In pursuit of a cure


Novartis, one of the world’s largest pharmaceutical companies, invited Middle East Health to its headquarters in Basel, Switzerland in April for a tour of their campus to show off their recently opened state-of-the-art research laboratory and to provide a series of presentations about the company and on drug discovery. Callan Emery reports.

Novartis is one of the largest drug companies in the world and with operations in some 140 countries their impact on the lives of the world’s people is huge. They are in the business of saving peoples’ lives, or as they put it ‘meeting the needs of patients and societies worldwide’ through medications, vaccines, diagnostic tools and consumer health products.

With such an expansive global reach, it is big business. In 2010 Novartis had net sales of US$50.6 billion across all its divisions. The pharmaceuticals division alone accounted for $30.6 bn. This figure is a reflection of the company’s success with a range leading pharmaceuticals, including products such Exjade, Afinitor, Gleevec, Ritalin, Sandostatin, Tasigna and Voltaren, among others.

The company prides itself on its ability to be innovative and it has to be in order to maintain its leading position in a highly competitive market. One of its most innovative products is the recently launched Gilenya – the first in a new class of drugs for Multiple Sclerosis (MS) and the first US FDA approved oral disease-modifying therapy for MS. It will help tens of thousands of people suffering from this debilitating disease.

As well as at its campus in Basel, the company has major Research and Development sites in the USA, China, United Kingdom and Singapore and production sites in 15 countries around the globe.

Innovation is at the core of this company’s priorities. David Epstein, division head of Novartis Pharmaceuticals, explained that the company takes great effort to “bring together the best people in the industry – to be innovative”.

He said that the company strives to continually innovate, particularly when it comes to drug discovery and R&D in which it invests heavily. In 2010 the company invested $9.1 bn in R&D.

“We have an extensive portfolio of new drugs – one of the largest in the industry,” Epstein said. “We’ve continued to invest in R&D, rather than concentrate only on the ‘block-buster’ drugs,” he added, referring to the big money-spinner drugs demanded by the developed world.

He explained that for such a large and profitable company – net income in 2010 was $10 bn – corporate social responsibility – or ‘corporate citizenship’ as Novartis calls it – is a very important facet.


“We are taking a leading role in providing medicines for the developing world,” he pointed out. Novartis’ nonprofit, anti-malaria drug Coartem and the decade-old Novartis Malaria Initiative is now reaping tangible benefits. This initiative is estimated to have saved the lives of more than 1 million people to date.

Business background

The Novartis Group’s wholly-owned businesses are organised in four globally operational divisions:

- Pharmaceuticals
- Vaccines and Diagnostics
- Sandoz – generic pharmaceuticals
- Consumer Health

The company has also recently acquired Alcon – one of the world’s leading eye care companies. Following regulatory approval they plan to merge Alcon into Novartis.

In a major effort to expand its business Novartis is shifting some of its focus to the emerging markets. They are doing this because life expectancy of people in these markets is growing as is their expenditure on healthcare; there is an emerging middle class in developing world countries and as they move to a more Western style of life their healthcare needs are expected to increase along with an increase in lifestyle diseases, such as obesity, diabetes and cardiovascular disease.


“Nearly 80% of patients in the world have no access to the drugs we have in the developed world,” Paul Herrling, the Head of Novartis Institutes for Developing World Medical Research (NIDWMR), explained. He said that although there won’t be much financial return, the company is committed to developing drugs for these communities – drugs to treat dengue, TB, malaria and Chagas disease, for example.

“Treatments will be made available to poor patients without profit, by leveraging funds from charities such as the Wellcome Trust and the Bill and Melinda Gates Foundation.”

He explained that there is a lot of work to be done as these diseases are spreading fast and their resistance to certain drugs is growing.

“In 1970 only five countries in Southeast Asia had dengue; in 2007 dengue was found in more than 100 countries,” he said. “Drug-resistant TB is growing. Often associated with HIV, in Cape Town, South Africa, more than 50% of XDR (extensively drug resistant) TB cases are now HIV negative.”

Drug discovery

Herrling explained that within modern science the rate of knowledge generation is increasing exponentially and this opens the opportunity for many potential new drug discoveries with the combined efforts of research teams.

However, he explained that “making medicine is one of the most complex scientific endeavours. On average it takes around 14 years and costs $2 bn to bring a drug to market from initial concept.

“Many of these drug discovery projects fail during the rigorous trial phases, thus the high cost,” Herrling pointed out.


Interestingly, in the past few years there has been a fundamental shift in the way drugs are discovered, researched and developed. Using the knowledge acquired following the completion of the human genome project in 2003, which resulted in the sequencing of the entire human genome, drugs could be developed on a molecular basis to interact with specific gene mutations, for example, rather than, as they had been developed in the past, to interact with a specific tissue type or histopathology. With this development the molecular basis of disease has become all important, which is resulting in a major reclassification of disease according to the molecular pathway through which it develops.

At the Novartis Institutes for Biomedical Research (NIBR) this new approach is helping to speed the development of new drugs. The NIBR is a global network of some 6,000 scientists, physicians and business professionals, which is developing drugs in several defined disease areas, such as cardiology, oncology and neurology.

A spokesperson for NIBR explained one of their key strategies: “We don’t select areas where we think there are millions of patients. Rather we select areas in which we understand the molecular basis [of a specific disease] and adapt the tools we have developed for this disease to be used with other diseases that share the same molecular pathway.”

This new focus on the genetic underpinnings and molecular basis of disease has enabled the drug research-to-development transition to be redefined through much faster and more rigorous ‘proof of concept’ trials.

For example, without going into specifics, certain breast cancers can be defined according to specific gene mutations. Take one specific gene mutation – it causes a specific type of breast cancer. By developing a molecular compound to block this gene mutation, it can prevent the development of this specific breast cancer by preventing the mutated gene producing abnormal (cancerous) protein.

By reclassifying breast cancer, for example, into a variety of diseases each dependent on a specific metabolic pathway and then developing specific molecular compounds to block each pathway, has the effect of preventing the development of the disease.

This reclassification of disease based on it genetic makeup, molecular structure and metabolic pathway is enabling the development of drugs (molecular compounds) that have a much greater efficacy, than those developed from a histopathological basis.

The drugs are much more targeted in blocking disease development. Further, bringing these drugs to market should be quicker than in the past as proof of concept trials can be very specifically designed to test the molecular interaction of the compound on the disease, the molecular basis of which is known. No more shots in the dark, as such.


What’s more – and this looks particularly promising – researchers at Novartis are also discovering that some seemingly unrelated diseases are in fact related by their sharing the same molecular pathway. It could be a certain type of colon cancer, for example, that shares the same molecular pathway as a particular type of breast cancer. The upshot of this is that the molecular compound (drug) that they have developed, tested and proven works for the breast cancer, they are finding also works to treat this specific colon cancer. So rather than develop completely new compounds (they are, of course, doing this for some disease areas) they can adapt the compound and test it on other diseases which share the same molecular pathway.

This is an exciting new development in drug discovery and although it is still relatively early days, it has massive potential to fundamentally change the way we treat disease.

With this new approach to drug development Novartis has many new drugs in the pipeline – although some of the molecular compounds aren’t new, their applications are.

“We have generated one of the largest research pipelines in the industry,” the NIBR spokesperson said. “We expect more than 60 submissions for regulatory approval over the next five years.” Many of these will be for new applications for already developed molecular compounds, although he added, confirming Novartis’ emphasis on innovation, “more than 20 of these will be for new molecular compounds”.

 Date of upload: 15th Aug 2011


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