Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

	2012 will be a transition year for pharma, one of the most important in the industry’s history of product cycles that spin from plenty to penury. On the positive side, the fires of drug discovery are finally being stoked by a growing understanding of how genomics shape the biology of disease. This is leading to promising new treatments that target critical areas of unmet medical need while also increasing the efficacy of interventions geared to the individual patient. Evidence that these next-generation innovations can advance the science while improving outcomes will hopefully lead to ready acceptance in the market, despite the growing leverage of a much more skeptical and discerning customer base.

	The challenge is that many new treatments may not complete the move from ‘bench to bedside’ in time to plug the yawning revenue gap from a second record year of patent expiries. This year’s drop off the patent cliff is the longest and steepest, with a $50 billion loss coming on top of the $30 billion ceded to generics in 2011. Most companies will struggle to play catchup, with margins under intense pressure due to the immediate fallout from genericization of the product base; in the U.S. alone, off-patent penetration has reached 80 percent of all scrip, and IMS forecasts this figure will rise to 86 percent by 2015.

	Meanwhile, the fiscal crisis in Europe has voided the entire concept of patenting as a reward for innovation in providing a temporary period of price exclusivity. Therapeutic reference pricing is clustering brands with the cheapest generics, and some countries in the region are now moving toward a straight bulk procurement model for drugs reimbursed through state-sponsored systems. Quality? Innovation? These are yesterday’s questions.

	So what is the preferred Big Pharma strategy to manage through this year of transition? Pharm Exec highlights four strategic drivers that should compel the attention of our “C-suite” readers in 2012.

	1) A reinvented business model won’t change what is fundamental: Higher pipeline productivity in the form of new patented products is still the best source of future profits.â¨This year will see new therapeutic breakthroughs that may revitalize the blockbuster, to include biologic drugs intended for targeted patient populations with few treatment alternatives. Many are novel not only for their indications and superior efficacy and safety profiles; they also mark an advance in the mode of delivery, replacing injectables with a once-a-day pill or acting in combination with other compounds to provide more precise dosing with fewer side effects.

	Overall, the trend illustrates the impact of company efforts to integrate within their R&D organizations a more overt commercial benchmark in addition to science and regulatory indicators. If trial and regulatory milestones are an ingrained part of the development timeline, why not add criteria for achieving access or reimbursement as well? Few companies today are inclined to say no.

	Growing optimism about a return to innovation doesn’t mean that the debate over the best blueprint  for R&D will be resolved-at least not in 2012. It takes on average a decade to commercialize a promising compound from proof of concept, so much of the current discussion around alternative approaches-from outsourcing key aspects of development to the “string of pearls” focus on science generated in-house-amounts to sheer background noise. Consultants can’t charge for this, and the evidence is purely anecdotal, but what does seem to matter is a long-term commitment to the science; retaining good people; acknowledging that internal competition can boost overall productivity and performance against agreed targets; a knack for finding and keeping a diverse circle of partners; and a healthy helping of luck. Analysts call it the “hybrid” model and companies will continue to tailor R&D strategies to fit their own circumstances.

	2) 2012 will signal the industry is transitioning to an era of lowered expectations; pricing, reimbursement, value, and policy will combine in complex ways to drive down margins.â¨The bottom line is that it is becoming harder to make the contacts that drive sales with providers and the patient. Consolidation in the payer community gives them greater leverage in controlling the use of medicines, generic penetration limits the scope of argument about competitive differentiation, and increased government regulation has ended many of the promotions that helped build relationships with physicians. More therapeutic “crowding” in the specialty segment is another trend that will depress margins because payers now have a choice and can restrict access or demand rebates and discounts, as they have done with devastating effect in primary care.

	Moreover, to cope with these developments, brand manufacturers are spending heavily on incentive programs like copay cards as well as patient support activities geared to raising adherence to therapy. Much of this activity is geared toward influencing the commercial business, and the added cost exposures will sharply depress margins there just as higher rebates mandated by health reform turn the public Medicaid and Medicare Part D programs into loss makers.

