SMA CLINICAL CARE

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SMA CLINICAL CARE MEETING

2 | 3RD ANNUAL SPINAL MUSCULAR ATROPHY CLINICAL CARE MEETING 2020

Dear Clinicians,

Welcome to the Clinical Care Session of the 2020 SMA Research & Clinical Care Meeting!

In our virtual format, Cure SMA is pleased to bring together the SMA care community to exchange ideas, challenges, and successes as we work together to provide every person with SMA optimal care and treatment. We encourage you to ask questions, and we hope you will participate in our virtual Friday evening celebration with families, researchers, and healthcare providers.

The Cure SMA mission is to lead the way to a world without spinal muscular atrophy (SMA). We fund and direct com-prehensive research that drives breakthroughs in treatment and care, and we provide families the support they need for today. We believe that hosting and financially supporting this meeting helps achieve this mission by promoting discussions about clinical innovations and the impact of new therapies on the clinical landscape. Our specific meeting goals are to:

· Provide an opportunity for SMA healthcare providers across disciplines to share knowledge.· Facilitate collaborative discussions between healthcare providers to achieve improved care for SMA.· Foster clinical care research collaboration across Cure SMA Care Centers.

The Cure SMA Care Center Network and SMA Clinical Data Registry is advancing the collection of clinician-entered data on people with SMA. The data generated will help to create evidence-based guidelines for care, better characterize the changing SMA phenotype, and move care and new treatments forward. SMA newborn screening is also moving forward and as of May 1, 2020, 26 states are screening for SMA either permanently (23) or as a pilot (3). This represents screening approximately 50 percent of all infants born in the U.S.

We thank our presenters for their work and contributions to the conversation today.

We thank the Cure SMA Medical Advisory Council for their time and effort reviewing presentation abstracts and orga-nizing this meeting. Their help is invaluable. We also thank our generous sponsors whose support made this meeting possible.

Cure SMA appreciates your ongoing commitment to the care of all with SMA and to the SMA Community. Your par-ticipation is essential in our mission for a world without SMA.

Sincerely,

Mary Schroth, MDCure SMA Chief Medical Officer

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Abigail ParasCure SMA Clinical Care Program Manager


12:00 PM to 12:15 PM Welcome and CMO UpdateMary Schroth, M.D., Chief Medical Officer, Cure SMA

12:15 PM to 12:30 PM Effect of Nusinersen on Respiratory Muscle Function in Different Subtypes of SMA1

Antonella LoMauro

12:30 AM to 12:45 PM Two-Year Follow Up of Treatment with Intrathecal Nusinersen and Its Effects on Motor, Respiratory and Bulbar Function in Children with SMA Types 1b-3a

Feline Scheijmans

12:45 AM to 1:00 PM Early Intervention of Augmentative Alternative Communication (AAC) the Importance of Supporting Speech and Communication in SMA1 Children

Grazia Zappa

1:00 AM to 1:15 PM Standardized Videofluoroscopic Swallow Study Protocol for Evaluating SMA Treatment Response and Predicting Disease Trajectory

Katlyn Elizabeth McGrattan, PhD

1:15 PM to 2:30 PM Special Session: Ethics Case Study

Moderator: Julie Parsons, MD

Panelists: Tom Crawford, MD, John Brandsema, MD, and Bakri Elsheikh, MD

Ethicists: Alyssa Burgart, MD, MA, and Brian Jackson, MD, MA

2:30 PM to 2:45 PM BREAK

2:45 PM to 3:00 PM Combination Gene Modifying Therapies for Type 1 SMA: Real World Clinical Experience

Aravindhan Veerapandiyan, MD

3:00 PM to 3:15 PM Early Single Center Clinical Experience with Onasemnogene Abeparvovec-xioi in SMA Type 1 and 2 Patients Over Age 7 Months

Susan Matesanz, MD

3:15 PM to 3:30 PM The Canadian Neuromuscular Disease Registry: A National SMA Registry for Real World Evidence

Victoria Hodgkinson-Brechenmacher, PhD

3:30 PM to 3:45 PM Validity and Reliability of the Neuromuscular Gross Motor Outcome (GRO) in SMALindsay Alfano, PT, DPT

3:45 PM to 4:00 PM End of CME/CE Sessions - BREAK

NOT FOR CME/CE CREDIT

4:00 PM to 4:15 PM Long-Term Follow-Up (LTFU) of Onasemnogene Abeparvovec Gene Therapy in SMA Type 1 (SMA1) from Phase 1 START TrialJerry Mendell, MD

4:15 PM to 4:30 PM Intravenous Onasemnogene Abeparvovec Clinical Development Programs in SMA: Integrated Safety ReportDeepa Chand, MD

4:30 PM to 5:10 PM SHINE Panel

Motor Function Change Over Time Among Nusinersen-Treated Participants with Infantile-onset SMA in the ENDEAR-SHINE Study who met the Permanent Ventilation Definition Diana Castro, MD

Nusinersen in Infantile-onset SMA: Results from Longer-term Treatment from the Open-label SHINE Extension Study Richard Finkel, MD

Longer-term Treatment with Nusinersen: Results in Later-onset SMA From the SHINE Study Basil Darras, MD

Nusinersen in Adolescents and Young Adults with SMA: Longitudinal Experience from an Expanded Basil Darras, MD

JUNE 1O, 2020

WEDNESDAY12:00 PM – 5:10 PM (CT)

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CME INFORMATION Clinical Care CME Session is jointly provided by Postgraduate Institute for Medicine and Cure SMA.

The Clinical Care CME Session is supported in part by independent educational grants from Biogen, AveXis, and Genentech, a member of the Roche Group.

TARGET AUDIENCEThis activity is intended for physicians, registered nurses, advanced practice registered nurses, pharmacists, social workers, and other healthcare providers engaged in the care of patients with spinal muscular atrophy (SMA).

EDUCATIONAL OBJECTIVESAfter completing this activity, the participant should be better able to:Demonstrate knowledge of multidisciplinary team roles and responsibilities in care management to optimize SMA outcomes.

• Describe the existing and evolving treatment options for patients with SMA.• Describe the impact of new treatments on the SMA phenotype.• Analyze the treatment options for management of infants with SMA identified by SMA newborn screening.• Evaluate strategies for assessing motor function outcomes.• Describe the considerations for SMA treatment recommendations when evidence is limited.

FACULTYMary Schroth, M.D., Chief Medical Officer, Cure SMA

Antonella LoMauro, Polytechnic University of Milan

Feline Scheijmans, Utrecht University

Grazia Zappa, CSCA, Center for Augmentative Communication

Katlyn Elizabeth McGrattan, Ph.D., University of Minnesota

Julie Parsons, M.D., Children’s Hospital Colorado

Tom Crawford, M.D., John’s Hopkins University

John Brandsema, M.D., Children’s Hospital of Philadelphia

JOINT ACCREDITATION STATEMENTIn support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and Cure SMA. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.

PHYSICIAN CONTINUING MEDICAL EDUCATIONThe Postgraduate Institute for Medicine designates this live activity for a maximum of 3.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Bakri Elsheikh, M.D., The Ohio State University

Alyssa Burgart, M.D., MA, Stanford University

Brian Jackson, M.D., MA, Children’s Hospital Colorado

Aravindhan Veerapandiyan, M.D., Arkansas Children’s Hospital

Susan Matesanz, M.D., Children’s Hospital of Philadelphia

Victoria Hodgkinson-Brechenmacher, Ph.D., University of Calgary

Lindsay Alfano, PT, DPT, Nationwide Children’s Hospital


CONTINUING PHARMACY EDUCATIONPostgraduate Institute for Medicine designates this continuing education activity for 3.5 contact hour(s) (0.35 CEUs) of the Accreditation Council for Pharmacy Education.

(Universal Activity Number - JA4008162-9999-20-2095-L01-P)Type of Activity: Application

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Mobile device: iPhone 4S or later, iPad 2 or later

CONTINUING NURSING EDUCATIONThe maximum number of hours awarded for this Continuing Nursing Education activity is 3.5 contact hours. Pharmacotherapy contact hours for Advance Practice Registered Nurses will be designated on your certificate.

