Building bridges: A new dawn of collaboration for the pharmaceutical industry

Medical Tribune June 2009 P2

Pharmaceutical companies must branch out and forge new collaborations if they are to survive the global economic crisis, says Mr. Abhijit Ghosh, life sciences leader, PricewaterhouseCoopers Services LLP, Singapore.

The pharmaceutical industry is entering a challenging era of uncertainty. The global economic crisis has intensified the strain on a marketplace which was already struggling to come to terms with soaring costs, the drying up of drug pipelines, and the pricing pressures created by the emergence of generic medications. We predict that by 2020 the current business model will become unsustainable, and a new landscape will arise for companies, healthcare providers and patients alike.

Pharmaceutical companies must adapt quickly if they are to survive these challenges and emerge stronger in the new marketplace. The days of ‘blockbuster’ drugs are coming to an end, and companies can no longer rely on a strategy of making huge investments to single-handedly develop and market their most promising molecules. Public expectations, too, are changing: as patients become better informed they demand a more holistic approach to healthcare, shifting the balance away from universal, one-size-fits-all treatments and into the realms of prevention and personalized medicine. Moreover, by 2020, medicines will be paid for on the basis of results, not products, and companies will be forced into offering broader health management services to ensure that they achieve the best outcomes.

Few companies will be able to meet these daunting goals on their own. In an industry where ‘profiting alone’ has long been the mantra, it is now ‘profiting together’ that offers the key to survival.

We predict that pharmaceutical companies will join forces with a range of external organizations in future: from hospitals and academic centers to companies which offer physiotherapy, stress management, nutritional advice and health screening. Many of these collaborations will be unconventional, as an increasing number of non-pharmaceutical companies enter the arena. The technology sector in particular is one where partnerships with the pharmaceutical industry will be beneficial, as drug providers team up with manufacturers of portable devices and implants.

Two models are proposed for the strategy of collaboration. The first is the federated model, which would see a network of separate entities coming together with a common goal and a shared supporting infrastructure. Each partner could play to their strengths and expertise: for example, the pharmaceutical company could focus on drug development while other players worked on improving patient compliance and encouraging them to lose weight. One such example of federated collaboration is already underway in Spain, where Vodafone has joined forces with Aerotel Medical Systems, a device manufacturer, and Medcronic Salud, a telemedicine provider, with a view to providing wireless home monitoring services. Bringing clinics and hospitals into such partnerships in future could even provide medical companies with access to outcomes data, allowing them to monitor the long-term effects of treatment outside the clinical setting.

The second approach to collaboration is the fully diversified model, in which a pharmaceutical company expands to provide related products and services. This enables them to spread their risk away from reliance on blockbuster drugs and into other market areas. Johnson & Johnson, for example, has branched out from drugs into medical devices and diagnostics, and has recently begun building a web-based wellness and prevention platform. GlaxoSmithKline (GSK) and Novartis have both invested heavily in vaccines, while Roche is translating its expertise in molecular diagnostics into consumer products for measuring allergen levels indoors. These diversification approaches, however, require substantial investment, and may detract from the core business and create risks which might even alienate investors.

Besides the financial and commercial benefits of increased collaboration, there are also obvious public health implications, particularly as the global burden of chronic disease continues to rise. Research by the RAND corporation shows that the US alone could save some US$28 billion if all diabetes, asthma, pulmonary disease and congestive heart failure patients enrolled in disease management programs – not to mention the considerable economic benefits in terms of working days saved.

Pharmaceutical companies will need to make their own decisions on how to move forwards, depending on their individual circumstances. Some are already exploring collaborations which previously may have seemed unlikely. In April this year, for example, GSK and Pfizer announced the joint formation of a new firm for HIV drug development, with 11 existing products and a further 17 in the drug-discovery pipeline. It is hoped that this combined venture will offer a broad and sustainable approach, with potential for growth in future.

Some companies, however, will find it harder than others to survive the current economic crisis, and it is small biotech firms that may face the roughest ride. Those with one or two promising molecules in the pipeline will most likely need to collaborate with big companies for their development, or seek to sell their stake entirely and join the ever-growing number of mergers and acquisitions.