	As a result, 2012 will see more effort to change the incentive package for sales reps, on the premise that “not all prescriptions are considered equal.” Pay incentives will motivate reps to win more non-controlled, third-tier reimbursed prescriptions rather than just focusing on the volume of scrip. This in turn will provide the rationale for more culling of the ranks-selective deployment of this human resource is key.

	3) Advances in information technology will continue to shape the conversation with customers on access, value, and price.â¨That conversation is going to take place in public, as evidenced by the growth of cloud computing, which “hyper-democratizes” access to the vast resources of the Web-it’s the everyman’s Google. But Big Pharma is a business, with proprietary interests, so a key priority that will play out through 2012 is marking progress in defining basic standards on the application of IT. The goal is to ensure those business interests are protected while adding benefits through agreed channels for data sharing-the new Pistoia Alliance of companies engaged in precompetitive research is a good example-as well as improved IT management processes that raise efficiencies and lower costs.

	Government regulators can help speed this trend-or delay it. The problem is that key agencies like the FDA are way behind industry in adapting to the IT revolution. Internal reforms are vital, because done right IT can help advance the portfolio through faster lead times and building that better case for competitive differentiation.

	4) Preserve those reputational assets. â¨Maintaining a “license to operate” is becoming more important as the reach of governments extend from regulatory oversight to direct involvement in the business-as a payer and customer. The gap between strict legal prohibition and the more murky terrain of ethical lapses is narrowing; overall, the “zone of vulnerability” is expanding and is now global in scope. 2012 will see major new efforts by U.S. and European regulators to apply anti-bribery statutes to companies’ overseas promotional activity, including inducements by CROs and other third parties to influence the conduct of foreign clinical trials. Active management of the drug shortage problem is another imperative; it is not enough to blame the problem on FDA or on quality issues linked to generics.

Articles

2012 will be a transition year for pharma, one of the most important in the industry’s history of product cycles that spin from plenty to penury. On the positive side, the fires of drug discovery are finally being stoked by a growing understanding of how genomics shape the biology of disease.

Pharma 2012: Hard Times Before the Harvest

It is in the New Year that we often set goals to improve ourselves, whether it's trying to get fit, move up the career ladder, spend more time helping others in need, or any other number of personal quests. But individuals aren't the only ones who make long-term goals—so do governments, organizations, and for our purposes, this industry. Harmonization of drug development and manufacturing approaches comes to mind.  

I'm a big supporter and follower of harmonization initiatives, but I get the feeling that not everyone in industry is as gung-ho about the idea. At several industry meetings during the past year, I've asked people what they think of harmonization and whether they believe certain aspects of pharma manufacturing will ever be harmonized (e.g., elemental impurity limits).  

I've asked conference participants, for example, about why it's necessary for each nation or region to have its own pharmacopeial guide 

 for an international pharmacopeial guide to exist. And, for drug-applicants working to bring a product to the global market, is there a way to avoid filling out the same information on 20 different forms? Inspections are another area lacking harmonization. We all know how many audit or inspection teams companies must accommodate in a given year.  

Most of the answers I've gotten are along the lines of, " I don't know," or "They would never agree to compromise on that," or, "There's too much national pride for one country to change its standards to match another's."			

I get that compromise is difficult. In fact, before coming to 

, I spent several years working for a nonprofit focused on the work of the United Nations. So I understand how much effort is required to engage productive dialogue and garner compromise among a diverse and global audience. I also get that the bio/pharmaceutical industry is highly protective of its information and practices—it is a competitive, patent-based, trillion-dollar industry after all.  But I also think that some of the key elements of harmonization are getting lost in translation. 

Industry seems to want globally standardized approaches to their processes and quality systems as well as minimal routes for filing marketing applications and other required documents. Reaching these goals would make life easier for all parties involved. Having an agreed-upon, worldwide approach to quality and supply-management, for example, could literally solve many of the drug-product contamination and adulteration issues that have plagued the industry in recent years. And yet, many companies and national regulatory or standard-setting bodies seem unwilling to give up their current practices or accept that another company, organization, or nation for that matter, may have a better way of doing things.  

