11
ACTs in East AfricaACTs in East AfricaREALITY CHECKREALITY CHECK
Nathan Mulure MDNovartis Pharma
22
AgendaAgenda
Introduction and backgroundIntroduction and backgroundDrug resistance to antimalarialsDrug resistance to antimalarialsPolicy changePolicy changeAntimalarial marketAntimalarial marketChallenges Challenges
33
Malaria BurdenMalaria Burden
34,000 deaths in Kenya every year. 34,000 deaths in Kenya every year. 20 million cases/annum20 million cases/annum
9.8million people infected in Uganda 9.8million people infected in Uganda (2003 data)(2003 data)
Tanzania: 18 million cases/yearTanzania: 18 million cases/year14000 deaths in 200314000 deaths in 2003
Zambia: 3.5 million cases/ annum (2003)Zambia: 3.5 million cases/ annum (2003)
44
MalariaMalaria
Main challengesMain challenges
Rapid development of resistanceRapid development of resistance
Inadequate resource allocationInadequate resource allocation
Poor quality drugsPoor quality drugs
55
Malaria drug resistanceMalaria drug resistance
66
Efficacy studies: Efficacy studies: CQ resistance in E.AfricaCQ resistance in E.Africa
77
Clinical efficacy SPClinical efficacy SP
88
Amodiaquine cure rates low in KenyaAmodiaquine cure rates low in Kenya
0.020.0270/98(71%)70/98(71%)77/98(79%)77/98(79%)
80/94(85%)80/94(85%)85/94(90%)85/94(90%)
GabonGabon28 day cure rate28 day cure ratePCR correctedPCR corrected
0.690.69123/156 (79)123/156 (79)
,,,,130/159(82%)130/159(82%),,,,
SenegalSenegal28 day cure rate28 day cure ratePCR correctedPCR corrected
<0.001<0.00141%41%
54%54%123/180(68%)123/180(68%)144/180 (80%)144/180 (80%)
KenyaKenya
28 day cure rate28 day cure ratePCR correctedPCR corrected
95%CI95%CIPP
AQAQAQ+ASAQ+AS
Adjuick et al. AS+AQ vs AQ for uncomplicated P. falciparum Malaria in children. Lancet 2002
99
Efficacy StudiesEfficacy Studies
AL =98.8% AL =98.8% AS+MQ=96.3%AS+MQ=96.3%
Van Vugt et al 2005A randomized trial of artemether-lumefantrine versus Mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of ThailandPublished 2005
AL =96%AL =96%Makanga et al 2006Efficacy and safety of the six-dose regimen ofArtemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual Patient data.N=554. Am J trop med
AQ =62%AQ =62%AQ+AS=88%AQ+AS=88%AQ+SP =66.2%AQ+SP =66.2%AL =97.3%AL =97.3%
Mutabingwa et al 2005Mutabingwa et al 2005AQ alone, AQ+SP, AQ+AS, and AL for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial. Lancet 365:1474–1480.N=300N=300
28 day Cure rates28 day Cure ratesStudyStudy
1010
Change and implementation of policy change takes time Change and implementation of policy change takes time
20032003--20042004AL recommended AL recommended in 2002in 2002
CQ resistance widespread CQ resistance widespread in 2002.in 2002.Policy change to ALPolicy change to AL
Zambia Zambia
Late 2006Late 2006--early 2007early 2007
AL AL 20052005CQ resistance in 1978CQ resistance in 1978In 1990s, 70% resistanceIn 1990s, 70% resistancePolicy change to SP in Policy change to SP in 20002000
TanzaniaTanzania
Early 2006Early 2006ALALRecommended Recommended in 2005in 2005
CQ resistance 1978, CQ resistance 1978, policy change to CQ+SP policy change to CQ+SP in 2000in 2000
UgandaUganda
Mid 2006Mid 2006ALALRecommended Recommended in 2004in 2004
CQ resistance in 1978, CQ resistance in 1978, Policy change to SP in Policy change to SP in 2000. 2000. Resistance to SP @ 34%, Resistance to SP @ 34%, to Amodiaquine to Amodiaquine @25%(2000)@25%(2000)
KenyaKenya
DeploymentDeploymentCurrent Policy Current Policy 11stst lineline
Old policy and Old policy and ResistanceResistance
CountryCountry
1111
Obstacles in implementation of policy changeObstacles in implementation of policy change
Slow process due to funds transfer issuesSlow process due to funds transfer issuesHuge stock of monotherapies and other antiHuge stock of monotherapies and other anti--malarialsmalarialsPoor import controls to sustained use of Poor import controls to sustained use of monotherapymonotherapyLocal manufacturers inelasticity to changeLocal manufacturers inelasticity to changeInadequate monitoring and inspection by Inadequate monitoring and inspection by health authoritieshealth authorities
1212
