Long-Acting Contraception for the Developing World

Transcription

1 April 18, 2017 Long-Acting Contraception for the Developing World Greg Kopf FHI360 GSK-CRS Long-Acting Injectables and Implantables Conference Philadelphia, PA

2 FHI 360: A Comprehensive Approach to Human Development (Originally the International Fertility Research Program-1971) Education Civil Society + Peacebuilding Economic Development + Livelihoods Health Gender Equality Nutrition Environment Research Technology Social Marketing + Communications Youth 2

3 THE PROBLEM: Expanding access to contraception: The need is urgent. 225 million women in developing countries have an unmet need for contraception Global Impact: 80 million unintended pregnancies in 2012 Roughly 303,000 maternal deaths* in 2015 Photo: Claudia Napoli via Flickr from * 3

4 Cancer 8.2 million c a Guttmacher Institute (2012 Abortion/Maternal Deaths in Context with Cardiovascular and Cancer Deaths Abortion/Maternal Deaths in Developing Countries (2012) a Maternal deaths 0.3 million Abortion 49.6 million Global Deaths (2012) Cardiovascular Disease 17.5 million b b WHO Fact Sheet (2016) c ACS, Global Cancer Fact & Figures (2015) 4

5 ANOTHER PROBLEM: Financial Commitment: Contraceptive R&D Investment in Context In 2013: Globally, $63 million was invested in contraceptive R&D Policycures, 2014 Meanwhile In 2015, Americans spent $6.9 billion on Halloween $350 million on costumes for their pets 5

6 Reasons for Unmet Need Reasons for Unmet Need There is a need to expand the method mix 6

7 Family Planning is a Cost-Effective Intervention that can Substantially Improve Health Millennium Development Goal 5b: By 2015, achieve universal access to reproductive health, including contraceptives If unmet need for contraception met: Prevent over 70% of unintended pregnancies Prevent 25% of maternal deaths Avert almost 75% of abortions $1.00 spent on contraception = $1.47 saved in maternal and newborn health care costs Sources: Guttmacher, UNFPA, WHO; Population Reference Bureau; BMGF; Halperin et al., Prevent 20% of newborn deaths Among HIV+ women, if unmet need were met, over 90,000 infant HIV infections averted 7

8 London Summit on Family Planning July 2012 Mobilized governments, international agencies, civil society organizations, foundations, and the private sector to commit to dramatically expanding access to voluntary family planning Goal of FP2020: Expand access to family planning to 120 million additional women in the world s 69 poorest countries by yplanning2020.org/ UK Government Bill & Melinda Gates Foundation UNFPA USAID Others 8

9 The Need for Newer Technologies in the Contraceptive Space Existing methods do not meet the needs of all Methods based on old technologies; there have been significant scientific advancements Some methods are difficult to use consistently and correctly High typical use failure rates High discontinuation Side effects or fear of side effects Changing needs and desires over reproductive lifespan Missing a spectrum of male methods Enhance competition and reduce costs These needs are cited for both the developing and developed worlds 9

10 Contraception Market and Scientific Evolution TIME Choice / Mode of Action Hormonal (female/ male) Combined Steroid Formulations Contraception Paradigm Shifts Hormonal (female) Steroid Receptor Modulators Hormonal (male) Steroid Receptor Modulators Hormonal (female) Non-Steroid Based Non-Hormonal (female) Novel follicular, oocyte and ovulation genes Non-Hormonal (male) Novel spermatogenesis, germ cell, epididymal and sperm cell genes Selectivity / Specificity 10

11 Contraceptive Technology Innovation Initiative at FHI360 Department Goals Focusing on longer-acting family planning methods, we Develop and evaluate new contraceptive technologies to expand the existing method mix Refine existing methods to make them more acceptable, accessible, and affordable Support efforts to get products introduced at public sector pricing in FP 2020 countries to better meet the changing reproductive needs of women and couples, especially those living in low-resource settings

