccine in 4,080




US subjects. In the pediatric trial, the findings are based on 80% of first dose data from 1,360 subjects ages 3 to 8 at day 22. In the adult trial, the findings are based on 95% of first dose data at day 1 and day 8 and approximately 40% of first dose data at day 22 from 1,360 adult subjects and 1,360 elderly subjects. Second dose data and data in ages 6-36 months of age are expected in December 2009.


This excerpt taken from the NVS 6-K filed Nov 12, 2009.
Basel, November 12, 2009 — Novartis announced the availability of Prevacid®24HR (lansoprazole delayed-release capsules 15 mg/acid reducer) over-the-counter in pharmacies and retail stores across the US to treat frequent heartburn. Prevacid®24HR received US Food and Drug Administration (FDA) approval in May 2009. It is the first and only over-the-counter (OTC) Proton Pump Inhibitor (PPI) for the treatment of frequent heartburn in its original formulation.


“It is well known that Americans are taking more ownership of their health-care decisions. The launch of Prevacid®24HR for the treatment of frequent heartburn is a milestone in the over-the-counter medicine category, expanding the treatment choices for the millions of adults who suffer from frequent heartburn,” said Dirk Van de Put, Global Head, Over the Counter Business Unit, Novartis Consumer Health. “We’re looking forward to providing frequent heartburn sufferers with broad access to this very effective treatment and expect the launch to drive strong incremental growth for the OTC Digestive Health category.”


Prevacid® (lansoprazole)2 was one of the most prescribed acid reducer brands in the US over the last decade3 based on IMS Data. The same medicine in Prevacid is now available over-the-counter in Prevacid®24HR for the treatment of frequent heartburn. Frequent heartburn is defined as heartburn that occurs two or more days per week.


Prevacid®24HR is clinically proven to work for a full 24 hours, both day and night. It is the only PPI approved for OTC treatment of frequent heartburn that contains the active ingredient lansoprazole. Starting today, Prevacid®24HR is expected to be available in more than 100,000 pharmacies, drug stores, supermarkets, mass merchandisers and other retail locations throughout the US.


This excerpt taken from the NVS 6-K filed Nov 10, 2009.
Basel, November 4, 2009 — Novartis has reached an agreement to acquire an 85% stake in the Chinese vaccines company Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd. as part of a strategic initiative to build a vaccines industry leader in this country and expand the Group’s limited presence in this fast-growing market segment. This proposed acquisition will require government and regulatory approvals in China.


Tianyuan is a privately-owned vaccine company offering a range of marketed vaccine products in China and R&D projects focused on various preventable viral and bacterial diseases. Tianyuan has been delivering dynamic and profitable growth, having more than doubled its net sales to approximately USD 25 million in 2008 compared to 2006.


“Novartis has a long-standing commitment to improving healthcare in China. Our future activities with Tianyuan are an important step in our strategy to enhance the prevention of diseases in China with high-quality products,” said Dr. Daniel Vasella, Chairman and CEO of Novartis. “The leadership and associates of Tianyuan share with Novartis the same ambition of offering a broad range of vaccines that can prevent many potentially deadly diseases and greatly improve quality of life.”


As part of the collaboration, the two companies will work together to expand Tianyuan’s product portfolio and R&D pipeline through targeted investments in vaccines innovation, manufacturing technologies and commercial networks. This collaboration is also expected to facilitate the introduction of Novartis vaccines into China, where Novartis currently has a limited presence with an offering of vaccines against influenza and rabies.


“Our mission is ‘To build the Great Wall of Health for the people.’ I personally look forward to working with Novartis to continue our mission by bringing more innovative vaccines to China and building Tianyuan into a true international vaccines company,” said Mr. Ding Xiaohang, who is the founder, Chairman and CEO of Tianyuan and will continue to lead this business while holding a minority stake.




China is the world’s third largest vaccines market, with annual industry sales of more than USD 1 billion and expectations for sustained double-digit growth in the future given the government’s commitment to improve access to quality healthcare.


This excerpt taken from the NVS 6-K filed Nov 10, 2009.
Basel, November 5, 2009 — Novartis announced today that it received approval from the German regulatory authorities for its adjuvanted cell culture-based Influenza A(H1N1) 2009 monovalent vaccine, Celtura®. Novartis continues to pursue registration in other major countries, including Japan and Switzerland.