CONTINUING SOCIAL WORK EDUCATIONAs a Jointly Accredited Organization, Postgraduate Institute for Medicine is approved to offer social work continuing education by the Association of Social Work Boards (ASWB) Approved Continuing Education (ACE) program. Organizations, not individual courses, are approved under this program. State and provincial regulatory boards have the final authority to determine whether an individual course may be accepted for continuing education credit. Postgraduate Institute for Medicine maintains responsibility for this course. Social workers completing this course receive 3.5 clinical continuing education credits.

DISCLOSURE OF CONFLICTS OF INTERESTPostgraduate Institute for Medicine (PIM) requires instructors, planners, managers, and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.


FACULTYMary Schroth, MD

Consulting fees: Audentes

Antonella LoMauro – Has nothing to disclose

Feline Scheijmans – Has nothing to disclose

Grazia Zappa – Has nothing to disclose

Katlyn Elizabeth McGrattan, PhD

Receipt of Intellectual Property Rights/Patent Holder: nuBorn

Medical, Science Stand

Consulting fees: Biogen

Contracted Research: Biogen

Julie Parsons, MD

Consulting fees: AveXis, Biogen

Contracted Research: AveXis, Biogen, Scholar Rock

Tom Crawford, MD – Has nothing to disclose

John Brandsema, MD

Consulting fees: Audentes, AveXis, Biogen, Genentech, PTC

Therapeutics, Sarepta, and WaVe

Fees for Non-CME/CE Services: AveXis, Biogen

Contracted Research: Alexion, AveXis, Biogen, CSL Behring,

Fibrogen and WaVe

Bakri Elsheikh, MD

Consulting fees: Biogen, Argnex, BioStealth Contracted

Research: Biogen, Alexion, VCB, Celgene

Alyssa Burgart, MD, MA – Has nothing to disclose

Brian Jackson, MD, MA – Has nothing to disclose

Aravindhan Veerapandiyan, MD

Consulting fees: Avexis, Biogen, PTC Therapeutics

Fees for Non-CME/CE Services: AveXis

Contracted Research: Sarepta, AveXis, Genentech, Pfizer,

Amgen, Impax

Susan Matesanz, MD – Has nothing to disclose

Victoria Hodgkinson-Brechenmacher, PhD – Has nothing to

disclose

Lindsay Alfano, PT, DPT

Consulting fees: Biogen, Genentech

PLANNERS AND MANAGERSThe PIM planners and managers have nothing to disclose. The CureSMA planners and managers have nothing to disclose.

DISCLOSURE OF UNLABELED USEThis educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.


FEE INFORMATIONThere is no fee for this educational activity.

DISCLAIMERParticipants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient's conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

REQUEST FOR CREDITIn order to obtain your CME/CE certificate, please follow the steps below at the conclusion of the virtual meeting:

1. Go to www.cmeuniversity.com2. Login or Create a New Account (will take less than 1 minute)

a. If you receive a message when creating a new account that “the email you entered is already in use”, please click the Forgot my Username or Password link to have your Username and Password sent to you via email

b. After logging in, you may be asked to verify/update your information; after doing so, click Save at the bottom of the page

3. Type in 15413 at the top of the page, “Find Post-Test/Evaluation by Course”, and click enter4. Click on the activity title when it appears5. Choose the type of credit you desire6. Complete the online Evaluation7. Receive an immediate CME/CE Certificate to download and/or print for your files

For Pharmacists: Upon completion of the online evaluation, your credit will be submitted to CPE Monitor. Pharmacists have up to thirty (30) days to complete the evaluation and claim credit. Please check your NABP account within thirty (30) days to make sure the credit has posted.

If you have questions regarding the certification of this activity, please contact PIM via email at [email protected].


PROGRAMABSTRACTS

PLEASE DO NOT RECORD THE SESSIONS OR TAKE SCREENSHOTS OF THE SLIDES.

If you have any questions regarding this policy, please contact [email protected].

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3RD ANNUAL SPINAL MUSCULAR ATROPHY CLINICAL CARE MEETING 2020

Antonella LoMauro 1, Andrea Aliverti 1 1 Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano (Italy)

Background: Nusinersen was shown to have a significant motor milestone response, however, there is no information on its effects on respiratory function that strongly affects the prognosis in SMA1. Ribcage muscle weakness is a distinctive feature of SMA1 since infancy, while the diaphragm is spared and leads the breathing function. The non-invasive assessment of respiratory function in terms of respiratory and thoraco-abdominal pattern during quiet breathing by optoelectronic plethysmography is highly informative, even in uncooperative infants. We aimed to compare respiratory function of a group of 27 SMA1 nusinersen treated infants and children (age:2 yrs) with a control group of 32 natural history patients (0.8 yrs) to understand if and how nusinersen impacts on the respiratory function in SMA1.

Results: The ventilatory pattern differed according to the subtypes in natural history (17 A-B patients: ABnh and 15 C: Cnh): while total minute ventilation was similar, respiratory rate and tidal volume differed, resulting in more severe rapid and shallow breathing index (RSBi) in ABnh. In the treated group (15 A-B patients: ABtr and 12 C: Ctr), respiratory rate still remained higher in the ABtr, but tidal volume, minute ventilation and RSBi were similar between ABtr and Ctr. In addition to motor function improvement assessed by CHOP INTEND scale (ABnh =21; Cnh=26; ABtr=27; Ctr=44), the most striking difference between the groups emerged in the action of ribcage muscles, as indicated by the percentage contribution of pulmonary ribcage to tidal volume (%ΔVRC,p). In untreated patients, %ΔVRC,p did not differ (p=0.952) between ABnh and Cnh being always negative, thus confirming the systematic presence of paradoxical inspiratory inward thoracic motion. By contrast in the treated groups, %ΔVRC,p of ABtr was negative and similar to ABnh (p=0.664), while Ctr were characterized by highest and positive values of %ΔVRC,p (p< 0.001), thus demonstrating absence of thoraco-abdominal breathing asynchrony. In addition, Ctr were characterized by significantly lower daily hours of mechanical ventilation (4.5, p< 0.001) compared to ABtr (11) whose values did not differ to natural history groups (ABnh =20; Cnh=12). Both age of starting and treatment duration were similar between ABtr and Ctr and therefore they did not affect results. SMN2 gene copy number was significantly higher in Ctr (50% with two copies and 50% with three copies, with no difference between the two groups).

Conclusions: This is the first evidence of the efficacy of nusinersen on respiratory function in SMA1. However, the responsiveness was dramatically different according to disease subtypes, with Ctr being the best responders; ABtr showing significant improvement in motor function but respiratory function almost following natural history pattern even after 1 year of treatment. Future larger studies are needed to identify drug responders and nonresponders, with age of symptoms onset, clinical presentation and SMN2 copy numbers as independent factors. Although nusinersen has opened up scenarios of motivated hope, our data further highlighted that adequate supportive care should remain imperative for SMA1 infants and children, particularly subtypes 1A-B.

Acknowledgements: The authors thank the children and families who kindly participated to the study.

EFFECT OF NUSINERSEN ON RESPIRATORY MUSCLE FUNCTION IN DIFFERENT SUBTYPES OF SMA1

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Feline E.V. Scheijmans 1, MD, Inge Cuppen MD, PhD 1, Ruben P.A. van Eijk 2, MD,PhD, Marja A.G.C. Schoenmakers PhD 3, Danny R. van der Woude 3, Bart Bartels MSc 3, Esther S. Veldhoen MD, PhD 4, Fay-Lynn Asselman1, Renske I. Wadman MD, PhD1, W. Ludo van der Pol MD, PhD 1

1 Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, The Netherlands 2 Biostatistics & Research Support, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, The Netherlands 3 Department of Paediatrics, Child Development and Exercise Centre, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Utrecht University, The Netherlands 4. Department of Paediatric Intensive Care, University Medical Centre Utrecht, Utrecht, Utrecht University, The Netherlands.

