Pharmacy

 


Optaflu®, the Novartis Cell Culture-Derived Influenza Vaccine, Receives Positive Opinion  

---Novartis leading the introduction of influenza cell culture manufacturing - the first major innovation in influenza vaccine manufacturing in more than 50 years---

---Optaflu® to help meet growing need for seasonal influenza vaccines, production technology has potential for quick scale-up in case of an influenza pandemic--

---Novartis proprietary cell culture technology offers possibility to obtain a better matched vaccine with circulating viruses than currently available technology---

Basel, April 27, 2007 - Novartis has received a positive opinion supporting European Union approval of its cell culture-derived seasonal influenza vaccine Optaflu®, which is aiming to become the first influenza vaccine to utilize a mammalian cell line, rather than chicken eggs, for antigen production.

The Committee for Medicinal Products for Human Use (CHMP), which reviews applications for all 27 countries in the EU as well as Iceland and Norway, has recommended approval of this new vaccine. The European Commission generally follows the recommendations of the CHMP and delivers its final decision within two to three months.

"Novartis Vaccines is pleased with this positive recommendation for Optaflu, the first cell culture-derived influenza vaccine and the first major innovation in influenza vaccine manufacturing in more than 50 years," said Dr. Jörg Reinhardt, CEO of Novartis Vaccines and Diagnostics. "Optaflu contributes to meeting the growing demand for seasonal influenza vaccines, and this production technology offers the potential for quick scale-up of manufacturing in the event of an influenza pandemic."

A submission is anticipated in 2008 for US regulatory approval of this cell culture-derived seasonal influenza vaccine.

More than 3,400 people received Optaflu during the clinical development program evaluating the vaccine's safety and immunogenicity. Data reviewed by CHMP from the clinical program showed Optaflu fulfilled all of the Committee's immunogenicity criteria.

The data further showed the cell culture-derived influenza vaccine was comparable to conventional egg-based vaccines in efficacy and tolerability. Additives, such as antibiotics, are avoided in the Optaflu production process. Additionally, people allergic to eggs and egg products can benefit from receiving this vaccine since it is created without egg proteins.

Like established conventional egg-based vaccines, Optaflu is administered via intramuscular injection. Data from the Phase III clincial program were presented at the Influenza Vaccines for the World Congress (IVW) meeting in October 2006.

About cell culture technology and the Novartis proprietary cell line

Cell culture manufacturing is the first major innovation in influenza vaccine manufacturing in more than 50 years. It represents a new approach to vaccine production whereby influenza virus is propagated in readily available mammalian cell lines rather than in chicken eggs.

Virus cultivation utilizing the Novartis proprietary cell line as an exclusive host offers the possibility of more robust virus proliferation since most circulating viral strains are unable to replicate in chicken eggs. In a next generation of products, it also offers the possibility for vaccine seed strain development that more closely matches the original "wild" virus because cell culture technology eliminates the need for passage through eggs where the virus may be forced to adapt in order to replicate. As a result, the antigen included in the vaccine may express more authentically the surface of the wild type virus, potentially translating into a better immunogenic and effective response.

The Novartis proprietary cell culture technology enables flexible, faster start-up of vaccine manufacturing. With the advent of this technology, Novartis Vaccines is contributing  to meet the growing need for seasonal influenza vaccines and quickly respond to a potential pandemic influenza threat.

About influenza and pandemic influenza

Influenza can cause mild to severe illness and at times can lead to death. Worldwide, influenza epidemics result in approximately 250,000 to 500,000 deaths each year[1]. Influenza-related complications can include pneumonia and dehydration, and worsening of chronic conditions, such as congestive heart failure, asthma, or diabetes[2]. The World Health Organization (WHO) and its Global Influenza Surveillance Network recommend vaccination as the principal method for preventing influenza[1].  

Increased circulation of avian influenza A/H5N1 virus has been documented in Asia and Europe. On a pandemic threat scale of one to six, the World Health Organization currently ranks the H5N1 risk at phase three. This virus is highly contagious in chickens, adding the possibility that a pandemic strain could emerge at a time when egg supplies are lower than usual due to a previous epidemic in chickens. Novartis proprietary cell culture line offers an alternative to traditional egg-derived vaccines.

References

1. World Health Organization "Influenza Fact Sheet" http://www.who.int/mediacentre/factsheets/fs211/en/index.html Accessed October 10, 2006

2. Centers for Disease Control and Prevention (CDC) "Questions & Answers: The Disease" http://www.cdc.gov/flu/about/qa/disease.htm  Accessed October 10, 2006

Disclaimer

This release contains certain forward-looking statements, relating to the Novartis Group's business, which can be identified by the use of forward-looking terminology such as "to help," "potential," "possibility," "aiming to", "recommended", "generally follows the recommendations," "anticipated," "potentially, "can," "could," or similar expressions, or by express or implied discussions regarding potential marketing approvals or future sales of Optaflu. Such forward-looking statements reflect the current views of Novartis regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Optaflu to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Optaflu will be approved for any indications in any market or that Optaflu will reach any particular sales levels. In particular, management's expectations regarding Optaflu could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including additional analysis of existing clinical data and new clinical data; competition in general; the ability of Novartis to obtain or maintain patent or other proprietary intellectual property protection; increased government, industry, and general public pricing pressures; and other risks and factors referred to in the 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

Novartis Vaccines and Diagnostics is a division of Novartis focused on the development of preventive treatments and tools. Novartis Vaccines is the world's fifth-largest manufacturer and second-largest supplier of influenza vaccines in the US. The division's products also include meningococcal, pediatric and travel vaccines. Chiron, the blood testing and molecular diagnostics business, is dedicated to preventing the spread of infectious diseases through the development of novel blood-screening tools that protect the world's blood supply. For more information, please visit http://www.novartisvaccines.com.

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative-products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world.

For more information, please visit http://www.novartis.com

Novartis Suspends US Marketing and Sales of Zelnorm(R) in Response to Request from FDA  

30/03/2007, 2007. Retrospective analysis of pooled clinical trial data shows numerical imbalance in cardiovascular events in patients taking Zelnorm compared to those on placebo

FDA asks Novartis to suspend marketing and sales to permit further discussion of benefits and risks of Zelnorm

Novartis believes Zelnorm provides important benefits for appropriate patients suffering from irritable bowel syndrome with constipation

Discussions ongoing with FDA to evaluate best way to continue to make Zelnorm available to appropriate US patients

Basel, March 30, 2007 - Novartis is complying with a request from the Food and Drug Administration (FDA) to suspend US marketing and sales of Zelnorm®[*] (tegaserod maleate), a treatment for irritable bowel syndrome (IBS) with constipation and chronic constipation.