Celtura is manufactured in Marburg, Germany and is an MF59® adjuvanted inactivated influenza virus vaccine indicated for active immunization of persons six months of age and older against influenza disease caused by the novel pandemic A(H1N1) influenza virus. The vaccine contains 3.75 micrograms (ug) of antigen and 1.25 ml of MF59®. It will be offered in multi-vial doses and in single pre-filled syringes.


Clinical studies conducted with more than 1,850 subjects evaluated Celtura’s tolerability and immunogenicity. The studies showed that even with the lowest antigen content (3.75 ug) a single Celtura dose can induce immune responses associated with protection against influenza in individuals from 3 to 50 years of age. Safety and tolerability profiles were as expected. Local injection site (redness, swelling and pain) and systemic complaints of mild fever, headache and fatigue were the most frequent side effects reported.


Celtura uses a validated cell culture line for production of viral antigen components rather than traditional chicken eggs. The technology has previously been licensed in Europe for the production of the seasonal flu vaccine, Optaflu®.


“Our modern cell culture technology can enable a faster start-up of vaccine manufacturing, offering the ability to respond more quickly to future pandemic threats”, said Andrin Oswald, CEO of Novartis Vaccines and Diagnostics. “We quickly ramped up capacity at our licensed cell culture facility in Marburg, Germany to respond to the need for a pandemic vaccine. Also we are close to completion of a second cell culture-based influenza vaccine manufacturing site in the US(1), which is being built in partnership with the US Department of Health and Human Services (HHS).”




MF59 is an adjuvant with an established safety profile supported by more than 12 years of clinical safety data in Europe and more than 45 million doses of commercial use in the influenza vaccine Fluad® (licensed in Europe but not the US).


Novartis has already begun delivery of the company’s egg-based pandemic vaccines, Fluvirin® A(H1N1) monovalent vaccine to the US, and Focetria® A(H1N1) monovalent vaccine to countries around the world. The US Food and Drug Administration approved the Fluvirin A(H1N1) vaccine on September 15, 2009, and the EMEA approved the Focetria A(H1N1) vaccine on September 29, 2009.


This excerpt taken from the NVS 6-K filed Oct 30, 2009.
Basel, October 29, 2009 — Novartis confirmed today that it has shipped over 7.5 million doses of Influenza A(H1N1)(1) vaccine ready to use and expects 25 to 30 million doses of unadjuvanted vaccine to become available in pre-filled syringes and multi-dose vials by the end of November. Smaller changes in delivery timelines and volumes can result out of the variability of the underlying biological production process. The deliveries are in line with commitments made to the US Department of Health and Human Services (HHS).


In addition, the company is progressing with the production of its proprietary adjuvant MF59™ for the US. Adjuvants have shown to be antigen sparing and can double the number of vaccine doses produced.


“Overall, we are pleased with the progress achieved to date, given the many challenges and uncertainties of the current pandemic. Not only did we complete our commitment to provide seasonal vaccine ahead of schedule, we are making every effort to make as much H1N1 vaccine available as quickly as possible,” said Andrin Oswald, CEO of Novartis Vaccines and Diagnostics. “However, we acknowledge the limitations of the old manufacturing sites and technologies for influenza vaccines to rapidly respond to the needs of a pandemic. Over the last three years, Novartis has made major R&D investments to develop new technologies. And in partnership with HHS, we are building the first cell based flu manufacturing facility in the US. The opening of the site is planned later this year.”


Production of the H1N1 vaccine is progressing, despite the unexpected very low yields observed with the initial seed virus at 23 percent as compared to average yield seen with seasonal vaccines. Novartis started production with a new seed virus in the middle of September which provides an improved yield of 63 percent. To date, 42 million bulk units of vaccine have been produced. The company expects to complete production of 90 million doses of bulk antigen by




December and will continue to rapidly fill-finish the bulk antigen as it is produced and ordered by HHS.


Novartis is fully utilizing its manufacturing capacity and has entirely dedicated one of its two major flu manufacturing sites, based in Liverpool, U.K., to supplying H1N1 vaccine antigen for the US. Production capacity at the Liverpool site has been maximized by hiring and training 300 additional staff, as well as the acceleration of the opening of a new facility and egg incubation unit at the site. Following a more than USD 200 million investment over three years, the additional facility was recently approved by the US Food and Drug Administration (FDA) as suitable to manufacture vaccines for the USA.


