Transcript to - Malaria Consortium

MMV in ACCESS-SMC
2015 - 2016
PA R T N E R S M E E T I N G 1 8 - 2 2 JA N UA R Y 2 0 1 6 K A M PA L A
Outline
Introduction
MMV deliverables
2015 achievements and challenges
Looking forward for 2016
Introduction
Product development partnership
Swiss Foundation / US Charity
With 60 people working towards the same
mission:
ACCESS AND PRODUCT
MANAGEMENT DEPARTMENT
André Tchouatieu
[email protected]
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HOW
MMV Deliverables
Output 1: GLOBAL PRODUCTION OF QUALITY AND ACCEPTABLE SMC PRODUCTS INCREASED
Strengthening SMC product demand forecasting
Developing business case for entry of an additional manufacturer into SP+AQ market
Providing support for additional manufacturer to develop child-friendly dispersible SP+AQ
Developing acceptable new SMC products
Developing efficacy profiles and reviewing of alternatives
2015 achievements : Forecasting tool
DEVELOP AND IMPLEMENT SMC PRODUCT
DEMAND FORECASTING
•Develop standardized methodology and tools
for demand forecasting
•Create and maintain updated 3 year rollingforecast for supported countries
•Develop consolidated demand forecast for
SMC products for all eligible children in all
countries where SMC is recommended by
WHO
The ACCESS-SMC Web-Based Forecasting Platform will
enable users to perform 8 critical functions:
1
View forecast needs (number of treatments &
number of children per age group) at an
aggregate level
a) across all SMC eligible countries
b) across ACCESS-SMC countries exclusively
2
View forecast needs (number of treatments &
number of children per age group) within a
specific country
a) at an aggregate level
b) by individual districts
3
Compare forecast needs (number of treatments &
number of children per age group)
a) across countries (one year)
b) across years (one country)
View a Manufacturing/Production forecast
outlining aggregate needs (number of packs
by strength) across SMC countries and across
years
5 View breakdown of forecast needs by
funding partner
4
6
View and export raw data and visualizations
7 Upload forecast data
8 Toggle between English and French versions
of the platform
Web address: www.broadreachanalytics.ch
User Name + individual Password:
2015 Achievements
DEVELOPING BUSINESS CASE FOR ENTRY OF AN
ADDITIONAL MANUFACTURER INTO SP+AQ
MARKET
•Carry out break-even point analysis to
determine number of manufacturers needed
to meet the demand for SMC
•Develop a market entry business case for
additional SMC product manufacturer
•Carry out research and due diligence to
identify potential new manufacturers of
SP+AQ
•Assess production capacity and required leadin time of SMC pharmaceutical manufacturers
Criteria for selecting new manufacturer:
- Secured source of sulfadoxine API
- Proactivity
- Commitment of resources at risk
- Successful development of prototype
- Most favorable timelines
- Strategic focus in the group of companies
Price negotiations and transparency
2015 achievements
CONDUCT FIELD TESTING AND MARKET RESEARCH TO
PROMOTE COUNTRY LEVEL UPTAKE OF CHILD
FRIENDLY SMC PRODUCT FORMULATION
Field test child friendly formulation: packaging
Evaluate acceptability /feasibility /compliance
of dispersible formulation vs tablets:
Quantitative market research
Identify preferences for future SMC product
attributes through qualitative market research
Study conducted with mapping health UK
Research aims and objectives
Overall objective: Identify preferred attributes for future SMC medicines, to eventually replace SPAQ once
resistance emerges, and potentially expand SMC into seasonal transmission areas where SPAQ is not
therapeutically effective (primarily East and southern Africa).