This action has been taken after Novartis notified the FDA about a retrospective analysis of data from more than 18,000 patients in the clinical trial database. This was the result of an ongoing review involving a number of health authorities including the FDA.

A small (but not statistically significant) imbalance in cases of angina pectoris was recorded and included in the US label when Zelnorm was approved in 2002. A recent analysis of the entire clinical database revealed a statistically significant imbalance in the incidence of cardiovascular ischemic events in patients taking Zelnorm/Zelmac compared to those taking placebo. These events included myocardial infarction, stroke, and unstable angina pectoris.

The data, which were reviewed by independent experts, showed that events occurred in 13 out of 11,614 patients treated with Zelnorm/Zelmac (0.11%), compared to one case in 7,031 placebo-treated patients (0.01%). All patients affected had pre-existing cardiovascular disease and/or CV risk factors.

The rate of cardiovascular ischemic events seen in Zelnorm/Zelmac-treated patients in controlled trials corresponds approximately with the expected rates for such events in the general population.

"My review of the data suggested that a causal relationship is unlikely between tegaserod and the rare cardiovascular ischemic events observed in clinical trials," said Jeffrey L. Anderson, MD, Professor of Internal Medicine at the University of Utah and Associate Chief, Cardiology Division, LDS Hospital in Salt Lake City and an independent cardiologist who reviewed the data. "Furthermore, the data did not show any consistent pattern of event type, time to event or dose relationship in tegaserod-treated patients."

Multiple studies do not suggest any constrictive effects of Zelnorm on coronary arteries.

An estimated 12 million Americans suffer from the painful and disruptive symptoms of IBS with constipation. Many have symptoms for five to 10 years, which trigger missed work-days and often prevent them from participating in everyday activities with their family and friends.

"Zelnorm/Zelmac provides unique benefits to patients by treating the multiple symptoms of abdominal pain, bloating and constipation that are associated with IBS with constipation," said James Shannon, MD, Global Head of Development at Novartis Pharma AG. "Although we have complied with the FDA's request and are collaborating with the agency, we continue to believe that Zelnorm/Zelmac provides important benefits for appropriate patients."

Nevertheless, Novartis has suspended the marketing, sales and distribution of Zelnorm in response to the FDA's request, so that public discussion and an Advisory Committee meeting can take place to determine the risks and benefits of this medicine.

Novartis and the FDA will communicate this information to physicians and patients, and will discuss the best way to continue to make Zelnorm available to appropriate patients, including through a Treatment IND. US patients taking Zelnorm are being advised to consult their physicians.

Novartis is in discussion with health authorities in other countries where Zelnorm/Zelmac is available to determine next steps. Patients outside the US who have any concerns about Zelnorm/Zelmac should discuss the situation with their healthcare professional.

About Zelnorm

Zelnorm received FDA approval for the short-term treatment of women with IBS in the US on July 24, 2002. Zelnorm also received FDA approval for the treatment of men and women less than 65 years of age with chronic idiopathic constipation in the US on August 20, 2004.

Zelnorm/Zelmac is approved for the treatment of IBS with constipation in 50 countries including Australia, Switzerland, Canada, the US, Mexico, China and Brazil. Zelnorm/Zelmac is also approved for the treatment of chronic constipation in more than 20 countries including the US, Canada and Mexico. Novartis markets the therapy under the trademark Zelnorm (tegaserod maleate) in the US, Canada, Philippines and South Africa; and as Zelmac (tegaserod) in Switzerland, Latin America and the Asia-Pacific region.

Financial update

For its 2007 financial guidance, Novartis has revised its outlook for net sales growth, barring unforeseen events, for the Group to above five percent, and for the Pharmaceuticals division to a low- to mid-single-digit rate, both in local currencies.

Novartis is still evaluating the impact on the full-year 2007 operating and net income results from continuing operations (excluding the announced divestiture of Medical Nutrition expected to be completed in 2007).

An invitation will be issued to financial analysts to join an update telephone conference call at 19:00 Central European Summer Time (CEST) on Friday, March 30. A listen-only version of this event will be available on the Internet at www.novartis.com, where a recorded version of this conference call will be made available after the event.

Disclaimer

The foregoing release contains certain forward-looking statements that can be identified by terminology such as "will," "outlook," or similar expressions, or by express or implied discussions regarding potential future approvals to return Zelnorm/Zelmac to the market, or potential future sales of Zelnorm/Zelmac, or the potential impact of Zelnorm/Zelmac on the potential future sales or earnings of the Novartis Group or its Pharmaceuticals Division. Such forward-looking statements involve known and unknown risks, uncertainties or other factors that may cause the actual results to be materially different from any future results, performance, or achievements expressed or implied by such statements. There can be no guarantee that Zelnorm/Zelmac will be approved by the FDA or other health authorities for return to the market for any indication, or that Zelnorm/Zelmac will achieve any particular level of sales. Nor can there be any guarantees that the Novartis Group, or the Pharmaceuticals Division, will achieve any particular financial results.  In particular, management's expectations regarding these matters could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results or results of data analysis, including additional analysis of existing clinical data and other data regarding patients' experience with Zelnorm/Zelmac, or unexpected new clinical or other such data; competition in general; government, industry and general public pricing pressures; the ability to obtain or maintain patent or other proprietary intellectual property protection; as well as factors discussed in the Company's Form 20-F filed with the US Securities and Exchange Commission. 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

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 101,000 associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

# # #

Novartis Media Relations

John Gilardi

Novartis Global Media Relations

+41 61 324 3018 (direct)

+41 79 596 1408 (mobile)

[email protected]

* The information in the press releases on these pages was factually accurate on the date of publication. These press releases remain on Novartis' website for historical purposes only. Novartis assumes no duty to update the information to reflect subsequent developments. Readers should not rely upon the information in these pages as current or accurate after their publication dates. 

