gdhc102pidr pediatric respiratory syncytial virus rsv … · number of first-in-class prophylactics...

Pediatric Respiratory Syncytial Virus (RSV) Prophylactics US Drug Forecast and Market Analysis to 2022

GDHC102PIDR / Published April 2013

Executive Summary

© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. GDHC102PIDR / Published APR 2013

Table below provides a summary of the key metrics in

the pediatric RSV prophylactics market in the US, the

single market covered in this report.

Pediatric RSV Prophylactics Market: Key Metrics in the US

2012 Epidemiology

At-risk population 157,935

Treated population 82,901

2012 Market Sales

US $577.9m

Pipeline Assessment

Number of prophylactics in Phase I–II 2

Number of first-in-class prophylactics 2 (vaccines)

Key events (2012–2022) Level of Impact

Synagis (palivizumab) composition patent expiry None

Synagis formulation patent expiry ↓↓

2022 Market Sales

US $612.9m

Source: GlobalData

Sales Growth of Prophylactic Products for Pediatric RSV in the US Remains Low Between 2012 and 2022

GlobalData’s patient-based estimate of the US market

size for prophylactic products used for pediatric RSV,

which is based on the patient segments that are typically

provided prophylactic treatment, as per the American

Academy of Pediatrics (AAP) guidelines, was $578m in

2012. GlobalData estimates that by 2022 the market will

reach $612.8m, growing at a Compound Annual Growth

Rate (CAGR) of 0.6%. The size of the pediatric RSV

market during the forecast period is expected to be

impacted by two salient events: the loss of AstraZeneca’s

composition and formulation patents for Synagis

(palivizumab) in 2015 and 2023, respectively. While

GlobalData expects AstraZeneca to protect its

formulation patent fiercely, clinical trials by generic

manufacturers seeking to launch biosimilars within this

market in 2016 draw focus upon the potential strength of

AstraZeneca’s formulation patent. In addition to these

critical events, the growth of the pediatric RSV

prophylactics market during the forecast period from

2012–2022 will be driven by:

Lack of a prophylactic vaccine to prevent RSV

infection in both healthy and at-risk children

Increased diagnostic testing for conditions affecting

lung function in children to increase the number of

eligible patients receiving treatment

Increased awareness of RSV infections in areas of

high incidence, such as Florida

Executive Summary


Barriers to the growth of the pediatric RSV prophylactics

market include:

Low utilization and compliance rates associated with

the administration of Synagis in eligible patients

High cost of Synagis, which leads to payer pushback

and limited reimbursement

Seasonal nature of the infection, which is rampant for

approximately five months of the year

General mistrust of vaccines by the public

Manufacturers Focus on Development of Vaccines for Active Immunization Over Products for Passive Immunization

AstraZeneca, through its acquisition of MedImmune, has

remained the clear market leader in the pediatric RSV

prophylactics market. MedImmune developed and

currently markets the present gold standard, Synagis, in

the US. Due to the restrictive patient segments that are

eligible for treatment, AstraZeneca has maintained its

stronghold on the market, while newer companies have

been focused on targeting other at-risk populations for

prophylactic treatment. The high cost associated with

RSV prevention is a strong driver to motivate the

production of new early-clinical-phase treatments, as

indicated by the development of vaccines by Novavax

and AstraZeneca. While AstraZeneca is likely to maintain

its current patient share with Synagis, GlobalData

forecasts that newer players, like Novavax, will likely gain

market share among the underserved patient segments

beyond the present forecast period.

Figure below provides an analysis of the company

portfolio gap in pediatric RSV prophylactics during the

forecast period.

Company Portfolio Gap Analysis in Pediatric RSV Prophylactics, 2012–2022

Strength of Pipeline

Low HighH

igh

Low

Stre

ngth

of M

arke

ted

Pro

duct

s

Current and Future Players

Future Players

Current Players

Source: GlobalData

Executive Summary


The Pediatric RSV Prophylactics Market is Poised to Face Similar Unmet Needs for the Next Decade

The current status of the pediatric RSV prophylactics

market is based on the utilization of a single product:

AstraZeneca’s Synagis. While the prospect of biosimilar

entry within the US is a point of contention, GlobalData

acknowledges that significant unmet needs continue to

exist within this market as a result of there being a sole

prophylactic option. GlobalData’s primary research with

key opinion leaders (KOLs) indicated that primary clinical

unmet needs exist regarding the lack of a prophylactic

vaccines against RSV in both healthy and at-risk

children, the increased bioavailability of monoclonal

antibodies (mAbs) and the need for a cheaper

prophylactic option. In addition, environmental factors

reflect a need for increased availability of the therapy for

all eligible patient groups, which stems from reported

uneven reimbursement for at-risk groups, based on the

existing treatment guidelines. Due to the early

development stage of the existing pipeline drugs, these

unmet needs are unlikely to change during the forecast

period. However, the eventual launches of prophylactic

vaccines from Novavax and AstraZeneca will help

increase the market size of this indication by targeting

newer patient segments.

