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. Page 2 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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 3 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 4 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 5 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 6 GDHC102PIDR / Published APR 2013
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.”
US Key Opinion Leader, March 2013
“I think the real aim needs to be towards working on a
monoclonal that has more lasting power.”
US Key Opinion Leader, March 2013
“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.”
US Key Opinion Leader, March 2013
“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.”
US Key Opinion Leader, March 2013
Table of Contents
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 7 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 8 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 9 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 10 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 11 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 12 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 13 GDHC102PIDR / Published APR 2013
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
© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 14 GDHC102PIDR / Published APR 2013
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.