A
Identify the potential of existing anti‐malarial drugs as an alternative to SPAQ taking into account the
risk/benefit ratio
B
Assess implementers and users experience with current products for SMC, identifying drivers and limitations of
SPAQ
Identify attributes for SMC compounds in order to inform the development of next generation SMC drugs,
C through in-depth qualitative discussions with global and national KOLs, policy-makers, health workers and
caregivers
Cross-check SMC countries’ preferences with East and Southern Africa SMC eligible countries through
discussions with NMCPs
D
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Interviewees were selected based on profiles agreed with the MMV team
Category
Respondent Type
The Gambia
Burkina Faso
Caregivers
2 Focus Groups*
(12 participants)
Community health workers
2 Focus Group
(12 participants)
3 Focus groups*
(12 participants)
3 Focus Groups
(12 participants)
Dispensers
6 interviews
8 interviews
Regional public health deputy & medical store
pharmacist
2 interviews
9 interviews
Regional head and deputy
2 interviews
1 interview
National decision makers
NMCP managers, SMC coordinators
3 interviews
3 interviews
Researchers
SMC researchers
1 interview
1 interview
Implementers
CRS & MC (country leads SMC coordinator, pharmacist)
3 interviews
2 interviews
Interviewees were selected based on profiles agreed with the MMV team
Community level providers
Regional decision makers
At country level 41 participants
46 participants
WARN
Managers and meeting representatives
East & Southern Africa
NMCP and researchers
6 interviews (phone)
Global-level malaria experts
Key policymakers, researchers, program managers and clinicians (WHO, MSF, various researchers)*
5 interviews (phone)
Total Sample
10
*No TPPs were tested with this category
12 interviews
113
Repurposing and recombining current molecules seen as fastest
option to replace SPAQ
•In terms of alternatives to SPAQ, there were limited ideas, but agreement was that arguments used for choosing
SPAQ would still be valid today
• General consensus was that a combination should still be sought
• Ideally, repurposed older drugs are the favorite choice of SMC experts (safety assurance)
•Compounds mentioned:
• Piperaquine
“Whatever
it is is, we know it has to be a combination, not artemisinin based” – Global policymaker
 Long half life
“I think
we still need to define failure....resistance to the drug is not failure of SMC. Maybe if we add a 3rd drug, it could buy
 Prolonged QT unlikely to determine clinical symptoms unless underlying disease
some more time, and work at the safety profile of other drugs. Let’s see what comes out of the SPAQ plus azithromycin study” –
• Primaquine
Researcher, Mali
 Long half life
“Maybe
before
going to new molecules, we should explore mefloquine, primaquine and even chloroquine a bit more. Yes, safety
 Used
in elimination
is an issue, but even when giving aspirin as MDA you are still likely to have adverse events. With a good campaign, we explain
• Large spectrum antibiotics (azithromycin, doxycycline)
the risks, and the NMCPs can prepare accordingly. But we have to have the courage to try those old molecules we dismissed
 Antibiotic stewardship may need to be considered as an important negative factor
initially”
- Researcher, Senegal
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DHAPQ mentioned by several papers and researchers as potential
alternative to SPAQ once resistance extends
MSF has used DHAPQ for chemoprevention in Uganda (specific, out of ordinary situation) with similar
efficacy results as SPAQ
There are studies ongoing in Burkina Faso comparing DHAPQ to SPAQ for SMC suggesting the same
increased efficacy
NMCPs and WHO remain reluctant to consider an artemisinin-derivative as prevention strategy
Strengths
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Combination of two well known molecules
Known safety profile
Efficacy over 70%
PQ has a long half life
Opportunities


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Consider PQ as main compound and look for other potential
partners
Use DHAPQ for SMC only in countries close to elimination
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Weaknesses

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DHA is an artemisinin derivative
DHA has short/limited half life
Increased risk of resistance in areas with high transmission
rates
Threats

Increased risk of DHAPQ included as curative treatment for
uncomplicated malaria in several SMC countries
Interviewees were also asked to provide input on three potential
target product profiles
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Product Y
A. Interviewees were provided a base product profile (Product
X)
• Participants were then asked to score each product
attribute on a scale from 1 (no value) to 5 (highest value)
• Following that, the overall product value was also scored
on the same scale
B. Interviewees were presented with two additional scenarios
(Product Z and Y) with variations on only two attributes
(increased efficacy and increased administration
frequency)
• Interviewees were asked to score again the two attributes
• Participants were then asked to score again the overall
