New Biological Therapies for Asthma: Do the Benefits Justify the Cost?

New Biological Therapies for Asthma: Do the Benefits Justify the Cost?

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Description: The information in this report has been obtained from what are believed to be reliable sources and has been verified whenever possible. Nevertheless, we cannot guarantee the information contained herein as to accuracy or completeness. All expressions of opinion are the responsibility of Defined Health, and though current as of the date of this report, are subject to change.

Without the prior written consent of Defined Health, this report may not be relied on in whole or in part for any other purpose or by any other person or entity, provided that this report may be disclosed where disclosure is required by law.

 
Author: Aruni S. Arachchige Don PhD, Ed Saltzman, John Oppenheimer FACAAI MD (Senior) | Visits: 616 | Page Views: 888
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Contents:
New Biological Therapies for Asthma:
Do the Benefits Justify the Cost?
Aruni S. Arachchige Don, PhD
Consultant, Defined Health
Ed Saltzman
President, Defined Health
John Oppenheimer, FACAAI, MD
Director of Clinical Research
Pulmonary and Allergy Associates, and
Clinical Professor of Medicine, Rutgers University
May 17, 2016

The information in this report has been obtained from what are believed to be reliable
sources and has been verified whenever possible. Nevertheless, we cannot guarantee the
information contained herein as to accuracy or completeness.
All expressions of opinion are the responsibility of Defined Health, and though current as
of the date of this report, are subject to change.
Without the prior written consent of Defined Health, this report may not be relied on in
whole or in part for any other purpose or by any other person or entity, provided that this
report may be disclosed where disclosure is required by law.

Asthma Insight Briefing
© Defined Health, 2016

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Defined Health is Pleased to Present:

28h Annual Cancer Progress Conference
March, 2017
New York City
www.cancerprogressbyDH.com

BioEurope Spring 2017
March 20 – 22, 2017
Barcelona, Spain
www.therapeuticinsight.com

Defined Health will also be participating in the following industry events:
ASCO | June 3 - 7, 2016 | Chicago IL | http://dfndhlth.com/ASCO-2016
The 2nd Annual Immuno-Oncology: BD&L and Investment Forum | June 3, 2016 | Chicago, IL | http://dfndhlth.com/IOBDLI-2016
BIO International Convention | June 6 - 9, 2016 | San Francisco, CA | http://dfndhlth.com/BIO-2016
Oncology Market Access & Pricing 2016 | June, 16 - 17, 2016 | Philadelphia, PA | http://dfndhlth.com/OMAP-2016
Rational Combinations 360° | June 23 - 24, 2016 | New York, NY | http://dfndhlth.com/RC-360
Pharma CI USA Conference | September 13 - 14, 2016 | Parsippany, NJ | http://dfndhlth.com/PharmaCIUSA
The International Cancer Immunotherapy Conference |September 25 - 28, 2016 | New York, NY | http://dfndhlth.com/ICIC-2016
LES Annual Conference | October 23 - 2 6, 2016 | Vancouver, BC | http://dfndhlth.com/LES-2016
Bio-Europe| November 7 – 9, 2016 | Cologne, Germany | http://dfndhlth.com/Bio-Europe2016
SITC 2016 | November 9 – 13, 2016 | National Harbor, MD | http://dfndhlth.com/SITC-2016
ASH Annual Meeting | December 3 - 6, 2016 | San Diego, CA | http://dfndhlth.com/ASH-2016

Asthma Insight Briefing
© Defined Health, 2016

3

Asthma is a Highly Prevalent Disease
♦ 300 million people worldwide and 24 million or 8% of the US population are affected by

asthma, and the prevalence is expected to grow over the next decade.

♦ Asthma is a chronic lung disease that often starts in childhood and is characterized by repeated

episodes of wheezing, breathlessness, chest tightness, and nighttime or early morning
coughing.

♦ The asthma patient population is segmented based on disease severity:

Asthma Patient Population
24 million in the US (2014)

Intermittent
Asthma

Mild

Moderate

Severe

Persistent Asthma
Center for Disease Control, National Health Interview Survey Data, 2014; Cowen and Company, Mar 2016

Asthma Insight Briefing
© Defined Health, 2016

4

Asthma is Associated with Significant Healthcare Cost
♦ In the US, 1.8 million people visited an ER department for asthma-related care in 2010, and

439,000 people were hospitalized due to asthma.

♦ The yearly burden of asthma is ~$56 billion, and majority of it is direct cost, with hospital stay

being the biggest cost driver.

♦ Severe asthma accounts for an estimated 60% of the associated healthcare costs.

