Rising above Neglect

A study by Medicine Sans Frontiers and Drugs for Neglected Diseases (DNDi) published in December last year reveals that even as neglected diseases account for roughly 11 per cent of the world’s global disease burden, a meagre four per cent of the world’s new therapies and 1.2 per cent of new chemical entities (NCEs) were developed for them in the last decade. Clearly disease burden does not seem to be a criteria for new drug development for Neglected Tropical Diseases (NTDs). These diseases affect 1.4 billion of the world’s population, mostly the poorest of the poor even in countries such as the US and the UK and result in roughly 26 million DALYS (Disability-adjusted life years) lost (as published in Lancet 2012, if one were to go by the core group of 17 NTDs). However, momentum is building up, if the London declaration is anything to go by.

Moving beyond MDA

Mass Drug Administration (MDA) has so far been a tried and tested method utlised as a strategy to combat NTDs and as many as 13 pharmaceutical companies have pledged to amp up their efforts in January last year by donating preventive chemotherapy, an intervention that allows the regular and coordinated administration of quality-assured, safe, single dose medicines on a large scale for the treatment of foodborne trematode infections, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases and trachoma.

“The concept of ‘tool ready vs. ‘tool deficient’ diseases is no longer valid. Ultimately, almost all of the NTDs will require new drugs and vaccines to overcome resistance and water, sanitation and hygiene challenges. We also need new diagnostics to better quantify the number and severity of NTD infections in people.” Peter Hotez Dean, National School of Tropical Medicine at Baylor College of Medicine and President, Sabin Vaccine Institute

“Many individual countries have success stories to share about the control and elimination of several NTDs achieved through NTD plans, scaled-up MDA and remarkable political will. Highlights include onchocerciasis elimination in Colombia; LF elimination in China and the Republic of Korea and blinding trachoma elimination in Ghana and Mexico,” chips in Peter Hotez, Dean, National School of Tropical Medicine at Baylor College of Medicine and President, Sabin Vaccine Institute.

However, although such programmes have been running for a decade now and are riding on a success wave, expanding further, there’s much more to it than just doling out free, low cost medicines to the poor. They must also be continually assessed with respect to the effect they are having on the ground.

Margaret Chan, director-general of the WHO, in her foreword to the WHO report- “Sustaining the Drive to Overcome the Global Impact of Neglected Tropical Diseases” emphasised precisely this, when she said: “As more programmes approach their milestones and targets, new tools and protocols are needed to assess the intensity of transmission, support decision-making about when mass drug administration can be stopped, and then to verify interruption of transmission.”

The report has set down a target of eliminating rabies and yaws by 2020, the latter through an oral antibiotic treatment which would replace the one in use since 1950s (mainly centered on delivering injections of benzathine benzylpenicillin). Take for instance dengue, ranked as the fastest spreading vector-borne viral disease in 2012, with an epidemic potential in the world, registering a 30-fold increase in disease incidence over the past 50 years which is yet to have an effective treatment.

“Most of the 17 major NTDs can be treated by available drugs, but for diseases such as leishmaniasis, Chagas Disease and HAT (Human African trypanosomiasis ), these medicines can be highly toxic. The concept of ‘tool ready’ vs. ‘tool deficient’ diseases is no longer valid. Ultimately, almost all of the NTDs will require new drugs and vaccines to overcome resistance and water, sanitation and hygiene challenges. We also need new diagnostics to better quantify the number and severity of NTD infections in people,” adds Hotez.

“Anti-malarial combination products with new formulations have improved health outcomes. The Coartem story is a good illustration of this. It is a fixed dose combination product approved in 2002. New formulations of the product, including a cherry-flavoured drink for children, have improved adherence tremendously in malaria-endemic countries, such as Ghana.” Joshua Cohen Senior Research Fellow, Tufts Center for the Study of Drug Development

Not only novel drugs, but coming up with formulations and combinations to help reduce the time of treatment and increase adherence is also important. “Anti-malarial combination products with new formulations have improved health outcomes. The Coartem story is a good illustration of this. It is a fixed dose combination product approved in 2002. New formulations of the product, including a cherry-flavoured drink for children, have improved adherence tremendously in malaria-endemic countries, such as Ghana,” informs Joshua Cohen, Senior Research Fellow, Tufts Center for the Study of Drug Development.

Stepping up R&D

Although pharma companies have stepped up their commitment to supply existing drugs, the R&D scenario on NTDs remains grim. An analysis by MSF and DNDi in December last year revealed that of the 850 new therapies and vaccines approved by the US Food and Drug Administration(US FDA), the European Medicines Agency and other agencies between 2000 and 2011, 37 focused on neglected diseases, with a mere four of them being NCEs. An earlier paper published in 2002 by members of the Drugs for Neglected Diseases Working Group, counted 1,393 new drug approvals—16 of which focused on neglected diseases—between 1975 and 1999 (Lancet 359, 2188–2194, 2002). 11 of those 16 drugs were NCEs. The numbers suggest that although the rate of approvals for drugs for neglected diseases has gone up, the rate of approvals for NCEs seems to have remained relatively flat.

Recent analysis from the Tufts Center for the Study of Drug Development corroborates this further with statistics showing that an average of 2.6 new drug products—including new molecular entities, vaccines, indications, combinations, and formulations were approved each year from 2000-2008 to combat neglected diseases. The number rose to five per year in 2009—12, however, annual R&D spending to treat neglected diseases has leveled off at $3 billion in total, after rising rapidly from 2000 to 2007, which is a cause of concern.

“Our study only mentions the total (global) annual amount of funding, not solely by drug companies, but also PPPs and governments (mostly US),” clarifies Cohen. Rise in R&D funding by pharma companies might be a key to increased numbers of approvals targeting neglected diseases. Clearly, NTDs need to rank high on the priority.

Partnerships then, have emerged as the route to new drugs, diagnostics and vaccines with non-profit product development partnerships with developing countries’ manufacturers. According to a survey by the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) 132 R&D programmes were under way in 2012, a 40 per cent increase over 2011, with 112 in partnerships with key pharma players. Just 15 per cent or 20 programmes, are being driven entirely by companies. However, public sector rules the roost when it comes to funding, supplying $2 billion of the $3.05 billion spent in 2011. Philanthropic groups contributed another $570 million, with pharma companies at the lowermost rung with $525 million. There might be a reason for that, argues a paper by the Maastricht School of Management which in turn advocates funding through ‘push’ and ‘pull’ mechanisms to create more attractive markets, lower uncertainty, and support return on investment, thereby stimulating increased investment in R&D. Push funding in the early stages of scientific research should support translational research and academic-industry initiatives. As soon as the ‘proof-of-concept’ has been established, however, performance-based mechanism should be activated like the Advanced Market Commitment (AMC) and Priority Review Voucher (PRV). The authors developed a ‘risk-investment-incentive’ model that calculates the size of funds needed to sufficiently reward the innovator(s). However till then, PPPs shall strive to fulfill the targets set by the London declaration, even as pharma companies try to get their act together.

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