Background: Data on efficacy and adverse events from the treatment with nusinersen in SMA patients mostly results from clinical trials. In these trials, only younger patients with relatively short disease duration were included. Treatment efficacy in older SMA patients with longer disease duration is therefore uncertain. Next, primary and secondary outcomes in trials were survival and/or motor function, but effects on respiratory or bulbar function are as of yet unknown. We studied efficacy and adverse events in all Dutch children with SMA types 1, 2 and 3a treated with nusinersen between 2017 and 2019 and investigated effects on motor, respiratory and bulbar function in particular.

Results: In total 72 out of 81 eligible patients started nusinersen treatment. Sixty-nine patients were included in this cohort study: 23, 30 and 16 patients SMA types 1, 2 and 3a. Median follow-up was 24, 16 and 12 months (range 5-34 months) in SMA types 1, 2 and 3 respectively. None of the patients consistently declined on all motor function measures. Motor function improvement plateaued in the majority of patients, but timing of this plateau was variable. Eight SMA type 1 patients gained independent sitting. One lost this gained motor milestone during treatment due to severe scoliosis. Six type 2 patients gained a new motor milestone, none of these gained milestones was lost. None of the SMA type 3 patients gained or lost motor milestones during follow up. Longer disease duration before start of treatment correlated with stabilization on motor scores (CHOP-INTEND, HINE-2 and HFSME) rather than improvement. In patients with SMA type 1, in four non-invasive respiratory support was initiated, but none needed invasive respiratory support. Median respiratory hours per day declined in patients already receiving (non-)invasive respiratory support. Three patients with type 1 started enteral feeding. In SMA type 2 patients, there was a slight increase in de median hours of ventilation from 10.5 (10-12) to 12 (11-14) hours per day in patients already on respiratory support. One patient had to start non-invasive respiratory support during follow up. Two patients with type 2 started enteral feeding. None of the type 3 patients were in need of respiratory support or enteral feeding. In 579 intrathecal injections, ninety-one (16%) treatment related adverse events occurred in 52 (73%) patients.

Conclusions: Real-life data on nusinersen treatment in children with SMA type 1b-3a up to the age of 9.5 years shows a beneficial effect on motor function and scores, with virtually all patients improving or stabilizing during treatment. Despite improvement or stabilization on motor function, effects on respiratory and bulbar function are variable.

Acknowledgments: The authors would like to thank all patients and their families for participating in our Dutch SMA registry. This study was funded by Prinses Beatrix Fonds.

TWO-YEAR FOLLOW UP OF TREATMENT WITH INTRATHECAL NUSINERSEN AND ITS EFFECTS ON MOTOR, RESPIRATORY AND BULBAR FUNCTION IN CHILDREN WITH SMA TYPES 1B-3A

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Grazia Zappa, Emilia Cavallo, Nataly Vivenzio, Maria Antonella Costantino CSCA- Center for Augmentative Communication, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano

Background: Children with SMA Type 1 (SMA1) demonstrate severe oral motor weakness and flaccid dysarthria up to complete anarthria. Functional communication, a key quality of life feature, is significantly affected by SMA1. Despite clear evidence that AAC (Augmentative and Alternative Communication) improves communication for those with neuromuscular disorders, the dynamics that determine how to implement AAC for those with SMA1 are not clearly understood (e.g., referral process, assessment timing, staging interventions, optimizing communication development) (Ball & al, 2019). Ensuring successful communication between SMA1 children and their communication partners is a necessary element of SMA1 care, and we would like to describe SMA1 patients’ profile and phases of communication needs.

Results: Up to date a total of 101 patients with SMA1, 6 months to 14 years, have an active AAC intervention, 80 for non-speakers and 21 for speakers, in our service. For SMA1 children it is critical that a proactive focus on early introduction of AAC strategies, is implemented. It is so critical because considering AAC strategies only when speech difficulties are evident or when significant motor difficulties emerge could lead to losing the ‘window of opportunity’ that the first three years of life play in the child's development. It is within three years that the brain's compensatory possibilities are so vast that it is best to develop alternative mechanisms. If this period is neglected, the child's development potential in certain areas may be completely closed or extremely reduced. We developed a model of AAC for SMA1: counseling, assessment, customization and implementation, adapted to new SMA phenotypes emerging with new treatments. While there are always individual differences in how any kid with SMA1 is introduced to AAC following a feature matching process, a core list of considerations are part of the protocol of proactive strategies. Each of these considerations will be discussed in detail during this presentation and further highlighted through video demonstration. We will: - Discuss benefits of proactive intervention to successful use of AAC strategies throughout the course of the SMA1 disease - Describe at least six AAC strategies that can be introduced to support either speakers or non-speakers - Discuss and define protocols for supporting the communication environment.

Conclusions: We aim to highlight various facets of AAC delivery in SMA1 patients, assessment and intervention strategies. Our model provides a good deal of optimism about the effects of AAC early intervention on the development of language and communication skills in children who receive intervention from early in development. The data strongly suggests that families and practitioners should be very confident in using AAC interventions with very young children, from six months old. AAC interventions do not inhibit the development of speech; rather, they support the development of language and communication skills. This model has been further bolstered by positive feedback from people with SMA1 and their families who have been exposed to a proactive approach to exploring a range of AAC strategies.

Acknowledgements: The authors are grateful to children and their parents who participated in this study, without whom this effort would not have succeeded, and Italian "Famiglie SMA" Association.

EARLY INTERVENTION OF AUGMENTATIVE ALTERNATIVE COMMUNICATION (AAC) THE IMPORTANCE OF SUPPORTING SPEECH AND COMMUNICATION IN SMA1 CHILDREN

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Katlyn Elizabeth McGrattan1-2, Michael Murati 3-4, Katie Walsh 5, Kayla Hernandez 6, Vamshi Rao 7, Basil Darras 8, Peter Karachunski 9-10

1 Department of Speech-Language Hearing Science, University of Minnesota, Minneapolis, MN USA 2 Department of Rehabilitation, Masonic Children’s Hospital, Minneapolis, MN USA 3 Department of Radiology, Masonic Children’s Hospital, Minneapolis, MN USA 4 Department of Radiology, University of Minnesota, Minneapolis, MN USA 5 Department of Rehabilitation, Lurie Children’s Hospital, Chicago, IL USA 6 Department of Otolaryngology, Boston Children’s Hospital, Boston, MA USA 7 Department of Neurology, Lurie Children’s Hospital, Chicago, IL USA 8 Department of Neurology, Boston Children’s Hospital, Boston, MA USA 9 Department of Neurology, Masonic Children’s Hospital, Minneapolis, MN USA 10 Department of Neurology, University of Minnesota, Minneapolis, MN USA

Background: Dysphagia has historically been a leading source of morbidity and mortality among patients with infantile-onset type 1 SMA. Although the early provision of new disease modifying therapies enables this critical function to be preserved in some children, others, seemingly similar in clinical appearance, continue to exhibit profound bulbar degradation. Developing methods of delineating these groups is critical to proactively implementing the necessary clinical regimens. In this investigation, we will review how the standardized utilization of the videofluorosocpic swallow study can fill this void by enabling early detection of asymptomatic oropharyngeal weakness and quantifying the response of these deficits to disease modifying treatments.

Results: A series of investigations on non-SMA dysphagic infants were conducted to develop standardized fluoroscopic procedures, analysis metrics, and clinical protocols to enable standardized videofluoroscopic swallowing assessment among infants with spinal muscular atrophy. Procedural protocols guiding timepoints of fluoroscopic visualization include the evaluation of swallowing at four standardized timepoints (min:sec): 00:00, 00:30, 01:30, 02:30. During this time infants were provided thin Varibar barium contrast from a Dr. Browns bottle system. Following exam execution, exams were analyzed using the BabyVFSSImP, a validated rank ordered metric allowing clinical measurement of swallowing physiology and bolus flow. Results from these investigations demonstrated dysphagic infants exhibit a decline in oropharyngeal swallowing physiology throughout the course of the fluoroscopic exam (p< 0.001). Changes were characterized by an increase in the number of sucks per swallow (p=0.004), percent of swallows with incomplete bolus hold (p≤ 0.003), delayed initiation of pharyngeal swallow (p≤ 0.02), delayed timing of swallow initiation (p≤ 0.04), and bolus airway entry (p=0.0004). This procedural protocol was then implemented on newly diagnosed SMA patients at the time of diagnosis, regardless of symptoms, and following the provision of disease modifying treatment with the utilization of remote feeding monitoring by a speech-language pathologist in the interim period. Results demonstrate the feasibility of this workflow, and the potential to provide objective measures of SMA deficits and treatment response for direct clinical application.