Market Intelligence and Pharma Data Mining

e-Published, Feb 1st, 2007

By Dr. Krishan Maggon,  Ph.D., Pharmaceutical Biotechnology R&D Advisor

ICC- Route de Pré Bois 20, PO Box 1887, 1215 GENEVA 15, Switzerland, Email: [email protected]

Abstract

Biomedical journals have recently published several market analysis covering new drugs and sales data for rheumatoid arthritis, influenza vaccines, monoclonal antibodies and recombinant protein therapeutics derived from commercial databases. This paper will revisit and analyse some of the published sales and market data. Authors from firms selling commercial data bases to pharmaceutical and biotechnology industry present their own market data, sales forecast and identify brands, which will drive future growth and markets. Comparison of the sales figures of blockbuster medicines from company sources and commercial reports and databases reveals significant discrepancies. Three Datamonitor papers in 2006 provide different sales and forecast for influenza vaccines. Comparison data from different sources and projections from previous reports or forecasts with actual data is rarely presented or discussed. Such discrepancies may result in a misleading evaluation of product, markets, portfolio, research development and company. Biomedical publications should develop a new policy and apply the same high standards of data reporting as in regular publications for commercial data sources.

Introduction

Market intelligence, consultancy and knowledge providers to the pharmaceutical, biotechnology, device and diagnostic industry, had total global sales of $6 billion in 2005. Each year commercial data firms issue hundreds of research reports costing thousands of dollars each and 2007 will be the same. These reports cover global best selling medicines, new drugs and market analysis of selected therapeutic area. It is claimed that these exclusive research reports identify drivers of future growth and market size forecasts that drive decisions and shape strategies by executives. IMS with 2005 sales of $1.8 billion has a 30% market share and its global data, figures, graphs for top selling medicines are extensively covered in several popular news, financial, business, scientific and medical media thereby having a 100-fold multiplier impact factor as a yearly ritual. Similarly Ernst & Young, Accenture, IBM, Boston Consultancy, Price Waterhouse Cooper, Scrip, Reuters, Thompson-ISI and Datamonitor reports are quoted and reported extensively in new and old media. Unlike IMS, other data-mining firms do not report income/sales from pharmaceutical and biotechnology companies.

In addition to industry, hedge funds, venture capital, investment funds, industry specific funds, leading banks and traders use these reports and data to make decisions about trade, investment and profits. All major pharmaceutical and biotech companies in the world are customers of such reports and data.

The advantage of these reports is that they provide a comprehensive list of blockbuster drugs, sales and companies involved and market trends. The disadvantages are the high cost of these reports, somewhat outdated data, confidential nature of the data collection and evaluation and divergence of sales figures in comparison with company reports. All commercial databases take shelter behind the safe harbor statement “their models and methodologies for estimation of sales figures may give results which may differ from actual results”. Company annual and quarterly reports and presentations provide easy access to real data for their top selling products. The disadvantage is that some European and Japanese companies still do not provide sales data for their best selling products and use a different financial year than the calendar year.

Global Sales Data

Forecasting and predicting the future markets and trends for pharmaceuticals and monitoring the actual market sales remains an important tool for the industry to plan its growth, R&D and marketing strategy.  Several commercial reports cover global blockbuster drug sales and R&D trends (1-4) (Table 1). Differences of over $1 billion were observed for the top 1-2 brands and 0.5 billion for several brands (1-4) since 2002.  The ranking of best selling brands and growth rates were significantly different. Ranking of the companies based on sales of biologic drugs, R&D expenses and R&D budgets was different as well (5-8) (Tables 2, 3).

         Global Pharmaceutical Market  IMS Health         2005                603

Global Biotechnology Market  Ernst & Young      2005                63      

                                                   Datamonitor                                      40

                                                   IMS                                                  52

Leading therapeutic categories in 2005

Pharmaceuticals

Market size

Biotechnology

Protein

Market size

CNS

91

Anemia

Erythropoietin

12.3

Cardiovascular

85

Immuno Inflammatory

TNF Blockers

8.6

Infections

58

Diabetes

Insulin

7.2

Obesity

35

MS+ Hepatitis C

Interferon

6.8

Cancer

30

Cancer, Arthritis

Infection

Monoclonal Antibodies

14

Ulcer

27

Infections

Vaccines

14

Diabetes

20

Growth, fertility

Hormones

5

IMS Top Line Industry Data 2005; Ernst & Young 2006 Beyond Borders

Maggon K. R&D Paradigm Shift & billion dollar biologics. In Shayne C. Gad Ed. Handbook of Pharmaceutical Biotechnology. John Wiley, New York. 2007. In Press

Company

Sales $ billion

2005                            

Major Product Sale $ billion

2005                             

Amgen

13

Enbrel 3.7, Aranesp 3.3

Roche

9.3

Rituxan 3.2, Herceptin 1.7

J&J

6.8

Remicade 3.5, Procrit 3.3

Novo Nordisk

4.2

Novolin, analogs 3.6

Lilly

3

Humulin, Humalog 2.1

Merck Serono

2

Rebif 1.3

Bayer Schering

2

PegIntron 1.4

Genzyme

2

Cerazyme 0.93

Baxter

1.8

r Proteins 1.2

Biogen Idec

1.5

Avonex 1.2

Wyeth

1.5

Prevanar 1.5

Sanofi Aventis

1.4

Lantus 1.4

Abbott

1.4

Humira 1.4

Schering Plough

1.4

Remicade 0.9

MedImmune

1.2

Synagis 1.1



Table 3. Top Brand Human Medicines in 2005

Generic Name

Brands

Companies

Indications

2005 Sales $ billion

Company   IMS     Diff

Atorvastatin

Lipitor

Pfizer

Cholesterol

12.2          12.9      +0.7

Clopidrogel

Plavix

Bristol Myers Squibb, Sanofi Aventis

Atherosclerosis

6.2             5.9        -0.3       

Fluticasone Salmetrol

Advair

Glaxo Smith Kline

Asthma

5.5             5.6       +0.1

Amlodipine

Norvasc

Pfizer

Hypertension

4.76           5.0      +0.24

Esomaprazole

Nexium

AstraZeneca

Ulcers

4.63           5.7      +1.07

Simvastatin

Zocor

Merck

Cholesterol

4.4             5.3       + 0.9

Glanzapine

Zyprexa

Lilly

Schizophrenia

4.2             4.7        +0.5

Pentoprazole

Protonix

Atlanta, Wyeth

Ulcers

4.0             NA

Lansoprazole

Prevacid

Takeda, Abbott

Ulcers

3.8             4.0       + 0.2

Valsartan

Diovan

Novartis

Hypertension

3.67            NA

Risperidone

Risperdal

J&J

Schizophrenia

 3.55           4.0     +0.45

Venlafaxine

Effexor

Wyeth

Depression

3.5              3.8      + 0.3

Sales as reported by company’s annual results/reports. The IMS figures for 2005 are included if available.

