Title Layout Details on OMS Onset to Date August 20, 2017 OMS [PDF]

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Title Layout

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OMS Patient Registry – Natural History Study Details on OMS Onset to Date – August 20, 2017

OMS Patient Registry & Natural History Study OMSLife Foundation Caregivers Conference

September 29, 2018

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The OMSLife Foundation - Who we are

Founded in 2012 Our mission is

➢Raise awareness of OMS ➢Provide a support network for patients and caregivers ➢Fund OMS research

We now work with a network of 1,025 OMS patients in 56 countries We have hosted seven OMS caregivers conferences since 2014 We co-host the OMS Medical conference in Abingdon England And now, we are building the first OMS Patient Reported Natural History Study

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Before we discuss our Registry – A special thank you…

Our doctors / presenters:

Dr. Mark Gorman

Kitty Petty

Dr. Angela Waanders
Dr. Wendy Mitchell
Dr. Yasmin Khakoo

Sue Rossov Brian Cisneros Our Board of Directors: Christy Dennis Hank Holley Becky Jennings Bill Bradley Shandi Riccioti Billy Enochs Anja Norman

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Methodology – The OMS Patient Registry

▪ The OMS Patient Reported Registry is a natural history study over time chronicling changes in treatments, therapies, behaviors, relapses, education, and overall quality of life. ▪ Registry funding is supported by a 5 year cooperative agreement between National Organization of Rare Disorders (NORD) and the U.S. Food and Drug Administration (FDA). ▪ Data input is through an online portal housed and maintained by NORD. The portal allows customized data prompts and questions. ▪ Data are stored in a manner that meet all US government mandated standards for data security and PHI protection. ▪ The data collection forms, processes, and outputs were reviewed and approved by Hummingbird IRB. ▪ Data collection initiated Feb 2017. Data views provided in this presentation were as of April 2018.

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Our Survey Process - The OMS Patient Registry

▪ We had 2 teams assist in the survey generation:

▪ Development team – 4 OMS caregivers/stakeholders ▪ Medical team – Mitchell, Lotze, Gorman, Tardieu, Berg

▪ Surveys were created by development team / modified by medical team ▪ Surveys and reports are sent for IRB approval ▪ Programmed by NORD ▪ Then launched ▪ Analytics for this presentation were done with assistance from Trio Health

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What the Registry means to you

OMS Specialists ▪ Provides view on larger sample sets than they can otherwise access ▪ Allows opportunities to have surveys developed for trends they are seeing ▪ Allows quick turnaround on patient data Clinicians ▪ Provides reference materials on a variety of OMS topics ▪ Give alternative options when typical protocols are not working

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Researchers ▪ Provide secondary mechanism to validate findings

▪ Research ▪ Other OMS registries

▪ Provide a base of potential patients for clinical studies Patients and Caregivers ▪ Provide resource information for discussions with clinicians ▪ Provide data for fighting insurance claims ▪ Give realistic view into patient outcomes

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What the Registry means to you

OMS Specialists ▪ Provides view on larger sample sets than they can otherwise access ▪ Allows opportunities to have surveys developed for trends they are seeing ▪ Allows quick turnaround on patient data Clinicians ▪ Provides reference materials on a variety of OMS topics ▪ Give alternative options when typical protocols are not working

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Researchers ▪ Provide secondary mechanism to validate findings

▪ Research ▪ Other OMS registries

▪ Provide a base of potential patients for clinical studies Patients and Caregivers ▪ Provide resource information for discussions with clinicians ▪ Provide data for fighting insurance claims ▪ Give realistic view into patient outcomes

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Numbers have increased since February 2017 launch

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Demographics (n=139)

Age
Race
Ethnicity
Nationality
Gender
Sexual Preference
Occupation
Family
Income
Size
Education
Insurance Type

Onset & Diagnosis (n=123)

Age at time
Dates
Symptoms
Diagnosis
How
Who
Where
Severity

Therapies (n=97)

Type
Speech
Physical
Occupational
Behavioral
Reason for therapy
Start/Stop Dates
Frequency
Effectiveness
Care Agencies

Drug Treatments (n=104)

Type
IVIG
Chemo/Immuno
Steroids
Other
Route
Frequency
Duration
Side effects

OMS Natural History Study Forms and Fields

148 respondents across 4 primary forms as of April 2018..

