SAMPLE

Spinal Muscular Atrophy Market:

Pipeline Assessment, Size, Growth, Trends, and Forecast, 20152023

2015 Transparency Market Research, All Rights Reserved

Chapter 1 Introduction

2015 Transparency Market Research, All Rights Reserved

Introduction
Report Description
Pipeline analysis of spinal muscular atrophy (SMA) market report provides with comprehensive analysis of various drugs in clinical trials
for treatment for SMA. The report provides insights to SMA prevalence, and current treatment pattern. The report also identifies key
market drivers, restraints and opportunities in the global SMA therapeutics market. Detailed market attractiveness analysis by
geography provides future outlook to the SMA landscape. This analysis considers various factors such as patient population, drug
pricing policies, regulatory restrictions, current competition intensity, and current state of healthcare sector for assessing the potential
of each geographical market.
Market analysis and forecast has been provided for late stage (phase 3) candidates, and thorough qualitative information for other
candidates in early stage (phase 1 and phase 2). ISIS-SMNRx is the only late stage candidate in spinal muscular atrophy pipeline, while
three drugs are currently in phase 2 and three others in phase 1. The report provides overview of the clinical trials, and its current
status for each drug candidate. Details on mergers, acquisitions, and other collaborative agreements, updated on regulatory policies,
and expected study completion are also mentioned in the report. Market estimation and forecast for phase 3 drugs have been provided
from the expected year of drug approval, till 2023 (in USD Million) for the United States.
Pipeline market estimation adopts patient based approach, in which actual patient population that can be targeted by the new drug is
considered to arrive at probable sales of the drug in the launch year. Forecast model considers various macro- as well as microeconomic factors such as drug efficiency, side effects, prevalence and incidence rate, impact of regulatory policies, impact of
competitor drugs and generic competition (if applicable) and pipeline status.
Key players with potential candidates in clinical trials have been profiled in the report. These include AveXis, Inc., Cytokinetics, Inc., F.
Hoffmann-La Roche Ltd., Novartis AG, and Isis Pharmaceuticals, Inc.

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Introduction
Research Methodology
For the research report, we conducted in-depth interviews and discussions with a wide range of key industry participants and opinion
leaders. Primary research represented the bulk of our research efforts, supplemented by extensive secondary research. We reviewed
the key players annual reports, press releases and relevant documents for competitive analysis and market understanding. Secondary
research also included a search of recent technical writing, internet sources, and statistical data from government websites, and SMA
associations. This approach proved to be the most reliable, effective and successful approach for obtaining precise market data,
capturing industry participants insights, and recognizing business opportunities.
Patient based approach was adopted to estimate the potential of pipeline candidates in phase 3 clinical trials. Most accurate prevalence
and incidence rate coupled with diagnosis and treatment rates of spinal muscular atrophy revealed potential patient population which
can be targeted for marketing of new drug. Interaction with industry experts and key opinion leaders such as drug analysts and research
scholars assisted in predicting market penetration rate, which was further used to estimate potential market for phase 3 candidate.
Forecast model was based on various macro- as well as micro-economic factors such as drug efficiency, side effects, prevalence and
incidence rate, impact of regulatory policies, impact of competitor drugs and generic competition (if applicable) and pipeline status.
Secondary sources for our study included but are not limited to:

Company website sources such as:

Annual Reports
Press Releases
SEC Filings
Investor Presentations

2015 Transparency Market Research, All Rights Reserved

Introduction
Research Methodology
Stock analyst websites such as:

Seeking Alpha
Yahoo Finance
Wikinvest
Zacks Investment Research

Governmental organizations and public portals such as:

World Health Organization (WHO)

World Bank
U.S. FDA
Clinicaltrials.gov
Clinicaltrialsregister.eu
International SMA Patient Registry
CureSMA.org

Journals and other publications

We conducted primary interviews on an ongoing basis with pharmaceutical industry participants and key opinion leaders (KOLs) in
order to validate data analysis and further gain insights about the industry.