$ Billion

Asthma and Allergy Foundation of America; Asthma Disease Burden and Formulary Decision Making: MCO and Employer Perspectives; Cowen and Company, March 2016

Asthma Insight Briefing
© Defined Health, 2016

5

At Present, Relatively Inexpensive Inhalation Therapies
Dominate the Asthma Category
♦ According to the NHLBI guidelines, current treatment of asthma involves a stepwise approach.
♦ Vast majority of mild-moderate asthma patients can be adequately managed and well-

controlled on relatively inexpensive inhalation therapies; ~5 major pharmacological classes
(short- and long-acting bronchodilators, inhaled corticosteroids, anti-cholinergics, leukotriene
modifiers).

NIH, National Heart, Lung and Blood Institute (NHLBI), 2007

Asthma Insight Briefing
© Defined Health, 2016

6

Evolving 2013 Guidelines Suggest a Personalized, Evidencebased Approach for Treatment of Uncontrolled Asthma

J Allergy Clin Immunol Pract. 2015 ; 3(2): 152–161; 2013 ERS/ATS guidelines

Asthma Insight Briefing
© Defined Health, 2016

7

Until 2015, Xolair was the Only Approved Biologic for Asthma
♦ Xolair (omalizumab, Roche/Novartis) is an anti-IgE antibody approved in 2003 for treatment of

moderate to severe persistent allergic asthma in patients 12 years and older.

• 100K patients are treated WW with ~50% of the patients in the US
• $24K/$15K per year in the US and ex-US
• Global sales around $1.9B in 2015
♦ Use limited by a combination of biomarker selection criteria, weight-based / IgE based dosing and

reimbursement restrictions. Its efficacy varies considerably by biomarker specified subgroup.

http://www.xolair.com

Asthma Insight Briefing
© Defined Health, 2016

8

Omalizumab EXTRA Study – Exacerbations in Biomarker
Specified Subgroups of Uncontrolled Severe Persistent Asthma
Effects of Omalizumab in Allergic Asthma within biomarker specified subgroups

Am J Respir Crit Care Med 2013;187(8):804-811

Asthma Insight Briefing
© Defined Health, 2016

9

Omalizumab EXTRA Study – Exacerbations in Biomarker
Specified Subgroups of Uncontrolled Severe Persistent Asthma
Effects of Omalizumab in Allergic Asthma within biomarker specified subgroups

Am J Respir Crit Care Med 2013;187(8):804-811

Asthma Insight Briefing
© Defined Health, 2016

10

Asthma Biologics Focused on a Limited Set of Mechanisms and
Target a Small Subset of Patients with Overlapping Phenotypes
♦ The high level of unmet need in severe asthma and research breakthroughs surrounding the role of

inflammatory cytokines in asthma pathophysiology have spurred the development of multiple
cytokine-inhibiting agents that target Th2 and eosinophil (EOS)-driven phenotypes, and are expected to
be used in biomarker selected populations.

♦ However, there is significant overlap between the addressable patient populations with little guidance

or validated biomarkers to suggest which patients will benefit.

• High EOS present in 40-60% of severe asthmatics;

however, significant overlap between elevated
EOS and IgE (Xolair candidates);

• Elevated periostin is also associated with Th2

phenotype; 85% of periostin high patients also
have EOS phenotype but not all EOS patients have
high periostin

Allergy 2015; DOI: 10.1111/all.12580; NHLBI Expert Panel Report; Cowen and Company; March 2016; ; Image source AstraZeneca

Asthma Insight Briefing
© Defined Health, 2016

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Extent of Unmet Need in Uncontrolled Asthma Complicated by
Poor Adherence to Inhalation Therapy
♦ Estimating the severe asthma patient population is challenging – the current estimates range

between 5-25% for patients who remain uncontrolled despite the use of high dose inhaled
corticosteroids plus a second controller medication (e.g., LABA), and these patients also often
rely on long-term oral steroids.
♦ Patient adherence with inhalation therapy is quite poor which complicates the ability to assess
treatment response, and it also presents a challenge in justifying the use of asthma biologics.
• ~55% of adults and 78% of children do not strictly comply with their prescribed inhalation therapy

♦ Nevertheless, it is generally assumed that less than half of the asthma patients with

uncontrolled disease may in fact be candidates for additional treatments with biologics.
Therefore, payers are increasing likely to require documentation that patient strictly follow
adherence requirements prior to authorization of a biologic.

American Thoracic Society (ATS); European Respiratory Society (ERS); UpToDate, 2016

Asthma Insight Briefing
© Defined Health, 2016

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First Two in a Series of New Biologics Recently Approved
♦ Nucala (mepolizumab, GSK) is the first anti-interleukin 5 (IL-5) monoclonal antibody approved for

treatment of severe eosinophilic asthma. It was recently launched in the US in January of 2016.

♦ Cinqair (reslizumab, Teva) is also an anti-IL-5 approved in March 2016. It is expected to launch in the

US in 2Q 2016 and currently being reviewed by the EMA.