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Patient Demographics (n=139)

Female 53% Male 47%

Gender

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Birth Country

No. (%)

Australia 2/139 (2%) Brazil 1/139 (1%) Canada 5/139 (3%) Germany 5/139 (3%) Ireland 1/139 (1%) Netherlands 1/139 (1%) Paraguay 1/139 (1%) Spain 1/139 (1%) Sweden 1/139 (1%) United Kingdom 3/139 (2%) United States 118/139 (84%)

American Indian or Alaska Native 1% Asian 2% Black 2% White 85% Other 10%

Race

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Patient Demographics (n=139)

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Family Size

No. (%)

2 family members 4/139 (3%) 3 family members 31/139 (22%) 4 family members 48/139 (36%) 5 family members 35/139 (25%) 6 family members 7/119 (5%) 7 or more family members 8/119 (5%) Not Reported 6/139 (4%)

Yes 96% No 1% No Reply 3%

Health Insurance

49% 4% 10% 4% 4% 1% 1% 27% 0% 20% 40% 60% Private health… State-… Medicaid Medicaid|Privat… Military health… Other… SCHIP… Don't know

Primary Insurance

1% 2% 9% 9% 17% 35% 23% 2% 2% 0% 10% 20% 30% 40% Did not graduate GED High School Grad Trade school Went to College College Grad Post College work Don't Know No Answer

Mother’s Education

2% 3% 13% 5% 15% 35% 18% 5% 4% 0% 10% 20% 30% 40% Did not graduate GED High School Grad Trade school Went to College College Grad Post College work Don't Know No Answer

Father’s Education

24% 27% 18% 6% 8% 17% 0% 10% 20% 30% <$50K $50K<$100K $100K<$150K $150K<$200K $200+ Not reported

Household Annual Income

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87% of patients were ≤36 months at symptoms onset; median age of pediatric onset was 18 months

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4% 12% 36% 15% 13% 7% 10% 3% 0% 5% 10% 15% 20% 25% 30% 35% 40% 0-6 months 7-12 months 13-18 months 19-24 months 25-30 months 31-36 months 3-17 years Adult

Age at Onset N=123 Number Summary Overall Pediatric min 2.0 2.0 25th percentile 14.0 14.0 median 18.0 18.0 mean 32.3 24.2 75th percentile 29.8 29.0 max 420.0 120.0 n 123 120 Age at Onset (months)

Neurologist 84% Oncologist 11% Other 5%

Who diagnosed patient n=123

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Days to Diagnose has decreased; Initial Diagnosis has become more Accurate

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112 168 27 61 38 14 20 40 60 80 100 120 140 160 180 200 Pre 2010 2010-2014 2015-Present

Days to Diagnosis OMS

Mean Median 27% 44% 58% 45% 33% 22% 28% 23% 20% 0% 20% 40% 60% 80% 100% Pre 2010 2010-2014 2015-Present

Initial Diagnosis Trends

OMS Acute Cerebellar Ataxia Other

Initial Diagnosis (n=118*)

Onset Date Before 2010 2010- 2014 2015 – Present OMS 9 17 26 Misdiagnosed 24 22 19

Acute Cerebellar Ataxia

15 13 10

Other

9 9 9 n 33 39 45

Days to Diagnose OMS (n=118)

Onset Date Before 2010 2010- 2014 2015 – Present Min 1 1 1 25th Per 19 16 5 Median 61 38 14 Mean 112.2 167.6 26.8 75th Per 157 127.5 31 Max 922 2038 280 n 33 40 45 *Note – five people did not respond

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Ataxia was the most common symptom at onset, indicated in 85% of patients

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9% 13% 14% 26% 37% 44% 46% 58% 60% 85% 0% 20% 40% 60% 80% 100% Headache Fever Other* Vomiting Temper tantrums Sleep disturbances Tremors Opsoclonus Myoclonus Loss of balance (ataxia)

% Patients with a given symptom at onset (n=123)

*Other includes Clinginess (2), Depression (2), Diarrhea, Excessive Drooling (2), Head Tilt, Hypotonia, Loss of Appetite, Muscle Spams, Nystagmus, Seizures, and Spaced Out.

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Association of Symptoms at Onset

15 OMS Patient Registry – Natural History Study n=10 n=12 n=15 n=30 n=41 n=49 n=54 n=65 n=69 n=94 Headache Fever Other Vomiting Temper tantrums Sleep disturbances Tremors Opsoclonus Myoclonus Loss of balance (ataxia) Headache 33% 20% 17% 17% 14% 9% 12% 10% 11% Fever 40% 7% 23% 15% 10% 9% 15% 10% 11% Other 30% 8% 13% 15% 18% 17% 15% 13% 14% Vomiting 50% 58% 27% 29% 24% 28% 29% 29% 28% Temper tantrums 70% 50% 40% 40% 69% 52% 45% 38% 38% Sleep disturbances 70% 42% 60% 40% 83% 69% 57% 51% 46% Tremors 50% 42% 60% 50% 68% 76% 57% 65% 52% Opsoclonus 80% 83% 67% 63% 71% 76% 69% 75% 60% Myoclonus 70% 58% 60% 67% 63% 71% 83% 80% 67% Loss of balance (ataxia) 100% 83% 87% 87% 88% 88% 91% 86% 91%

Frequency of Symptoms at Onset (columns)

83% of patients with Temper Tantrum also had Sleep Disturbances at symptom onset 69% of patients with Sleep Disturbances also had Temper Tantrums at symptom onset

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OMS Severity

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2 5 4 3 7 9 9 13 6 5 16 14 14 16 2 4 6 8 10 12 14 16 18 5 6 7 8 9 10 11 12 13 14 15 16 17 18

No. Patients by aggregate OMS Severity Score (n=123, max score = 18)