2015 Transparency Market Research, All Rights Reserved

Introduction
Research Methodology
The primary research interviews fulfilled the following functions:
Provided first-hand information on the market size, market trends, growth trends, competitive landscape, future outlook, etc.
Helped in validating and strengthening the secondary research findings
Further developed the Analysis Teams expertise and market understanding
Primary research involved e-mail interactions and telephonic interviews
The participants who took part in such a process included:

Industry participants: VPs, marketing/product managers, market intelligence managers and national sales managers

Key opinion leaders specializing in different areas of pharmaceutical industry especially, rare diseases

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Introduction
Market Segmentation

Pipeline Analysis: Spinal

Muscular Atrophy

Late Stage (Phase 3)

ISIS-SMNRx

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Early Stage (Phase 1 and

Phase 2)

Phase 2

Phase 1

Olesoxime (TRO19622)

RG3039

LMI070

scAAV9.CB.SMN

RO6885247

CK-2127107
9

Introduction
Assumptions

Pipeline estimation provides market size and forecast for the U.S. only

Annual treatment cost of ISIS-SMNRx - USD 20,000

Market penetration rate for ISIS-SMNRx - 35%

Valproate/Levocarnitine was identified as phase 3 candidate according to clinicaltrials.gov. However the study has not been updated
since November 2013. All efforts of communication with AIIMS, New Delhi failed. Hence this drug was not considered in the SMA
pipeline analysis.

Olesoxime was identified as a phase 3 candidate by various SMA organizations. The company provides information about
completed phase2/3 trial; however, no confirmed data about ongoing phase 3 trial and its expected completion was recently
published. Hence this drug was considered in Phase 2.

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10

Executive Summary
Executive Summary
Spinal muscular atrophy (SMA) is a leading genetic disease causing mortality in infants. One infant in 6,000 births is estimated to
suffer from SMA. Furthermore, over 10 million people in the U.S. are carriers of SMA gene. Despite this, awareness about the
genetic disease is low globally.
Based on age of onset and symptoms, spinal muscular atrophy can be classified in four main types: type 1, type 2, type 3, and type
4. Each of these types has a characteristic disease progression and defined mortality rate. Type 1 SMA is the most severe form, and
affects infants aged between zero and six months. Approximately 65% of these cases are of type 1 SMA, wherein infants usually do
not survive for more than 2 years. Type 2 SMA is a moderate form affecting children aged between six months and eighteen
months. Type 3 and 4 are less severe and usually have a normal lifespan.
Currently, no cure exists for SMA, and the treatment is targeted toward management of symptoms. Spinal muscular atrophy
pipeline is dry; however, it has three drugs in phase 1, three in phase 2, and one in phase 3 clinical trials.
ISIS-SMNRx, an antisense therapy candidate by Isis Pharmaceuticals, is currently under phase 3 studies for treatment of type 1 and
2 SMA. If approved, ISIS-SMNRx would be the only drug available of the treatment of spinal muscular atrophy, creating lucrative
opportunity for Isis Pharmaceuticals and Biogen Idec. Phase 3 study is expected to complete in June 2017. The drug is projected to
record sales of US$ XXX Mn in the U.S. by 2023.
Olesoxime (TRO19622) has completed its phase2/3 trials, and has shown promising results, with potential to effectively treat type 2
and type 3 SMA

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Executive Summary
Market Snapshot
Sr. No.
1
2
3
4
5
6
7
8
9
10

Drug
Gene Therapy (adeno-associated virus vector)
Gene Therapy (adeno-associated virus vector)
BBrm02 (intrathecally-administered azithromycin)
CK-2127107
scAAV9.CB.SMN
RG3039
RO6885247
LMI070
Olesoxime (TRO19622)
ISIS-SMNRx

Company
Genzyme (Sanofi)
Genethon
BioBlast Pharma Ltd.
Cytokinetics, Inc.
AveXis, Inc.
Repligen Corporation
F. Hoffmann-La Roche Ltd.
Novartis International AG
Trophos SA
Isis Pharmaceuticals, Inc.

Preclinical

Phase 1

Phase 2

Phase 3

Status
NA
NA
NA
Completed
Recruiting
Discontinued
Suspended
Recruiting
Completed
Recruiting

North America is estimated to be the most attractive market in the near future due to higher diagnosis rate of spinal muscular
atrophy and high drug pricing policies. North America was followed by Europe, Asia Pacific, and Rest of the World in decreasing
order of attractiveness.
Government incentives for development of therapeutic drugs for rare diseases have been a major factor for investment in research
and development of SMA therapeutics. Organizations such as CureSMA, the SMA Foundation, and the National Organization of Rare
Disease (NORD) have helped in enhancing awareness about the disease and increasing the percentage of confirmed diagnosis of
SMA. These factors are likely to accelerate the growth of the market in the near future.