Despite the current crisis there is optimism in the industry: in a recent survey we found that CEOs of pharmaceutical companies were more confident about their prospects for growth than their peers in other industries. It remains to be seen how the landscape will evolve and whether this optimism will be justified, but it is clear that the industry cannot stand still. Profiting alone is no longer an option, and the sector must branch out into new partnerships if it is to continue to move forward.

hsCRP: A new player on the cardiovascular risk stratification stage

Medical Tribune January 2009 P2&3

Dr. Jacques Genest, director of cardiology and Novartis Chair in Medicine at McGill University, Montreal, Canada, addresses the emerging role of high-sensitivity C-reactive protein in predicting cardiovascular risk.

High-sensitivity C-reactive protein (hsCRP) represents a new paradigm in the assessment of cardiovascular risk. It is set to become the first new biomarker for 30 years to be incorporated into routine clinical practice alongside traditional tests such as blood pressure and cholesterol. Guidelines across the world are under review, and it is only a matter of time before hsCRP becomes an integral tool in the risk stratification armory of the primary care physician.

The recent Justification for the Use of Statins in Prevention (JUPITER) trial showed that treating patients who had elevated hsCRP in the absence of other risk factors could significantly reduce the incidence of major cardiovascular events. After a median of 1.9 years of follow-up, the occurrence of cardiovascular death, myocardial infarction, stroke, arterial revascularization or hospitalization for angina was reduced by 44 percent in those treated with rosuvastatin (20mg daily). [N Engl J Med 2008 Nov 20;359(21):2195-207]

These results do not justify testing everyone for hsCRP, but rather suggest that the test will be of great benefit for patients who occupy the grey area between low and high risk. A high hsCRP score can push a debatable case over the treatment threshold while a low score, conversely, can confirm that the patient does not require treatment. Those already deemed to be at high-risk should receive treatment regardless of hsCRP, so the test will add little prognostic value in these patients, while at the other end of the scale there is not sufficient evidence to support routine hsCRP testing in young, healthy people with no other risk factors.

Physicians should begin, therefore, by performing a full and complete cardiovascular risk stratification including sex (until menopause in women), age, physical activity levels, diet, diabetic status, blood pressure and LDL, HDL and total cholesterol levels. For patients who are not obviously at high or very low risk, the physician should now routinely include an hsCRP test. Present evidence suggests that this strategy should be adopted in all men aged over 50 and women aged over 60 – the population that was successfully targeted for treatment in JUPITER. In my opinion, hsCRP will ultimately prove to be of use in men aged over 40 and all postmenopausal women, since these years often herald an increasingly sedentary lifestyle whereby the long-term outcome is likely to be heart disease or cancer. We await the support of local guidelines on this point, however, and at present physicians should exercise their own judgment as to the appropriate age for introducing hsCRP testing.

JUPITER treated patients with hsCRP levels of 2.0 mg/l or higher, and physicians may wish to adopt this level as their cut-point for deciding whether to initiate treatment. There is, however, strong epidemiological data and an ongoing argument in support of adopting a threshold of 3.0 mg/l or higher. This, again, will prove a matter for the guideline makers to decide and is likely to vary from country to country. For those with socialized medicine the cost implications of adopting the lower threshold will be considerable, and will prove an important factor in this decision.

Introducing routine hsCRP testing will undoubtedly increase the number of patients being treated with statins. We must not lose sight, however, of the continued importance of diet and lifestyle interventions, for which there is incontrovertible evidence in favor. Physicians should continue to press the message on five fronts: smoking cessation, quality of diet, quantity of diet, daily exercise, and serenity. The latter encompasses both stress management and levels of social interaction – both important prognostic factors in long-term mortality outcomes. Addressing these issues in a single consultation can be difficult – particularly when seeing the patient only once every 6 to 9 months – and I would recommend that GPs refer certain cases to a dietician and kinesiologist in order to improve motivation through more regular advice and feedback.