IMS (1) and Ernst & Young (2) sales figures for pharmaceutical and biotechnology are considered Industry gold standard and are widely used.  IMS data for top selling global brands differs significantly from sales data reported by companies for the same year (Table 3). The differences of more than $1 billion and $ 0.5 billion for some brand were observed without any clear explanation or rationale. IMS figures for Lipitor sales in 2003 were $1 billion more than reported by Pfizer. Review of sales figures released by companies (6,7) producing medicines with sales in excess of $3 billion in 2004 (15 compounds in total), shows that the IMS figures differed by as much as $ 1 billion for two drugs (Lipitor and Nexium) and over $ 0.5 billion another four drugs in the year 2003 and two drugs in 2004. Differences in IMS values and company sales figures of less than $200 million was seen for only 2 drugs in the past  three years (Table 3). Variables like exchange rates, bulk discounts, Stockpiling, Parallel imports, Damages/returns and exclusion of certain developing countries may be contributing factors in data collection by IMS and companies may explain small differences of a few million dollars. Such differences were first reported by the author in 2003 for the year 2002 sales data and have persisted (5-7).

            TNF Antagonists

The market data presented for TNFα antagonists 2005 sales was included in a recent paper (9) covering rheumatoid arthritis drugs and markets published in March 2006. The companies (Amgen, Johnson & Johnson, and Abbott) had released their yearly earnings and top brand sales by last week of January 2006. The paper mentions a total market for the TNFα antagonists as more than $6 billion, the actual figure as reported by companies was $5.5 billion in 2004 and $8.6 billion in 2005 (Enbrel $ 3.7 billion, Remicade $ 3.5 billion, Humira $ 1.4 billion). Combined sales of Enbrel and Remicade are 83% and closer to the 80% of the total TNFα market mentioned in the paper (9). Only one monoclonal antibody in Phase III (Cimzia, UCB) for which NDA has been filed is mentioned. Twenty other monoclonal antibodies in Phase III trials in arthritis patients are not mentioned? The article fails to provide an updated 2005 sales or development status of Phase III/NDA projects in rheumatoid arthritis. There is a real need for a new agent, which in combination with methotrexate and TNFα antagonists will increase sustained response rate without increasing risk of infections or other cardiovascular adverse reactions (10-12). The success of future agents will depend on the real therapeutic gain achieved with $25000 annual cost and the ability of healthcare systems to cover all arthritis patients.

Monoclonal Antibodies

Reichert and Pavlou (9) analysis of the monoclonal antibody market in 2004 predicted the monoclonal antibody market to $16.7 billion in 2008, the combined sales of the top selling therapeutic monoclonal antibodies in 2005 were $14 billion as reported by companies. This figure excludes antibodies used for diagnostic tests and procedures. Datamonitor (14-17) projected figures for 2008 were reached in 2006 with sales of $18 billion. The sales figures for Avastin were $ 500 million lower than the actual sales figures reported by Roche for 2005 and for Erbitux higher by $ 140 million. With over 200 companies developing monoclonal antibodies and the total number of active projects in R&D and clinical development at 132 seems to be lower than the real figure (17-20). FDA approved only one monoclonal antibody Orencia in 2005 and  two Lucentis and Vectibix in 2006.

Influenza Vaccines

Two recent 2006 Datamonitor articles on influenza vaccine provide divergent sales and forecast. One article reports 2004 sales of $1.3 billion and a 2010 forecast of $3.7 billion (21), and another $1.1 billion sales and $3.1 billion forecast  (22). A news story (23) about Datamonitor Influenza vaccine reports 2005 sales of $1.6 billion and a 2010 forecast of $3.0 billion (Table 4).

Concerns about avian influenza and stockpiling by governments and the strong demand for influenza vaccines in 2006 were offset by mild influenza winter resulting in oversupply of the vaccine in USA and Europe.  If influenza vaccines accounted for 14% of total vaccine sales, the global market for vaccines was $14 billion in 2005.  Five top vaccine companies (Glaxo Smith Kline, Sanofi- Aventis, Merck, Wyeth and Chiron) (24) had combined sales of $8.6 billion in 2005.

Table 4. Influenza Vaccine Sales and Forecast

Sales  $  billion

2004                2005                2010 forecast                           Reference

---------------------------------------------------------------------------------------------

1.2                   1.8                   NA                                          Company* 2005

Annual report

Datamonitor Report 2006

1.3                   NA                  3.7                                           8

1.1                   NA                  3.1                                           9

NA                  1.6                   3.0                                           10

________________________________________________________________

* Sanofi Aventis, Glaxo Smith Kline, Merck,

   Chiron-Novartis, Solvay, Crucell-Berna, MedImmune

Therapeutic Proteins

Datamonitor (4, 25, 26) market analysis and forecasting methodology has been described. Once again the global market growth projections for therapeutic proteins from 2004 to 2010 are provided. The market for 2005 was estimated at $40 billion and for 2010 at 50 billion. IMS (1) data gave a figure of $ 52 billion and Ernst & Young (2) of $ 63 billion (Table 1). The sales of the top 20-biotechnology products (20) were $59.6 billion and assuming that these products account for 75% of the total market, the total market value is near $75 billion for 2005. Similar results are obtained if total sales of different therapeutic categories are added (Table 1). The listed brands driving future markets25 and growth missed out on several current blockbuster brand like Synagis, Rituxan, Herceptin, Prevanar, Copaxone, Avastin and blood factors (5). 

            Discussion

Variables like exchange rates, bulk discounts, stockpiling, parallel imports, damages/returns and exclusion of certain developing countries cited as contributing factors in data collection by commercial firms may explain small differences of a few million dollars. There is no logical explanation for differences of $500-1000 million in the same year for some best selling global brands or R&D expenses of top research driven companies. Such differences were first reported in 2003 for the year 2002 sales data and have continued (1-4). In the era of Global Accounting Standards and SEC requirements, company-reporting standards are well known and more reliable while commercial data collection methods remain confidential. Commercial firms have failed so far to correct the deficiencies in their methodology and require constant improvements to eliminate and minimize differences. Publications in biomedical journals of such reports as regular or invited features with significant discrepancies, missing data and lack of comparative data require new editorial policy and guidelines.

Commercial research reports and sales figures differ significantly in comparison to companies’ annual reports. The data, trends and predictions may significantly impact market value of companies, R&D projects, licensing, merger and acquisition, joint ventures, alliances and deals. Similarly ranking of companies by sales, profitability, R&D budgets, new blockbuster drugs may change market value, perceptions and cost of  loans or new funds for companies.

