Transcript Data presented at ECCMID 2015

Worldwide availability and pricing of antifungal drugs
Matthew Kneale,1 Emma Davies,2 Jennifer Bartholomew,3 and David W. Denning.4
1 National
www.gaffi.org
Aspergillosis Centre, University Hospital of South Manchester; 2 University of Leiden, Den Haag, The Netherlands; 3 The University of Manchester, Manchester, United Kingdom; and
4 Global Action Fund for Fungal Infections (GAFFI), Geneva, Switzerland
INTRODUCTION
DRUG AVAILABILITY
DAILY DRUG PRICES (US$)
Over 300 million people worldwide are affected by serious fungal infections, with 25 million at
high risk of dying or of losing their sight. These infections can be acute — such as cryptococcal
meningitis or Pneumocystis pneumonia, which together cause approximately 680,000 deaths
yearly — or chronic, such as with chronic pulmonary aspergillosis (CPA), which probably kills
almost half a million people per year.
US$
For many of these diseases, mortality is close to 100% when left untreated and outcome is poor
even with good medical intervention. Despite this, affordable access to effective antifungal
medications is a First World phenomenon and, globally, the poor are being excluded.
OBJECTIVES
We surveyed the global availability and pricing of four essential antifungal medications:
flucytosine, non-liposomal and liposomal amphotericin B, fluconazole, and itraconazole. The
incidence of serious and fatal fungal diseases due to Aspergillus and Candida species is rising
with growing immunocompromised populations, and antifungal drugs play an essential role in
treating these infections. Furthermore these drugs play pivotal roles in successful prophylaxis
of invasive fungal infections — both post-transplant and chemotherapy — and in the treatment
of rarer fungal infections, such as blastomycosis, histoplasmosis and sporotrichosis.
Figure 7: Global prices of flucytosine (5FC) at 5g/day
Figure 3: Global availability of flucytosine (5FC)
RESULTS
Availability of antifungals ranged between 24.7-98.2% of countries worldwide; fluconazole was
the most available drug (including PEPFAR provision) whilst 5FC was the least. Itraconazole and
amphotericin B were available in 93.5% and 49.0% of all countries reported, respectively. The
only country with no access to any of the antifungal drugs was Afghanistan. Other countries
lacking in one or more drugs include the Dominican Republic, Nigeria and Ukraine. Flucytosine
(on WHO Essential Medicines List, 2013) improves survival of patients with cryptococcal
meningitis and is used for invasive and urinary candidiasis and aspergillosis, but its availability
in countries who could readily use this cheaper medicine was poor.
All four drugs are off patent and therefore can be manufactured at a lower price, which has
reduced the cost. Zambia had the lowest daily costs of treatment for all drugs (<$0.01) except
flucytosine (unavailable), possibly due to drug donation schemes. The daily treatment costs
were notably highest in South Korea (for flucytosine) at $1319.39, and in the Philippines (for
fluconazole) at $659.30. Many countries only had single-dose fluconazole for candidiasis
treatment available, which is an expensive form of the drug, adding costs when longer
treatment is needed. Similarly for amphotericin B, some countries only had lipid formulations
available which are expensive.
CONCLUSIONS
US$
Figure 4: Global availability of amphotericin B (AmB)
Figure 8: Global prices of amphotericin B (AmB) at 50mg/day
Effective antifungal drugs are inaccessible to large numbers of the global population. The four
drugs studied here are crucial for systemic and certain topical fungal infections. Where there is
availability, prices are often in excess of many times the daily wage of many of their
population, making them inaccessible to many people. The drugs studied in this model are
licensed generically which reduces prices significantly.
The inequalities in access are exacerbated by improper drug formulations. Many countries only
have access to single-dose fluconazole, intended for vulvovaginal and oral thrush, usually in
50mg or 100mg dosages. For systemic treatment of critical infections, a dose of approximately
800mg is required to effectively treat cryptococcal meningitis (1). In addition, these singledose formulations are deliberately more expensive than formulations designed for systemic
use.
The lack of flucytosine in African countries & South America, where it would be very effective,
is a critical deficit.
Figure 1: Percentage of population living off less than 2 US$/day
US$
Figure 9: Global prices of fluconazole at 750-800mg/day
Figure 5: Global availability of fluconazole (outside AIDS programs)
Figure 2: GAFFI priority diseases and the role of critical antifungal drugs
Figure 11: Global gross national income per capita in US$. (StatWorld, StatSilk,
Australia: sourced from the World Bank International Comparison Program
MATERIALS AND METHODS
We sought information for all countries with populations >1 million (n=163). We
extracted availability data from Martindale: The Complete Drug Reference, MIMS
(www.mims.com), the WHO (www.who.int), and from Loyes A. et al., Lancet Infect Dis,
2013; 13:629-37. Purchase prices were contributed by individual country contacts.
Lowest, average and highest daily treatment costs were established on a national basis.
For each country and drug, WHO essential medicines lists were collated. All data was
tabulated and converted to US$ using conversion rates on XE.com. Data were displayed
using StatPlanet interactive maps (StatSilk, Australia) on the Global Action Fund for
Fungal Infections (GAFFI) website www.gaffi.org
RESEARCH POSTER PRESENTATION DESIGN © 2012
www.PosterPresentations.com
REFERENCES/RESOURCES
US$
Figure 6: Global availability of itraconazole
Figure 10: Global prices of itraconazole at 400mg/day
1.Loyes A, Thangaraj H, Easterbrook P, Ford N, Roy M, Chiller T, Govender N ... Bicanic T.
(2013) Cryptococcal meningitis: improving access to essential antifungal medicines in
resource-poor countries. Lancet Infect. Dis., 13(7), pp. 629-637.
MIMS (www.mims.com) — Pricing data
WHO (www.who.int) — Essential drugs and population data
World Bank International Comparison Program (http://data.worldbank.org/datacatalog/international-comparison-program) — GNI per capita income worldwide data