Many biomarkers have come and gone over the past 20 years of my research career but very few have proven to be clinically useful. Homocysteine, inflammatory factors, cell adhesion molecules, matrix metalloproteinases, and enzymes such as lipoprotein-associated phospholipase A2 have all failed or are still not ready for primetime use. These markers may predict disease but that does not mean that targeting them will automatically yield a reduction in hard clinical trial endpoints.

The journey towards hsCRP testing has been a long one but the marker has finally matched our ability to predict with our ability to prevent, while also asserting its independence from other risk factors. Guidelines will change in time, but in the face of the evidence from JUPITER physicians may decide not to wait. The time is right, in my opinion, to begin measuring hsCRP and implementing the appropriate strategies in the JUPITER-like patient while we await further international guidance. Unlike other biomarkers, hsCRP testing is here for good.

Dr. Genest is one of the investigators of the JUPITER trial and reports receiving consulting fees from AstraZeneca, Merck, Merck Frosst, Schering-Plough, Pfizer, Novartis, Resverlogix and Sanofi-Aventis.

Asia: The new frontier for cancer research

Medical Tribune November 2008 P2-3

Dr. Foo Chuan Kit, Bayer Schering Pharma’s medical director for South Asia and Hong Kong, addresses the importance of tackling cancer in Asia.

Asia is facing a population explosion which will change the global disease landscape. Sixty percent of the world’s inhabitants – some 4 billion people – currently live in Asia, with 40 percent in China and India alone. By 2050, the continent’s population is predicted to rise to a staggering 6.5 billion people.

As the population continues to grow it is also continuing to age. In 2005 just 10 percent of Asians were aged 60 and above; by 2050 this figure will be closer to 28 percent, with Japan and Singapore expected to have the world’s highest proportions of over-80s.

With these trends emerging it is no surprise that cancer rates are climbing fast. Asia is facing a new epidemic, and it will not be long before the majority of the world’s cancer patients will be living in the continent.

In the face of this threat there is an urgent need to redress the global balance of cancer research. Most clinical trials continue to take place in the US and Europe, yet there are many important differences in the evolution of the disease between continents which demand further investigation.

The distribution of cancer is different in Asia, where certain types predominate in comparison to the West. Stomach cancer was the most common newly-diagnosed cancer in East Asia in 2007, yet did not feature in the top four most common types for North America or Northern and Western Europe. Liver cancer is particularly common in both East and South-East Asia, with lung, breast, colorectal and nasopharyngeal cancers also highly prevalent in these areas.

For men, according to 2002 data, prostate is the most common cancer type in the US, Australia and most of Europe, yet lung, liver and oral cancer dominate in Asia. Breast cancer is the most common type for women in most countries worldwide whereas in China stomach cancer is the most prevalent. In India and several other South and South East Asian countries cervical cancer is the most common type among women.

Understanding the reasons for these discrepancies is an important emerging area of investigation. Liver cancer in Asians, for example, is largely caused by hepatitis B, whereas hepatitis C and cirrhosis from alcohol abuse are more common causes among Caucasians. For nasopharyngeal cancer, a higher prevalence has been observed in Southern Chinese than in Northern Chinese, so there appear to be intra-ethnic differences as well. For other cancers, however, these regional variations and their explanations remain unclear.

These geographical differences also raise interesting questions as to the efficacy of cancer drugs in Asian patients. Gefitinib, for example, yielded disappointing results in clinical trials of western adenocarcinoma patients but was recently shown to be effective in non-smoking Asians with this cancer.

The optimal dosing for Asian patients is another important area of research. Docetaxel and carboplatin for example, appear to induce more side effects among Asian lung cancer patients than among Caucasians, and the dosages need to be adjusted accordingly. The response to these drugs also seems to be higher among Asian patients, but more research is still needed to better understand these observed differences.

With so many unanswered questions the need to invest in Asia is greater than ever. At Bayer Schering Pharma we have committed S$20 million over the next 6 years into research in Singapore alone. In Asia Pacific as a whole we enrolled less than 100 patients in clinical trials in 2005; by the end of 2007 we had 3,700 patients participating in 64 different trials.

