[e-drug] WHO urges drug companies to stop selling single artemisinin malaria drugs

E-DRUG: WHO urges drug companies to stop selling single artemisinin malaria drugs
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[Press release of WHO, requesting drug companies to stop selling single artemisinine drugs. The arguments are good, but it will be hard to implement, as so there are several issues: quality, price, availability, registration.

Quality: so far only one artemisinine combination (Coartem, Novartis) and 2 single artesunate products (Sanofi, Guilin) have been prequalified by the same WHO. Several generic versions are available or being developed, but what can countries do? The Global Fund insists on prequalification or registration of a product in a "stringent" regulatory authority (FDA, EU, Japan, PIC/S countries). Is WHO slow or are the manufacturers not yet up to the right quality level?

Price & availability: there was a global shortage to get ACTs last year through the WHO-Novartis scheme. Will the supplier be able to deliver more this year? Can we expect prices to drop from the current USD 2.20 level per adult Tx? Maybe another job for the Clinton Foundation?

Registration: Will Drug Regulatory Authorities deregister single-artemisinine when the combinations are scarce? Unlikely. Maybe they will try to convince prescribers and pharmacies to dispense the single artemisinine drug ALWAYS with another malaria drug (amodiaquine or mefloquine?). But will consumers be willing to buy and use them in combination?

I vaguely remember that WHO proposed a similar strategy when Roche was to launch mefloquine; it was going to be available only as a fixed dose combination with SP (Brandname FANSIMEF). Which E-drugger can summarize that old story?

Anyway, let us discuss in E-drug how to provide effective malaria Tx in this world, and how to make this WHO recommendation work!

Credit should be given to MSF which started this debate a few years ago in WHO and African Ministries of Health; see their excellent ACT documentation at: http://www.accessmed-msf.org/prod/morepublications.asp?catid=1&subcatid=175&status=172 and especially the ACT publication that sparked the debate: http://www.accessmed-msf.org/prod/publications.asp?scntid=2442003111212&contenttype=PARA&

WHO's general malaria page is at http://www.who.int/topics/malaria/en/index.html

Wilbert Bannenberg, E-drug moderator (wjb@wxs.nl)]
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http://www.who.int/mediacentre/news/releases/2006/pr02/en/index.html

WHO calls for an immediate halt to provision of single-drug artemisinin malaria pills

New malaria treatment guidelines issued by WHO

The World Health Organization (WHO) today requested pharmaceutical companies to end the marketing and sale of “single-drug” artemisinin malaria medicines, in order to prevent malaria parasites from developing resistance to this drug.

The use of single-drug artemisinin treatment – or monotherapy – hastens development of resistance by weakening but not killing the parasite. When used correctly in combination with other anti-malarial drugs in Artemisinin Combination Therapies (ACTs), artemisinin is nearly 95% effective in curing malaria and the parasite is highly unlikely to become drug resistant. ACTs are currently the most effective medicine available to treat malaria.

"It is critical that artemisinins be used correctly," said Dr LEE Jong-wook, WHO's Director-General. "We request pharmaceutical companies to immediately stop marketing single-drug artemisinin tablets and instead market artemisinin combination therapies only. The new treatment guidelines we are releasing today provide countries with clear and evidence-based direction on the best treatment options for malaria."

According to the new WHO malaria treatment guidelines, uncomplicated falciparum malaria must be treated with ACTs and not by artemisinin alone or any other monotherapy.

“So far, no treatment failures due to artemisinin drug resistance have been documented, but we are watching the situation very attentively,” said Dr Arata Kochi, the newly appointed director of WHO's malaria department. “We are concerned about decreased sensitivity to the drug in South-East Asia which is the region that has traditionally been the birthplace of anti-malarial drug resistance.”

In Thailand, sulfadoxine-pyrimethanime (SP) was initially almost 100% effective in curing malaria when introduced in 1977, but within five years was curing only 10% of cases due to drug resistance. The once-popular chloroquine has lost its effectiveness in almost every part of the world. Between 1999 and 2004, 95% of African children treated for malaria were given chloroquine, even though the drug only cured half of malaria cases in many countries. Resistance to atovaquone developed within one year of introduction in 1997.

WHO also announced other measures it will take to maximize the benefits and correct use of ACTs. In order to contain the circulation and use of counterfeit antimalarial medicines, WHO plans to strengthen its collaboration with international and national health and regulatory authorities. It is estimated that up to 25% of medicines consumed in developing countries are counterfeit or sub-standard. In parts of Africa and Asia this figure exceeds 50%, according to a WHO report on counterfeit drugs.

Additionally, to anticipate and prevent the onset and spread of drug resistance in the long term, WHO urges the global malaria research community and the pharmaceutical industry to rapidly invest in the design of the next generation of antimalarial drugs. By creating ACTs with multiple-drug combinations and transmission blocking components, resistance can be prevented.

“Our biggest concern right now is to treat patients with safe and effective medication and to avoid the emergence of drug resistance. If we lose ACTs, we’ll no longer have a cure for malaria,” said Dr Arata Kochi,“ and it will probably be at least ten years before a new one can be discovered.”

For more information contact:

Melanie Zipperer
Communications Officer
Mobile phone: +41 79 477 1722
E-mail: zippererm@who.int

E-DRUG: WHO urges drug co's to stop selling single artemisinin malaria drugs(3)
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As an increasing number of countries opt for the use of ACTs as a first line treatment for malaria it is crucial that both supply and demand for these are well adjusted. While restricting supply of artemisinins as monotherapy is a necessary step in delaying the onset of resistance to this class of drugs, in some ways this could have negative ramifications as long as presumptive treatment is the norm.

There is a growing body of evidence indicating to the gross overdiagnosis of malaria, resulting in both provision of inadequate treatment for other diseases, and the misuse of ACTs which with current patterns of supply will result in further shortages in their availability. This is likely to be followed by higher market prices, the pursuit of other ineffective treatment, and act as a stimuli for the production of counterfeit drugs.

With the introduction of more expensive antimalarials alongside ever-diminishing health budgets it is imperative to see improved case-management strategies which target the delivery of ACTs to those in need (true positives) and minimize their use where unwarranted. Clearly rapid diagnostic tests could play a crucial part in this, along with the improvement in quality of slide readings where these services exist.

Thus while WHO's efforts to limit the supply of artemisinins to combination therapies are to be welcomed, these must be complemented by improving case management of malaria suspected cases to guarantee that the appropriate drugs reach the right people.
  
Yoel Lubell
Research Degree Student
Health Policy Unit
London School of Hygiene and Tropical Medicine
Keppel Street,
London WC1E 7HT

020 79272942
07812-194425