This excerpt taken from the NVS 6-K filed Oct 27, 2009.
Basel, October 23, 2009The European Commission has granted Novartis marketing authorization for Exforge HCT®, a new 3-in-1 treatment for people with high blood pressure.


Exforge HCT combines in a once-daily single pill the efficacy of three widely prescribed blood pressure medications: the angiotensin receptor blocker valsartan (Diovan®), the calcium channel blocker amlodipine, and the diuretic hydrochlorothiazide (HCT). All three have been used extensively for many years in patients with hypertension.


“Novartis is committed to helping patients improve their treatment compliance. Simplified treatment regimens and reduced pill burdens have been shown to help achieve this,” said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division. “We are pleased that with the approval of Exforge HCT, a new 3-in-1 treatment for high blood pressure is now available to patients in the EU. With Diovan as the foundation of this new therapy, we are confident that it will become an important new treatment option.”


In the EU, Exforge HCT is indicated for substitution therapy in adult patients whose blood pressure is adequately controlled on the combination of valsartan, amlodipine and HCT, taken either as three single-component formulations or as a dual-component and a single-component formulation(4).


High blood pressure, or hypertension, is one of the most important but treatable risk factors for cardiovascular disease – the number one cause of death worldwide(5). Nearly half of Europeans suffer from high blood pressure(6) and up to 85% of these patients may need multiple medications to help reach treatment goals(1),(2). The primary patient-related factor for hypertension treatment failure is non-compliance with the prescribed antihypertensive medication(7). Patients therefore may find treatment more convenient with one single pill rather than multiple separate pills. One recent, large-scale study showed that approximately 75% of patients achieved their blood pressure treatment goal after switching to a single-pill combination therapy(8).


“It is not uncommon for patients with severe hypertension, or those requiring stricter blood pressure control, to need three or more medications,” said Professor Rainer Düsing, MD, of the Faculty of Medicine, University of Bonn, Germany. “Now that this new single-pill triple-




combination option is available, appropriate patients may find it easier to comply with their prescribed treatment regimens involving a once-daily single pill versus multiple medications, especially if it has also been proven to be highly effective at helping patients reach their blood pressure goals.”


Exforge HCT was approved in the United States by the Food and Drug Administration (FDA) in April 2009 for the second-line treatment of high blood pressure(9). It was approved in Switzerland in September 2009 for the treatment of patients whose blood pressure is not adequately controlled by dual therapy(10).


The EU approval was supported by the results of Study 2302(11), a multinational, randomized, double-blind, parallel-group, Phase III study designed to compare the efficacy and safety of triple therapy (valsartan, amlodipine and HCT) with the various dual combinations of its components – valsartan/HCT, amlodipine/valsartan or amlodipine/HCT – in patients with moderate-to-severe hypertension. The trial was conducted in 15 countries, with 2,271 patients randomized to double-blind treatment.


Study 2302 showed that triple therapy was more effective in reducing systolic and diastolic blood pressure than dual combinations of its components in patients with moderate-to-severe hypertension(11). Reductions in mean sitting systolic blood pressure of 40 to 50 mmHg were achieved, with up to 58% more patients receiving triple therapy achieving overall blood pressure control versus dual therapy (i.e. blood pressure <140/90 mmHg). The maximum dose of triple therapy (valsartan/amlodipine/HCT 10/320/25 mg) demonstrated additional reductions of 18–29% in systolic blood pressure and 19–32% in diastolic blood pressure when compared to all dual combinations of its components at the same doses. Ambulatory blood pressure monitoring showed that the blood pressure- lowering effect of triple therapy was maintained throughout the 24-hour period(12). In addition, the study showed that triple therapy was highly effective regardless of patients’ age, gender, race, ethnicity or baseline blood pressure, and was generally well tolerated versus dual therapy(11).


The core of the Novartis portfolio is its cardiovascular and metabolic medications for the treatment of high blood pressure and diabetes. These include Diovan® (valsartan), the number one selling blood pressure medication worldwide; Exforge® (valsartan/ amlodipine), a single pill combining two leading medicines for high blood pressure; Exforge HCT® (valsartan/amlodipine/HCT); and Rasilez® (aliskiren), the first and only approved direct renin inhibitor, and two single pill combinations of Rasilez, Rasilez HCT (aliskiren/HCT) and Valturna (aliskiren/valsartan). For the treatment of type 2 diabetes, these include Galvus® (vildagliptin, a novel DPP-4 inhibitor) and Eucreas® (vildagliptin and metformin).