Perhaps my vision of global harmonization is too lofty or naïve. But there is reason to hope. The International Conference on Harmonization was established in 1990 with the aim of increasing "international harmonization of technical requirements to ensure that safe, effective, and high quality medicines are developed and registered in the most efficient and cost-effective manner." In its 20-plus years, ICH has managed to gain consensus across North America, the European Union, and Japan, on 16 Efficacy guidelines, 10 Quality guidelines, nine Safety guidelines, and has several multidisciplinary guidelines in the pipeline. The members of ICH's Global Cooperation Group extend the reach of these guidelines to eight additional countries, including the leading markets in Asia. 

Other global standard-setting bodies, such as the International Pharmaceutical Excipients Council and the International Society for Pharmaceutical Engineering, are working to shape global industry practice. And new industry groups working to share best practices throughout the world seem to be popping up every month (e.g., the Rx–360 and IQ consortiums). 

I hope you will take time to learn more about global harmonization efforts and talk with your colleagues about how your organization might become involved, whether that means providing feedback, working to implement harmonized guidelines, or sharing them with your global partners. In the meantime, 

will do its best to keep you apprised of happenings tied to harmonization and what it means for your day-to-day operations—and that's just one of many resolutions we intend to keep this year.  

The benefits of harmonization may be on industry's wish list, but buying into change is another story.

Here's to a Year of Compromise

It has been noted that Brazil's northern region is growing at the same pace as most of China and that Brazil expects to continue to grow its economy.  Are there key goals for the bio/pharmaceutical sector in particular? 

Brazil should continue growing at a rate of 5% per year in the next few years, largely driven by its internal market. In the case of the pharmaceutical market, the past few years have been prosperous, due to the increased income in the lowest levels of the population that began to acquire more health products, and to the increased public spending to attend the new public health needs of the population.  

This positive environment of the past 10 years has allowed for the modernization of the Brazilian pharmaceutical industry and its increased production capacity. The main challenge in the next few years will be to uphold the supply of health products for the increasing demand, while at the same time consolidating research, development, and innovation efforts within the country, especially in the area of biotechnology products. 

The Brazilian government plans to move 16 million people out of poverty and into the healthcare system during the next 10 years. Is this part of a larger government initiative? What progress been made to date?   

 The recent economic boom in Brazil..., together with the government policies for income transfer, have taken more than 36 million Brazilians out of poverty, which increased the middle class by more than 50% of population. This result is extremely relevant for a country that still has a very high rate of income inequality. Even so, it is estimated that there are around 16 million Brazilians with a family income of less than US$45 per month, which are families that are difficult to reach by the traditional measures of the state.  

It was for these reasons that the Brazilian government created the Programa Brasil Sem Miséria (Brazil without Poverty) in 2011 to take this underprivileged group of Brazilians out of poverty and give them access to the country's main social services. Within the scope of the program, healthcare is included as a fundamental right and an important pillar in the public policy to include this part of the population.  

 Moving so many people into the healthcare system will provide great business opportunity—as well as challenges—for the healthcare and drug sectors. What steps is the government taking to address these? What advantages may exist for bio/pharmaceutical companies outside of Brazil?  

 The key word to healthcare in Brazil is access.  The government has been working hard to increase the supply of medicines to the populace. On the side of development and production in the country, this effort involves several fronts: technology transfer agreements via public-private partnerships; finance for the development and production of strategic products for the Brazilian health system; continued improvement of the regulatory regime; and centralized purveying and negotiating directly with producers.   

The opportunities for companies arise inasmuch as the government is able to acquire more products and sustain the adoption of new protocols in the Brazilian Universal Health System.  

What is your country's short- and long-term perspective on the manufacture of biopharmaceuticals, including biosimilars?  

The Brazilian government is working to construct an industrial platform for biotechnology within the country that, in the short-term, produces biological products that are not new (biosimilars). This industrial structure should, however, include the possibility to innovate and develop new biotechnolgy products in the longterm.   

GE Healthcare and Amgen have recently made bold moves to acquire facilities and companies in São Paulo. Have you seen increased action along these lines from multinational bio/pharmaceutical firms? Do you expect more? 