The growing investment from pharmaceutical companies is great news for Asia. The increasing number of research collaborations, such as our recently-signed agreement with the National University of Singapore, will give patients unprecedented access to exciting new drugs. The increasing focus on translational research, meanwhile, will help to minimize the time from bench to bedside, enabling new compounds to enter clinical trials as early as possible. The recruitment of patients also seems to be quicker in Asia Pacific, with our data suggesting that the enrollment process here is twice as fast as the global average.

As our understanding of cancer in Asia improves so too will our treatments. This investment in Asia-specific research must be sustained in order to strengthen our defences in the face of the future epidemic.

The benefits of combining women’s and children’s healthcare

Medical Tribune August 2008 P2-3

Associate Professor Tay Eng-Hseon reflects on the advantages offered by centers such as KK Women’s and Children’s Hospital, Singapore

A mother and her child share a special relationship that begins even before birth. Having a combined hospital to attend to both of their needs provides continuity of care for the new family, and can help to develop and strengthen this bond. The ability to deliver specialist pediatric care on-site removes the potential need to separate a mother from her newborn baby within moments of delivery, enabling the family unit to remain intact within the same hospital. And as the child continues to grow, mothers can enjoy the convenience of having their own health needs attended to at the same place as those of their children. Joint visits such as this can help to reinforce the social support network and cohesion within a family.

Combining women’s and children’s healthcare is also beneficial from a medical standpoint as well as a social one. Delivery of crossover services becomes quicker, easier and more efficient within a single site. Many times at KK Women’s and Children’s Hospital (KKH) we have witnessed a neonatologist supervise the birth of a child before handing over to the pediatric urologist or cardiac surgeon, thereby allowing treatment to continue promptly without interruption or the need for further travel, with the associated delays and costs that this entails.

KKH treats a more specific section of the community than a general hospital, and this has proved to be beneficial from a practical point of view as well. With the field of potential patients narrowed we can reduce the range of equipment that we need, keep a more specific selection of drugs at the pharmacy, and standardize the hospital wards to a greater degree. We can also provide more specialized training for physicians, who can gain hands-on experience of a wide spectrum of conditions within their discipline.

Specializing in this way also has benefits for research, enabling a greater focus which in turn improves the ease of execution. Consequently KKH has participated in several large-scale international trials, including those of the rotavirus and cervical cancer vaccines. Entry into trials such as these can be competitive, but the ability to accrue large numbers of subjects quickly and easily has enabled our hospital to stay ahead of the competition. Furthermore we can provide a different patient perspective to centers in Europe and the US, and for these particular studies KKH was the main provider of Asian subjects.

Until 1997, pediatric hospital care in Singapore was spread between Tan Tock Seng, Singapore General and National University Hospitals. The visionary decision to consolidate these services into KKH – previously a dedicated women’s hospital – has enabled the hospital to expand into new areas and provide further dimensions of care to its patients. Examples include the development of highly specialized breast surgery and plastic and reconstructive surgery teams, and the opening of the Women Wellness Centre and Department of Child Development. Promoting mental health within the same vicinity as physical health also has the added benefit of reducing the stigma that can be associated with conventional psychiatric settings.

In a large specialist center such as KKH, the progression to higher-level services is a natural one, and it would not be surprising to see the private sector develop along these lines in future. High-end secondary and tertiary care such as this can only be feasible when there is access to a high volume of primary care patients, however, otherwise the demand will not match the capacity for supply and an expensive excess will develop.

In Singapore, patients from all corners of the country can reach the hospital within 30 minutes, making the concentration of care into one specialist centre very feasible. By virtue of its size and position within a dense population, KKH delivers a third of the 38,000-odd babies born each year in Singapore and provides care for around 80 percent of the country’s children. This model of centralized combined healthcare might not be feasible in all countries, however, and smaller hospitals in more sparsely-populated areas may not be able to match the volume of patients needed to sustain a dedicated center.

By focusing and centralizing our services we have been able to enhance our international reputation and provide regional leadership, and over the years we have attracted many foreign doctors on training fellowships. Other countries have begun looking into our model of hospital structure, and there has been a lot of interest from China in particular. For now women’s and children’s hospitals remain a rarity within Asia but, as KKH demonstrates, this system can provide many important benefits to both doctors and patients at all levels of care.