Opinion: Open Innovation: An Answer for Neglected Diseases

In 2003, Henry Chesbrough, a professor and executive director at the Center for Open Innovation at University of California Berkeley (UC Berkeley), first coined the term ‘open innovation’, in his book Open Innovation: The New Imperative for Creating and Profiting from Technology[1]. According to him:

“Open innovation is a paradigm that assumes that firms can and should use external ideas as well as internal ideas, and internal and external paths to market, as the firms look to advance their technology”[1].

In recent years, tremendous growth has occurred in internet-based information and research networking among companies and customers, resulting in a massive distribution of knowledge in the public domain. Companies are taking this opportunity to connect directly with the customers in order to understand their needs and tap into ideas for product development. Procter & Gamble (consumer product), Nokia (mobile technology), Linux (software) and Goldcorp (mining) are a few examples of companies that have successfully adopted this open-innovation/crowd-sourcing model [2]. Although the business model of these fast-moving consumer goods companies (FMCG) and pharmaceutical companies are entirely different, the pharmaceutical companies are facing many of the same challenges as other sectors; for example, low number of drugs approved by the US FDA in recent years, declining innovation, high risk, pressure for cheaper medicines and less expensive development programs, faster and robust diagnostic methods, and demand for medicines that are stable under different climatic as well as environmental conditions (an important factor to be considered in developing drugs for poor countries, as these countries often lack proper infrastucture for the shipping and storage of medicines).

According to the Kellogs Report, pharmaceutical companies are facing an innovation gap and productivity crisis as the number of approved drugs has declined in recent years [3]. In order to get out of this productivity crisis, pharmaceutical companies have increased their spending (~US$90 billion per year on global R&D); however, they will be losing US$32 billion in cash flow over the next few years as many of key drugs will become generic [101]. As a result, many phamaceutical companies are trying to incorporate ways to reduce R&D costs by adopting new approaches such as open innovation, open source, outsourcing, collaboration and intellectual property (IP) sharing in their existing business model [4]. Pharmaceutical companies are looking for collaboration with academia and outside sources for sharing talent, resources, tools and technologies, such as high-throughput screening assays, for identifying drug targets for a particular disease.

Open innovation is a new idea, and even a few years ago the whole concept of open innovation in the pharmaceutical industry was unthinkable. But there is enough evidence to show there is a growing trend in major pharmaceutical companies such as GlaxoSmithKline (GSK), Novartis, Merck, Lupin, Bayer, Sanofi-Aventis, Pfizer and Advinus Therapeutics for supporting open innovation and the open-source model. Pharmaceutical companies started seeking solutions for the challenges/problems (e.g., solution for drug targets, screening techniques and assay development) from scientists/researchers outside the company in exchange for reward/incentive in the form of prize money. They post these challenges in various internet-based open innovation service companies such as Innocentive, Innoget, Presans and Ideaconnections. These are very recent developments in the pharmaceutical industry; they did not exist even a few years ago. The open-innovation concept has become so important for pharmaceutical companies that we are seeing more and more symposia and conferences on the subject of open innovation in pharmaceuticals. In June 2010, Oxford Global organized a symposium on pharmaceutical open innovation at Le Monteux Palace, Switzerland. The main purpose of the symposium was to analyze the critical importance of open innovation within the pharmaceutical industry. Major pharmaceutical companies such as Pfizer, GSK, Eli Lilly and others attended the symposium.

With all these changes in the global research environment, the question arises of whether this open-innovation/open-source model could be successfully implemented at the earlier phase (R&D) of the drug-development process (idea generation and sharing of data, technologies, diagnostic assays and screening assays) to discover novel drugs for the millions of people who are dying each year in developing countries from malaria, tuberculosis (TB) and many other neglected diseases such as human African trypanosomiasis, leishmaniasis, schistosomiasis, Chagas disease, lymphatic filariasis and onchocerciasis [5].

Neglected diseases & open innovation

Each year, millions of people, especially children, in low-income populations mainly in the developing regions of Africa, Asia and South America become victims of malaria, TB and many other infectious diseases. These diseases affect poor people living in rural areas, city slums or in zones of conflict in unsanitary conditions with little or no infrastructure. Malaria is a mosquito-borne infectious disease that is widespread in tropical and subtropical regions, including parts of the Americas, Asia and Africa. Malaria is the second leading cause of death from infectious diseases in Africa after HIV/AIDS. Approximately 3.3 billion people (half the world’s population) live in areas at risk of malaria transmission in 109 countries and territories. An estimated 863,000 malaria deaths occurred in 2008 and 89% of the malaria deaths worldwide occur in Africa [102]. TB is a common and often deadly infectious disease caused by Mycobacterium tuberculosis in humans. One-third of the world’s population is infected with TB and each year over nine million people around the world become sick with TB, leading to almost two million TB-related deaths worldwide per year [103].