62 million treatments delivered by Novartis in 62 million treatments delivered by Novartis in 20062006
Total needs: Not coveredTotal needs: Not covered--Stock outsStock outs--Inadequate distributionInadequate distribution--Non premium private market unsupportedNon premium private market unsupported
Gap exists despite implementation of policyGap exists despite implementation of policysupply chain needs to be properly managed to meet demandsupply chain needs to be properly managed to meet demand
1313
Proportion of Health facilities where Coartem was seen,Proportion of Health facilities where Coartem was seen,Uganda Survey of Health FacilitiesUganda Survey of Health Facilities
Proportion of H.F with Coartem
010203040506070
5-<15 kg 15-<25 kg 25-<35 kg >35 kg
Category
Prop
ortio
n in
%
Ref: Rapid assessment of new treatment policy implementation , Uganda- August-Sept 2006 Dr Kato et al, Dr Kato et al, NMCP meeting Kampala 2007NMCP meeting Kampala 2007
1414
Health Facilities with antiHealth Facilities with anti--malarials other than malarials other than CoartemCoartem®®Uganda AugustUganda August--Sept 2006Sept 2006
01020304050607080
ACTQuinin
e inj
CQ in j SPQuinin
e Tabs
CQ tabs
Homepack
red
Hgreen
Drugs
% Series1
1515
Stock out reports in KenyaStock out reports in KenyaSource NMCP*Source NMCP*
On average only 16% of sites are reportingOn average only 16% of sites are reporting5151141141288288Jan 2007Jan 20075656184184422422Dec 2006Dec 20066060147147371371Nov 2006Nov 20067171157157546546Oct 2006Oct 20067272111111397397Sept 2006Sept 2006555513132929August 2006August 2006
1001000011July 2006July 20061001000011April 2006April 2006
Proportion % Proportion % reporting no stockreporting no stock
Facilities with Facilities with stock outsstock outs
Facilities Facilities reportingreporting
MonthMonth--yearyear
1616
Improving situation in KenyaImproving situation in Kenya
A recent health facility survey showed that A recent health facility survey showed that over 85% of dispensaries and health centers over 85% of dispensaries and health centers had AL available on the day of the survey. For had AL available on the day of the survey. For hospitals (both Mission and GOK) it was hospitals (both Mission and GOK) it was 100% availability100% availability
Need for continuous vigilance on stocksNeed for continuous vigilance on stocks
1717
Availability of AL packs and stock outs Availability of AL packs and stock outs in Zambia preceding survey 2006in Zambia preceding survey 2006
34%34%12312381%81%39%39%AL 24AL 24packpack
34%34%12312391%91%27%27%AL 18 AL 18 packpack
30%30%10810889%89%31%31%AL 12 packAL 12 pack
31%31%11311395%95%18%18%AL 6 packAL 6 pack
% time out of % time out of stockstock
Mean No of Mean No of stock out daysstock out days
HFsHFs with with stock outstock out
In stock on In stock on survey daysurvey day
Ref Ref DejanDejan ZurovacZurovac, Quality of care: AL case management in Zambia and Kenya, Quality of care: AL case management in Zambia and Kenya
1818
Non premium private marketNon premium private market
Consist of rural and urban poorConsist of rural and urban poor
Big proportion of populationBig proportion of population
Most affected during stock outsMost affected during stock outs
Cannot afford prices in pharmaciesCannot afford prices in pharmacies
1919
Private MarketPrivate Market
AN EXCESS !AN EXCESS !Of anti Malarials Of anti Malarials
2020
Antimalarials in Antimalarials in a pharmacy in Nairobia pharmacy in Nairobi
2121
Antimalarials in a Kampala PharmacyAntimalarials in a Kampala Pharmacy
2222
Antimalarials in Tanzania pharmacyAntimalarials in Tanzania pharmacy
2323
AntiAnti--malarials in East Africa malarials in East Africa Retail price/treatmentRetail price/treatment
262611RocheRocheFansidarFansidar
10101.61.6MetakelfinMetakelfinPharmacia Pharmacia UpjohnUpjohn
SulphamethoxazoleSulphamethoxazole--PyrimethaninePyrimethanine
20206.86.8CamoquineCamoquine--Park Park Davis FranceDavis France
AmodiaquineAmodiaquine552020--3030LariamLariam--RocheRocheMefloquineMefloquine
No. of branded No. of branded generics in generics in MktMkt
Price Price range range USDUSD
innovatorinnovatorProductProduct
2424