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Market Definition and Overview

Spinal Muscular Atrophy: Market Definition and Epidemiology
Spinal muscular atrophy (SMA) is a hereditary autosomal recessive disease affecting areas of the nervous system that control
voluntary muscle movement. Mutation in survival motor neuron (SMN) gene causes deficiency of SMN protein. This results in
motor neurons to lose control over voluntary muscle movement.
Spinal muscular atrophy is classified into four main types depending upon age of onset and symptoms.

Type 1 SMA is the most severe form and affects infants aged zero to six months. This form is characterized by generalized weakness and
hypotonia, decreased fetal movement in utero, absent tendon reflexes, and sunken chest. Mortality rate in type 1 SMA is high, and infants
usually do not live more than two years of age. Globally, type 1 SMA accounts for 60% to 70% of newly diagnosed SMA patients annually.

Type 2 SMA is a moderate form affecting children aged six months to eighteen months. Symptoms include hypotonia, weak muscles,
difficulty in maintaining posture, and inability or difficulty to walk. Survival varies between four years to six years depending on respiratory
distress.

Type 3 and Type 4 are less severe and patients usually have a normal lifespan. Patients diagnosed with Type 3 or Type 4 SMA could have
difficulty in walking or getting up from a sitting position, and experience fine tremors in fingers.

Spinal muscular atrophy is diagnosed by identifying mutation in survival of motor neuron (SMN) gene. Other tests include muscle
biopsy, electromyogram (EMG), and nerve conduction velocity.
According to CureSMA, the orphan disease has a prevalence of 1 in 6,000 to 1 in 10,000 births, and has a carrier frequency of 1 in
50 individuals in the U.S. Trends in prevalence and incidence of SMA variants is difficult to analyze due to lack of epidemiological
research.

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Market Definition and Overview

Market Dynamics

Drivers:

High carrier frequency for SMA would act a major driver in the near future: xxxxxxxxx

Restraints:

Insufficient research hindering spinal muscular atrophy market growth: xxxxxxxxx

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Market Definition and Overview

Market Attractiveness Analysis
North
America

Market attractiveness analysis is a qualitative

analysis that considers various factors to
determine attractiveness of a particular
geographical market. These factors include
patient population, drug pricing policies,
regulatory restrictions, current competition
intensity, and current state of the health care
sector. Depending on these factors, each of
the geographical regions are rated on a scale
of 0 to 10 (10 being the highest).

XXXXX

Europe
ScoreX/10

ScoreX/10

Rest of
the World
Score-3/10

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XX

XXX

XXX

XXX

xxx

Asia
Pacific
Score-X/10

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Pipeline Analysis: Spinal Muscular Atrophy

Spinal Muscular Atrophy: Pipeline Overview
The spinal muscular atrophy pipeline is dry, however it consists of some of the most advanced medical technologies. Currently,
three drugs are in phase 1, three in phase 2, and one in phase 3 clinical trials.

Sr.
No.

Drug

Phase

Company

Orphan Drug
Designation

ISIS-SMNRx

Isis Pharmaceuticals

U.S. and EU

Olesoxime (TRO19622)

XX

Trophos SA

U.S. and EU

LMI070

XX

Novartis International AG

No

RO6885247

XX

F. Hoffmann-La Roche Ltd.

No

CK-2127107

XX

Cytokinetics, Inc.

No

scAAV9.CB.SMN

XX

AveXis, Inc.

RG3039

XX

Repligen Corporation

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U.S. and EU
U.S.

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Pipeline Analysis: Spinal Muscular Atrophy

Spinal Muscular Atrophy: Late Stage Candidates (Phase 3)

Drug - ISIS-SMNRx

Drug Class - Antisense drug

Indication - Type 1 and type 2 SMA

ISIS-SMN Rx, developed by Isis Pharmaceuticals, is the only drug in phase 3 clinical trials
XXX

XXXXX
If approved, ISIS-SMNRx would be the only drug available of the treatment of spinal muscular atrophy, creating lucrative
opportunity for Isis Pharmaceuticals and Biogen Idec. Hence, the market for this drug candidate is expected to grow rapidly post its
approval in 2018.
In January 2012, Biogen Idec and Isis Pharmaceuticals, Inc. entered into a collaborative agreement for the development and
commercialization of antisense treatment for spinal muscular atrophy. In July 2015, Isis Pharmaceuticals received US$ 2.15 Mn
milestone payment from Biogen for advancing ongoing phase 3 trials.