 In the past two years, BNDES has received a growing number of consultations, both formal and prospective, from foreign companies in the health industry that are interested in the Brazilian market. Yes, we do expect more—and that these activities come to be real investments in the Brazilian health industry. Investments that contribute to the established industrial technology and that contribute to the challenge of increasing the access of the Brazilian public to health products and services will be very welcome.  

 Brazil's regulatory system and healthcare policies seem to be stable and well-respected on a global scale, which have contributed to its role as a pharmerging nation. What components of this governance structure hold advantages for outside bio/pharmaceutical companies wanting to do business in Brazil (e.g., IP rights, taxes, regulatory approvals, market access)?  

 Companies that wish to invest in the Brazilian health industry will encounter an extremely favorable environment, especially for projects regarding the abovementioned question. Brazil has a regulatory regime and intellectual property environment that are in compliance with global standards, as well as a scientific and technological base that is consolidated and expanding. Finally, regarding long-term credit, BNDES and other government agencies offer favorable conditions to support industrial investments in production facilities as well in research, development, and innovation activities.  

 Brazil is known as a "pharmerging" market by the bio/pharmaceutical industries in North America and Europe. How do you view this label? How do you see your country in the global marketplace in terms of the bio/pharmaceutical space?  

 Today, Brazil is among the 10 largest economies in the world. With a population of 180 million, a vast territory, and immense mineral wealth, the country is positioned as a promising economy. With a robust middle class, a diversified industrial base, a sustainable energy matrix, and a stable democracy that is anchored in solid institutions, the country is clearly on a path for growth—led not only by internal consumption, but also by a significant volume of exports. In this scenario, Brazil can legitimately aspire to be one of the world's five foremost economies.  

As far as the health industry is concerned, the scenario is even more promising as it is challenging. As mentioned, the income-transfer programs, together with economic growth, have brought 36 million Brazilian out of poverty to become real citizens able to consume goods and services. The improvements in quality of life of Brazilians have made demographic changes that will give Brazil, in just a few decades, a demographic pyramid similar to that of Europe. Life expectancy in Brazil is currently 73 years old. The change in the epidemiological profile of the populace is also impressive: today, the average Brazilian has more chronic-degenerative diseases than infecto-contagious illnesses. At the same time, it is important to point out the ambitious public health system which covers more than 100 million people. According to the Constitution of Brazil, health is the right of everyone and it is an obligation of the State to provide it.  

Our pharmaceutical industry, which today holds the 7th rank in the world, grows by double digits, without indications of slowing down. Projections indicate that Brazil will occupy the 6th position by 2015. The Brazilian government has been stimulating the industry by supporting and financing projects that contribute to reducing the vulnerabilities of our health system—a fact that together with a continually improving regulatory regime have shown signs of the strategic nature of our health industry. Therefore, in this promising scenario it is indeed possible to affirm that, more than having a label of 'pharmerging market,' Brazil is has all the conditions to become a solid and developed pharmaceutical market in the short run, and it has huge opportunities for those that wish to take part. 

 The growing occurrence of South–South trade is leading to some multinational companies (as well as nations) to question their current market-growth strategies. How does your organization view South–South trade in terms of benefits, and perhaps disadvantages?  

From our viewpoint, the increased volume of South–South trade reflects the search for opportunities and exchange among commercial partners with complementary interests. Regarding Brazilian interest in developing a strong biotechnology industry in line with national interests, our country is obviously seeking partnerships with enterprises and governments where this technological wave has been consolidated, regardless of the regions or geographic location. 

As part of the BRIC bloc with Russia, India, and China, Brazil is one of the world's leading emerging economies and is also considered by IMS Health to be one of seven pharmerging nations, which also include Mexico, Turkey, and South Korea.

Global Healthcare on the Ground: Brazil's Development Bank Leader Discusses the Country's Pharma Future

President Obama launched the Global Health Initiative in May 2009 to introduce an integrated approach to the government's investments in global health. The initiative involves programs of the US Agency for International Development (USAID), the Department of Health and Human Services (HHS), PEPFAR, and the Peace Corps, among other agencies. Innovation and development are key components of the initiative's and the administration's goals. 

spoke with Amie Batson, appointed by Obama to lead USAID's role in the initiative, about progress thus far and plans forward.