Since commercial reports are used for strategic decision-making, it is obvious that significant discrepancies in sales data, market projections may contribute to the market failure of some new drugs and decline in R&D productivity and current low public perception of the pharmaceutical industry. Significant variations in past predictions concerning present trends and markets forecasts have been observed. The data mining firm’s recent data should match or come closer to company’s latest annual reports for top selling global brands, sales growth, R&D budgets and total market size in different indications.  Significant and persistent discrepancies in data from different sources will ultimately undermine the current reliance of industry on commercial data and research reports.

It is relatively difficult to publish an article challenging big commercial firms. The present article challenges commercial research report figures, marketing and growth forecast and future trends published in selected biomedical journals. Editors of journals when contacted about discrepancies in data decided to ignore the differences and not publish the corrections. One editor decided that an article pointing out data differences was not worth publishing as it did not go beyond discrepancies. When additional comments were added, the editor decided that the article was not balanced and must include positive aspect of commercial research reports.

There is no independent comparative evaluation of past predictions and actual results or any oversight by regulators or SEC for commercial reports. In the era of Global Accounting Standards and SEC requirements, company-reporting standards are well known and more reliable while commercial data collection methods remain confidential. The sales projections for the same product for any year should converge for all validated methods for data collection, forecast and analysis.

References

1.      IMS Top Line Global Industry Data (2005). www.imshealth.com, http://www.ims-global.com/insight/insight.htm

2.      Ernst & Young. (2005 & 2006). Global Biotech Report and Global Pharmaceutical Trends. Levinson A.D. (2005). What distinguishes biotech from big pharma? Global Industry Perspectives.

3.      Reuters Health. Reports (2004) The Pharmaceutical Market Outlook to 2010. http://www.reutersbusinessinsight.com/content/rbhc0091t.pdf.

4.    Datamonitor Potential blockbuster drugs (2004). www.datamonitor.com

5.      Gray N. (2006). Changing Landscape The World top 50 Pharmaceutical Companies. Pharmaceutical Exec. 26, 78-101.

6.      Maggon K. R&D paradigm shift and billion dollar biologics. In Handbook of Pharmaceutical Biotechnology. Ed Gad, S. C. John Wiley, New York. 2007 In Press

7.      Maggon K. The ten billion dollar molecule. Pharmaceutical Executive, 23, 60-68, 2003.

8.    Maggon K. Best Selling Human Medicines 2002-2004. Drug Discovery Today, 10, 738-742 (2005).

9.      Moreland, L.,Bate G. & Kirkpatrick, P. Abatacept. Nature Reviews. 5. 185-186(2006).

10.  Sesin, C. A. & Bingham, C. O. Remission in Rheumatoid Arthritis: Wishful Thinking or Clinical Reality? Seminars in Arthritis and Rheumatism, 35, Issue 3, 185-196 (2005).

11.  Hochberg, M. C. et al. The Benefit/Risk Profile of TNF-Blocking Agents: Findings of a Consensus Panel. Seminars in Arthritis and Rheumatism, 34, 819-836(2005).

12.  Miossec P. Therapeutic targets in rheumatoid arthritis: More to come but which one(s) to select? Drug Discovery Today: Disease Mechanisms, 2, 327-330 (2005).

13.  Reichert J. M.& Pavlou A. K. Monoclonal Antibody Market. Nature Reviews 3, 383-384, (2004).

14.  Evans, D. & Das, R. Monoclonal Antibodies : evolving into a $ 30 billion market. Datamonitor Report. (2005).

15.  Reichert J. M. et al. Monoclonal antibodies success in the clinic. Nature Biotechnology. 23, 1073-1078 (2005).

16.  Pavlou, A. K. & Belsey, M. J. The therapeutic antibodies market to 2008  Eur J Pharmaceut Biopharmaceut., 59, 389-396 (2005).

17.  Scannes, L.& Branca, M. A. The evolving market for monoclonal antibodies : Facing new opportunities and pitfalls. Pharmaweek 1-23 (2006).

http://www.pharmaweek.com/Exclusive_Content/2_23%20test.asp

18.   Baker, M. Upping the ante on antibodies. Nature Biotechnology  23, 1065 - 1072 (2005).

19.  Liossis, S. N.C. & Tsokos, G. C. Monoclonal antibodies and fusion proteins in medicine.  J Allergy Clin Immunol. In Press, Corrected Proof, Available online 1 September 2005.

20.  Qu, Z.et al. Development of humanized antibodies as cancer therapeutics.  Methods, 36, 84-95 (2005).

21.  Belsey M. J. et al. Influenza Vaccines. Nature Reviews. 5, 183-184, 2006.

22.  Belsey M. et al. (2006). Growth Drivers and resistors of the influenza market: The importance of cell culture flu. J. Commerc. Biotechnol.

12, 150-155.

23.  Datamonitor report (2006). Pandemic threat reignites influenza vaccine market. Webbolt. April 20, 2006. webbolt.ecnext.com.

24.  Quigley, E.(2006). Influenza therapies: vaccines and antiviral drugs. Drug Discovery Today 11, 478-480.

25.   Pavlou A. K. & Reichert, J. M. Recombinant protein therapeutics—success rates, market trends and values to 2010. Nature Biotechnology  22, 1513 – 1519 (2004).

26.  Pavlou A.K. The immunotherapies markets, 2003–2008 Journal of Commercial Biotechnology, 10, 273-278 (2004).

* Please reference or credit any material, article, table or figure cited from http://www.medicineandbiotech.com as: Copyright 2004-2007. MedicineandBiotech.com, http://www.medicineandbiotech.com/

In Interests of Patient Safety, Pfizer Stops All Torcetrapib Clinical Trials; Company Has Notified FDA and is in the Process of Notifying All Clinical Investigators and Other Regulatory Authorities  

Decision Based on Recommendation Received Today of Independent Data Safety Monitoring Board for ILLUMINATE Trial; Pfizer Will Discontinue Development of Compound

Pfizer Reaffirms Financial Guidance into 2009

Pfizer to Accelerate Timetable for Transformation of Operations; Will Invest in Diverse Range of Pipeline and External Opportunities

NEW YORK, Dec. 2 /PRNewswire-FirstCall/ -- Pfizer Inc said that in the interests of patient safety it is stopping all torcetrapib clinical trials and that it has informed the Food and Drug Administration. The Company is in the process of notifying all clinical investigators in the program as well as other regulatory authorities.

The Company was informed today that the independent Data Safety Monitoring Board (DSMB) monitoring the ILLUMINATE morbidity and mortality study for torcetrapib recommended terminating the study because of an imbalance of mortality and cardiovascular events.

