The Council of Scientific and Industrial Research?s (CSIR) open source drug discovery (OSDD) programme seems to have hit a rough patch. Even 15 months after the launch, there is lukewarm interest from the pharmaceuticals and biotech industry in partnering in the drug discovery programme. None of the top 10 global pharmaceutical majors, including those in India, have shown any interest in joining the venture. Only fringe players like Chembiotech, Cellworks and Jubilant have shown interest. Even non-government organisations (NGOs), that are otherwise supportive of such drug discovery initiatives, have remained aloof from the OSDD programme. The reason: The OSDD programme is focused on developing drugs for neglected diseases, which do not have the market potential to attract the interest of the big pharmaceutical companies.
Misery of the OSDD programme does not end here. While 2,300-odd researchers have joined the venture, an overwhelming number of them have no prior research experience of tuberculosis or other infectious diseases that the OSDD programme is focused on. They are all from the academic arena and not from the drug industry. In addition, as multiple government research institutes such as Institute of Genomics and Integrative Biology (IGIB), Central Drug Research Institute (CDRI), Institute of Microbial Technology (IMT), Centre for DNA Fingerprinting and Diagnostics (CDFD) and Institute of Life Sciences (ILS) are involved, there is a lack of coordinated research in the programme. The only saving grace is that IT behemoth Infosys has recently joined the initiative and is developing a next generation collaborative website for the OSDD programme.
In such a bleak scenario, a key question arises: While the pharmaceuticals industry spends billions of dollars in drug research and development (R&D), question marks hang on sustainability of CSIR?s open source drug discovery programme. CSIR director-general Samir K Brahmachari says, ?With respect to diseases of the poor, for example, tuberculosis, where the market incentive is very small, it is not possible to convince the pharma companies to work on these drugs.? Besides tuberculosis, the OSDD programme is focusing its efforts on developing drugs for malaria and leshmaniasis.
Industry has its own reasons for giving the CSIR drug discovery programme a cold shoulder. ?There are no incentives for the pharmaceuticals and biotech industry. It is an open source drug discovery programme and there is no novelty attached to it. Moreover, in the absence of any intellectual property (IP), why would a company take the risk of going through the highly expensive and time-consuming drug development phase,? questions Venkat Jasti, the chairman and managing director of Hyderabad-based Suven Life Sciences. ?There is no clarity on fixing responsibility in case something goes wrong in the clinical trials phase. We are dealing with human lives here, not software,? he reasons.
According to Uday Baldota, vice-president (investor relations), SunPharmaceuticals, the question of sustainability depends on how the overall process is integrated with the understanding of current therapies and the unmet therapeutic needs, besides identification of new targets?that would address the needs in terms of safety and efficacy. This requires comprehensive in-vitro and invivo biological programmes, good laboratory practice (GLP) laboratories and clinical programmes. This needs to be meticulously coordinated, tracked and funded over a period spanning more than a decade. Further, an important aspect for sustainability is the motivation of scientists involved.
?A clear formulation of policies on how the outcomes of the research would be addressed in terms of intellectual property protection and profit sharing would go a long way in attracting the pharmaceuticals industry to the open source drug discovery programme,? says Baldota.
However, Cellworks Research chairman and managing director Anand Anandkumar is quick to defend the OSDD programme. ?Tropical diseases do not have the market potential, which will attract the interest of the big pharmaceutical companies. But for drugs that are not driven by the market and those are needed by the poor, open source is an advantage.?
OSDD project director Zakir Thomas has a more pragmatic view on the lukewarm involvement of pharmaceutical industry in research into drugs for neglected diseases. Even the largest killer among the neglected diseases, tuberculosis has only an estimated market of $300 million.
This is one reason for the lack of serious research-based pharma interest.
Tuberculosis is a disease caused by an organism called mycobacterium tuberculosis. The World Health Organisation (WHO) reports that one-third of the world?s population is currently infected with tuberculosis. The estimated incidence of tuberculosis in India is 1.8 million new cases annually. This amounts to three tuberculosis deaths every two minutes. The current tuberculosis therapy called directly observed treatment, short course (DOTS) was developed in the 1960s and no major advancement in treatment has emerged for almost half a century. The treatment continues for 6-9 months. Problem with the present treatment is that tuberculosis patients find it difficult to continue, as a result there is multi-drug resistance. Therefore, there is a need for a more effective and affordable drug with shorter treatment duration. After 12 years of research, researchers at Indian Institute of Integrative Medicine are believed to have developed a drug for tuberculosis called Risorine. This is expected to be launched later this week and will be marketed by Cadila Pharmaceuticals.
OSDD?s collaborating institutes like CDRI, IMTECH, Chandigarh, Indian Institute of Integrative Medicine, Jammu and Indian Institute of Chemical Biology, Kolkota, have established tuberculosis programmes and experience in the field of drug discovery for years.
Infosys is developing a next generation collaborative website for OSDD. The present website has some elements of Web 2.0 but not all features. The website which Infosys develops will have Web 2.0 features, including social networking for research groups. More importantly, it is based on semantic Web tools (based on resource description framework). ?All components used in this portal are strictly open source. It is quite a challenging task as developing something of this nature is a very complex task. The Infosys team is highly research oriented and is addressing the challenges,? he adds.
So far, OSDD has set up high performance computing facilities at IGIB, Delhi, JNU Delhi and IMTECH, Chandigarh and have connected them through the National Knowledge Network. All the projects are available online and undergo an open peer review process. The comments of the peer reviewers as well as the responses of the project investigators are also available online.
OSDD researchers are pursuing both target-based as well as cell-based drug discovery process. Scientists are also doing screening of compounds. It connects computational biologists and experimental biologists as well as chemists. Therefore, it is a novel platform of collaboration which otherwise is missing in the conventional set up. Multiple targets of mycobacterium tuberculosis are being pursued by different groups of OSDD.
?We are in the process of involving industry to put projects on fast track. We had recently called for industry expression of interest (EOI) for protein expression, purification and assay development. We had a good response and it is expected that they will start working soon,? says Thomas.
Drug discovery is a long drawn process, involving scientists from several disciplines working concertedly, and is associated with a high degree of uncertainty at each phase of the discovery process. It requires perseverance and demands commitment from all the concerned participants till the molecule reaches market. Further, the new drug has to withstand in the market maintaining efficacy across large diverse population and without any adverse effects that might have not been noticed in a smaller population during trials.
Typically, pharmaceutical companies thrive in a highly competitive environment. The industry in general pursues research projects in a focused manner, on well defined objectives and timelines. Yet, there are stories on birth of blockbusters which have basically stemmed out of academic pursuits. Clearly, the OSDD team has to keep such lessons in mind as it gears up for the acid-test ahead.