Why are innovation and development such a big push now now compared with past years? 

 At USAID, we realize the benefits of investing in innovation for global health go well beyond improvements in health. Some of the greatest advances in development have come from extending the reach of innovative breakthroughs to those who lack access health facilities. We are looking to build stronger partnerships with the development and scientific communities to support the creative thinkers who are developing the next generation of health technologies capable of reaching more people at reduced costs to maximize impact.   

USAID Administrator Dr. Rajiv Shah has stated on several occasions that the largest opportunities to improve human health and the human condition do not lie in optimizing services to the 10–20 % of people in the developing world who have access to world-class health facilities.  They lie in extending our reach to the 80-90% of people who do not. 

 What are some examples that have come about from the initiative to date?

 This year, at the Bill and Melinda Gates Malaria Forum in Seattle, USAID welcomed the initial news of the Phase 3 efficacy trial that confirmed the RTS,S malaria vaccine is safe and effective, and could eventually add  to our present package of malaria control interventions saving more lives among young children in Africa.  In 2010, USAID proudly announced the first-ever proof of concept that a microbicide gel can effectively and safely reduce the transmission of HIV from men to vulnerable women, and placing the power of HIV prevention in the hands of women. The Global Alliance for TB Drug development is bringing a new drug combination to Phase III trials that could cut the duration of treatment by half and help overcome MDR-TB. With each advancement, we come closer to delivering more effective aid at a lower cost. In tough economic climates like this one, the question we should all be asking is what tangible benefits we will see for each dollar spent. There is no question that investing in the health technologies of tomorrow will reap incredible returns on our original investment, in lives and money saved.

 USAID Administrator Shah has spoken about how the agency is trying to improve its relationship with the private industry to make communication easier and less bureaucratic. What is USAID looking to do in this regard? What types of new partnerships is the agency forming?  

 Cultivating a productive investment environment will require partnerships with a range of stakeholders in donor and host countries, including the private sector, civil society organizations, research institutions, foundations, and emerging and traditional donors.  Our partnerships should reflect new models such as South–South and trilateral cooperation, and include meaningful roles for civil society and the private sector.    

Leveraging the collective resources of partners through public-private partnerships allows the development community to capitalize on opportunities to extend the reach and depth of our programs. USAID's Global Development Alliance (GDA) is a premiere model for public-private partnerships, helping to significantly expand and deepen the impact of development assistance by linking US foreign assistance with the resources, expertise, and creativity of private sector partners. Since 2001, USAID has formed more than 900 alliances with over 1,700 distinct partners to leverage more than $9 billion in combined public and private resources. Across industry and sectors, USAID is working in partnership with both global and local corporations to increase our reach and the effectiveness of development projects. 

 Some goals of the administration and of USAID are to increase access to healthcare and treatment in developing nations, shorten the time of getting new vaccines to market (moving a 15-20 year timeframe closer to 1-5 years), and accelerating scale up of drug development. In what ways is USAID working to achieve these goals? Are there other important goals on USAID¹s agenda in terms of global health efforts? 

One of the major obstacles to providing timely and quality treatment in the developing world is the inability to access health facilities. The reasons for this are many. Often times the nearest clinic is simply too far from the community where an individual lives. Other times the costs of services are too high or social norms prohibit women from seeking the care they so desperately need.

Through the Global Health Initiative, we are working to integrate healthcare services, so that when a woman travels to a clinic to receive treatment for HIV, she doesn’t have to travel to another clinic for pediatric services for her child. We are also working to train and empower community health workers who bring critical health services directly to the communities. The idea of offering health services at the community levels is critically important when you consider that 80%of people in the developing world will likely never set foot in a health facility.

