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HEPATITIS C MEDICINES Technology and Market Landscape

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HEPATITIS C MEDICINES Technology and Market Landscape 2015 HEPATITIS C MEDICINES Technology and Market Landscape FEBRUARY 2015 UNITAID Secretariat World Health Organization Avenue Appia 20 CH-1211 Geneva 27 Switzerland T +41 22 791 55 03 F +41 22 791 48 90 [email protected] www.unitaid.org UNITAID is hosted and administered by the World Health Organization © 2015 World Health Organization (Acting as the host organization for the Secretariat of UNITAID) The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind either expressed or implied. The responsibility and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This report was prepared by Mike Isbell and Renée Ridzon (Ahimsa) and Karin Timmermans (UNITAID). All reasonable precautions have been taken by the authors to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall UNITAID or the World Health Organization be liable for damages arising from its use. CONTENTS Foreword ............................................................................................ vi Abbreviations ....................................................................................... vii Executive summary .................................................................................. 8 1. Introduction ..................................................................................... 10 2. Methodology .................................................................................... 11 3. Public health problem ........................................................................... 12 Basic facts about HCV ............................................................................ 12 Global health burden associated with HCV ....................................................... 13 HIV/HCV coinfection ............................................................................. 14 4. Factors that can facilitate the uptake of new HCV medicines .................................... 16 Initial regulatory approval ....................................................................... 16 Role of WHO ..................................................................................... 16 National action ................................................................................... 17 5. Technology landscape ........................................................................... 18 Overview ......................................................................................... 18 Treatments for HCV infection ..................................................................... 18 1. Pegylated interferon and ribavirin ............................................................ 18 2. Direct-acting antivirals ........................................................................ 20 a. HCV protease inhibitors .................................................................... 21 Boceprevir and telaprevir .................................................................... 21 Simeprevir .................................................................................. 22 Asunaprevir ................................................................................. 22 Paritaprevir ................................................................................. 22 Vaniprevir .................................................................................. 22 Pipeline for HCV protease inhibitors ........................................................... 22 b. Nucleoside/tide polymerase inhibitors ..................................................... 23 Sofosbuvir .................................................................................. 23 Pipeline for nucleoside/tide polymerase inhibitors ............................................. 24 Technical Report iii Hepatitis C Medicines Technology and Market Landscape c. NS5A inhibitors ............................................................................ 24 Daclatasvir ................................................................................. 25 Ledipasvir .................................................................................. 25 Ombitasvir .................................................................................. 25 Pipeline for NS5A inhibitors .................................................................. 25 d. Non-nucleoside polymerase inhibitors ..................................................... 26 Dasabuvir .................................................................................. 26 Pipeline for non-nucleoside polymerase inhibitors ............................................. 27 3. Target product profile . 27 4. Combination regimens versus target product profiles .......................................... 28 a. Approved sofosbuvir-based combination regimens ........................................... 29 Sofosbuvir + ribavirin ........................................................................... 29 Sofosbuvir/ledipasvir ........................................................................... 30 Sofosbuvir + simeprevir ......................................................................... 30 b. Additional SOF-based combinations .......................................................... 31 Sofosbuvir + daclatasvir ........................................................................ 31 Sofosbuvir + GS-5816 ........................................................................... 32 Other studies involving SOF ..................................................................... 33 c. Non-sofosbuvir combinations . 33 Ombitasvir/paritaprevir/ritonavir + dasabuvir .................................................... 33 MK-5712/MK-8742 .............................................................................. 34 Other combinations ............................................................................ 34 6. Market landscape ................................................................................ 35 Market for existing products . 35 1. Regulatory approval .......................................................................... 35 2. Sales to date .................................................................................. 36 3. Originator market dynamics/prices ............................................................ 39 4. Patents and licences ........................................................................... 41 Voluntary licences on sofosbuvir ............................................................... 42 Generics under development .................................................................. 44 5. Production costs .............................................................................. 44 Market forces .................................................................................... 45 1. Access to date ................................................................................. 45 2. Funding availability for procurement of DAAs ................................................. 46 3. Demand impediments . 46 4. Other potential impediments to uptake ....................................................... 47 7. Market shortcomings ............................................................................ 48 Situation analysis – key issues .................................................................... 48 Summary of shortcomings and their reasons ..................................................... 48 8. Potential market interventions .................................................................. 51 References .......................................................................................... 53 iv CONTENTS ANNEXES ........................................................................................... 65 Annex 1. Hepatitis C medicines on the market and in the pipeline (Phase II and beyond) ...... 65 Annex 2. Overview of sustained virological response with sofosbuvir-based combination regimens . 66 Annex 3. Summary assessment of selected DAA regimens against target product profiles .... 70 Annex 4. Registration status of sofosbuvir in developing countries ............................ 72 Annex 5. Summary of the available patent information of selected direct-acting antivirals .... 73 Annex 6. Overview of countries included in voluntary licences ................................. 74 Annex 7. Methodology for estimating the number of patients who have been able to access sofosbuvir and simeprevir (Q4 2013–Q3 2014) ....................................... 75 Technical Report v Foreword In October 2013, UNITAID published its first scoping paper
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