12 Contraceptive Technology Innovation Initiative: Bridges multiple R&D stages and focuses on longer-acting approaches KEY FUNDING CTI Initiative Sino-implant (II) Longer Acting Injectable Envision FP KEY FUNDERS Bill & Melinda Gates Foundation NICHD (collaboration) USAID Early R&D Development Preclinical Clinical Phase I Clinical Phase II Clinical Phase III Regulatory Approval Intro/ Scale-up Global collaboration Cross-cutting research (acceptability, market pricing, registration, introduction) Knowledge sharing 12

13 Leveraging FHI 360 s Broad Experience Base FP commodity quality assurance; training and implementing global product quality standards Market assessments, developing service delivery tools, supporting policy/program change Product Introduction Product Quality Compliance Lab Clinical Research Decades of global technical leadership. Preferred PDP provider for implementing Phase II-III trials in developing countries Quantitative and qualitative research, including acceptability work Formative assessments, program evaluations, cost effectiveness studies to improve service delivery systems Social & Behavioral Research Operations Research Contraceptive Technology Innovation Biostatistics and Data Management Regulatory Affairs Innovative approaches for data management and analysis Experience in meeting rigorous regulatory requirements given developing country realities Together, we believe we represent the largest, deepest team of researchers focused on family planning method research and contraceptive innovation

14 What Technologies Might We Envision? On-demand methods for infrequent sex Non-surgical permanent contraception Reversible male options Multipurpose technologies (e.g., with HIV treatment) Biodegradable implants Unique delivery systems User-controlled toggle methods 14

15 Key Target Product Profile (TPP) Attributes Product-dependent duration of efficacy (1-6 months; 18 months; 5 years; 15 years) Product-dependent release profile (e.g., zero order release profile) Lowest safe and effective dose Side effect profile (no worse than current products) Additional health benefits Rapid and predictable return to fertility Acceptable Removable (product-dependent) Easy administration (lower level healthcare workers; self) Simplicity of presentation (e.g., single vial vs. multi component) Discreet No sharps waste (product-dependent) Stability (no cold chain) [Stable 3 years under Zone 4b conditions] Low cost (for procurement agencies) 15

16 Positive Impact of TPP on Procurement Agencies, Target Country Health Systems and End Users Product cost Avoidance of stock outs through extended product stability Simplicity of presentation Compatibility with existing products (e.g., implants compatible with existing trocars) Lower level healthcare worker administration or selfadministration Extended duration of efficacy would reduce rate of end user time, travel costs and return to clinic Increased compliance and continuation rates Products that permit appropriate birth spacing

17 Contraceptive Technology Innovation Initiative Pipeline Biodegradable implants Longer-Acting Injectables Single Rod Implant BMGF CTII USAID EnvisionFP Sino-implant (II) Alternative LNG- IUS in Kenya Early R&D Development Preclinical Clinical Phase I Clinical Phase II Clinical Phase III Regulatory Approval Intro/ Scale-up Microneedles Nonsurgical permanent contraception Microneedles Low dose DMPA Sayana Press Extension Comparative trial of alternative copper IUDs Acceptability research Over 75 organizations engaged including product development scientists, universities, pharmaceutical companies, service delivery groups and government agencies. 17

18 Progestins of Interest Levonorgestrel Etonogestrel Progesterone Nestorone Medroxyprogesterone Acetate

19 Schematic Comparison of Contraceptive Pharmacokinetics Predictable tail contraceptive effectiveness range

20 Biodegradable Microneedles Partners: Mark Prausnitz (Georgia Tech); Steven Schwendeman (Michigan) API: Levonorgestrel (LNG); Etonogestrel (ENG); Nestorone (NES) Delivery: PLA:PLGA microneedles containing API or microsphereloaded API; intradermal Target Contraceptive Duration: 1 month or longer Properties: Discreet self-administration Reduced pain Benefits to supply chain storage and distribution Microneedles that separate from patch upon application No sharps waste B C 20

21 Long Acting Injectable Partner: Linglin Feng (Shanghai Institute of Planned Parenthood Research) API: Levonorgestrel (LNG) Delivery: Microspheres (PLGA; PLGA:PLA) ; SQ Target Contraceptive Duration: 6 months Properties/Activities: Release duration tailored through changes in polymer composition Injectable through a 23-gauge needle Minimal release tail observed in rats QC of key materials Sterilization optimization Optimization of formulation/process Scale up Pilot scale study Further stability testing 21