Conclusions: The use of a standardized procedural protocol is necessary to ensure the validity and reliability of fluoroscopic results. Implementation of these standardized fluoroscopic methods and referral workflows is feasible and may aid in proactive management of aerodigestive deficits. Future work is necessary to delineate differences in dysphagia phenotypes and remote monitoring methods for continuous monitoring of SMA patients.

Acknowledgments: The team would like to thank the support of Biogen for fostering international discussion of bulbar physiology and function in patients with SMA in their online medical forums.

STANDARDIZED VIDEOFLUOROSCOPIC SWALLOW STUDY PROTOCOL FOR EVALUATING SMA TREATMENT RESPONSE AND PREDICTING DISEASE TRAJECTORY

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Yohei Harada MD 1, Vamshi K. Rao MD* 2, Kapil Arya MD* 3, Nancy Kuntz MD 2, Christine DiDonato PhD 2, Galia Napchan-Pomerantz MD 4, Amit Agarwal MD 5, Vikki Stefans MD 6, Aravindhan Veerapandiyan MD 3 *authors contributed equally 1 Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 2 Division of Neurology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois 3 Division of Neurology, Department of Pediatrics, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas 4 Department of Pediatric Pulmonology, Joe DiMaggio Children’s Hospital, Hollywood, Florida 5 Division of Pulmonology, Department of Pediatrics, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, AR 6 Department of Pediatrics and Physical Medicine and Rehabilitation, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Background: Two disease modifying therapies with different mechanisms of action for spinal muscular atrophy generates a potential for combination therapy: nusinersen and onasemnogene abeparvovic (previously labeled as AVXS-101 in clinical trials/managed access program and Zolgensma after FDA approval). Data on experience with combining gene modifying therapies for spinal muscular atrophy is lacking. The objective is to describe our centers’ experience in treating patients with spinal muscular atrophy type 1 with dual gene modifying therapies in the clinical setting. This is a retrospective study conducted at Arkansas Children’s Hospital, and Ann and Robert H. Lurie Children's Hospital of Chicago. Patients with spinal muscular atrophy type 1 that received combination therapy were included.

Results: Five children with spinal muscular atrophy type 1 (2 copies of SMN2) received both nusinersen and AVXS-101/Zolgensma. Four patients (patients 1, 2, 4, and 5) were receiving nusinersen prior to administration of AVXS-101/Zolgensma. Subjective and objective improvements were noted. They received AVXS-101/zolgensma at 21 (9.5 Kg), 18 (10.5 kg), 23 (10.5kg), 23 months (8.46kg) of age respectively and continued to show improvements. Nusinersen was continued on 3 of these patients. Significant elevation of liver enzymes was noted in patients 1 and 2 that resulted in hospitalization, liver biopsy, and intravenous corticosteroids for patient 2, and prolonged steroid course for both. Mild elevation of liver enzymes noted after AVXS-101/zolgensma was treated with oral steroids in the other 2 cases. One patient (patient 3) diagnosed at 5 months of age received AVXS-101 at 6 months. Nusinersen was started around 9 months as there was no functional motor improvement after AVXS-101. No adverse effects were noted in this patient. More data on motor functional assessments and follow-up will be presented at the meeting.

Conclusions: Our cases represent a cohort of older and heavier patients that received gene replacement therapy compared to the clinical trials. Since the therapies have different targets and the therapeutic response could vary from one to the other, combination therapy can be a consideration. However, closer and longer monitoring for adverse events and prolonged use of steroids will likely be required based on individual patient response. Key players in treatment decisions including physicians and families of patients with spinal muscular atrophy should be aware of such possible deviations from the recommended surveillance and management. Further studies are needed to better understand the combination of gene modifying therapies.

Acknowledgements: We thank our patients and their families for their contribution.

COMBINATION GENE MODIFYING THERAPIES FOR TYPE 1 SMA: REAL WORLD CLINICAL EXPERIENCE

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Susan E. Matesanz 1, Vanessa Battista 1, Jean Flickinger 2, Jennifer Jones 2, Elizabeth A. Kichula 1

1 Children's Hospital of Philadelphia, Division of Neurology 2 Children's Hospital of Philadelphia, Department of Physical Therapy

Background: Onasemnogene abeparvovex-xioi (onasemnogene) was approved by the Food and Drug Administration in May 2019 for treatment in children with all types of SMA under age 2. The initial clinical trials leading to approval only included children 7 months and younger. With FDA approval, dosing began in older Type 1 patients as well as in Type 2 patients, many of whom were previously treated with nusinersen. Here, we aim to report our single center early clinical experience with onasemnogene in SMA type 1 and 2 patients > 7 months, given the lack of data from prior clinical trials in this patient population.

Results: Seven children > 7 months received onasemnogene from July 2019 to February of 2020. Four were classified as SMA Type 2 and three as SMA Type 1. Type 2 patients were diagnosed at an average (avg) age of 11.7 months and Type 1 at avg of 3.32 months. 5/7 patients received nusinersen at avg of 8.7 months prior to treatment with onasemnogene. Onasemnogene was given at avg of 16.9 months in type 2 patients and 11.6 months in type 1 patients. Avg weight was 10.1 kg and 9.1 kg in Type 2 and Type 1 patients, respectively.

5/7 patients were febrile and 4/7 had emesis within 2-3 days of dosing which resolved within 1-2 days. Two were hospitalized for monitoring. All had a drop in platelet count one week after dosing, and 4/7 had thrombocytopenia < 100 K/uL (avg 45), none were symptomatic; all platelets improved to > 100 K/uL by 2 weeks post-infusion.

All had elevations of AST one week after dosing, averaging 2.7x upper limit of normal (ULN). 6/7 had ALT elevation ALT (avg 2.1 ULN). In patients with > 2 months of follow-up (n=4), peak AST was 4.24x ULN (range 3.7-5.8) occurring at an avg of 22.5 days post dosing. ALT (7.1x ULN, range 3.7-12.9) and GGT (2.7x ULN, range 1.5-4.7) peaks occurred later, at avg of 40 and 41.5 days, respectively. All 4 required prolonged steroid courses and ¼ required IV pulse dosing.

In first month of follow-up after onasemnogene, Hammersmith Functional Motor Scale Expanded (HMFSE) increased by average of 5 points (n=3) in Type 2 patients; the 4th Type 2 patient had no increase in CHOP-INTEND, but regained the ability to sit. At 6 months of follow-up, HMFSE increased an average of 8 points (n = 3). Follow-up data in Type 1 patients (n= 3) is pending.

Conclusions: Early clinical experience with onsasemnogene in SMA type 2 patients suggests improvement in motor function as measured by HMFSE and CHOP-INTEND. Data in older Type 1 patients is pending. Additional data on those not treated prior or concurrently with nusinersen is necessary to be able to fully analyze and understand the effect of treatment with onsasemnogene alone and with concurrent nusinersen. Side effects of onsasemnogene, including acute viral syndrome, thrombocytopenia, and transaminitis, may be higher in older (> age 7 months) than those reported in younger, smaller patients.

Acknowledgments: We would like to thank the amazing multi-disciplinary neuromuscular team at the Children’s Hospital of Philadelphia, as well as our patients and their families.