This excerpt taken from the NVS 6-K filed Oct 27, 2009.
Basel, October 22, 2009Commenting on the results, Dr. Daniel Vasella, Chairman and CEO of Novartis, said: “I am pleased with our strong underlying performance, led by the momentum of our Pharmaceuticals business, outpacing the competition and benefiting from innovative product growth rejuvenating the portfolio. Our investments in R&D show excellent results, with many key approvals in 2009, most notably the anti-cancer therapy Afinitor and the biotechnology medicine Ilaris. Deliveries of H1N1 pandemic flu vaccines are underway as Novartis works at full capacity to meet public health demands. The Sandoz generics business also made good progress, coupled with a turnaround in the US. We expect record full-year underlying results based on the significant progress to date in 2009.”


This excerpt taken from the NVS 6-K filed Oct 21, 2009.
Basel, October 20, 2009 — Novartis announced today that Tasigna® (nilotinib) met its primary endpoint in the first head-to-head comparison with the company’s groundbreaking drug Glivec® (imatinib).* Tasigna produced faster and deeper responses than Glivec when given as first-line therapy for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Tasigna was well tolerated in the study(5),(6).


The Phase III clinical trial, Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd), is the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients. Designed to detect a difference in major molecular response (MMR) between Tasigna and Glivec after 12 months of treatment, it is also the first registration study in which molecular traces of a key biomarker specific to Ph+ CML have been used as a primary endpoint for regulatory review. The comparison study also met its secondary endpoint, a difference in complete cytogenetic response (CCyR) in favor of Tasigna(5),(6).


“We developed Tasigna to be a potent and selective inhibitor of Bcr-Abl, with the goal of eliminating the underlying cause of Ph+ CML. We now know that Tasigna reduces the level of Bcr-Abl faster and to a lower level than Glivec, with profound implications for improving patients’ outcomes,” said David Epstein, President and CEO of Novartis Oncology and Novartis Molecular Diagnostics. “Molecular monitoring enables us to evaluate whether patients have achieved this deep level of CML residual disease, reducing the fundamental biomarker of leukemia to nearly undetectable levels.”


The blood test used to determine molecular response can detect a single cell containing traces of Bcr-Abl in up to one million normal blood cells(7). In addition to being simpler and less invasive for patients, the test has a much greater sensitivity than standard cytogenetic tests, which require a sample of bone marrow to be drawn for visual detection of cells containing the Ph chromosome(1). Molecular monitoring measures the deepest level of CML residual disease(13).




In earlier clinical trials, molecular responses were found to be predictive of better patient outcomes: 100% of Ph+ CML patients who achieved MMR (defined as a thousand-fold or greater reduction in Bcr-Abl relative to standardized baseline level) in the first 12 months of treatment survived without disease progression for at least five years8. Follow up of patients in these studies is ongoing.


Details of the ENESTnd findings will be submitted as a late-breaking abstract to the 51st annual meeting of the American Society of Hematology (ASH), to take place in December, in New Orleans, Louisiana, USA.


Previous studies of Tasigna as first-line therapy for patients with newly diagnosed Ph+ CML include the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) study, an ongoing, open-label, single-stage, multicenter Phase II clinical trial; and NCT00129740, an ongoing, open-label, single-center Phase II clinical trial undertaken at M.D. Anderson Cancer Center in Houston, Texas, USA. New data from the GIMEMA study presented earlier this year at the European Hematology Association (EHA) congress show that at 12 months, 85% of patients taking Tasigna achieved MMR. These data indicate a more rapid reduction in disease burden compared to that seen in previous studies with Glivec9.


This excerpt taken from the NVS 6-K filed Oct 20, 2009.
Basel, October 20, 2009 — New Phase II results show that the novel biological therapy ACZ885 (canakinumab) is significantly more effective than an injectable corticosteroid at reducing pain and preventing recurrent attacks or ‘flares’ in patients with hard-to-treat gout, one of the most painful forms of arthritis(1).