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Pipeline Analysis: Spinal Muscular Atrophy

Spinal Muscular Atrophy: Late Stage Candidates (Phase 3)

U.S. ISIS-SMNRx Market Forecast, 20182023 (US$ Mn)

2018

2019

2020

2021

2022

2023

ISIS- SMNRx is expected to launch in the U.S. in 2018, post completion of phase 3 clinical trials in June
2017. The drug is projected to record sales of US$ XX Mn in the U.S. by 2023. Isis Pharmaceuticals is
likely to extend the drugs indication for the treatment of other types of spinal muscular atrophy,
thereby expanding patient pool.
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Pipeline Analysis: Spinal Muscular Atrophy

Spinal Muscular Atrophy: Early Stage Candidates (Phase 1 and Phase 2)

Drug - Olesoxime (TRO19622)

Drug Class - Cholesterol oxime

Indication - Type 2 and type 3 SMA

Trophos SA completed the phase 2/3 clinical trials for the treatment of type 2 and type 3 SMA using TRO19622 in Europe in 2014.
The drug candidate was found to be effective in the treatment of various neurodegenerative diseases.
XX

Drug - LMI070

Drug Class - Not disclosed

Indication - Type 1 SMA

Novartis International AG is currently recruiting patients for conducting phase 2 clinical trials to evaluate the safety and tolerability
of LMI070 in the treatment of type 1 SMA. Phase 2 study is expected to complete in November 2016.
XX

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Recommendations
Creating awareness and encouraging SMA carrier screening
XXX
XXX

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Cytokinetics, Inc.

Business Overview

Company Details
Inception

1997

Cytokinetics, Inc. is a clinical stage pharmaceutical

company engaged in the development of novel small

Contact

molecules

+1-650-624-3000

Website

The company entered into a strategic partnership with

Amgen for the development of omecamtiv mecarbil, and

www.cytokinetics.com

Astellas for the development of CK-2127107

Headquarters

South San Francisco, U.S.

Cytokinetics has two potential candidates in the phase 1

and phase 2 stages

Public/Private

Public

Key Business
Segments

Cardiac muscle contractility

Skeletal muscle contractility
Smooth muscle contractility

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Product Portfolio

CK-2127107 (small molecule) in phase 1 clinical trials for

the treatment of spinal muscular atrophy

32

Cytokinetics, Inc.
Financial Details, 20122014 (US$ Mn)
46.9

30.7

7.6

2012

2013

2014

Cytokinetics, Inc. recorded a consistent rise in revenue due to receipt of research and development funds from Amgen
and Astellas. The company suffered a net loss of US$ 14.6 Mn in 2014 as compared to US$ 40.4 Mn in 2012.

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Cytokinetics, Inc.
Strategic Collaborations
In June 2015, Cytokinetics, Inc. partnered with ALS Association for the development of amyotrophic lateral sclerosis (ALS)

therapeutics. Tirasemtiv (CK-2017357) is currently in phase 3 of the clinical trials for the assessment of effects of the drug
vis-a-vis a placebo. The phase 3 trial for Tirasemtiv is expected to be completed in March 2017.

Recent Developments
In July 2015, Cytokinetics announced the initiation of phase 3 clinical trials of Tirasemtiv in the U.S. The trial is expected to
enroll 445 patients with possible, probable, or definite ALS, diagnosed within 24 months and with percent predicted SVC at
baseline 70%. The patients would receive two weeks of open-label treatment with tirasemtiv administered at 250 mg per
day.

In June 2015, Cytokinetics announced the results of phase 1 trials of CK-2127107. The data suggested that the drug was
well tolerated by the patients, and also showed an increase in the force of muscle contraction in dose, concentration, and
frequency-wise studies. The company may initiate phase 2 trials by the last quarter of 2015 in collaboration with Astellas
Pharmaceuticals.

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