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