New Entrants Set to Gain Inroads by Targeting New Patient Segments

Due to the high cost of AstraZeneca’s biologic, Synagis,

treatment guidelines have focused on preventing the

severity of RSV infection in high-risk patients, such as

premature neonates. However, with the launch of

prophylactic vaccines by newer manufacturing

companies like Novavax, new patient segments are likely

to receive appropriate preventative treatment. Novavax,

with its Phase II F-protein vaccine, is currently testing the

vaccine in women of childbearing age to achieve

protection of the target population through maternal

immunization. Prevention of neonatal infections through

maternal immunization is a new market segment within

the pediatric RSV prophylactics market and one that is

unlikely to usurp the role of existing mAbs that are

administered to premature neonates. As the majority of

maternal antibodies to RSV are conferred later during the

gestational period, these patients are unlikely to benefit

from vaccines that utilize this route of administration.

Executive Summary


Vaccines Pave the Way for Newer Target Segments within the Pediatric RSV Prophylactics Market

Given the current standing of the Synagis’ patent and the

scant product pipeline associated with RSV, vaccines are

likely to become the wave of the future beyond the

current forecast period. These vaccines, developed by

both Novavax and AstraZeneca, are currently seeking

approval for use in maternal and infant immunization,

respectively. These new prophylactic options will confer

immunization in those currently not protected under the

existing AAP treatment guidelines — that is, children not

at high risk and possibly children older than two years.

With the approval of these vaccines, the landscape of

pediatric RSV prophylactics market is expected to grow

dramatically, since they are indicated specifically for

women of childbearing age and will be incorporated into

routine immunization schedules for children. GlobalData

forecasts a surge in the market size for eligible patients,

while the existing treatment populations will not be

affected.

Figure below provides a competitive assessment of the

early-stage pipeline agents in pediatric RSV

prophylactics during the forecast period.

Competitive Assessment of Early-Stage Pipeline Agents in Pediatric RSV Prophylactics, 2012–2022

Clinical AttributesLow High

Hig

hLo

wC

omm

erci

al A

ttrib

utes

Note: Bubble size represents approximate peak year sales of pipeline drug

Novavax’s F-Protein Vaccine

AstraZeneca’s MEDI-559

Source: GlobalData

Executive Summary


What Do the Physicians Think?

GlobalData’s primary research with KOLs revealed that

physicians are generally satisfied with Synagis, but

recognize the need for more prophylactic interventions.

These would mainly include vaccines for both active and

maternal immunization. They also recognize the

challenges associated with the development of novel

mAbs, especially because of Synagis’ strong safety and

efficacy profile. Finally, the KOLs expressed concerns

about the AAP guidelines and the discrepancies between

the FDA label of Synagis and the 2009 policy statement

issued by the AAP’s Committee on Infectious Diseases

(COID).

“There is a really high water mark to achieve to really get

into this field, and when people see what happens with

palivizumab, a drug that is going to be very hard for them

to emulate or even to surpass in terms of their efficacy”

US Key Opinion Leader, March 2013

“I think MedImmune [AstraZeneca] has done a pretty

good job in pricing it [Synagis] at the limit of cost

effectiveness, so that it’s right at the borderline.”


“I think the real aim needs to be towards working on a

monoclonal that has more lasting power.”


“I would love to see some sort of maternal immunization

study being done. But the problem with maternal

immunization, again, is that it doesn’t protect the preterm

kids, because maternal antibodies are transferred in the

late stage.”


“If you looked at it from the perspective of what [the] AAP

is doing, and the Committee on Infectious Diseases, the

so-called COID, it’s largely focused on balancing [the]

books on the backs of our babies, as opposed to

achieving a reasonable or meaningful way of

prophylaxis.”


