Between 1975 and 1999, only 15 new products were developed for the treatment of tuberculosis and of tropical diseases like Chagas’s disease, malaria, leishmaniasis and sleeping sickness. In comparison, in the same period, 179 new drugs arose just to cater to the victims of cardiovascular diseases. It is worth registering that both these diseases neglected, for which treatment, when it exists, is inadequate and the cardiovascular diseases account for practically percentage, around 12%, of the total number of diseases of the planet. The development of new drugs for diseases that affect populations in developing countries is of little interest to the pharmaceutical industry. In spite of covering around 80% of the world population, is not very attractive, as it accounts for only 20% of the overall sales of medicines. And this disregard is responsible for the death of millions of persons all over the world.
Recently, thanks to the initiative of the humanitarian institution Médecins Sans Frontières (MSF), with which the World Health Organization (WHO) has allied itself, the first fruits are starting to burgeon of a program focused on the development of innovative products, medicines and vaccines for ailments like these, whose treatment does not feature on the map of the industry’s priorities, and have likewise not been a target of firm and structured public policies.
Called the Drugs for Neglected Diseases Initiative (the acronym for which is DNDi), this program interlinks the efforts of scientific, government and private institutions from several countries. The forecast investments are in the order of US$ 250 million for a 12-year term, a period in which the calculation is to get six or seven new drugs registered and a portfolio of eight projects under way.
The MSF’s proposition, initially financed with from the proceeds of the Nobel Peace Prize, awarded to the organization in 1999 is, basically, to use in this initiative the same standard that the pharmaceutical industry adopts in the production of “profitable” drugs, usually with the seal of cutting edge technology. That is, to develop medicines that represent veritable innovations for old illnesses, many of which no longer respond to the conventional medicines.
Disease and market
The initial resources for the period 2003-2004 are in the region of US$ 20 million. As the initiative advances, the expectation is that other partners will join the program, weaving, in the field of health, a humanitarian, scientific and social network perhaps without precedent in the world. Typical of the underdeveloped regions of the planet, the neglected diseases are generally those linked to undernourishment and the lack of sanitation. From the business point of view, it is not worth the trouble investing time and money in this field: the financial return is very low and in some cases practically nil.
The statistics show that less than 10% of total spending on health research is applied in diseases that account for 90% of the global volume. And the neglected diseases are given an even smaller slice: of the US$ 70 billion or so spent on Research&Development (R&D) in 2001, it is estimated that less than 1% was set aside for developing treatments for these maladies. Seeking to turn around this picture in a lasting and professional way, the MSF officially launched the DNDi in July this year, in Geneva. Its bases of action are propped up by the proposals of a group that has been working on the theme for roughly three years.
Under the coordination and management of the MSF and the WHO, the intention is to involve public and private institutions, as well as laboratories and companies, in a real international crusade for the cure of these diseases. In the outline of this model, the development of new medicines will result in a dialog between various research centers, using the already existing apparatus and infrastructure in a more rational, productive and efficient manner.
This is what is happening in Brazil, with the participation of the Oswaldo Cruz Foundation (Fiocruz), whose Drug Technology Institute (Far-Manguinhos) is one of the founding members of the DNDi. The doctor and sanitarian Paulo Buss, Fiocruz’s president, explains that the institution has been working on a new pharmaceutical formulation that associates two substances, artesunate and mefloquine (AS/MQ), in the treatment of malaria. In this project, Far-Manguinhos heads up a partnership with two other Brazilian research centers, which have passed muster by the WHO technicians.
The sophisticated tests for toxicity one of the areas in which the country is most technologically out of date are carried out by the Unitox laboratory of Santo Amaro University (Unisa), in São Paulo. And Genotox, a company incubated at the Biotechnology Center of the Federal University of Rio Grande do Sul (UFRGS), is in charge of the tests of genotoxicity, which detect the possibility of genetic mutation induced by chemical substances that make up the medicines and assess the potential damage. The international partnership for getting this medicine which, depending on the results of the clinical phase, may be launched on a timescale that varies between three and six years also involves institutions from Thailand and Malaysia (clinical tests) and from the United Kingdom (in vitro and molecular studies).