The Company has terminated ILLUMINATE and is in the process of asking all clinical investigators conducting trials in this development program to inform patient participants to stop taking the study medication immediately. The Company has also ended the development program for this compound.

Dr. Philip Barter, Director of the Heart Research Institute in Australia and Chairman of the Steering Committee overseeing the ILLUMINATE study, said, "Based on all the evidence we have seen regarding torcetrapib and in light of prior study results, we were very surprised by the information received from the DSMB, the only body with access to the unblinded safety data. We believed that the study was coming along as expected, and this new information was totally unexpected and disappointing, given the potential benefits of this drug."

Pfizer's Chief Executive Officer Jeffrey B. Kindler said, "While the DSMB information we received today was both surprising and disappointing, our focus is on the best interests of patients and making sure all this information is communicated to appropriate medical and regulatory authorities as quickly as possible.

"With regard to our business, we understand the challenge that this represents and we will respond quickly and aggressively to it. It is important to put this information in the context of both our commitment to transform Pfizer and our overall product and financial strength," Mr. Kindler added.

  He emphasized three key points:

   * First, Pfizer has a broad and diverse in-line and new product

     portfolio, as well as substantial operating and financial strength.

     Our financial guidance for 2006 is unchanged.  As well, we continue to

     forecast revenues in 2007 and 2008 that are comparable to 2006, a

     return to revenue growth in 2009, and high single-digit average growth

     in adjusted diluted EPS(1) over the next two years.  We will further

     enhance total returns to shareholders through dividends and share

     purchases.

   * Second, Pfizer's previously announced plan for transforming the company

     will now be accelerated.  Pfizer will focus on its core research and

     development, manufacturing and commercial operations, as well as

     procurement and other areas, to improve efficiency and lower its costs

     as expeditiously as possible.

   * Notwithstanding the acceleration of the Company's transformation,

     Pfizer's substantial financial strength will enable it to continue to

     invest in a wide range of pipeline opportunities across a diverse range

     of therapeutic areas, capitalizing on the largest pipeline in its

     history. It will bring forward these major new product opportunities as

     aggressively as possible.  In addition, Pfizer will bring increased

     focus and emphasis to its business development and licensing efforts in

     order to identify new products and technologies that will supplement

     its pipeline.  As a result, Pfizer continues to target the introduction

     of about six new products a year starting in 2010.

It is important to note that in the ILLUMINATE trial, Lipitor was used as a comparator for safety and efficacy. It is the most studied statin in reducing cardiovascular outcomes. "The only reason the study was stopped early was due to the torcetrapib data. The ILLUMINATE Steering Committee wants to reassure physicians and patients that nothing in today's information has any impact on the safety or efficacy of Lipitor whatsoever," said Dr. Barter.

DISCLOSURE NOTICE: The information contained in this document and the attachment is as of December 2, 2006. The Company assumes no obligation to update any forward-looking statements as a result of new information or future events or developments.

This document and the attachment contain forward-looking information that involves substantial risks and uncertainties about the Company's in-line products and product candidates, financial results and estimates, and business prospects. Among other things, this document and the attachment contains, in particular, forward-looking information that involves substantial risks and uncertainties about improvements in the Company's research and development productivity and about various products in development and potential additional indications for various in-line products, including their potential benefits and, in certain cases, projections with respect to their advancement within the research and development pipeline, regulatory authority filing and approval dates and launch dates. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "project," "intend," "plan," "believe," "target," "forecast" and other words and terms of similar meaning. Among the factors that could cause actual results to differ materially are the following: the uncertainties inherent in research and development activities; decisions by regulatory authorities regarding whether and when to approve drug applications and supplemental drug applications that have been or may be filed for such products in development and for such additional indications for in-line products as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such products and such additional indications; the speed with which regulatory authorizations, pricing approvals and product launches may be achieved; competitive developments, including with respect to competitor drugs and drug candidates that treat diseases and conditions similar to those treated by our drugs and drug candidates; the ability to successfully market both new and existing products domestically and internationally; difficulties or delays in manufacturing; trade buying patterns; the ability to meet generic and branded competition after the loss of patent protection for our products or competitor products; the impact of existing and future regulatory provisions on product exclusivity; trends toward managed care and health care cost containment; possible U.S. legislation or regulatory action affecting, among other things, pharmaceutical pricing and reimbursement, including under Medicaid and Medicare, the importation of prescription drugs that are marketed outside the U.S. and sold at prices that are regulated by governments of various foreign countries, and the involuntary approval of prescription medicines for over-the-counter use; the potential impact of the Medicare Prescription Drug, Improvement and Modernization Act of 2003; legislation or regulations in markets outside the U.S. affecting product pricing, reimbursement or access; contingencies related to actual or alleged environmental contamination; claims and concerns that may arise regarding the safety or efficacy of in-line products and product candidates; legal defense costs, insurance expenses, settlement costs and the risk of an adverse decision or settlement related to product liability, patent protection, governmental investigations, ongoing efforts to explore various means for resolving asbestos litigation and other legal proceedings; the Company's ability to protect its patents and other intellectual property both domestically and internationally; interest rate and foreign currency exchange rate fluctuations; governmental laws and regulations affecting domestic and foreign operations, including tax obligations; changes in generally accepted accounting principles; any changes in business, political and economic conditions due to the threat of future terrorist activity in the U. S. and other parts of the world, and related U. S. military action overseas; growth in costs and expenses; changes in our product, segment and geographic mix; and the impact of acquisitions, divestitures, restructurings, product withdrawals and other unusual items, including our ability to realize the projected benefits of our Adapting to Scale multi-year productivity initiative, including the benefits of the planned broadening of this initiative in 2007 and 2008, and the ability of the Company and Johnson & Johnson to satisfy the conditions to closing the sale of the Company's Consumer Healthcare business, including receiving the required regulatory approvals A further list and description of these risks, uncertainties and other matters can be found in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2005, and in its reports on Forms 10-Q and 8-K.

This document includes discussion of certain clinical studies relating to various in-line products and product candidates. These studies typically are part of a larger body of clinical data relating to such products or product candidates, and the discussion in this webcast should be considered in the context of the larger body of data.