The most transformative technology at our disposal, vaccines, ensures protection against killer diseases, whether children are immunized by pediatricians in the U.S. or by health workers in rural clinics in Africa.  By making quality vaccines available at affordable and sustainable prices, manufacturers are contributing to an international commitment to protect more children. If we expand the coverage of existing vaccines and introduce new vaccines against pneumonia and diarrhea, we can save the lives of 4 million children over the next five years.

 How can new drug products, including vaccines, be better introduced to developing populations? What are the key priorities in terms of advancing technology (e.g., meeting transportation or distribution challenges)?

 Countries need to know how best to use data to find their greatest numbers of missed children and target those children with optimal approaches whether that means outreach, quarterly child health days, school-based approaches or targeting indigenous populations.  Distribution and cold-chain challenges vary from country to country and in some larger countries, state to state.  Clearly countries have identified cold chain as a rate-limiting step with regard to new vaccine introduction.  The supply chain has largely been undervalued and many countries do not have an adequate record of the status of cold chain equipment, maintenance requirements and trained logisticians.   

What can industry expect going forward in terms of working with USAID to get its new products or vaccines to developing nations? What type of assistance may be provided and what are the timeframes?  

 USAID is going to continue to focus on what we do best.  That is we will continue to work with our partners at global, regional, and country levels to provide varying support.  We work with WHO and UNICEF, as well as our other donor partners, GAVI, the Gates Foundation, and most importantly, countries themselves.  USAID is not the only partner to industry with regard to getting programmatically suitable vaccines developed and used in developing countries.  Together, the US government makes tremendous investments in vaccines from basic research and development to field level strengthening of immunization programs.   

Can you talk about the large commitment the US recently made to GAVI and what this will achieve? Does USAID have any other financing programs in the pipeline? 

 To reiterate, one of the most transformative technologies at our disposal is vaccines. The United States' coordinated support for GAVI complements the efforts of the National Institutes of Health, the Centers for Disease Control and Prevention, and USAID in the research, development and sustained use of vaccines in robust, country owned immunization programs.  

The US commitment leverages the billions of dollars that other donors have committed to GAVI, multiplying the impact of our funding more than eight-fold, and allowed GAVI to negotiate a price reduction of 67% on rotavirus vaccines so more of the world's most vulnerable people will be protected against preventable diseases.  

Combined with other donors, our funding will enable the Alliance to provide countries with sufficient amounts of programmatically suitable vaccines to immunize an additional 243 million children in the poorest countries with vaccines against pneumococcal disease, rotavirus, Haemophilus influenzae type b (Hib), hepatitis B, meningitis A, and yellow fever, and ensure the complete rollout of pentavalent vaccine. Experience delivering vaccines to expanded target populations could also serve to strengthen immunization programs to put the world in a position to save more lives with potential future vaccines against malaria, tuberculosis, and HIV.  

Once a new drug or vaccine is introduced a developing-nation market, what are USAID's goals for ensuring that the country can sustain the administration, purchase, and distribution of that product?   

 We strongly support the GAVI co-financing strategy that requires all countries to make a co-payment for every dose of vaccine provided to that country through GAVI procurement.  The relatively recent revisions to the GAVI's co-financing policy requires a larger payment for countries closer to 'graduation.'  We want countries to be mindful of their financial obligations but we want to continue working with our partners on the expansion of the evidence base for decision making so that when countries have to make hard decisions about how to spend their money, they will realize the tremendous health impact vaccines have.   

 Many individuals seem to be opposed to global health efforts compared with say, focusing on the US healthcare system at home. What can be done to overcome this perspective?

We recognize that global health is vital to our national security.  Improving the health of people in the developing world drives economic growth, fights poverty, and strengthens families, communities and countries.  Investing in the health of people in developing countries reduces the instability that fuels war and conflict. Fighting global disease directly protects our health in the United States because infectious diseases know no borders. A continued effort to communicate the value and incredible return on investment from our global health efforts will be key to maintaining this support through the uncertain economic times ahead. 

Cultivating a productive investment environment will require partnerships with a range of stakeholders.