EARLY SINGLE CENTER CLINICAL EXPERIENCE WITH ONASEMNOGENE ABEPARVOVE -XIOI IN SPINAL MUSCULAR ATROPHY (SMA) TYPE 1 AND 2 PATIENTS OVER AGE 7 MONTHS

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Victoria Hodgkinson 1, Maryam Oksoui 2, Craig Campbell 3, Josh Lounsberry 1, Bernard Brais 4, Alex MacKenzie 5, Hugh McMillan 5, Jiri Vajsar 6, Lawrence Korngut 1, and the CNDR Investigator Network 1 University of Calgary, Calgary, Canada2 Montreal Children's Hospital, McGill University, Montreal, Canada 3 Western University, London, Canada4 Lucie Bruneau, McGill University, Montreal, Canada5 Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada6 Sick Kids Hospital, University of Toronto, Toronto, Canada

Background: The effectiveness of nusinersen for SMA must be assessed across a broad range of patients with multiple comorbidities and variable disease severity over a long timeframe. The Canadian Neuromuscular Disease Registry (CNDR) is a nationwide pan-neuromuscular disease registry that prospectively collects SMA-specific data in 31 clinics (15 pediatric and 16 adult) across Canada. The objective of the study is to describe real-world evidence from the Canadian Neuromuscular Disease SMA Registry. Therapy availability in Canada is provincially regulated with inclusion criteria.

Results: The CNDR has 256 individuals with SMA registered. Data is presented on 146 individuals, collected between 2015-2020. Nusinersen therapy was used in 78, 58, and 43% of type I, II, and III respectively. The median age of therapy initiation was 3, 7.2, and 12.5 years for type I, II, and III. Longitudinal analyses of motor outcome measures from 100 patients (29 type I; 40 type II; 31 type III) are presented in year one post-treatment with median follow-up period. The median age of individuals included in motor outcome analyses are SMAI 4.7y (2.1 months- 17.7 years); SMA II 10.17y (1.2-44.3y); and SMA III 15.2y (3.1-68.4y). Type I patients’ CHOP-INTEND scores increased 14.8 points per year (median follow-up 12.0 months; range 7.8-15.0 months). Type II patients had HFMSE scores increase 3.25 points/year, and RULM increase 2 points/year (4.8 months follow-up; range 3.3-12.2 months). Type II naïve patients decreased -2.67 points/year on the HFMSE and -0.75 points per year on the RULM. Type III patients had an increase of 5.4 points/year (7.5 months; 5.2-14.4 months) on the HFMSE. For type III naïve patients, HFMSE increased 1 point per year. Data on the treatment impact over time will be presented. Additional data including comorbidities and hospitalizations from both pediatric and adult patients regardless of therapeutic status are presented.

Conclusions: The CNDR captures a comprehensive SMA dataset to evaluate long-term real-world experience with available and emerging therapies.

Acknowledgements: We would like to thank the patients who participate to make this possible. Funding support for this investigator-initiated study is provided by Biogen. Biogen had no role in project design or analyses.

THE CANADIAN NEUROMUSCULAR DISEASE REGISTRY:A NATIONAL SPINAL MUSCULAR ATROPHY (SMA) REGISTRY FOR REAL WORLD EVIDENCE

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Lindsay N Alfano1, Megan A Iammarino1, Natalie F Miller1, Brenna R Powers1, Kiana Shannon1, Anne M. Connolly1-3, Megan A. Waldrop1-3, Garey H. Noritz2, Richard Shell2, Chang-Yong Tsao2, Kevin M Flanigan1-3, Jerry R Mendell1-3, Linda P Lowes1,2

1 The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Center for Gene Therapy, Columbus OH2 The Department of Pediatrics, The Ohio State University College of Medicine, Columbus OH 3 The Department of Neurology, Wexner Medical Center at The Ohio State University, Columbus OH

Background: The availability of approved treatments in spinal muscular atrophy (SMA) has resulted in a new phenotype. Continued characterization of this new phenotype over time is needed to understand ongoing treatment response, durability of effect, and to guide clinical care. Payors frequently mandate the use of a specific outcome to obtain initial or ongoing authorization. At times, the recommended or required tool is not optimal for the child’s age, functional level, or temperament. Additionally, as function improves, transition to a new scale may be required resulting in a battery of testing and leading to increased burden of testing and fatigue. The purpose of our study was to validate the Neuromuscular Gross Motor Outcome (GRO) as a single tool to quantify function in SMA.

Results: A total of 92 patients with genetically-confirmed SMA types 1-3 between 8 days - 31.1 years completed GRO and other functional testing appropriate for the patients age and function. The 50-item GRO scores gross motor function 0-2 point scale with items scored in supported sitting, supine, prone, unsupported sitting, standing, and walking. Fifty-two patients had at least 1 follow up visit ranging 1 to 16 months after baseline. Twelve of those were included in our test-retest reliability cohort as they had 2 visits within 2 months without treatment being initiated during that time. GRO scores in our cross-sectional cohort ranged between 1-94 points, with no floor or ceiling effect occurring. GRO scores were significantly different across functional categories (P< 0.001), treatment status (P< 0.05), and was correlated to other functional assessments (P≤0.001). Test-retest reliability was excellent (ICC: 0.99, r=0.97, P< 0.001). The GRO measured change over time, as expected with functional improvement noted in patients receiving treatment. Two treated patients demonstrated a decline in function as measured by the GRO consistent with a spinal fusion or prolonged hospitalization. The GRO was responsive to treatment effect in 13 patients initiating treatment during the study period.

Conclusions: The Neuromuscular GRO quantifies function across the age range and span of abilities to allow continuous longitudinal monitoring on 1 scale to reduce the burden of testing. The overall excellent correlation between the GRO and other functional tools suggests the GRO measures a similar construct while minimizing the need to transition across scales. To ensure the GRO was applicable to a wide range of abilities, 7 items assessing small movements were included that can be completed in a wheelchair. Conversely, achievement of a full score on the GRO requires the ability to run at typical speeds. The intent of this scale was to provide the community with an additional scale in the “SMA toolbox” to measure motor function over time in this exciting new era of available treatments.

Acknowledgments: This study was not supported by external funding.

VALIDITY AND RELIABILITY OF THE NEUROMUSCULAR GROSS MOTOR OUTCOME (GRO) IN SPINAL MUSCULAR ATROPHY


END OF CME/CE PROGRAM

ABSTRACTS

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Jerry R. Mendell 1-3, Richard Shell 4,5, Kelly J. Lehman 1, Markus McColly 1, Linda P. Lowes 1,2, Lindsay N. Alfano 1, Natalie F. Miller 1, Megan A. Iammarino 1, Kathleen Church 1, Sandra P. Reyna 6, Francis G. Ogrinc 6, Haojun Ouyang 6, Douglas M. Sproule 6, Matthew Meriggioli 6, Douglas E. Feltner 6, Samiah Al-Zaidy 7

1 Center for Gene Therapy Nationwide Children’s Hospital Columbus OH United States2 Department of Pediatrics, Ohio State University Columbus OH United States3 Department of Neurology Ohio State University Columbus OH United States4 Section of Pulmonary Medicine Nationwide Children’s Hospital Columbus OH United States5 Department of Pediatrics Ohio State University Columbus OH United States6 AveXis, Inc. Bannockburn IL United States7 Al-Zaidy and Associates LLC Columbus OH United States

Background: Onasemnogene abeparvovec (formerly AVXS-101) is designed to address the genetic root cause of SMA1. In the phase 1 trial (START; NCT02122952), patients who received a high-dose infusion (proposed therapeutic dose, n=12) demonstrated significantly improved outcomes vs untreated natural history. We evaluate long-term safety in patients previously treated in START and long-term efficacy in patients from both Cohorts. START patients could electively enroll into a LTFU study (NCT03421977). Primary objective: long-term safety. Patients have annual visits (5 years) followed by annual phone contact (additional 10 years). Assessments include medical history/record review, physical examination, clinical laboratory evaluation, pulmonary assessments, and milestone maintenance.