Drug
Company

Target Patient Population

Dosing

Nucala
GSK

Patients with severe asthma aged 12 years and older,
and with an eosinophilic phenotype
(>300 cells/mCL)

Subcutaneous (SC)

Cinqair
Teva

Treatment of inadequately controlled severe
eosinophilic asthma (>400 cells/mcL)

Intravenous infusion,
SC expected in 2018

Company Websites

Asthma Insight Briefing
© Defined Health, 2016

13

Other Biologics in Development for Severe Asthma in Phase 3
Drug
Company

Mechanism

Patient Population

Efficacy Data

Benralizumab
AZN

Anti-IL-5

• Uncontrolled
eosinophilic asthma
(>300 cells/mCL)

• Met the primary endpoint in 2 pivotal Phase 3 studies;
• US and EU regulatory submissions expected 2H 2016;
• 43-57% reduction in exacerbations, depending on the dose
and baseline blood eosinophil level;
• Decreased blood eosinophil counts to low levels after the
first dose (Phase 2b data)

Tralokinumab
AZN

Anti-IL-13

• severe uncontrolled
asthma
• High Periostin

• 67% reduction in asthma exacerbations (Phase 2b data);
• Phase 3 data expected in 2017

Lebrikizumab
Roche

Anti-IL-13

• Severe uncontrolled
asthma despite high
dose ICS+ second
controller
medication

• Mixed top-line results from two identical Ph 3 studies -significant reduction in exacerbations and improvement in
FEV1 in patients with high periostin or blood eosinophils
(LAVOLTA I) but no statistical significance observed in
(LAVOLTA II) with the rate of asthma exacerbations over 52
weeks as the 1 endpoint in both studies.
• Strong Phase 2 data (60% reduction in exacerbation vs. 5%
placebo in periostin high patients; FEV1 increased 9% in
high periostin group vs. placebo compared to 2.6%
improvement vs. placebo in the low periostin group)

Dupilumab
Regeneron

Anti-IL-4/
IL-13

• Moderate to severe
uncontrolled
eosinophilic asthma

• Phase 2b study met its primary endpoint of improving lung
function; 64-75% reduction in exacerbations compared to
placebo; Phase 3 data expected in 2017

1. Company Press Releases; 2. ClinicalTrials.gov

Asthma Insight Briefing
© Defined Health, 2016

14

Pricing of Nucala Already Creating Controversy

FiercePharma

Asthma Insight Briefing
© Defined Health, 2016

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Nucala Broadly Indicated for Severe Asthma with Eosinophilic
Phenotype

Asthma Insight Briefing
© Defined Health, 2016

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But Payers are Requiring Stringent Documentation of Patient
History and Medication Use for Prior-Authorization of Biologics
♦ Nucala is considered medically necessary for the add-on maintenance treatment of persons

with severe asthma aged 12 years and older who meet the following criteria:

• Persistent airflow obstruction as indicated by FEV1; and
• Evidence of asthma, as indicated by FEV1 reversibility of at least 12% and 200ml after albuterol

(salbutamol) administration; and
• Eosinophilic asthma phenotype, as determined by blood eosinophils ; and

• Previously confirmed history of > 2 exacerbations requiring treatment with systemic steroids in

the 12 months prior to initiation of mepolizumab, despite the use of high-dose ICS; and
• History of 2 or more exacerbations in the previous year despite regular use of high-dose inhaled
corticosteroids with oral corticosteroids for at least 6 months or high-dose ICS without oral
corticosteroids for at least 12 months; and
• Current treatment with an additional controller medication, besides ICS, for at least 3 months or
a documented failure in the past 12 months of an additional controller medication for at least 3
successive months; and
♦ Continued use of Nucala is considered medically necessary for persons who have evidence of
improvement, as indicated by reduction in frequency of exacerbations, reduced use of controller
medications, reduction in asthma symptoms, or increase in FEV1 from pretreatment baseline.
http://www.aetna.com/cpb/medical/data/800_899/0897.html

Asthma Insight Briefing
© Defined Health, 2016

17

Future Outlook for Asthma Biologics
♦ Two new asthma biologics (Nucala and Cinqair) have now been approved, and positive Phase 3 trial

read-outs expected for other late-stage anti-cytokine biologics in the near future. However, the
actual sales for Nucala has been lower than anticipated with $12M in sales for Q4 2015-Q1 2016.

♦ We also expect slow uptake of these novel asthma biologics due to empirical use, high cost of

therapy, and stringent prior-authorization requirements for reimbursement.