Global Healthcare on the Ground: USAID Works to Carry out President Obama's Global Health Initiative

Novartis AG, headquartered in Basel, Switzerland, and Novartis Pharmaceuticals Corporation headquartered in East Hanover, New Jersey, have been focusing research efforts on rare diseases since the company was established in 1996. The Novartis Institutes for Biomedical Research (NIBR) is a global network consisting of approximately 6000 scientists working across various scientific disciplines around the world. Headquartered in Cambridge, MA, NIBR has offices in Basel, Switzerland; Horsham, UK; Siena Italy; East Hanover, NJ; La Jolla, CA; Emeryville, CA; Forth Worth, TX, and in Singapore and Shanghai.  

"Our overarching goal is to help patients," says a company spokesperson. "We do not select research programs based on potential market size, but rather based on unmet medical needs and scientific tractability. In other words, we focus on the patient and follow the science." 

This approach has led many of the company's decisions to focus on rare diseases. "What makes these diseases attractive is that they are mechanistically well understood—making tackling the scientific challenges simpler and the development more efficient," adds the company spokesperson. "Additionally, the mechanisms that underlie these diseases are usually shared by more common diseases, so understanding them can shed light on multiple ailments." 

What makes rare diseases attractive is that they are mechanistically well understood.

Novartis Pharmaceutical Corporation currently markets 11 products that have been approved  by FDA for their orphan designated indication(s), covering a total of 20 orphan indications. The company has 25 approved products that hold orphan designation in the European Union. Here's a look at just a few of them:  Afinitor (everolimus), which is used to treat progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced, or metastatic disease; Gleevec (imatinib mesylate) tablets are used to treat certain life-threatening cancers; Tasigna (nilotinib) capsules, a signal transduction inhibitor of the BCR-ABL tyrosine kinase, is used to treat patients with a form of chronic myeloid leukemia in chronic and/or accelerated phase patients who are resistant or intolerant to existing treatment options; Ilaris (canakinumab), which is used to treat adults and children aged four years and older suffering from cryopyrin-associated periodic syndrome, a group of rare auto-inflammatory disorders that affect approximately one out of 1 million people worldwide; and Exjade (deferasirox) targets chronic iron overload caused by blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. Other rare-disease products in the company's pipeline include treatments for myelofibrosis, Cushing's disease, and Fragile X syndrome, which affects one in 5000 children.  

NIBR's approach is to focus on the subset of rare disorders that appear mechanistically homogeneous, explains the Novartis spokesperson. "Fundamental mechanisms can predictably be expected to explain subsets of more common disorders, so indication expansion, often based on biomarkers, is expeditious.  All drug candidates enter the clinic through small proof-of-concept trials.... We are currently evaluating more than 40 rare diseases, about half in oncology and the remainder across a broad disease spectrum." 

Another unique aspect of Novartis' work is that NIBR does not separate out a team, unit, site, or budget dedicated to rare-disease research, says the company's spokesperson. Rather, rare-disease research is central to the company's overall drug discovery approach and threads throughout each component of its work. 

Because drug discovery for rare diseases is so complex, Novartis also relies on partnerships. "No one company or organization can possibly do everything on its own," says the company spokesperson. "Therefore, we collaborate with academic institutions and biotechnology companies around the world to work towards the common goal of developing new medicines. These relationships come in varying shapes and sizes." 

For example, Novartis is an active member of the joint task force on rare diseases and orphan medicinal products that is run by the European Federation of Pharmaceutical Industries and Associations–European Biopharmaceutical Enterprises and Europa BIO. The company is also involved in Eurordis' roundtable for companies engaged in the orphan drug field. Eurordis is a nongovernmental patient-driven alliance of rare disease patient organizations in Europe. Novartis Pharmaceuticals Corporation is also an active member of the National Organization for Rare Disorders Corporate Council in the US. 

Looking ahead, the company says that more funding is crucial to continuing rare-disease research and discovery. "One of the great challenges in drug discovery is finding novel targets, whether they are in rare or common diseases.  Much of the fundamental research to find new targets is done by scientists funded by government research grants. Because this process can take decades, it is important that governments maintain or increase funding for basic research," says the spokesperson. "This will ensure that this important work continues." 