Results: As of 31 Dec 2019, 13 patients (low dose Cohort, n=3; therapeutic dose Cohort 2, n=10) were enrolled. The oldest patient in the low dose Cohort was 6.2 years of age and the oldest patient in the therapeutic dose Cohort was 5.6 years of age. Only serious adverse events (AEs) and AEs of special interest are collected in the LTFU study. Serious AEs were reported in 8/13 patients; no new treatment-related AEs have emerged, supporting a favorable risk:benefit profile. There were no fatal AEs, and no serious AEs led to study discontinuation. All patients who received the therapeutic dose have survived and are free of permanent ventilation (mean [range] age at last datacut: 4.8 [4.3–5.6] years; mean [range] time since dosing: 4.5 [4.1–5.2] years). All patients in the therapeutic dose Cohort have either maintained all previously attained milestones or even gained new milestones; 2 patients have newly achieved standing with assistance, demonstrating the sustained effect of onasemnogene abeparvovec. These 2 patients were not receiving concomitant survival motor neuron (SMN2) upregulating therapy at any point; thus, this benefit can be attributed solely to onasemnogene abeparvovec. The maintained and/or new milestones in 10/10 patients originating from the therapeutic dose Cohort are unprecedented in patients with SMA. Of the 10 patients enrolled in the therapeutic dose Cohort, 6 require no regular, daily respiratory support more than 4 years after dosing, and 6 are not receiving concomitant SMN2 upregulating therapy.

Conclusions: Data from LTFU suggest that one-time intravenous administration of onasemnogene abeparvovec at the proposed therapeutic dose in START continues to demonstrate durable and prolonged efficacy with the possibility for new milestone developments in some patients with SMA. Patients have remained alive and free of permanent ventilation for over 5 years and are thriving without loss of therapeutic benefit following dosing. Data from the LTFU study does not reveal any new safety signals based on the reported events. The reported events are consistent with those seen in the AVXS-101 development program.

Acknowledgments: The authors thank the investigators, site coordinators, patients, families, and caregivers. Medical writing assistance was provided by Ashfield Healthcare Communications.

LONG-TERM FOLLOW-UP (LTFU) OF ONASEMNOGENE ABEPARVOVEC GENE THERAPY IN SPINAL MUSCULAR ATROPHY TYPE 1 (SMA1) FROM PHASE 1 START TRIAL

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Deepa Chand 1, Richard S. Finkel 2, Eugenio Mercuri 3, Riccardo Masson 4, Julie Parsons 5, Aaron Kleyn 1, Melissa Menier 1, Kyle Montgomery 1, Douglas M. Sproule 1, Sandra P. Reyna 1, Douglas E. Feltner 1, Sitra Tauscher-Wisniewski 1, Jerry R. Mendell 6 1 AveXis Inc., Bannockburn, IL, United States2 Nemours Children's Hospital, Orlando, FL, United States 3 Catholic University, Rome, Italy 4 Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy 5 University of Colorado School of Medicine, Aurora, CO, United States 6 Nationwide Children's Hospital, Columbus, OH, United States

Background: Intravenous (IV) onasemnogene abeparvovec (formerly AVXS-101) gene therapy addresses the genetic root cause of spinal muscular atrophy (SMA), survival motor neuron 1 gene (SMN1) deletion/mutation. This report describes the safety of IV onasemnogene abeparvovec in SMA patients across 4 clinical trials. Symptomatic or presymptomatic SMA patients (2–4 copies of SMN2) received a single IV onasemnogene abeparvovec dose. Adverse events (AEs) were assessed per Common Terminology Criteria for Adverse Events and monitored/reported in accordance with study protocols.

Results: As of 8 March 2019, 75 patients received IV onasemnogene abeparvovec at the therapeutic dose (1.1e14 vg/kg). The mean (standard deviation, range) age at dosing was 2.5 (1.8, 0.37.9) months and the mean weight was 5.33 (1.33, 3.08.4) kg. Two deaths were reported: one patient, aged 7.8 months, died of respiratory arrest 5.7 months post-dosing; the death was deemed unrelated to treatment. One patient, aged 6.8 months, died of hypoxic/ischemic encephalopathy due to respiratory distress. Sixty-four (85%) patients reported ≥1 AE; 33 (44%) patients had ≥1 treatment-related AE; 29 (39%) patients had ≥1 serious AE. Vomiting and pyrexia have been reported as treatment-emergent AEs at rates of >5% in the clinical development program (considered treatment-related). Pyrexia was reported in 30 (40%) patients (9 patients ≤1 week after dosing) and was considered treatment-related in 4 (5%) patients. Increased liver transaminase (>upper limit of normal) were observed in 8 (11%) patients. These increases were considered treatment-related, clinically asymptomatic, and generally resolved with prednisolone. Transient thrombocytopenia was reported, without clinically significant bleeding or bruising. There is no consistent evidence of cardiac safety concerns associated with onasemnogene abeparvovec. Updated safety data (31 December 2019 datacut) will be presented.

Conclusions: As of 8 March 2019, the IV onasemnogene abeparvovec safety profile remains consistent with the United States package insert and continues to be monitored across multiple settings.

Acknowledgements: The authors thank the investigators, site coordinators, patients, families, and caregivers for their participation. Medical writing assistance was provided by Ashfield Healthcare Communications.

INTRAVENOUS ONASEMNOGENE ABEPARVOVEC CLINICAL DEVELOPMENT PROGRAMS IN SPINAL MUSCULAR ATROPHY: INTEGRATED SAFETY REPORT

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Diana Castro 1, Janice Wong 2, Boris Kandinov 2, Richard Foster 3, Angela Paradis 2, Nicole Johnson 2 1 University of Texas Southwestern Medical Center Dallas TX USA 2 Biogen Cambridge MA USA3 Biogen Maidenhead UK

Background: Participants with infantile-onset spinal muscular atrophy (SMA) who completed the Phase 3 ENDEAR study (NCT02193074) were eligible to receive nusinersen in the open-label extension, SHINE (NCT02594124). At final analysis of the ENDEAR study, 68% of control and 39% of nusinersen-treated participants had died or received permanent ventilation (PV; defined as tracheostomy or ≥16 hours/day of ventilatory support continuously for >21 days in absence of an acute reversible event). Post hoc analyses (15 October 2018 SHINE data cut) evaluated motor function change of nusinersen-treated participants in ENDEAR, who continued into SHINE and reached PV in either study.

Results: The median (min, max) time from first nusinersen dose to date of PV (in ENDEAR or SHINE) was 90.5 (38, 525) days (n=24). For participants on nusinersen, median (min, max) time was 207 (23, 387) days from date of PV to last assessment in ENDEAR (n=18) and 922 (272, 1300) days to last assessment in SHINE (n=24). The majority of participants who reached PV in ENDEAR-SHINE (n=24) demonstrated improvements in total Hammersmith Infant Neurological Examination Section 2 (HINE-2) and Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores over time following PV. Among participants with ≥2 evaluable efficacy assessments following PV (n=21), mean improvements (standard deviation) in HINE-2 and CHOP INTEND scores from first available assessment following PV to last study visit were 3.0 (3.4) and 4.1 (7.6), respectively; range of time between assessments was 126–1234 days.

Conclusions: Participants treated with nusinersen who reached PV during ENDEAR-SHINE continued to demonstrate clinical benefit assessed via motor function change over time.

Acknowledgements: Writing and editorial support for the preparation of this abstract were provided by Excel Scientific Solutions (Fairfield, CT, USA): funding was provided by Biogen.