The study met its primary endpoint by showing that during acute gout flares, ACZ885 reduced pain faster and more effectively than the injectable corticosteroid triamcinolone acetonide(1), a potent steroid with sustained effect used to treat severe inflammatory conditions (p<0.05)(7).


At the end of the eight-week study, the risk of flare recurrence was 94% less for patients on ACZ885 than on the steroid (p=0.006)(1). The results were presented today at the American College of Rheumatology (ACR) Annual Scientific Meeting in Philadelphia, USA.


“If not appropriately treated, gout can be a devastating condition. Current therapies can have limited efficacy and tolerability, and may be unsuitable for some patients(8),(9),” said Professor Alexander So, MD, Department of Rheumatology at the University of Lausanne, Switzerland. “These results are important as they indicate that canakinumab may provide significant benefit in both the prevention and treatment of painful acute flares in these hard-to-treat patients.”


ACZ885 is a fully human monoclonal antibody which blocks the action of the inflammatory protein interleukin-1 beta (IL-1 beta). It has already been approved under the brand name Ilaris® in a number of countries for treating cryopyrin-associated periodic syndrome (CAPS), a rare life-long auto-inflammatory disease with debilitating symptoms and few treatment options.


Studies with ACZ885 are ongoing in other diseases in which IL-1 beta plays an important role, such as chronic obstructive pulmonary disease (COPD), type 2 diabetes and systemic juvenile idiopathic arthritis (SJIA). Not all potential patients with these diseases would be eligible for treatment with ACZ885, if approved.


Gout, also known as gouty arthritis, affects more than 1% of adults in Western countries(10),(11). It is more common in older people, with around 10% of men and 6% of women over 70 years old




suffering from the disease(6),(12),(13). Approximately one in 10 patients have poorly controlled gout resulting in more frequent flares(14). They are regarded as being ‘hard-to-treat’ as they are often intolerant or unresponsive to standard medications such as colchicine or non-steroidal anti-inflammatory drugs (NSAIDs)(15). Corticosteroids have traditionally been given to these patients as a last resort to treat acute pain, but they may have significant side effects(7),(16).


Gout is caused by the accumulation of uric acid crystals leading to severe inflammation in the joints and surrounding tissue(2),(3). Recent advances in the understanding of the disease have shown that uric acid crystals activate production of IL-1 beta, which is responsible for the inflammatory symptoms experienced by gout patients(6). ACZ885 provides a potent and selective blockade of IL-1 beta for a sustained period, neutralizing it and reducing inflammation(4),(17),(18).


“The devastating impact of chronic gout is often underestimated by both healthcare professionals and the general public, and there is a real unmet need among patients,” said Trevor Mundel, MD, Head of Global Development at Novartis Pharma AG. “The latest data are encouraging for patients with hard-to-treat gout in whom the disease is not effectively managed, resulting in chronic pain. These findings also reinforce the potential of ACZ885 in a number of inflammatory diseases where IL-1 beta plays a key role.”


The results presented at ACR were from a randomized, single-blind, double-dummy Phase II study involving 200 patients aged 18-80 years old with chronic gout, designed to assess the efficacy and optimum dose of ACZ885 in patients for whom current treatments (colchicine and/or NSAIDs) are ineffective or contraindicated(1).


The study showed that patients given ACZ885 150 mg experienced faster and more effective pain relief than those given the corticosteroid triamcinolone acetonide from 24 hours up to seven days(1). ACZ885 was given by subcutaneous injection, i.e. under the skin, whereas the steroid was given by intramuscular injection, i.e. into the muscle.


No pattern of adverse events was seen in any of the treatment groups and the incidence of adverse events was similar for both medicines(1). Serious adverse events occurred in two patients receiving ACZ885 and one receiving triamcinolone acetonide. Investigators reported that these events were not related to the study drug(1). There were no discontinuations due to adverse events(1).


Ilaris has been launched in the US and Switzerland, and received a positive opinion recommending approval in the EU in July 2009 to treat adults and children over four years old with CAPS. In the US, Ilaris is approved to treat adults and children four years of age and older with CAPS, including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS). Reviews are ongoing in other countries including priority review in Australia, Brazil and Canada. Ilaris has been designated as an orphan drug for treating SJIA in the US, EU and Switzerland, and has fast-track status for SJIA in the US.



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