Rationalizing Pediatric ARV Formularies:The IATT Optimal Pediatric ARV List

Presented at IAS - July 2012 Dr. Nandita Sugandhi Clinical Advisor at the Clinton Health Access Initiative (CHAI)

Released April 23, 2012:

• Who is the IATT?

• Why do we need an “optimal pediatric list”?

• How will this list help scale up treatment for children?

• How was this list created?

• What are the next steps?

Questions you may be asking yourself

Developed

IATT Overview• Established in 1998 - included 5 UN agencies working in HIV and health:

– (WHO, UNICEF, UNFPA, UNAIDS, World Bank)• 2003: membership expanded to include global partners in PMTCT and HIV care

and treatment in children (23 agencies currently involved)• Provides a forum for:

– Information sharing– Consensus building

Intra-agency Task Team on Prevention of HIV Infection in Pregnant Women, Mothers IATT and their Children (IATT)

Pediatric Working Group (PWG)

Child Survival Working Group

Infant feeding Working Group

Pediatric Working Group• Sub-committee of the main IATT• Focused on issues related to pediatric

care and treatment issues• 2011 restructuring of IATT: consolidation

of 2 working groups

+

IATT Subcommittees

Optimal Pediatric Formulary List

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Consensus amongst all stakeholders

Patients and FamiliesClinicians

National ProgramsGlobal Partners

IATT: Consensus amongst stakeholders

May 2011: Creation of the 1st IATT Optimal Pediatric Formulary List

Reasons for Development

WHO guidelines only recommend particular regimens but do not specify formulations of each drug to use

Proliferation of product choices and market fragmentation leading to instability in the pediatric marketplace

Normative guidance was needed on the best options to deliver all required 1st and 2nd line regimens for pediatric HIV patients

An optimal formulary can serve as guidance for national programs, procurement agencies, manufacturers

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Yet pediatric ART coverage is less than half that of adult ART coverage

Source: WHO TUAPR 2011, published November 2011.

2005 2006 2007 2008 2009 201071,500.000M 125,700.000M 196,700.000M 275,400.000M 354,600.000M 456,000.000M

1,258,500.0M

1,908,300.0M

2,773,300.0M

3,777,600.0M

4,900,400.0M

6,194,000.0M

0.2123353293413170.225742574257426

0.421358555460017

0.508538587848929Adults Receiving ART

Children Receiving ART

Coverage % - Children

Coverage % - Adults

Patie

nts

on A

RT C

overage %

A dramatic scale-up of children on ART has been achieved with improved treatment options introduced over the past five years

+45% CAGR

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Current Number of Pediatric ARV formulations available: 43

NRTI’s: NNRTI’s: PI’s:ABC 60mg disp scored NVP 50mg/mL oral liquid LPV/r 80/20 oral liquidABC 20mg/mL oral liquid NVP 50mg disp scored tab LPV/r 100/25 FDC tabd4T 1mg/mL oral liquid EFV 200mg scored tab RTV 80mg/mL oral liquidd4T 15mg cap EFV 30mg/mL oral liquid RTV 100mg heat stable tabd4T 20mg cap EFV 50mg tab or cap ATV 100mg capddI 100mg buffered tab EFV 100mg tab ATV 150mg capddI 299mg buffered tab EFV 20mmg nonscored tab or cap DRV 100mg/mL ddI 50mg buffered tab DRV 75mg tabddI 125mg EC cap FDC’s: DRV 150mg tabddI 200mg EC cap ABC+3TC 30/60 fAMP 50mg/mLddI 25mg buffered chew tab AZT+3TC_NVP 60/30/50 TIP 100mg/mL solutionddI 2 or 4g powder AZT+3TC 60/30AZT 50mg/5mL oral liquid d4T+3TC+NVP 6/30/50AZT 100mg cap d4T+3TC 6/30AZT 60mg tab d4T/3TC 12/603TC 50mg/mL d4T+3TC+NPV 12/60/100

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Adult AZT Formulations1. AZT 300 mg2. AZT/3TC 300/150 mg3. AZT/3TC/NVP 300/150/200 mg

Pediatric AZT Formulations1. AZT 50 mg/5 ml2. AZT 100 mg3. AZT/3TC 60/30 mg4. AZT/3TC 60/30 mg dispersible5. AZT/3TC/NVP 60/30/50 mg6. AZT 300 mg7. AZT/3TC 300/150 mg8. AZT/3TC/NVP 300/150/200 mg

The pediatric market is relatively small: ~456,000

on ART in 2010

Small volumes are further fragmented into sub-groups by

age and weight bands

Uncoordinated transition to new products further

spreads volumes

Proliferation and Market fragmentation

2007 2008 2009 2010196,700.000M 275,400.000M 354,600.000M 456,000.000M

2,773,300.0M

3,777,600.0M

4,900,400.0M

6,194,000.0M

Patients on ART (in millions)Adults Receiving ARTChildren Receiving ART

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Low individual country demand volumes and fragmentation continue to be problematic

Drug manufacturers are limited by minimum batch requirements

• Manufacturers produce a minimum of generally several thousand packs of a particular product, called the “minimum batch requirement”

• A product will not be produced until orders are meet the minimum batch requirement; otherwise, supplier risks incurring losses from carrying stocks which fall below country shelf-life requirements

• Supply timelines can become highly unstable without ordering coordination

Benin

Botswan

a

Burundi

Cambodia

Camero

onChina

Ethiopia

India

Malawi

Mali

Mozambique

Nigeria

Seneg

al

Uganda

Vietnam To

tal0

5,000

10,000

15,000

20,000

25,000LPV/r (100/25mg) example:

# Packs Ordered in Q3 2010 by Country

# Pa

cks

Minimum batch size for LPV = 13.3k packs

What is fragmentation? What is rationalization?