Novartis AG and Novartis Pharmaceuticals Corporation have been focusing research efforts on rare diseases since the company was established in 1996.

Global Healthcare on the Ground: Novartis Focuses on Treating Rare Diseases

The American Association of Pharmaceutical Scientists (AAPS) established a Pharmaceuticals in Global Health Focus Group in 2009 to raise awareness among the pharmaceutical development and manufacturing community about global health issues. The focus group is advocating for the inclusion of global health topics in all AAPS activities, including programming at meetings, strengthening networking opportunities among members and other professional organizations, and promoting educational and training programs for students about global health. 

The focus group grew out of a larger AAPS task force on global health, and after speaking to the chair-elect, Kishor M. Wasan, it's clear that this group is not only serious about its goals, but also extremely passionate about why it's focusing on global health. Wasan is a professor and distinguished university scholar in pharmaceutical sciences at the University of British Columbia in Canada, and the director and cofounder of the university's Neglected Global Diseases Initiative. 

"Now is the time to have this discussion and this group," says Wasan, offering a host of reasons why. Industry—and the world, for that matter—have changed dramatically during the past 15 years or so, he explains. For starters, the influx in the late 1990s of nongovernmental organizations led to a major social change. "We didn't have the Gates Foundation, or the Clinton initiative before the 1990s. We didn't have targeted programs for diseases in developing countries, or World Health Organization indicators for fighting neglected diseases. These programs have provided global funds for research and projects that deal with worldwide infectious disease and with problems that were being neglected," he explains. 

That's only half of the story. Social media has made a huge difference in bringing the world together to discuss and work on broad challenges such as global health. "We can Skype with laboratories in Uganda, there are diagnoses being done with individuals in Kenya via cell phones, we can coordinate a project with people in 14 or 15 countries at a time," he says. And this technology has engaged young people, adds Wasan, who has witnessed first-hand in his University of British Columbia students the excitement about the limitless opportunities that exist today. "They feel the world as a closer place. They want to tackle these types of problems, and the problems are more accessible to them." 

Indeed, global diseases are starting to touch lives in the developed world. Air travel, for example, has brought some new parasitic cases from developing countries into developed countries. But there's also a larger concern today for diseases that affect developing nations because the world's economies are so integrated. "If China, for instance, has some serious health issues, it's going to affect their productivity, which affects our productivity," explains Wasan. "It's beneficial to everyone to improve health on a global level."  

For all these reasons, Big Pharma has decided that it wants global health and access programs, says Wasan. He admits that there are some politics that have gone into this decision,  but at the end of the day, industry is doing more to saves lives, he says Wasan.  

Some of the target areas that the AAPS Pharmaceuticals in Global Health Focus Group plans to address through educational and networking programs include: the development of treatments, vaccines, and diagnostics for neglected diseases; assuring the quality and safety of active pharmaceutical ingredients and drug products that are produced and sold throughout the world; the development of vaccine formulations that are stable without a cold chain; small-molecule formulations that can withstand the rigors of tropical environments; and assuring that developing-country populations have access to routinely used vaccines, medicines, and diagnostics.  

A key component of the focus group's work, explains Wasan, is to highlight the technical aspects of global health efforts. "Eighty percent of our members are industrial scientists," he says. "They want to know, for example, how to make a drug that is stable in a tropical environment. They want to know how to make an oral formulation versus a parenteral (which also can be applied to countries in the developed world). Overall, our goal is to address the global healthcare and pharmaceutical issue while also tackling topics that are of interest to the scientific community so that they can apply what they've learned."  

AAPS plans to address these challenges through one of the most basic forms of communication—dialogue. "We have all these groups coming to meetings and we have members around the globe," says Wasan. "Innovation occurs by people talking, and we can coordinate that." 

The focus group also plans to get young people involved. "These problems are not going to be solved in our lifetime," says Wasan. "They are generational, and the kids who are in school now are going to be the ones that will have the energy to carry out solutions." 

The next global health focus group meeting is taking place at the October 2011 AAPS annual meeting in Washington, DC. 

AAPS Global Health Focus Group's Kishor M. Wasan discusses new initiatives.