Table of Contents


1 Table of Contents

1 Table of Contents ............................................................................................................... 7

1.1 List of Tables ............................................................................................................. 11

1.2 List of Figures ........................................................................................................... 13

2 Introduction ....................................................................................................................... 14

2.1 Catalyst ..................................................................................................................... 14

2.2 Related Reports ........................................................................................................ 14

2.3 Upcoming Related Reports ........................................................................................ 15

3 Disease Overview ............................................................................................................. 16

3.1 Etiology and Pathophysiology .................................................................................... 16

3.1.1 Pathophysiology.................................................................................................. 20

3.1.2 Prognosis ............................................................................................................ 21

3.1.3 Quality of Life ...................................................................................................... 21

3.2 Symptoms ................................................................................................................. 22

4 Epidemiology .................................................................................................................... 23

4.1 Risk Factors and Comorbidities ................................................................................. 24

4.1.1 Re-hospitalization rate increases with lower gestational age ................................ 24

4.1.2 Congenital respiratory or neuromuscular diseases are more often re-

hospitalized ....................................................................................................... 24

4.1.3 Re-hospitalization is more frequent in chronic lung disease infants ...................... 24

4.1.4 More complications in children with hemodynamically significant congenital

heart disease ..................................................................................................... 25

4.1.5 Hospitalized cases likely to develop long-term respiratory problems .................... 25

4.2 Trends in the US ....................................................................................................... 26

4.2.1 RSV Infections and Hospitalization Rates ............................................................ 26

4.2.2 Preterm Births and Infant Mortality ...................................................................... 26

4.2.3 Congenital Respiratory or Neuromuscular Diseases ............................................ 26

4.2.4 Neonatal Chronic Lung Disease .......................................................................... 27

4.2.5 Hemodynamically Significant Congenital Heart Diseases .................................... 27

Table of Contents


4.3 Forecast Methodology ............................................................................................... 28

4.3.1 Sources Used ..................................................................................................... 30

4.3.2 Forecast Assumptions and Methods (US)............................................................ 32

4.3.3 Sources Not Used ............................................................................................... 37

4.4 Epidemiological Forecast of RSV Infections and Prophylactic Populations ................. 38

4.4.1 Primary, Secondary, and Hospitalizations of RSV Infections ................................ 38

4.4.2 Preterm Population ............................................................................................. 40

4.4.3 Congenital Respiratory or Neuromuscular Diseases Population........................... 44

4.4.4 Neonatal Chronic Lung Disease Population ......................................................... 44

4.4.5 Hemodynamically Significant Congenital Heart Diseases Population ................... 45

4.4.6 RSV Infections and Prophylactic Populations Segmented by Sex ........................ 46

4.5 Discussion................................................................................................................. 48

4.5.1 Conclusions on Epidemiological Trends and Forecast ......................................... 48

4.5.2 Limitations of the Analysis ................................................................................... 49

4.5.3 Strengths of the Analysis ..................................................................................... 50

5 Disease Management ....................................................................................................... 51

5.1 Treatment Overview .................................................................................................. 51

5.2 Diagnosis .................................................................................................................. 52

5.3 Clinical Practice ......................................................................................................... 54

6 Competitive Assessment ................................................................................................... 58

6.1 Overview ................................................................................................................... 58

6.2 Product Profiles – Major Brands ................................................................................ 59

6.2.1 Synagis (palivizumab) ......................................................................................... 59

7 Opportunity and Unmet Need ............................................................................................ 64

7.1 Overview ................................................................................................................... 64

7.2 Unmet Needs ............................................................................................................ 65

7.2.1 Unmet Need: Lack of Prophylactic Vaccines........................................................ 65

7.2.2 Unmet Need: Increased Bioavailability of Monoclonal Antibody ........................... 66

Table of Contents


7.2.3 Unmet Need: Lower-Cost Prophylactic Interventions ........................................... 67

7.2.4 Unmet Need: Updated Guidelines with Wider Inclusion Criteria ........................... 68

7.3 Unmet Needs Gap Analysis ....................................................................................... 69

7.4 Opportunities ............................................................................................................. 70

7.4.1 Opportunity: Novel Approaches to Prophylactic Vaccine Development ................ 70

7.4.2 Opportunity: Small-Molecule Option .................................................................... 70

7.4.3 Opportunity: Maternal Immunization .................................................................... 71

7.4.4 Opportunity: Adult Vaccination to Confer Herd Immunity...................................... 71

8 Pipeline Assessment......................................................................................................... 72

8.1 Overview ................................................................................................................... 72

8.2 Clinical Trial Mapping ................................................................................................ 73

8.3 Clinical Trials by Phase and Trial Status .................................................................... 74

8.4 Promising Prophylactic Interventions in Clinical Development .................................... 75

8.4.1 RSV F-Protein Vaccine ....................................................................................... 76

8.5 Promising Prophylactic Interventions in Early Clinical Development ........................... 80

8.5.1 MEDI-559 ........................................................................................................... 80

9 Current and Future Players ............................................................................................... 83