Rationalization = Balancing the Need

Individualized Treatment

Public Health Approach

• Essential Medicines – satisfy the needs of the majority of the population and, therefore, should be available at all times, in adequate amounts, in appropriate dosage forms at a price the individual and community can afford.

• EML list – used as a model list for developing countries to prioritize the selection and procurement of drugs that meet the needs of the population

The Public Health Approach: WHO Essential Medicines List

Creation of the IATT Optimal Pediatric Formulary List: Selection Process

Additional considerations include: Historic global volumes Manufacturing capacity Characteristics of drug formulations (administration, transport, stability,

cost)

Formulations, or products, reviewed

NRTI’s: NNRTI’s: PI’s:ABC 60mg disp scored NVP 50mg/mL oral liquid LPV/r 80/20 oral liquidABC 20mg/mL oral liquid NVP 50mg disp scored tab LPV/r 100/25 FDC tabd4T 1mg/mL oral liquid EFV 200mg scored tab RTV 80mg/mL oral liquidd4T 15mg cap EFV 30mg/mL oral liquid RTV 100mg heat stable tabd4T 20mg cap EFV 50mg tab or cap ATV 100mg capddI 100mg buffered tab EFV 100mg tab ATV 150mg capddI 299mg buffered tab EFV 20mmg nonscored tab or cap DRV 100mg/mL ddI 50mg buffered tab DRV 75mg tabddI 125mg EC cap FDC’s: DRV 150mg tabddI 200mg EC cap ABC+3TC 30/60 fAMP 50mg/mLddI 25mg buffered chew tab AZT+3TC_NVP 60/30/50 TIP 100mg/mL solutionddI 2 or 4g powder AZT+3TC 60/30AZT 50mg/5mL oral liquid d4T+3TC+NVP 6/30/50AZT 100mg cap d4T+3TC 6/30AZT 60mg tab d4T/3TC 12/603TC 50mg/mL d4T+3TC+NPV 12/60/100

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15 formulations were identified by PWG IATT for inclusion on list of optimal paediatric ARV products that serve all recommended WHO regimens across all weight bands

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IATT Optimal, For Limited Use and Non-Essential Pediatric AntiretroviralsItem Formulation Dose(s)Optimal ABC Tablet (dispersible, scored) 60mgABC+3TC Tablet (dispersible, scored) 30+60mgddI Capsule (unbuffered, enteric coated) 125mg, 200mgddI Tablet (buffered, chewable, dispersible) 25mgEFV Tablet (scored) 200mgAZT+3TC+NVP Tablet (dispersible, scored) 60+30+50mgAZT+3TC Tablet (dispersible, scored) 60+30mgd4T+3TC+NVP Tablet (dispersible, scored) 6+30+50mgd4T+3TC Tablet (dispersible, scored) 6+30mgLPV/r Oral liquid* 80+20mg/mlLPV/r Tablet (heat stable) 100+25mgNVP Tablet (dispersible, scored) 50mgNVP Oral liquid** 50mg/5mlAZT Oral liquid** 50mg/5mlLimitedUse ABC Oral liquid 100mg/5mlATV Solid oral dosage form 100mg, 150mgDRV Oral liquid 500mg/5mlDRV Tablet 75mg, 150mgddI Powder for oral liquid* 2g, 4g bottle3TC Oral liquid 50mg/5mlRTV Oral liquid* 400mg/5mlRTV Tablet (heat stable) 100mgd4T Powder for oral liquid* 5mg/5ml

* Requires cold chain (2-8*C) for transport and/or storage and is not adapted for resource limited settings where refrigeration may not be accessible.** Use should be reserved for PMTCT ONLY.

LPV/r is the only pediatric treatment syrup on the optimal list outside of

PMTCT use

15 optimal products serve all regimens and all weight-bands (including 2 syrups for PMTCT)

Dispersible tablets of each drug , where available, were prioritized for inclusion

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An additional 11 products were

recognized to be of limited-use

• Not definitive

• Not all-inclusive – Adult formulations not included– Only currently approved products listed

• Needs to be updated regularly

Challenges and Limitations

• Adaptation required at a national level to meet local needs that can then be used to guide procurement

• Development of a standardized “toolkit” to assist programs to rationalize themselves

• See Poster THPE704

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Next steps: National-level adoption

Revision Process

• Include new products and remove outdated ones

• Adapt for new treatment recommendations

• Consider the evolving epidemic and program needs

• Implementation of Treatment 2.0 for children

• Enables sustainable access to paediatric ARV’s for continued scale-up

• Creates a stable environment for further research and product development

• Better outcomes for children living with HIV

Why this matters…

Thanks!Poster #: THPE673 Poster #: THPE704