Artemisinin Monotherapies in East AfricaArtemisinin Monotherapies in East AfricaRetail price/treatmentRetail price/treatment
66--77SanofiSanofi--AventisAventisArsumaxArsumax
5.25.2HolleyHolleyCotexinCotexin (DHA)(DHA)
4.74.7GVS LabsGVS LabsGsunateGsunate
44--55DafraDafraArinateArinate/Artesian /Artesian (suspension)(suspension)
4.74.7GVS LabsGVS LabsGsunateGsunate
44--55DafraDafraArinateArinate/Artesian /Artesian (suspension)(suspension)
33--44CosmosCosmosConsunateConsunate
1717SanofiSanofi--AventisAventisPalutherPaluther (Artemether)(Artemether)
PricePriceUSDUSD
CompanyCompanyProduct Product
2525
ALsALs in East Africa Private Marketin East Africa Private Market
33--55GVSGVS--labs labs IndiaIndia
ALALLonartLonart2424--TabletsTabletsAnd dry Syrup*And dry Syrup*
33--55AjantaAjanta IndiaIndiaALALArtefanArtefan16 Tabs16 Tabs
44--66CiplaCipla IndiaIndiaALALLumartemLumartem2424--TabletsTablets
55--77DafraDafraBelgiumBelgium
ALALCoartesianeCoartesianePowder, OD dosePowder, OD dose
55--77NovartisNovartisALALCoartemCoartem24 Tablets24 Tablets
Price USD Price USD Average retail price Average retail price per treatmentper treatment
ManufacturerManufacturerINNINNProductProduct
2626
Other ACTs in E. AFRICA. Private MarketOther ACTs in E. AFRICA. Private MarketRetail price/treatmentRetail price/treatment
55--88Holley Holley CotecCotecDHT+PPQDHT+PPQArtekinArtekinFixed combinationFixed combination
55--77MephaMephaAS +MQAS +MQArtequinArtequin
33--44CosmosCosmosAS+AQAS+AQFalcimonFalcimonLoose blister packLoose blister pack
44--66CosmosCosmosAS+AQAS+AQAmqunateAmqunateLoose blister packLoose blister pack
44--66IPCAIPCAAS+AQAS+AQLarimalLarimalLoose blister packLoose blister pack
55--7.37.3SanofiSanofi--AventisAventisAS+AQAS+AQArsucamArsucam
Price USDPrice USDManufacturerManufacturerGenericGenericProductProduct
2727
How can we Increase Access in How can we Increase Access in Premium Private marketPremium Private market
OPTIONSOPTIONS
1.1. General price controls on essential General price controls on essential medicines?medicines?
2.2. ACT global subsidy for informal private ACT global subsidy for informal private sector (exclude regular pharmacy channel)?sector (exclude regular pharmacy channel)?
3.3. Repackaging : Ensure local Repackaging : Ensure local GMP facilities for GMP facilities for repackaging?repackaging?
4.4. High quality generics with WHO High quality generics with WHO prequalification?prequalification?
2828
What drives the uptake and penetration of ACTs What drives the uptake and penetration of ACTs in private sectorin private sector
Biggest driver is Government policy. Biggest driver is Government policy. 11stst line treatment line treatment
Efficacy *Efficacy *Price*Price*Tolerability*Tolerability*National registrationNational registration
*AC. Nielsen 2006 Malaria market survey*AC. Nielsen 2006 Malaria market survey
2929AminAmin, Kokwaro, Bob Snow et al. Health policy and planning 2007. A co, Kokwaro, Bob Snow et al. Health policy and planning 2007. A commentarymmentary
Continued registration of antimalarials despite change in policyContinued registration of antimalarials despite change in policy
3030
Challenges facing policy Challenges facing policy implementationimplementation
Lack of efficacy studies in the majority of Lack of efficacy studies in the majority of genericsgenericsDifficult to withdraw existing antiDifficult to withdraw existing anti--malarials malarials which are not conforming to policy changeswhich are not conforming to policy changesNeed to regulate quality of antimalarials to Need to regulate quality of antimalarials to avoid development of resistance plausible with avoid development of resistance plausible with substandard moleculessubstandard moleculesNeed for comprehensive Need for comprehensive PHARMACOVIGILANCEPHARMACOVIGILANCE
3131
AcknowledgementsAcknowledgements
MMVMMV
NMCP NMCP Kenya, Uganda, Tanzania, ZambiaKenya, Uganda, Tanzania, Zambia
Manuscripts: Prof Bob Snow, Dorothy Manuscripts: Prof Bob Snow, Dorothy MemusiMemusi, , DejanDejanZurovacZurovac, FK Kato, (for articles and presentations during , FK Kato, (for articles and presentations during NMCP meeting in Kampala)NMCP meeting in Kampala)
Novartis PharmaNovartis Pharma