   (1) "Adjusted income" and "adjusted diluted earnings per share (EPS)" are

       defined as reported net income and reported diluted EPS excluding

       purchase-accounting adjustments, merger-related costs, discontinued

       operations, and certain significant items. As described under

       Adjusted Income in the Management's Discussion and Analysis of

       Financial Condition and Results of Operations section of Pfizer's

       Form 10-Q for the quarterly period ended October 1, 2006, management

       uses adjusted income, among other factors, to set performance goals

       and to measure the performance of the overall company. We believe

       that investors' understanding of our performance in enhanced by

       disclosing this measure. The adjusted income and diluted EPS measures

       are not, and should not be viewed as, substitutes for U.S. GAAP net

       income and diluted EPS.

Photo: A free corporate logo to accompany this story is available

immediately via Wieck Photo Database to any media with telephoto receiver or

electronic darkroom, PC or Macintosh, that can accept overhead transmissions.

To retrieve a logo, please call 972-392-0888.

SOURCE: Pfizer Inc

CONTACT: Andy McCormick of Pfizer, +1-212-733-5469

Web site: http://www.pfizer.com/

EU Approves Cervical Cancer Vaccine  

The European Union has approved the cervical cancer vaccine Gardasil, which could prevent nearly 3,000 cancers each year in the UK alone. An independent expert advisory committee to the Department of Health will now decide whether it should be made available on the NHS. Gardasil, made by Merck and Sanofi Pasteur, is designed to be given to girls and women aged nine to 26. It works against human papillomavirus, which can lead to cervical cancer. Gardasil protects against cervical cancer caused by HPV strains 6, 11, 16 and 18, and also against genital warts. The vaccine has been in fierce competition with a rival from UK-based GlaxoSmithKline, called Cervarix, which is still a year off the European approval stage.

Around 80% of sexually active women can expect to have an HPV infection at some point in their lives. The vaccines have caused controversy over plans to give it to girls as young as nine, before they become sexually active. Boys could also be vaccinated in the hope of eventually eradicating HPV. Cervical cancer kills 274,000 women worldwide every year.

Trials suggest vaccinating all 12-year-old girls against HPV could cut deaths from the disease by 75%. Women will soon be able to go along to clinics and request the jab at a cost of around £65 per dose. Three doses are usually given over six months.

Doctors stress that the vast majority of HPV cases do not go on to cause cervical cancer. Women can protect themselves against HPV by having regular smears, not having unprotected sex and not smoking.

Gardasil has already been approved for use in the US, Mexico, Australia, Canada and New Zealand. Impact of Vioxx on the pharmaceutical R&D; By Dr. Krishan Maggon, Ph.D., Pharma Biotech R&D; Advisor

ICC- 20 route de Pre Bois, 1215, Geneva 15, Switzerland

[email protected]

Volume 4, November 2004. The withdrawal of rofecoxib (Vioxx) by Merck [1-3] has put pressure over the research based pharmaceutical industry, which is driven by unmet medical needs. The current drug approval system, marketing of drugs, directed consumer advertising, high priced new medicines coupled with the end of the blockbuster drug model, low R&D; productivity, increasing costs and generic drugs have collectively put the future growth of the big pharma at risk. Merck has been the dominant R&D; driven and most admired company during the 1980s and 1990s and had one of the highest market valuations in the industry. During the past two years, it has lost 55% of the market value including the loss of 40% of market value after rofecoxib news [1-3]. Thus, a sale loss of $2.5 billion of rofecoxib resulted in a loss of $27 billion market value in one day and another $20 billion within the next month. Several analysts had downgraded the stock due to late termination of two R&D; projects in Phase III last year, rofecoxib withdrawal, federal, states and SEC investigations, product injury and litigations costs and the patent expiry of Zocor in 2006. Drug stocks of research based companies have lost 5-10% of the market value (total loss $50 billion) due the intense media coverage and concerns about the class cardiotoxicity of all Cycooxygenase II inhibitors (coxibs) [4-7]. Every day since withdrawal of rofecoxib, new class action lawsuits are filed in courts against Merck. Wyeth, Pfizer, and Bayer made provisions of $15 billion for previous withdrawals like Phen-fen (Redux), Glitazone (Rezulin) and Cerivastatin (Baycol) respectively. Analysts have provided estimates of up to $20 billion for rofecoxib litigation.

Four selective COX II inhibitors are marketed in Europe and two in USA. Celecoxib (Celebrex) and valdecoxib (Bextra) are approved in the USA, while Parecoxib (Dynastat), Etoricoxib (Arcoxia) and Lumiracoxib (Prexige) are marketed in European countries. Celecoxib was the top selling coxib in 2000 and 2001 with sales of $2 billion and $3 billion, respectively but lost market leadership to rofecoxib in 2002 and 2003 due to better gastrointestinal (GI) tolerance. In the first half of 2004, global sales of COX II inhibitors were: celecoxib $1.5 billion, rofecoxib $1.3 billion, valdecoxib $545 million and etoricoxib $92 million. Celecoxib is expected to reach annual sales of $3 billion in 2004. Worldwide 80-100 million patients have used celecoxib and rofecoxib and 40 million in USA.

The history of modern drug regulations is closely linked to the incidence of drug induced injury, organ failure and deaths (Table 1). Each tragedy linked to marketed drugs resulted in increased regulations and additional testing to prevent future episodes with new drugs of the same class (Table 2). The Elixir of Sulfanilamide tragedy resulted in the Food, Drug and Cosmetic Act of 1938. The Thalidomide tragedy in early 1960 resulted in requirements for safety and efficacy testing for drugs in animals and humans. Safety testing includes testing new drugs for adverse effects; for example, can a new chemical entity (NCE) cause birth defects, cancer, organ failure, organ toxicity or some other problem. Willman of The Los Angeles Times was honored with a Pulitzer Prize in 2001 for his investigative reporting of FDA fast track approval and seven deadly drugs in 2000 including Rezulin, Fen-Phen and Duract (bromfenac) [8].

All drug withdrawals are followed by regulatory review of similar drugs to rule out a class effect, additional safety data for marketed drugs and additional requirements for drugs in development. The withdrawal of benoxaprofen resulted in a ten fold increase in number of patients (from 200-400 patient year exposure to 2500-5000 patient year exposure to the study drug) required for newer NSAID (Non Steroidal Anti Inflammatory Drugs) and trials in elderly, hepatic and renal impairment and drug interactions. International guidelines require that for long-term treatment of non-life-threatening conditions, 1500 patients should be treated with the drug: for safety-300-600 treated for at least 6 months, and for efficacy at least 100 for 12 months. FDA has routinely required 200 patients treated for 1 year. Astra Zeneca total patient exposure in clinical trials submitted for approval for rosuvastatin (12,500) was considerably greater than the 2,000-3,000 patients submitted for most of the other marketed statins. Since the withdrawal of troglitazone (Rezulin), no other Peroxisome Proliferator Activator Receptor (PPAR) agonist has been approved because of the concerns about the class carcinogenicity, hepatotoxicity and cardiotoxicity.

