Access to Antimalarial Medicines Dr Clive O Ondari Essential Drugs and Medicines Policy Dept & Roll Back Malaria Department World Health Organization March 2004

Malaria in the World Coding: Red indicates malaria-endemic.

Current Situation: Quality of antimalarial drugs has been declining. The efficacy of (affordable) antimalarial drugs has been declining and high cost of replacement options. Over 50% of the population does not have regular access to most vital essential drugs. 60-90% of the population seek initial treatment from unqualified sources, i.e. street vendors, kiosks. Supply of drugs is often inefficient and unreliable. Use of ineffective drugs leads to inadequate treatment and leads to drug resistance.

% of all deaths Rank Malaria 1 20.3 Respiratory inf. 2 17.2 Diarrhoea Leading causes of death for children under 5 yrs, in the WHO African Region, 2000 % of all deaths Rank Malaria 1 20.3 Respiratory inf. 2 17.2 Diarrhoea 3 12.3 HIV/AIDS 4 9.0 Measles 5 8.4 Low birth weight 6 5.8

Therapeutic efficacy of SP in Africa: evidence to guide action THRESHOLD FOR CHANGE 15 West Central East

Problems of resistance to antimalarial drugs Era of availability of cheap and effective drugs has come to an end Both CQ & SP cost <US$0.2/adult treatment course, but resistance to CQ widespread, and to SP increasing Alternatives for multi-drug resistant falciparum malaria are x10 expensive

Factors leading to development of resistance Lack of guidelines/poor drug treatment policies Irrational prescribing Irrational drug use Drug concentration “tail” Liberalized, uncontrolled drug market leading to poor quality products circulating in international and domestic markets

The Abuja Declaration, African Summit on Roll Back Malaria (Abuja, Nigeria), April 2000 Call upon all member states to: “Make treatment of malaria available as peripherally as possible including home treatment” “Make appropriate treatment available and accessible to the poorest groups in the community”   Pledge to: “Reduce or waive taxes and tariffs for …antimalarial drugs” “Explore and develop traditional medicine in the area of malaria control”

Artemether/lumefantrine Rational Selection FDC Artemether/lumefantrine MDT Artesunate + amodiaquine ACTs Artesunate + SP Artesunate + mefloquine Amodiaquine + SP

Cost implications of combination therapy Average cost per adult treatment (US$)

Number of countries deploying ACTs for malaria as first-line treatment 13 15 9

Challenges Only one fixed dose combination available: artemether- lumefantrine (Coartem®), patented and single-source All other ACTs: multi-source products, generally off-patent generics, available as individual products to be co-administered (preferably in course-of-therapy blister packs). Market not primed - few manufacturers, limited experience with manufacturing and packaging of artemisinin derivatives (highly hygroscopic), API linked to natural plant production Relatively new products on the international market – limited country experience in regulation and procurement

Global negotiation to reduce price of new antimalarials Expert consensus that co-formulated artemisinin combination best option for use where multi-resistant malaria Artemether/lumefantrine (Coartem) is only medicine of this type currently licensed Novartis has agreed to provide drug at cost through WHO for 10 years – US$ 2.40 for adult treatment Countries to request, direct or through NGOs

The GFATM is the largest financial supporter of ACTs in countries. A total of US$30 million has been committed over the full 5-year life of GFATM Board-approved proposals from African countries for the purchase of ACTs in three proposal rounds. Total annual number of ACT treatments (eq. adult doses) funded by GFATM

Total Morbidity estimates Global Forecasts Forecasts for procurement Total Morbidity estimates 2004 30,007,678 50,012,796 2005 - 2006 131,583098 219,305,163 These are conservative (cautious) estimates of the countries that have changed, that are changing, and that are expected to change, and which will be deploying ACTs in 2004 and 2005

Pilot Project on Quality of Antimalarial Products Project Design : Country selection criteria: “spot light countries” in AFRO and EMRO Evaluation of the most widely used antimalarials products in the regions Sampling from various levels of the distribution chain (household, private sector pharmacy, peripheral health units, district hospital, teaching/referral hospital and district and/or central medical store Evaluation of samples in a central laboratory (pharmacopeal tests) in CENQAM, South Africa

Failure rates (%) - Content

Failure Rates (%) - Dissolution

Pre-qualification of ACT Manufacturers and Products Objectives: To accelerate sustained access to, and use of, good quality ACTs To ensure that adequate and effective treatment reaches significantly greater numbers of people in need To assist/support the implementation of ACTs in ways that respond to the specific needs and requests of individual countries To support drug regulatory agencies in regulating ACTs

RBM/EDM Collaborative Activities Strengthening drug supply, quality assurance and regulatory systems Develop common guidelines for registration of new antimalarials Assist countries to evaluate quality and monitor inspection activities (including pre-qualification of sources of products) Provide support to training in the areas of pharmaceutical inspection (GMP) - manufacturing and distribution channels Initiate the development of monographs for new AM

Making Artemesinin Products Available Availability Procurement Selection Registration