Besides the AS/MQ formulation, carried out by Far-Manguinhos, there is another project connected with malaria under way. This is one that associates artesunate and amodiaquine (AS/AQ), whose pharmaceutical development is being handled in France, with Brazil doing the tests for toxicity and genotoxicity and Burkina Faso the clinical tests on human beings. Also to be found at the stage of development, in the international ambit, is paromomycin, a drug for veterinary use that is being rejuvenated for human use, in an injectable form, to combat leishmaniasis. The creation of other medicines should, generally speaking, follow this same cooperative scheme: different centers around the world are in charge of different stages, from formulation to production.
Competence and results
Eloan Pinheiro, a former director of Far-Manguinhos and a member of the international DNDi, points out that the presence of Brazil in this initiative represents the consolidation of Far-Manguinhos in the world scenario, after the institution having developed the formulations for the cocktail of drugs to combat the Aids virus. The scientific qualification that there is today in the country is “extraordinary”, reckons Paulo Buss. What is lacking, in his opinion, is a more consistent project that combines the scientific part with the industrial area.
“Because research produces scientific goods: producing something tangible is not an everyday practice, it’s not part of the Brazilian university culture.” In this sphere, the representative of the MSF’s Campaign for Access to Essential Medicines in Brazil, Michel Lotrowska, suggests that Brazilian finance institutions should adopt specific support lines for projects that focus on the development of new products, that is to say, projects that offer concrete results for the patients.
Eloan Pinheiro observes that the country has good scientific competence installed in several universities and institutes. This base is fit for the development of new products for neglected diseases, using both medicinal plants and weapons of biotechnology and chemical synthesis.In spite of this, there are great gaps in the areas of pharmacology, toxicology, clinical tests and the development of clinical methodology. “We have the brains in the country, but there is a lack of structured areas in quantity and quality for doing the testing. I regard this as a consequence of the lack of an industrial policy in the sector of therapeutically active inputs. There is still no policy for producing consumables that are no longer patented”, is Eloan’s finding.
In the last few decades, scientific knowledge in the area of health has evolved considerably, and new medicines have been introduced for global diseases, such as cancer and cardiovascular diseases. Even for problems connected with “life style”, such as cellulite, baldness and jet leg, innovative medicines have arisen.In contrast to this picture of progress, the abyss that separates tropical diseases from the non-tropical ones has deepened.
In the last 25 years, practically no more “modern” medicines have been launched for controlling or overcoming the former. Many of these ailments are fought even today with formulations that have been in existence for some 40 years and no longer produce the desired effects, increasing people’s suffering. A document from the MSF points out that until very recently patients who suffered from sleeping sickness, for example, had to submit themselves to a painful treatment based on arsenic, for the unavailability of any more effective remedy.
In spite of these findings, the specialist who outlined the guidelines of the DNDi do not blame only private enterprise for the lack on the market of new products, of diagnostic kits, or even of vaccines for the neglected diseases. The program also indicates failures in the public sphere. In the less developed countries, there is, amongst other factors, a perverse combination of a lack of financial resources and of establishing policies for fostering production and technological development for treating these pathologies.
In the current phase of the program, 71 projects were pre-selected, says Michel Lotrowska. The next step will be to sift through them, to choose those that will actually be developed. The participation of the private sector is still being outlined; there have been some meetings with the pharmaceutical industry, but the types of collaboration have not yet been formatted. The representative of the MSF says also that the DNDi is setting up, in various parts of the world, a network of regional offices to synchronize the different projects better. The “arm” of the initiative for Latin America and the Caribbean should work in Brazil, probably starting in 2004. The target is to organize a network, for the professionals involved to share researches, human resources and the use of laboratories, besides identifying opportunities for projects and fundraising.
Each one of the stages defined for the projects approved may be carried out in different countries, but they will all be under the institutional umbrella of the MSF and the WHO as far as the coordination and management of the projects are concerned. The idea is that the innovations that result from the works of investigation will constitute public patents, which will guarantee ample access of the target populations to the medicines produced.Republish