9.1 Overview ................................................................................................................... 83

9.2 Trends in Corporate Strategy..................................................................................... 84

9.3 Company Profiles ...................................................................................................... 86

9.3.1 AstraZeneca (MedImmune) ................................................................................. 86

9.3.2 Novavax.............................................................................................................. 88

10 Market Outlook ................................................................................................................. 91

10.1 US ........................................................................................................................... 91

10.1.1 Forecast.............................................................................................................. 91

10.1.2 Key Events ......................................................................................................... 93

10.1.3 Drivers and Barriers – Global Issues ................................................................... 93

11 Appendix .......................................................................................................................... 98

Table of Contents


11.1 Bibliography .............................................................................................................. 98

11.2 Abbreviations .......................................................................................................... 109

11.3 Methodology ........................................................................................................... 111

11.4 Forecasting Methodology ........................................................................................ 111

11.4.1 Number of eligible patients for prophylaxis ........................................................ 111

11.4.2 Utilization rates of Synagis ................................................................................ 112

11.4.3 Patient share and generic erosion ..................................................................... 113

11.4.4 Weight of high risk infants ................................................................................. 113

11.4.5 Cost per day ..................................................................................................... 113

11.4.6 Number of prophylaxis days per year ................................................................ 113

11.4.7 Annual cost of therapy ...................................................................................... 114

11.4.8 Patient compliance ............................................................................................ 114

11.4.9 Total sales ........................................................................................................ 114

11.4.10 Drugs Included in Each Therapeutic Class ....................................................... 114

11.4.11 Launch and Patent Expiry Dates ...................................................................... 114

11.4.12 General Pricing Assumptions ........................................................................... 115

11.4.13 Individual Drug Assumptions ............................................................................ 115

11.5 Physicians and Specialists Included in this Study .................................................... 116

11.6 About the Authors ................................................................................................... 117

11.6.1 Authors ............................................................................................................. 117

11.6.2 Epidemiologist .................................................................................................. 118

11.6.3 Global Head of Healthcare ................................................................................ 118

11.7 About GlobalData .................................................................................................... 119

11.8 Contact Us .............................................................................................................. 119

11.9 Disclaimer ............................................................................................................... 119

Table of Contents


1.1 List of Tables

Table 1: Symptoms of RSV infection .................................................................................. 22

Table 2: Sources Used for Incidence or Prevalence ............................................................ 29

Table 3: Definitions of Neonatal Chronic Lung Disease....................................................... 36

Table 4: Respiratory Syncytial Virus Infections, 0–2 Years, Boys and Girls, N (Column %)*,

Select Years 2012–2022 ....................................................................................... 38

Table 5: Preterm Population, Boys and Girls, 0–2 Years, N (Column %)*, Select Years

2012–2022 ........................................................................................................... 41

Table 6: Congenital Respiratory or Neuromuscular Diseases Population*, Boys and Girls, 0–

2 Years, N (Column %), Select Years 2012–2022 ................................................. 44

Table 7: Neonatal Chronic Lung Disease Population, Boys and Girls, Age 0, N (Column %),

Select Years 2012–2022 ....................................................................................... 44

Table 8: Hemodynamically Significant Congenital Heart Diseases Population, Boys and

Girls, N (Column %), 0–2 Years, Select Years 2012–2022 .................................... 45

Table 9: RSV Infection and Prophylactic Populations by Sex, 0–2 Years, N (Row %), 2012 46

Table 10: Treatment Guidelines for Pediatric RSV Prevention .............................................. 51

Table 11: Most Prescribed Prophylactics for Pediatric RSV in the US, 2013 ......................... 51

Table 12: Leading Prophylactic Treatments for Pediatric RSV, 2012 ..................................... 59

Table 13: Product Profile – Synagis ...................................................................................... 60

Table 14: Synagis SWOT Analysis, 2012 ............................................................................. 62

Table 15: US Sales Forecasts ($m) for Synagis, 2012–2022 ................................................ 63

Table 16: Overall Unmet Needs – Current Level of Attainment ............................................. 64

Table 17: Clinical Unmet Needs – Gap Analysis, 2012 ......................................................... 69

Table 18: Clinical Trials for RSV Prophylaxis and Treatment by Phase and Status, 2012 ...... 74

Table 19: Pediatric RSV Prophylactic Vaccines – Phase Pipeline, 2013 ............................... 75

Table 20: Comparison of Therapeutic Classes in Development for RSV, 2012 ...................... 75

Table 21: Product Profile – RSV F-Protein Vaccine .............................................................. 76

Table 22: RSV F-protein vaccine SWOT Analysis, 2012 ....................................................... 79