MOTOR FUNCTION CHANGE OVER TIME AMONG NUSINERSEN-TREATED PARTICIPANTS WITH INFANTILE-ONSET SPINAL MUSCULAR ATROPHY IN THE ENDEAR-SHINE STUDY WHO MET THE PERMANENT VENTILATION DEFINITION

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Richard S. Finkel 1, Diana Castro 2, Michelle A. Farrar 3, Mar Tulinius 4, Kristin J. Krosschell 5, Kayoko Saito 6, Giulia Gambino 7, Richard Foster 7, Daniela Ramirez-Schrempp 8, Janice Wong 8, Boris Kandinov 8, Wildon Farwell 8 on behalf of the SHINE Study Group

1 Division of Neurology, Department of Pediatrics Nemours Children’s Hospital Orlando FL USA2 Department of Pediatrics Neurology and Neurotherapeutics University of Texas Southwestern Medical Center Dallas TX USA3 Sydney Children’s Hospital and UNSW Sydney Randwick Sydney NSW Australia4 Department of Pediatrics Gothenburg University The Queen Silvia Children’s Hospital Gothenburg Sweden5 Department of Physical Therapy and Human Movement Sciences and Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago IL USA6 Institute of Medical Genetics Tokyo Women’s Medical University Tokyo Japan7 Biogen Maidenhead Berkshire UK8 Biogen Cambridge MA USA

Background: Several clinical trials have demonstrated a favorable benefit:risk profile for nusinersen and established clinically meaningful efficacy on motor function. We aim to present interim results from the SHINE open-label extension study (NCT02594124) for participants with infantile-onset SMA who transitioned from ENDEAR, CS3A or EMBRACE. Following protocol amendment, all are receiving the Modified Maintenance Dosing Regimen (MMDR; 12 mg nusinersen every 4 months). Previous ENDEAR participants initiated the MMDR at the end of the SHINE blinded loading dose period or 120 days after date of last loading period dose (MMDR Day 1). Participants from CS3A and EMBRACE directly entered the MMDR period or if already participating in SHINE transitioned to the MMDR at their next study visit.

Results: Endpoints were assessed from MMDR Day 1 and the reported data are based on the SHINE 27 August 2019 data cut. MMDR Day 1 data are available for 60 participants treated with nusinersen in ENDEAR and SHINE, and 22 with sham-procedure in ENDEAR and nusinersen in SHINE. The median (range) age at MMDR Day 1 was 2.57 (1.7–3.8) years for those treated with nusinersen in ENDEAR and SHINE, and 2.69 (1.8–3.7) years for those treated with sham-procedure in ENDEAR and nusinersen in SHINE. The median (range) time on study from first nusinersen dose to MMDR Day 1 was 2.08 (1.3–3.4) and 1.34 (0.5–1.9) years for these two groups, respectively. Mean (±SD) CHOP INTEND scores were 26.63 (8.13; n=80) at ENDEAR baseline, 44.6 (11.33; n=59) at MMDR Day 1, and 45.8 (13.27; n=56) at MMDR Day 480 for participants treated with nusinersen in ENDEAR and SHINE, and 28.43 (7.56; n=41) at ENDEAR baseline, 22.5 (10.07; n=22) at MMDR Day 1, and 24.5 (12.33; n=20) at MMDR Day 480 for those treated with sham-procedure in ENDEAR and nusinersen in SHINE. The WHO motor milestones of sitting unassisted, standing with assistance, and walking with assistance were achieved by 22/59 (37%), 5/59 (8%), and 3/59 (5%), respectively, of participants treated with nusinersen in ENDEAR and SHINE at MMDR Day 1, and 37/58 (64%), 11/58 (19%), and 4/58 (7%), respectively, at MMDR Day 480. None of those treated with sham-procedure in ENDEAR and nusinersen in SHINE (n=22) had achieved these milestones at MMDR Day 1; 1/20 (5%) was sitting without support at MMDR Day 480. Results for participants who transitioned from the CS3A and EMBRACE studies and an updated safety profile will be presented.

Conclusions: These data show that motor function continues to improve in the majority of participants with infantile-onset SMA over up to 3.4 years of observation and treatment with the currently recommended nusinersen maintenance schedule. Continued analysis of SHINE study data will increase the information available on the long-term safety/tolerability and efficacy of repeated nusinersen doses in patients with infantile-onset SMA.

Acknowledgments: Study sponsored by Biogen (Cambridge, MA, USA); writing and editorial support for abstract preparation was provided by Excel Scientific Solutions (Horsham, UK): funding was provided by Biogen.

NUSINERSEN IN INFANTILE-ONSET SPINAL MUSCULAR ATROPHY: RESULTS FROM LONGER-TERM TREATMENT FROM THE OPEN-LABEL SHINE EXTENSION STUDY

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Basil T. Darras 1, Claudia A. Chiriboga 2, Michelle A. Farrar 3, Eugenio Mercuri 4, Janbernd Kirschner 5, Nancy L. Kuntz 6, Gyula Acsadi 7, Mar Tulinius 8, Jacqueline Montes 9, Giulia Gambino 10, Richard Foster 10, Daniela Ramirez-Schrempp 11, Janice Wong 11, Boris Kandinov 11, Wildon Farwell 11 on behalf of the SHINE Study Group 1 Department of Neurology Boston Children’s Hospital and Harvard Medical School Boston MA USA 2 Departments of Neurology and Pediatrics Columbia University Irving Medical Center New York NY USA3 Sydney Children’s Hospital and UNSW Sydney Randwick Sydney NSW Australia4 Department of Paediatric Neurology Universit’ Cattolica del Sacro Cuore Rome Italy5 Department of Neuropaediatrics University Hospital Bonn Germany6 Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago IL USA7 Division of Pediatric Neurology Connecticut Children’s Medical Center University of Connecticut School of Medicine Farmington CT USA8 Department of Pediatrics Gothenburg University The Queen Silvia Children’s Hospital Gothenburg Sweden9 Departments of Neurology and Rehabilitation and Regenerative Medicine Columbia University Irving Medical Center New York NY USA10 Biogen Maidenhead Berkshire UK, 11 Biogen Cambridge MA USA

Background: Several clinical trials have demonstrated a favorable benefit:risk profile for nusinersen and established clinically meaningful efficacy on motor function. Our objective was to present results from the SHINE open-label extension study (NCT02594124) for participants with later-onset SMA who transitioned from CHERISH, CS2/12, or EMBRACE. Following protocol amendment, all participants transitioned to the Modified Maintenance Dosing Regimen (MMDR; 12 mg nusinersen every 4 months). Previous CHERISH participants initiated the MMDR at the end of the SHINE blinded loading dose period or 120 days from the date of the last visit. Participants from the open-label CS2/12 study transitioned to the MMDR at their next study visit. Participants from EMBRACE initiated SHINE at MMDR Day 1.

Results: Endpoints were assessed from MMDR Day 1 using SHINE 27 August 2019 data. 83 participants (81 with MMDR Day 1 data) treated with nusinersen and 42 with sham-procedure in CHERISH transitioned to SHINE. Median (range) age in years at MMDR Day 1 was 6.62 (4.1’11.5) for those who received nusinersen in CHERISH/SHINE and 5.98 (4.0’10.2) for those who received sham-procedure in CHERISH/nusinersen in SHINE. Median (range) of SHINE study days at MMDR Day 1 was 399 (211’631) and 393 (206’673) for these groups, respectively. Among participants with an MMDR Day 480 visit, mean (‘SD) Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were 26.5 (10.85) at MMDR Day 1 and 26.1 (11.94) at MMDR Day 480 for participants who received nusinersen in CHERISH/SHINE (n=79), and 21.5 (7.79) at MMDR Day 1 and 21.2 (8.75) at MMDR Day 480 for those randomized to sham-procedure in CHERISH/nusinersen in SHINE (n=40). For comparison, mean (‘SD) HFMSE scores at CHERISH baseline were 22.4 (8.3; n=84) for the nusinersen group and 19.9 (7.2; n=42) for the sham-procedure group. Mean (‘SD) Revised Upper Limb Module (RULM) scores were 24.1 (5.64; n=78) at MMDR Day 1 and 25.4 (6.07; n=79) at MMDR Day 480 for participants who received nusinersen in CHERISH/SHINE, and 21.0 (4.28; n=41) at MMDR Day 1 and 22.7 (4.65; n=41) at MMDR Day 480 for those randomized to sham-procedure in CHERISH/nusinersen in SHINE. Baseline mean (‘SD) RULM scores in CHERISH were 19.4 (6.2; n=84) and 18.4 (5.7; n=42) for the nusinersen and sham-procedure groups, respectively. Results for participants who transitioned from CS2/12 and EMBRACE, and an updated safety profile across all cohorts with later-onset SMA, will be presented.