♦ According to current estimates, the asthma biologics may generate approx. $6B in WW sales in 2022,

but this may be an overestimation as it does not sufficiently account for biomarker driven selection
of these agents within a small subset of ~5-10% of asthma patients with overlapping phenotypes.
8

Asthma Biologics Market ($B)
WW 2015-2022

WW Sales

6

Tralokinumab (anti-IL-13)
Lebrikizumab (anti-IL-13)
Benralizumab (anti-IL-5)
Dupilumab (anti-IL-4/IL-13)
Cinqair (anti-IL-5)
Nucala (anti-IL-5)
Xolair (anti-IgE)

4
2
0

2015

2016

2017

2018

2019

2020

2021

2022

EvaluatePharma, 2016

Asthma Insight Briefing
© Defined Health, 2016

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Discrepancy Between Company Forecasts & Analyst Projections

FirstWord Pharma

Asthma Insight Briefing
© Defined Health, 2016

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John Oppenheimer, FACAAI, MD, Director of Clinical Research, Pulmonary and
Allergy Associates, and Clinical Professor of Medicine, Rutgers University
Dr. John Oppenheimer is the Director of Clinical Research at Pulmonary and Allergy
Associates as well as Clinical Professor of Medicine at UMDNJ-Rutgers He is board
certified in Internal Medicine and Allergy and Immunology. He trained and was on
faculty at the National Jewish Center in Denver Colorado. Dr. Oppenheimer has
participated in over 100 clinical studies with over 100 publications. He serves as the
Associate Editor of the Annals of Allergy Asthma and Immunology, co-section editor of
Current Reports of Allergy and Immunology and serves as a reviewer for several journal
including the Journal of Allergy and Clinical Immunology and JAMA. He is the past
Chairman of the ADT section as well as the Interest Section Coordinating Committee of
the AAAAI, serves on the Joint Task Force of the Practice Parameter Committee for
Allergy Immunology, the writing committee of the cough guidelines committee for the
American College of Chest Physicians, a voting member of PCPI and member of the
measures development for atopic dermatitis, is on the Board of Directors of the
American Board of Allergy and Immunology 2010-15 and is the past Chairman of the
ABAI. He has focused his career on guideline development and has been actively
involved in measurement development in the field of allergy and immunology.

Asthma Insight Briefing
© Defined Health, 2016

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Aruni S. Arachchige Don, PhD, Consultant, Defined Health
Aruni's client work encompasses opportunity assessments, therapeutic area growth
strategy and search projects, as well as the identification and evaluation of partnering
opportunities. Since joining Defined Health in 2013, Aruni has contributed to projects
that span the therapeutic landscape, with special emphasis on projects in respiratory
diseases.
Prior to Defined Health, Aruni conducted translational research on targeting mTOR
signaling for treatment of CNS injuries (e.g., traumatic brain and spinal cord injuries)
and cancer. She is a published author of 7 peer-reviewed articles, including an expert
review (in collaboration with Dr. Wise Young, the Founding Director of the W.M. Keck
Center for Collaborative Neuroscience and a world renowned neuroscientist in the field
of spinal cord injury at Rutgers University). Aruni completed a 3-year postdoctoral
fellowship from the New Jersey Commission on Spinal Cord Research. During her
postdoctoral tenure, Aruni also interned at the Office of Technology Transfer and
Business Development, where she was involved in various aspects of business
development and licensing and developed proficiency in evaluation and identification of
novel technologies appropriate for commercialization. She is knowledgeable in the
areas of intellectual property and technology transfer, the drug development process
and related regulatory issues.
Aruni received a PhD in Pharmacology from the University of Iowa, Carver College of
Medicine. She also earned Bachelor of Science degrees in both Biology and
Microbiology from the University of Wisconsin, Madison and from the University of
Minnesota, Twin Cities.
Asthma Insight Briefing
© Defined Health, 2016

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Ed Saltzman, President, Defined Health
Ed is President and Founder of Defined Health. He possesses a vast knowledge of the
pharmaceutical and biotechnology industry accumulated over Defined Health’s 27 years
of consultancy to pharma, biotech, specialty pharma and investors. From this unique
perspective, he manages business development and disease area strategy projects
and also provides guidance on most of Defined Health’s project work.
Prior to founding Defined Health, Ed held positions at the Ayerst Laboratories unit of
American Home Products, where he had responsibility for evaluation and forecasting of
compounds being considered for licensing, and at FIND/SVP, where he managed the
Healthcare Information Center.
Ed is a well regarded and in demand speaker on industry issues. He has spoken over
the past 10 years to large audiences at Defined Health’s Therapeutic Insight
conferences, the Licensing Executives Society Annual Meeting and various industry
conferences. In addition to these public events, Ed has presented targeted strategy
briefings and held discussions privately with scores of boards of directors, executive
management committees and licensing and business development teams at large
pharma, specialty pharma and biotech companies. Ed is a member of the Licensing
Executives Society and the New York Pharma Forum and is a graduate of New York
University.

Asthma Insight Briefing
© Defined Health, 2016

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