value of each product
C. Throughout the process, interviewees were asked to also
provide a qualitative rationale for each of their scores
Product Z
• Methodology:
Product X
• Aim: obtain interviewees preferences in terms of product
attributes for the next generation SMC
In the MDA context, analysis shows four attributes are as
critical for the development of new SMC products
Well-known, safe
product (suitable for
MDA)
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Efficacy at least equal
to SPAQ
Child friendly
formulation
Frequency of
administration (able
to maintain current
very effective door to
door campaign)
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Other Main Findings
Conclusions & Recommendations
SMC acceptability is high among all
stakeholders, including eligible countries not
implementing it
Increased interest likely to translate into faster adoption if a
new product becomes available
Drivers for SPAQ as SMC drug: efficacy, long
half life, known safety, two different MoA,
availability and affordability
Similar arguments are likely to be considered when
evaluating the new proposed drugs
Increased willingness to use (repurposed) well
known drugs rather than new compounds which
may require country pilots
Repurposing and recombining current molecules may still be
the fastest option to replace SPAQ
Even in current “non SMC countries”, door-todoor campaign format considered the most
appropriate one for MDA
A different campaign format would have to ensure /
demonstrate similar adherence levels (e.g. polio or measles
like campaigns)
Injection generally considered more effective
(by the general population)
If the frequency is low (e.g. one injection per season),
consider developing an injectable rather than an oral
Already done in 2016
INVESTIGATE PREFERENCES AND POSSIBLE
OPTIONS FOR REPLACEMENT TO SP+AQ
Convene SMC Expert Consultation Group
◦ Meeting convened in London 13 and 14 of
January
◦ 24 participants from various institutions
◦ Meeting report in preparation
OBJECTIVES
Refine MMV’s target product profiles for
future chemoprevention treatments
Consider perspectives on existing medicines
that may be re-purposed in the short- and
medium-term to support development of
chemoprevention medicines
Understand evidence required for normative
policy change and regulatory pathways for
chemoprevention medicines.
Topics discussed
Need to have a gradual approach
◦ Medium term by repurposing existing drugs
◦ Long term with new compound
A dosing schedule favoring a door to door
distribution
Injection of a depo for 3 four months feasible
but safety issues to be considered
Which drug to repurpose? Piperaquine ?
Pyronaridine ?
Choroquine ? Back to “chloroquinization” ?
Development of new compound for
chemoprevention: regulatory considerations
not clear, need to discuss with RA
No place for artemisinin derivatives
Drug should consider preserving premunition
to form: no liver stage action
Make available piperaquine monotherapy for
chemoprevention studies
Effectiveness analysis in a multi intervention
context?
Possibility of associating a new compound
with an established antimalarial drug
Looking forward for
2016
PROVIDE INFORMATION AND SUPPORT TO
ADDITIONAL MANUFACTURERS OF CHILD
FRIENDLY DISPERSIBLE SP+AQ
•Provide information on market opportunity
and support to new potential manufacturers
•Support additional manufacturers to develop
and register a prequalified dispersible SP+AQ
Signature of the partnership on going with a
fairly acceptable price
Prototype development done (video)
Protocol for BE studies validated with WHO PQ
Secure AQ comparator stock with MC Nigeria
Sulfadoxine API prequalified
CMC specialist consultant already identified
Pyrimethamine API method development as
per WHO – PQ requirement
Timelines for file submission to WHO PQ: 12 months
Looking forward for
2016
To be done in 2016?
CONDUCT FIELD TESTING AND MARKET RESEARCH TO
PROMOTE COUNTRY LEVEL UPTAKE OF CHILD
FRIENDLY SMC PRODUCT FORMULATION
Field test child friendly formulation: packaging
To be planned with the new manufacturer
Evaluate acceptability /feasibility /compliance
of dispersible formulation vs tablets:
Quantitative market research
Experience with AL dispersible showing good
uptake of the product
Identify preferences for future SMC product
attributes through qualitative market research
Child friendly formulation recognized as a key
attribute in recent survey
is another research being required to confirm
the need for a dispersible formulation vs hard
tablets ?
2016 production / supply
Pyrimethamine + sulfadoxine + amodiaquine dipersible dossiers for both strengths:
manufacturer requested for new documentation that was submitted on Dec 25, 2015,
Decision awaited
SP+ AQ 12.5/250 + 75mg : 2.1 million blisters per month
SP+AQ 25/500 + 153 mg : 4.2 million blisters per month
10 million treatments already produced for the 2016 campaign
Questions
Is there a need for a third dosage for
kids 59 – 120 months ? What is the
practice in Senegal? Are scored tablets
a solution ?
What regulatory synergies (partners
and countries) could be put in place for
filing the dossier for submission to
country regulatory while filling dossier
for PQ?
Thank you