The published and available clinical data indicates an increased cardiac risk to patients linked to the long term use of rofecoxib [9-11]. Cardiovascular (CV) events linked to Cox-II inhibitors, include heart attack, stroke, high blood pressure, fluid retention and heart failure. After rofecoxib, a winning strategy for a safe and effective anti-inflammatory and analgesic COX-II agent is to reduce GI toxicity and not have any cardiovascular, renal, hepatic, neurological or any other toxicity. Toxicology studies in monkeys, in addition to rodents and dogs may help identifying CV risks early in drug development. Clinical trials to generate data for approval and show reduced GI toxicity and CV safety will require 25,000-30,000 patients with several thousands treated for 2-3 years. This is confirmed by recent FDA stance for additional long term safety data for the approval of etoricoxib and lumiracoxib. This has been the requirement for approvals of some new vaccines and drugs for common cold. The industrial R&D; should move away from the twin focused NSAID induced GI toxicity and total COX II inhibition. The optimum COX II inhibition may provide cardiac, hepatic, renal, immunological and CNS safety [12, 13]. The total R&D; costs for such a drug will be $1.5 billion over 12-15 years. If successful, the rewards are a blockbuster analgesic drug with potential annual sales of $5 billion.

The available data indicates a differentiation of available COX-II inhibitors with respect to GI and CV effects [14]. Etoricoxib (Arcoxia) show reduced GI toxicity without increased CV risk but long term data is not available. Valdecoxib (Bextra), Parecoxib (Dynastat) and Lumiracoxib (Prexige) show reduced GI toxicity with increased CV risk. Rofecoxib showed reduced GI toxicity with increased CV risk. Celecoxib (Celebrex) has a similar GI toxicity as popular NSAIDS but may have a potential cardioprotective effect according to Pfizer but increased CV risk according to its critics.



   

  References Combination Therapy to Fight Cancers

We are in the era of designer drugs. However, cancers result from complex genetic alterations with multiple genes being cancer culprits. Companies like Bayer, GlaxoSmithKline, Pfizer and Wyeth are following the trend of developing combination therapy regimens where targeting multiple targets simultaneously may prove to be a more effective therapeutic strategy.

Majority of the biotech companies and big Pharma have at least one favorite designer drug for treatment of a particular cancer. Most researchers and drug companies had hoped that one super drug could destroy that one critical cancer-causing protein, resulting in remission of cancer, followed by a long-term cure.

The problem with this scenario at a molecular level, is that every cancer or tumor has multiple defective genes, which are driving the cancers or tumors towards uncontrolled cellular proliferation and persistent genetic instabilities. Therefore, targeting one particular gene, especially in the case of breast, colon, lung, and prostate cancers may not be the ultimate cure.

Currently, Bayer, Pfizer, Genentech and other firms are developing combination therapy, with the ability to inactivate multiple defective cancer causing proteins with diverse molecular structures. Another strategy is to combine two or more drugs targeted at one particular target. This strategy can be effective when targeting multiple kinases, which are well-known cancer promoting proteins and may have similar structures.

Combination therapy has shown some positive impact in treatment of certain kidney, breast, and lung cancers. The table here summarizes the current stage of combination therapy being tested by various companies.

  • Merck Background Information Vioxx. http://www.merck.com/newsroom/vioxx_withdrawal/
  • Henry D. (2004) Market Lessons From Merck's Decline. Business Week. October 18, 2004.
  • Maggon K. Shock and pain after rofecoxib. Express pharma Pulse 21 October 2004. http://www.expresspharmapulse.com/20041021/edit02.shtml
  • FitzGerald, GA. Coxibs and Cardiovascular Disease. N Engl J Med 2004; 351:1709-1711.
  • Topol, EJ. Failing the Public Health -Rofecoxib, Merck, and the FDA N Engl J Med 2004; 351:1707-1709.
  • Dieppe P. et al. Balancing benefits and harms: the example of non-steroidal anti-inflammatory drugs. BMJ 2004; 329: 31-4.
  • Howard, PA. and Delafontaine, P. Non steroidal anti-inflammatory drugs and cardiovascular risk. J. Am Coll. Cardiol. 2004; 43: 519.525.
  • Willman. D. The new FDA; How a New Policy Led to Seven Deadly Drugs; The Los Angeles Times ; Dec 20, 2000; pg. A.1 http://www.pulitzer.org/year/2001/investigative-reporting/works/rezulin.html
  • Bombardier C, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343:1520-8.
  • Ott, E. et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J. Thorac. Cardiovasc. Surg. 2003; 125: 1481-1492,
  • Farkouh ME, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet 2004; 364: 675-684.
  • Maggon K. The future of the research based pharmaceutical industry. Editorial Express Pharma Pulse. January 29, 2004. http://www.expresspharmapulse.com/20040129/oped01.shtml
  • Maggon K. Cardiotoxicity of Selective COX II Inhibitors. Express Pharma Pulse 25 November 2004.In Press.
  • American College of Rheumatology Meeting Hotline 2004. Cardiovascular Complications Related to COX-2 Inhibitors. http://www.rheumatology.org/publications/hotline/0904chfvioxx.asp

    Dr. K. Maggon, Ph.D. is International industry consultant based in Geneva, Switzerland with a successful track record in new drug development, project management, clinical trials, business development, licensing, market introduction/support, contract and R&D; evaluation, external research management and training. New drug development experience in Cardiovascular, CNS, Biotechnology Products, Imaging agents, Immune disorders, Anti Cancer and Infectious Diseases. Established leadership skills and ability to get results. Extensive contacts with key scientific, medical and technical academic and industrial leaders worldwide. 90 publications. Contributed to the development of over 50 products from Phase 1-IV. Added significant value to drug candidates. Annual sales of marketed products were over $4.5 billion in the year 2003.

    Dr Krishan Maggon, an alumnus of Delhi University, did post doctoral research at the University of Geneva. With more than 20 years experience in new drug R&D; at reputed pharma and start up companies, Dr Maggon was involved in the early development of Losartan (2003 sales $2.5 billion) and has authored over 90 research publications in various international journals.

    *Please reference or credit any material, article or figure cited from http://www.medicineandbiotech.com as: Copyright 2004. MedicineandBiotech.com, http://www.medicineandbiotech.com/

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