MITCHELL-PIKE OMS SEVERITY SCALE

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OMS Severity by Individual Measures

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Stance Score DESCRIPTION NO. % Standing and sitting balance normal for age 1 1% 1 Mildly unstable standing for age, slightly wide based 19 17% 2 Unable to stand without support but can sit without support 19 17% 3 Unable to sit without using hands to prop or other support 71 65% Total 110 Gait Score DESCRIPTION NO. % Walking normal for age 1 1% 1 Mildly wide-based gait for age, but able to walk indoors and

utdoors independently

14 13% 2 Walks only or predominantly with support from person or equipment 34 31% 3 Unable to walk even with support from person or equipment 61 55% Total 110 Arm/Hand Function Score DESCRIPTION NO. % Normal for age 4 4% 1 Mild, infrequent tremor or jerkiness without functional impairment 13 12% 2 Fine motor function persistently impaired for age, but less precise manipulative tasks normal or almost normal 22 20% 3 Major difficulties in all age-appropriate fine motor and manipulative tasks 71 65% Opsoclonus Score DESCRIPTION NO. % None 4 4% 1 Rare or only when elicted by change in fixation or "squeeze test" 16 15% 2 Frequent, interferes intermittently with fixation or tracking 50 45% 3 Persistent, interfering continuosly with function and tracking 40 36% Total 110 Mood/Behavior Score DESCRIPTION NO. % Normal 6 5% 1 Mild increase in irritability but consolable; and/or mild sleep disturbances 18 16% 2 Irritability and sleep disturbances interfering with child and family life 49 45% 3 Persistent severe distress 37 34% Total 110 Speech Score DESCRIPTION NO. % Normal for age, no loss 23 21% 1 Mildly unclear, plateaued in development 14 13% 2 Loss of some words or some grammatical constructs (i.e. from sentences to phrases) but still communicates verbally 22 20% 3 Severe loss of verbal communication and speech 51 46%

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OMS SEVERITY SCORES OVER TIME

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* Four (4) participants did not have onset date validated

MITCHELL-PIKE OMS SEVERITY SCALE (N=123) OMS Severity Scores Onset Date Before 2010 2010- 2014 2015 – Present Min 8 5 6 25th Per 13 10.3 10 Median 16 15 12 Mean 14.9 13.3 12.3 75th Per 17 16 15 Max 18 18 18 n 37 38 46

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Days to Diagnose has decreased; Initial Diagnosis has become more Accurate; Scores are Down

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112 168 27 61 38 14 20 40 60 80 100 120 140 160 180 200 Pre 2010 2010-2014 2015-Present

Days to Diagnosis OMS

Mean Median 27% 44% 58% 45% 33% 22% 28% 23% 20% 0% 20% 40% 60% 80% 100% Pre 2010 2010-2014 2015-Present

Initial Diagnosis Trends

OMS Acute Cerebellar Ataxia Other

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Therapies Consistently Showed Favorable Results (n=97)

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Therapies Consistently Showed Favorable Results (n=97)

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31 32 8 1 1 33 23 11 2 37 25 8 2 1 17 3 2 1

Behavioral Therapy Occupational Therapy Physical Therapy Speech Therapy

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Here are the Next Steps on our 5 Year Roadmap

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March 2016

NORD Grant

February 28 2017

Registry launch – Rare Disease Day

2017 Goal: 100 Registered participants 2017 total: 190 Registered participants March 2018

First pass analytics

October 2018

Detailed analytics of 150 OMS patients

December 31, 2018

Goal: 400 registered OMS patients Goal: 150 patients completed all surveys

December 31, 2018

Goal: 5 additional surveys developed Goal: 3 OMS SC surveys developed

2019 - Beyond

Detailed analytics Publications and papers produced

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Our next steps

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▪Working on surveys for doctors:

▪ Adolescent and young adult trends (Wendy Mitchell) ▪ Vaccine schedules post remission (Lotze, Mitchell) ▪ Rituximab trends in treatment (frequency, dosage) ▪ Relapse Trends

▪Patient Roadmap ▪Health Tracker

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Would you consider participating in the Registry???

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▪Work on your surveys ▪Keep your surveys updated as life events change ▪Suggest topics and/or questions for the registry

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Ways you can help OMSLife

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▪Amazon Smile – sign up, tell your friends and family ▪Social media help – YouTube, Instagram, Twitter, OMSLife en Espanol ▪Wiki – help us build the Wiki ▪Donate

▪ Fun runs, walks, Facebook events, write a check, buy a t-shirt, etc…

▪Other help

▪ Web site development, help with conferences, etc…

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Special thanks to

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The OMS Registry Project Team Brooke D’Souza Christy Dennis Kellee Miller Our Medical Advisory Team

Dr. Wendy Mitchell
Dr. Mark Gorman
Dr. Tim Lotze
Dr. Marc Tardieu
Dr. Anne Berg

…And NORD who provided the 5 year grant to The OMSLife Foundation

Trio Health Scott Milligan

The patients and caregivers who contributed to the registry The OMSLife Foundation Board of Directors

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