According to the WHO, one-third of the world’s population lacks basic access to essential drugs. According to reports, only 10% of the global R&D funding goes towards research on neglected diseases, which affect 90% of the world’s population. This phenomenon is known as the 10/90 gap [6]. Despite major advances in drug development technologies, there is a lack of essential medicines for neglected diseases in developing countries. The R&D system remains very much focused on developing new drugs for the diseases of affluent countries (e.g., arthritis, acid reflux, bipolar syndrome, diabetes and depression). Current R&D and innovations are market driven and often dictated by pharmaceutical companies. Pharmaceutical companies are taking advantage of the situation and asking for the highest return by setting very high prices for the drugs for malaria, TB and other infectious diseases, thus making these drugs inaccessible to poorer people. Moreover, pharmaceutical companies own the patent rights to these drugs and often use different strategies to extend the IP rights for certain drugs to block competition and innovations. There are however, exceptions. In 1987, Merck & Co. Inc., set a precedent by spending millions to develop Mectizan, a human formulation of Ivermectin that kills the worm that causes onchocerciasis/river blindness. River blindness is a parasitic worm disease that affects millions of people, mostly in Africa and other developing countries. Until the late 1980s, there was no cure against the parasite. Merck collaborated with the WHO, the World Bank, other nongovernmental organizations and local people in many countries to distribute Mectizan free of cost to those at risk. By 2001, drug treatment combined with insect control had alleviated the risk of river blindness disease in over 200 million people, mostly in Africa. It is estimated that 16 million children have been spared from the infection and that 600,000 cases of blindness have been prevented [104].

Both R&D and innovation are the key solutions for neglected diseases. Future open-innovation models call for more collaboration between pharmaceutical companies and biotechnology companies, universities, researchers, government sponsored public–private–partnerships (PPPs), nonprofit drug R&D organizations [4,7]. Nonprofit organizations such as the Drug for Neglected Diseases Initiatives (DNDi), Médecins Sans Frontières (MSF), Medicine for Malaria Venture (MMV) and the Global Alliance for TB Drug Development (TB Alliance) have played a major role in working with big pharmaceutical companies to reduce the cost of research through the voluntary sharing of knowledge, data, tools and infrastructure in the last few years. Only 10 years ago, the scenario was entirely different. There were no collaborations, no IP sharing and pharmaceutical companies were not publicly interested in neglected diseases. Recently, many pharmaceutical companies have shown interest in developing drugs for neglected tropical diseases [8,9]. GSK has made available data that it has generated on 13,500 antimalaria compounds. They have also created a patent pool (pool for open innovation), which aims to remove IP rights for the neglected diseases. The 16 diseases targeted by the pool are identified by the FDA for its own neglected tropical diseases (NTD) initiative: TB, malaria, blinding trachoma, buruli ulcer, cholera, dengue/dengue hemorrhagic fever, racunculiasis, fascioliasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and yaws. The main aim of the open-innovation patent pool is to accelerate innovation and drug-discovery efficiency of biotechnology-based drugs, vaccines and diagnostics for neglected diseases, thereby saving lives in developing countries. In return, GSK expects that reserachers working with the free information will contibute their new findings/data to the online data source and donate any IP for the neglected diseases of the developing world into the patent pool. GSK is also working closely with Alnylam pharmaceuticals, an RNAi therapeutic company, which has added another 1500 patents into the pool. GSK will spend US$8M seed money for ‘Open Lab’ and new collaborations to share IP rights for neglected diseases [105]. The GSK–African Malarial Partnership will award four new grants worth US$2.5M and will make available in the public domain the data that if generated on 13,500 compounds that are potential candidates for malaria drug development. In May 2010, the Massachusetts Institute of Technologies (MIT) announced that it would join the open-innovation patent pool begun by GSK, by contributing its IP rights/know-how on neglected tropical disease research. MIT will be the first organisation to join upto this noble cause [106]. At present the patent pool has more than 2300 patents that are freely accessible to the public.