Table 23: Product Profile – MEDI-559 .................................................................................. 81

Table 24: MEDI-559 SWOT Analysis, 2012 .......................................................................... 82

Table of Contents


Table 25: Key Companies in the Pediatric RSV Prophylactic Market – United States, 2012 .. 83

Table 26: AstraZeneca’s RSV Prophylactics Portfolio Assessment, 2013.............................. 87

Table 27: AstraZeneca SWOT Analysis, 2012 ...................................................................... 87

Table 28: Novavax’s Pediatric RSV Prophylactics Portfolio Assessment, 2012 ..................... 89

Table 29: Novavax SWOT Analysis, 2012 ............................................................................ 90

Table 30: US Sales Forecasts ($m) for Synagis, 2012–2022 ................................................ 92

Table 31: Key Events Impacting Sales for RSV Prophylactics in the US, 2012 ...................... 93

Table 32: Pediatric RSV Market – Drivers and Barriers, 2012 ............................................... 93

Table 33: Key Launch Date ................................................................................................ 114

Table 34: Key Patent Expiries ............................................................................................ 114

Table of Contents


1.2 List of Figures

Figure 1: Schematic Representation of the RSV Virion ........................................................ 18

Figure 2: Population Estimate and Births Forecast in the US, Boys and Girls, 1997—2022 .. 34

Figure 3: Respiratory Syncytial Virus Infections by Age and Infection Type, Boys and Girls, N

(Millions), 2012 and 2022 ...................................................................................... 39

Figure 4: Preterm Population, Boys and Girls, 0–2 Years, N (Millions), 2012–2022 .............. 42

Figure 5: Preterm Population (<36 Weeks of Gestation) Segmented by Sex, 0–2 Years, N

(Thousands), 2012 ............................................................................................... 43

Figure 6: Respiratory Syncytial Virus Infections Segmented by Sex, 0–2 Years, N (Millions),

2012 ..................................................................................................................... 47

Figure 7: Respiratory Syncytial Virus Prophylactic Populations Segmented by Sex, 0–2

Years, N (Thousands), 2012 ................................................................................. 47

Figure 8: Clinical Trials for RSV Treatment Versus Prophylaxis in the US, 2012 .................. 73

Figure 9: Competitive Assessment of Early-Stage Pipeline Agents in Pediatric RSV,

2012–2022 ........................................................................................................... 75

Figure 10: Company Portfolio Gap Analysis in Pediatric RSV, 2012–2022 ............................. 83

Introduction


2 Introduction

2.1 Catalyst

The pediatric respiratory syncytial virus (RSV) prophylactic market has remained relatively stagnant

over the past decade following the 1998 launch of AstraZeneca’s (MedImmune) Synagis

(palivizumab). However, since then, the high cost of Synagis has rendered it as an expensive

resource, which has resulted in its strict use only in severely high-risk patients.

The expected 2015 composition patent expiry on Synagis in the US will potentially draw entry

from biosimilar manufacturers, who will attempt to steal patient share away from Synagis.

These manufacturers will be held at bay with Synagis’ formulation patent, which is likely to end

up in litigation.

The new guidelines released in 2012 by the National Perinatal Association (NPA) regarding

RSV prophylaxis in children deviate slightly from the existing 2009 guidelines of the American

Academy of Pediatrics (AAP), which will result in more physicians adopting methods that are

better aligned with the needs of their clinical practice.

The development of more diagnostic methods that are designed to identify patients with

serious genetic disorders that can affect their lung function will increase the pediatric RSV

prophylactics market size considerably within the US.

The advancement of Novavax's F-protein vaccine based on positive top-line Phase II study

results reaffirms the movement from passive to active prophylaxis of RSV. These results

indicated that the adjuvanted vaccine elicited a significant immune response after

immunization.

2.2 Related Reports

GlobalData (2013). PharmaFocus: Vaccine Adjuvants in Infectious Disease, March, 2013,

GDHC001PFR.

Appendix

© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 119 GDHC102PIDR / Published APR 2013

11.7 About GlobalData

GlobalData is a leading global provider of business intelligence in the Healthcare industry.

GlobalData provides its clients with up-to-date information and analysis on the latest developments

in drug research, disease analysis, and clinical research and development. Our integrated business

intelligence solutions include a range of interactive online databases, analytical tools, reports, and

forecasts. Our analysis is supported by a 24/7 client support and analyst team.

GlobalData has offices in New York, Boston, London, India, and Singapore.

11.9 Disclaimer

All Rights Reserved.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any

form by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior

permission of the publisher, GlobalData.

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