22 Biodegradable Implant Partner: Mark Saltzman, Yale University API: Levonorgestrel (LNG) Delivery: Poly(ω-pentadecalactone-co-p-dioxanone) [poly(pdl-co-do)] implant Target Contraceptive Duration: 18 months Properties/Activities: In vitro release rates can be tuned through various fabrication methods and drug loading In vitro release demonstrate near zero order release rates and comparable to a commercial LNG implant Mouse biocompatibility study completed and positive Rat PK studies ongoing Implant removability/implant site histology to be examined Exploring core-shell options to reduce initial burst and shorten tail 22

23 Biodegradable Implant Partner: Gesea, ph Sciences API: Etonogestrel (ENG) Delivery: Cholesterol-based pellet implant Target Contraceptive Duration: 18 months Properties/Activities: Inexpensive materials Simple production Validating various in vitro dissolution assays In vivo study to evaluate erosion and ENG release from different monolithic and core/shell pellets Stability and sterilization studies underway 23

24 Biodegradable Implant Partner: Buddy Ratner (U. Washington) API: Levonorgestrel (LNG) Delivery: Biodegradable hydrogel rod containing 3 types of microspheres encased in a sheath biocompatible with tissue Target Contraceptive Duration: 18 months Properties/Activities: Sheath elicits a vascularized, non-fibrotic biointegration into subcutaneous tissue In vitro LNG release testing of the microspheres Fabricating hydrogel rods containing microspheres Development of an accelerated in vitro release method Further refining microsphere fabrication protocols 24

25 Sino-implant (II) Registration Status March 2015 Registered under multiple trade names: Zarin, Femplant, Trust, Simplant Bolivia Fiji Burkina Faso Ghana Cambodia Guatemala Chile* Indonesia China Jamaica Ethiopia** Kenya Madagascar Registered (n=26) Malawi Mali Mongolia Mozambique Nepal* Nigeria Pakistan Senegal Sierra Leone Uganda Vietnam Zambia Zanzibar Under review in over 10 additional countries Distributed by Marie Stopes International (MSI); Distributed by Pharm Access Africa Ltd. (PAAL) * Distributed by WomanCare Global ** Distributed by DKT International Distributed by APROFAM 25

26 1 Million units distributed to date in countries supported under project Impact of Sino-implant II According to the MSI Impact Calculator: 1.4 million unintended pregnancies averted Over 3000 maternal deaths averted Over 175,000 abortions averted In addition, units translate into $10.5 million units in commodity cost savings* Savings mean that an additional 1.3 million units of Sino-implant (II) could have been purchased *Impact is estimated based on distribution of 1,000,100 units. Savings are based on a price of US$8 per unit for Sino-implant (II), assuming the alternative would have been to purchase Jadelle. The average price for Jadelle was US$24 in 2009, US$22 in 2010, US$19 in 2011, US$18 in 2012, and $8.50 in 2013 and beyond according to information from the RHSC ( 26

27 Key Milestones Contraceptive Implant Prices : Changes Since Global Introduction of Sino-implant (II) $30 $25 $20 Jadelle Implanon Sino-implant (II) $15 $ prices based on weighted averages from RH Interchange in Kenya, Ethiopia and Sierra Leone prices from RHSC and press releases issued by the manufacturers $5 Prices established through volume guarantees last through 2018 $ : Sino-implant (II) registered in Kenya under trade name Zarin; first registration outside of Asia : Under agreement with partners, Merck/MSD reduces price of Implanon to $18/unit, with retro-active reduction to $16.50 when volume thresholds reached in Dec : Bayer HealthCare reduces price of Jadelle to $19/unit and then subsequently to $18/unit : Bayer HealthCare and Merck/MSD lower the prices of Jadelle and Implanon to US$8.50 per unit as part of volume guarantees : Over 1 million Sino-implant (II) units procured in countries under Gates initiative since 2009, resulting in over $10 million in commodity savings 27