In 2009, Novartis, announced that it will partner with the Institute for OneWorld Health, a nonprofit organization, and give the Institute access to its proprietary research data for the development of a drug for diarrhea, a leading disease among children in poor countries due to unhygienic living conditions [107]. In 2008, Cambia, another nonprofit group in Australia, backed by a US$3M grant from the Bill and Melinda Gates’ Foundation, partnered with Queensland University of Technology, Australia, and established a global open innovation initiative, which will promote patent system transparency worldwide. This will be a giant step towards making the IP system more open and effective for developing new drugs for poor countries [10]. These events helped in changing the dynamics and led many pharmaceutical companies such as GSK, Bayer and Novartis to start a collaboration and partnership with Global TB Alliance. DNDi is partnering with GSK to develop treatments for diseases such as leishmanias (Kala-azar). Sanofi-Aventis is collaborating with the DNDi developing an antimalarial drug for less than US$1 in Africa. Novartis collaborated with the Institute for Microbiology and Epidemiology in Beijing to develop an antimalarial drug, Coartem^®, combining a traditional Chinese plant-based malarial remedy with a synthetic compound. This drug has a 95% cure rate and is very effective. Pfizer undertook initiatives in Africa for eliminating trachoma, a disease that causes blindness [108]. Recently, Indian scientists at the Open Source Drug Discovery organization (OSDD) and the Council for Scientific Industrial Research (CSIR) mapped the entire Mycobacterium tuberculosis (Mtb) genome and put the map on the web with free access. Rajesh Gokhle, a senior scientist at OSDD commented, “Here we are making all our progress available to public. Anyone can take advantage and develop a drug based on our research. The aim here is not patents but drug discovery for a neglected disease” [109].

The OSDD–CSIR team is working with Systems Biology International of Japan in this project. Samir Brahmachari, director general of the CSIR said “the Indian and Japanese scientists have created a ‘designer platform’ whereby a map of the data generated has been created, thereby leading to an actual visualisation. This ‘Connect @ Decode’ project will help experts re-annotate biological and genetic information” [109]. New initiatives such as the African Network for Drugs and Diagnostics Innovation (ANDI), which promotes and sustains African-led product R&D activities, discovery, development and delivery of new drugs. This is a good example of an open-access initiative that supports scientific networking, exchange of information and interaction between African scientists, policy makers and their peers in other continents [11].

Future challenges

Open innovation in the field of drug discovery is still in its infancy. In finding a cure for malaria and other neglected diseases, the conventional patent-based drug-discovery approach will be less effective in addressing the public health needs of developing countries. A collaborative, open-source, open-innovation model will demand a new form of patent system, a system where we will see more IP sharing, patent transparency and cost effectiveness. Although a new patent system for drug discovery may sound unrealistic at present, there is a growing awareness of the need for open-source models, particularly for the the neglected tropical diseases, as well as AIDS/HIV. Things are changing slowly, major pharmaceutical companies such as GSK, Pfizer, Novartis, Eli Lilly and many more are actively participating in open innovation, and using a collaborative and open-source model for developing drugs for the treatement of neglected diseases. The past 2–3 years have seen tremendous awareness among pharmaceutical companies around the world to open up and give away many of their resources, such as rights to patents or IP, information about compounds, databases (genome sequence and proteomic database), screening techniques and diagnostic assays, which will be very helpful for future drug development efforts.

For a future open-innovation business model for neglected diseases it is absolutely necessary to scale up the global capacity for R&D, and to build a more efficient and more open mechanism for the discovery of new drugs [12]. One of the recommendations for the future open-innovation model for neglected diseases will be to establish a consortium composed of major pharmaceutical laboratories and academic institutions whose aim will be to initiate a ‘research pool’ into which to donate compounds, drug candidates, genome maps, IP rights, diagnostic assays, novel technologies and high-throughput screening capabilities. Each member of the consortium would evaluate its compound collection using assays/technologies available for the neglected diseases. Any active compound could be optimized and developed under international grants administered by the WHO and other nonprofit organizations (e.g., DNDi, MSF or MMV).

Companies and organizations can seek solutions to challenges directly from the world talent pool. Global scientists/researchers who are familiar with the art of research and drug development can submit novel ideas for drug targets or come up with low-cost screening assays for neglected diseases for developing countries and put their findings into the open-innovation pool. This will accelerate the efficiency of the drug-discovery process. More participation and collaboration between the drug companies, nonprofit organizations and researchers in developing countries will lead to the faster availability of novel drugs and medicines for neglected diseases [13]. A future open-innovation model will help scientists generate safe, effective and inexpensive next-generation medicines for millions of people around the world.

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