avac | - february 26, 2019 · aged 18-24 vs 25+ 2.0 (1.2, 3.4) expanding the method mix...
TRANSCRIPT
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February 26, 2019
Expanding Choices: A look into the Population Council's Multipurpose Prevention Technology (MPT) Product Pipeline
Big ideas supported by evidence:
It’s our model for global change.
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The Population Council conducts rigorous
research and delivers solutions to improve
lives around the world.
WHO WE ARE
• WHAT WE DO
• We conduct research and deliver solutions to drive progress in three high-impact areas.
• IDEAS• EVIDENCE • IMPACT
• Advancing reproductive health and enabling couples to plan their families.
• Helping people avoid HIV infection and access life-saving treatment and services.
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WHAT WE DO
We conduct research and deliver solutions to drive progress in three high-impact areas.
REPRODUCTIVE HEALTH
HIV/AIDS POVERTY, GENDER & YOUTH
Advancing
reproductive health
and enabling
couples to plan
their families.
Helping people
avoid HIV infection
and access life-
saving treatment
and services.
Empowering all
people, especially
young girls, to lead
successful and
productive lives.
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• Non-profit R&D entity
• Partners with pharmaceutical companies to manufacture and market products, securing public sector pricing
• 5 FDA-approved products reaching 170 million, or one in five women using modern contraception
DEVELOPING BIOMEDICAL INNOVATIONS
CHOICE, CONVENIENCE AND CONTROL
Female-initiated HIV Prevention MethodsAdvocacy Research
Share.Learn.Shape Global Internet Survey
1. Do women prefer a contraceptive MPT versus a method
only for HIV/STI prevention?
2. Which characteristics are most important in a method?
3. Which products are women interested in using?
On-demand: gel before sex, gel after sex, fast dissolve vaginal insert (FDI), vaginal film, pill before sex
Long-acting, provider initiated: implant, injectable
Long-term, user-initiated: daily pill, intravaginal ring (IVR)
4. What different clusters of women exist based on
prevention needs and preferences?
Understanding End Users’ Needs
>700 women
>50 countries
SA 39%, US 18%
>80% completion rate
Survey Results
• 94% interested in at
least 1 product
• High interest in all
products – on-demand
and long-acting
methods
• 83% prefer cMPT
• #1 reason for NOT
wanting to use an MPT:
side effects (43%)
64% 63% 62%58% 57%
52% 51% 51%48%
0%
20%
40%
60%
80%
FDI Vaginal gelbefore sex
Pill beforesex
Vaginal film Vaginal gelafter sex
Implant (1month)
IVR(1 month)
Daily pill Injection(1 month)
Interest in using 9 different formulations
Predictors of Interest
ON-DEMAND METHODS LONG-ACTING METHODS
Characteristics Odds Ratio
(95% CI)
Characteristics Odds Ratio
(95% CI)
Has used female
condoms for
contraception
11.6 (1.5, 87.7) Has used implant for
contraception
3.9 (1.9, 8.1)
Interested in cMPT 3.0 (1.6, 5.8) Has used injectable for
contraception
2.3 (1.5, 3.7)
Has used withdrawal for
contraception
2.8 (1.4, 5.6) Did not finish high
school vs. finished high
school
2.0 (1.1, 3.6)
Aged 18-24 vs 25+ 2.0 (1.2, 3.4)
Expanding the Method Mix
Reproductive Health Program
HIV and AIDS Program
• ARV and non-ARV-based products
• HIV/STI protection and HIV/STI/unintended pregnancy protection
• Multiple drug delivery systems
OUR MPT PIPELINE
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BASIC RESEARCH CLINICAL RESEARCH & DEVELOPMENT
Pre-clinical Phase 1 Phase 2 Phase 3
PC-1005 (MIV-150/zinc acetate/carrageenan ring, douche)
PC-1005(MIV-150/zinc acetate/carrageenan gel for rectal & vaginal use)
Mechanisms of HIV/STI disease transmission & progression
PC-6500(Griffithsin /carrageenan ring, fast-dissolving insert)
PC-6500(Griffithsin/carrageenan gel for vaginal use)
Effect of sex hormones and other STIs on HIV transmission
Truvada/levonorgestrel/ethinyl estradiol (Oral cMPT)
• MIV-150, zinc acetate, and carrageenan• Broad-spectrum antiviral activity against HIV, HSV-2 and HPV in preclinical
animal models
• For rectal and vaginal use
• In Phase I testing
• PC-558 vaginal trial completed; once daily dosing for 14 days
• Gel was well tolerated
• Low systemic levels of MIV-150 were observed; plasma zinc levels were unchanged
• CVLs had anti-HIV and anti-HPV activity
• MTN-037 rectal trial ongoing
• Escalating dose study: 4 ml to 32 mL
• Exploring other delivery systems
• Vaginal rings
• Rectal or vaginal douche
MPTs: PC-1005 (ARV-based)
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• Griffithsin (GRFT) and carrageenan
• Broad-spectrum antiviral activity against HIV, HSV-2 and HPV in preclinical animal models
• For vaginal use
• In Phase I testing• PC-728 vaginal trial completed; once daily dosing for 14 days
• Gel was well tolerated
• No GRFT was detected in plasma
• CVLs had anti-HIV activity in cell-based assay and cervical explants
• Exploring other delivery systems• Vaginal rings
• Fast dissolving insert (FDI)
MPTs: PC-6500 (Non-ARV)
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FDIs are poised for a Phase 1 clinical trial:
• Good handling properties and stability under
accelerated temperature and humidity conditions
• Disintegrated completely in the macaque vaginal lumen
• Are safe (no pH changes or inflammation)
• Rapidly deliver therapeutic levels of GRFT and CC
• Significantly protected animals from SHIV, HSV-2 and
HPV infections
PC-6500 Series: GRFT/CG FDI as PrEP
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GRFT/CG FDI in Animal Models
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0 2 4 6 8101
102
103
104
105
106
107
108
0 2 4 6 8101
102
103
104
105
106
107
108
p=0.0004, Fisher ’s2
3
4
5
6
no PsVHPV 16 PsV
HEC GRFT/CG
D-PBS
p<0.0001, ANOVA, Bonferroni
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Log R
adia
nce
(P/S
/cm
2/s
r)
0 5 10 15 200
20
40
60
80
100GRFT/CGHEC
p<0.0001, Fisher ’s
days
% U
nin
fecte
d
GRFT/CG CG
RN
A c
opie
s/m
l
d e fSHIV Macaque HSV-2 Mouse HPV Mouse
weeks weeks
a b cHuman-size Macaque-size Mouse-size
Formulation: Lal M et al. J Pharm Sci, 2018 Oct; 107(10): 2601-2610
In vivo testing: Derby N et al. Nat Commun. 2018 Sep 24; 9(1):3881
• Truvada + combined oral contraceptive
• Combines the proven PrEP efficacy of Truvada with the established pregnancy protection of oral contraceptives
• Compressed development timeline and regulatory submission
• GRFT + non-hormonal female contraceptive
• On-demand product for women who choose a hormone-free method of contraception
• Early pre-clinical stage
Contraceptive MPTs
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