PHASE 3 NON-ABULATORY STUDY
What is “CHERISH?”
CHERISH is a multi-center Phase 3 clinical study evaluating the efficacy of the investigational
compound, ISIS-SMNRx, in children Spinal Muscular Atrophy (SMA). The study is a double-blind,
randomized, sham-procedure (or placebo) controlled pivotal study, designed to examine the
efficacy and safety of ISIS-SMNRx in approximately 117 children with SMA over a 15 month
period. This study is designed to support potential regulatory filings. The study recently
initiated in November and will be open for enrollment at multiple study sites as they receive
regulatory approval.
What will the entry criteria be?
The study will enroll children who are 2 -12 years of age and who have been diagnosed with
Spinal Muscular Atrophy, and who pass additional screening evaluations conducted at the study
site to confirm eligibility. The main inclusion/exclusion criteria for this trial are onset of signs
and symptoms of SMA >6 months of age; 2-12 years of age; can sit independently but has never
had the ability to walk independently; without severe scoliosis. A complete list of study related
criteria for this trial which can also be found here at www.clinicaltrials.gov (search for ISIS + SMA
or NCT02292537).
What does “double-blind” mean?
“Double-blinded” means none of the patients, the parents or the study staff will know if the
patient is assigned to the drug or placebo group.
What is a “sham-procedure?”
The sham-procedure is analogous to the “placebo” group in other studies and is necessary to
ensure the only difference between the groups is whether or not they are exposed to drug, in
order to allow for the best evaluation of the effects of the drug. The sham-procedure consists of
a needle prick on the skin at the site of the lower back where an injection would occur, but no
injection or needle insertion will occur.
Why does there have to be a sham-procedure or placebo group in this study?
As we enter the final stage of development, the regulatory bodies responsible for determining
whether ISIS-SMNRx is a safe and effective treatment for children with SMA have indicated that
well-controlled trials are necessary to establish the benefit and risk of the compound. Due to
the nature of administration, the sham procedure is the most appropriate way to meet this
requirement.
How many patients will be in the sham-procedure group?
The study will be randomized 2:1 so that two-thirds of the patients will receive ISIS-SMNRx and
one-third of the patients will receive the sham-procedure. Our study is designed 2:1 with the
fewest number of sham-procedure patients as possible to meet the statistical standards
necessary to adequately determine the benefit-risk of ISIS-SMNRx. None of the patients,
parents and physicians participating in the study will know whether the patients receive ISISSMNRx or sham-procedure.
What happens to those in sham-procedure or placebo group of the study?
All patients in the study, including those who receive the sham-procedure, will receive the same
care and monitoring. At the end of each subject’s participation in the study, all eligible subjects
(including those in the sham-procedure group) will be able to participate and receive ISIS-SMNRX
in an extension or follow-on study.
Where is the study being conducted?
The study will be conducted at centers in the United States, Canada, Europe and Asia Pacific.
Study sites will be listed on www.smastudy.com and www.clinicaltrials.gov (NCT02292537).
Are there international travel restrictions?
Because the study complies with all applicable international, federal, state and local laws and
regulations regarding the conduct of its clinical trials, including good clinical practices,
international travel restrictions may apply. In addition, to ensure clinical study integrity, there
may be relevant ethical and practical issues to consider when enrolling pediatric SMA subjects.
Eligibility will be determined by the clinical trial investigator at each site, who may consider
factors such as travel distances, medical insurance and their specific institutional policies
regarding international patients.
What if I am willing to relocate to a center outside of my own country in order to participate
in one of your trials?
Your ability to relocate and participate in one of the studies is dependent on local laws and
regulations. Each situation would need to be addressed on a case-by-case basis by the clinical
trial investigator. In assessing the situation, the investigator may want to talk with you about
your unique family situation and may ask you to consider factors such as medical insurance. We
encourage you to contact a study site to discuss your specific circumstances.
What if my child doesn’t qualify for the study?
Unfortunately, we will not be able to immediately meet the needs of every family through our
clinical development program, and for that we are truly sorry, but we are committed to
completing the Phase 3 pivotal studies as quickly as possible so that if ISIS-SMNRX is safe and
effective, it can be made available to the SMA community in the shortest period of time.
You have two Phase 3 studies for Type 1 & 2 children with SMA. Will you have something for
Type 3s?
We believe our best chance of accomplishing this goal is to study ISIS-SMNRX in individuals with
Type 1 & Type 2 SMA through our pivotal studies, ENDEAR & CHERISH. At this time, we have no
plans to initiate a clinical study for individuals with Type 3 SMA. Our ultimate goal is to prove
the safety & efficacy of ISIS-SMNRX as quickly as possible so that we can hopefully obtain
approval as rapidly as possible.
We know that each decision made about our clinical program impacts patients and families
around the world, but believe this decision is necessary to definitively learn as quickly as
possible whether or not ISIS-SMNRX is a safe and effective treatment option for patients with
SMA.
Will I still be able to take the approved drug if I can’t participate in the trial or if my patient
type is not included in the trial?
As with any treatment, the conversation about the best and most appropriate treatment option
takes place between you and your physician.
The actual labeled indication for the drug, if approved, will ultimately be a discussion between
the company and regulators following the submission of the new drug application to regulatory
agencies. The current clinical development program is designed to demonstrate the
effectiveness and safety of the drug in the shortest time possible in hopes of making the drug
available to the SMA community.
Are you not studying my type because you don’t think the drug will work for me?
At this time, the safety and effectiveness of ISIS-SMNRX is not yet proven in any population. The
pivotal studies in the clinical program have been designed with the intent of robust evaluation
of the safety and efficacy of the drug in as short a time frame as possible.
Do you have any additional clinical studies in development?
In addition to our current Phase 3 clinical studies ENDEAR & CHERISH, our partner Biogen Idec
will be conducting two additional studies which could begin in the first half of 2015:
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NURTURE will be a Phase 2 clinical study evaluating ISIS-SMNRx in up to 25 presymptomatic newborns that are genetically predisposed to the disease.
EMBRACE will be a Phase 2 clinical study evaluating safety and exploratory
efficacy of ISIS-SMNRx in approximately 20 patients with infantile or childhoodonset SMA. This study will bridge the gap in a small subset of patients that do
not meet the age and inclusion criteria of the current Phase 3 studies ENDEAR
and CHERISH.
As the ongoing trials progress we will be evaluating our clinical program and communicate any
changes to our plans at that point in time.
Where can I go for further information about SMA?
The website www.LearnAboutSMA.org has some excellent information about SMA –
information specifically about ISIS-SMNRx can be found on that website under the heading
“antisense”. Other good resources are www.curesma.org, www.smafoundation.org, and
www.mda.org.
Where can I get more information about this study?
If you would like further information, please contact your study site directly or visit
www.clinicaltrials.gov (NCT02292537) or www.smastudy.com.