Conclusions: Continued analysis of SHINE study data will increase the information available on the long-term safety/tolerability and efficacy of repeated nusinersen doses in patients with later-onset SMA.

Acknowledgements: Study sponsored by Biogen (Cambridge, MA, USA); writing and editorial support for abstract preparation was provided by Excel Scientific Solutions (Fairfield, CT, USA): funding was provided by Biogen.

LONGER-TERM TREATMENT WITH NUSINERSEN: RESULTS IN LATER-ONSET SPINAL MUSCULAR ATROPHY FROM THE SHINE STUDY

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Basil T. Darras 1, John W. Day 2, Kathryn J. Swoboda 3, Claudia A. Chiriboga 4, Susan T. Iannaccone 5, Darryl C. De Vivo 4, Nicolas Deconinck 6, Richard S. Finkel 7, Mar Tulinius 8, Kayoko Saito 9, Jacqueline Montes 10, Peng Sun 11, Daniela Ramirez-Schrempp 11, Boris Kandinov 11, Janice Wong 11, Wildon Farwell 11

1 Department of Neurology Boston Children’s Hospital and Harvard Medical School Boston MA2 Department of Neurology Stanford University School of Medicine Stanford CA3 Department of Neurology Massachusetts General Hospital Boston MA4 Departments of Neurology and Pediatrics Columbia University Irving Medical Center New York NY5 Department of Pediatrics University of Texas Southwestern Medical Center Dallas TX6 Hôpital Universitaire des Enfants Reine Fabiola Université Libre de Bruxelles Brussels Belgium7 Division of Neurology Department of Pediatrics, Nemours Children’s Hospital Orlando, FL8 Department of Pediatrics at Institute of Clinical Sciences University of Gothenburg Gothenburg Sweden9 Institute of Medical Genetics Tokyo Women’s Medical University Tokyo Japan10 Department of Neurology and Rehabilitation and Regenerative Medicine Columbia University Irving Medical Center New York NY11 Biogen, Cambridge MA

Background: Longitudinal outcomes for SHINE (NCT02594124) participants with symptomatic SMA Type II or III who initiated nusinersen as an adolescent in CS2 (NCT01703988) were evaluated. Five teenagers age 14 to nearly 16 y initiated nusinersen in CS2, received intrathecal nusinersen 12mg in CS12 on Days 1, 169, 351 and 533, transitioned to the SHINE long-term extension, in which, after a protocol amendment they receive the modified maintenance dosing regimen (MMDR) of nusinersen 12mg every 4 months. As of the SHINE 27 Aug 2019 datacut, the 5 participants were age 20–22 y and HFMSE, WHO Motor Milestones (All), ULM (non-ambulatory), 6MWT (ambulatory), and Assessment of Caregiver Experience with Neuromuscular Disease (ACEND; caregivers) are reported up to MMDR Day 480 (last assessment in this analysis).

Results: Participant 1 had SMA Type II; all others had SMA Type III. At CS2 baseline, Participants 2–4 were ambulatory, Participants 1 and 5 non-ambulatory. Participant 2 could not complete 6MWT at CS2 baseline and ULM was assessed. Participant 1 voluntarily withdrew from the study 1927 days from CS2 baseline; 4 others remain in SHINE. From CS2 baseline to SHINE last interim visit (median time: 2185 [range:1927–2394] days), HFMSE scores changed by +5 pts in Participant 1, +4 pts in Participant 5, 0 pts in Participant 2, -2 pts in Participant 4 and -6 pts in Participant 3. ULM scores were stable in Participants 1, 2, and 5 (0-pt change) between CS2 baseline and SHINE Day 361, after which ULM was no longer assessed following a protocol amendment. 6MWT distance changed by +50 m in Participant 2, +79 m in Participant 3 and -20 m in Participant 4. Within SHINE, Participants 2, 3 and 4 maintained the ability to walk independently up to SHINE MMDR Day 480. Participant 5 stood with assistance up to SHINE MMDR Day 480; and demonstrated the ability to walk with assistance at SHINE screening. Participant 1 sat without support throughout SHINE. Caregivers reported stable or improved ACEND scores in the majority of the 7 ACEND domains from CS2 baseline to the last SHINE interim visit for all participants. The most common AEs were related to lumbar puncture or consistent with SMA disease. Two participants had serious AEs: post-lumbar puncture headache that resolved with treatment (n=1) and pyuria and hematuria (n=1). Data from an expanded cohort who were age ≥13 years at time of initiation of nusinersen will be presented.

Conclusions: In this cohort, most teenagers who had symptomatic SMA Type II or III and initiated treatment with nusinersen as an adolescent demonstrated generally stable or improved motor function and stable or reduced impact on caregivers over 5 to >6 years of treatment, in contrast to the expected decline based on SMA natural history. The safety profile of nusinersen with extended treatment was consistent with previous experience.

Acknowledgments: This study was sponsored by Biogen. Writing and editorial support for the preparation of this abstract were provided by Excel Scientific Solutions (Fairfield, CT, USA): funding was provided by Biogen.

NUSINERSEN IN ADOLESCENTS AND YOUNG ADULTS WITH SMA: LONGITUDINAL EXPERIENCE FROM AN EXPANDED COHORT OF CS2/CS12 AND SHINE PARTICIPANTS


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Friday, June 12th at 7:00 p.m. CT

#SMAConferenceAtHome and #CureSMA


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CURE SMA CARE CENTER NETWORK

The Cure SMA Care Center Network is made up of clinics who are partnering with Cure SMAto share consented electronic health record data with the SMA Clinical Data Registry to achievethe following goals:

1. Quality improvement of SMA clinical care and disease management leading to creation of evidence to support a robust standard of care for SMA.2. Standardize care across the U.S. to facilitate more rapid therapeutic development.3. Expand clinical care center capacity to deliver new therapies to individuals with SMA, increase patient access to new treatments, and increase the number of sites for SMA clinical trials.4. Resource for local patient services and family support and regional healthcare providers.

The Cure SMA Care Center Network now includes 20 centers geographically dispersed throughout the U.S., representing 14 pediatric centers, 2 adult centers, and 4 combined pediatric and adult centers. To date, 16 of these centers have fully integrated into the SMA Clinical Data Registry, where we have 274 patients enrolled. Patient enrollment is ongoing. The next expansion phase for the Cure SMA Care Center Network is planned for late 2020, and data collected in the SMA Clinical Data Registry will be utilized to evaluate current care practices and develop accreditation standards for the Care Centers.

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CURE SMA CARE CENTER NETWORKApril 2019

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Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disease caused by deletion/mutation in SMN 1 gene, which is critical to the development of muscle mass and strength. It is characterized by progressive hypotonia and weakness. SMA puts a significant financial, logistical, and emotional strain on affected individuals and families.1,2 Literature reviews indicate a significant diagnostic delay in SMA, during time periods that overlap with major motor neuron loss. For instance, in individuals affected by SMA Type 1, the average age of diagnosis is documented to occur between 5.3 to 6.3 months.2,3 Yet, the onset of irreversible denervation occurs within the first 3 months, with loss of 90 percent of motor units occurring within 6 months of age.4 However, clinical and preclinical studies indicate that treatment exposure early is critical to modifying the rapid and irreversible loss of motor neurons.5-8

The diagnosis of SMA, especially Type 1, is a medical emergency. To promote reduction of diagnostic delays, Cure SMA launched SMArt Moves, a disease awareness and educational campaign to empower parents, pediatricians, and other healthcare professionals to promptly recognize and diagnose the early signs of SMA.

Central to the SMArt Moves effort is a special section dedicated to healthcare professionals, detailing current diagnostic criteria, educational resources, and the latest treatment options and protocols. Available resources include:

• SMA Diagnostic Toolkit: Summarizes clinical trial data supporting early treatment, provides a table of clinical signs and symptoms by SMA type, and features a list of disorders to consider in the differential diagnosis of SMA

• SMA 1-Page Quick Reference Guide: An abbreviated version of the SMA Diagnostic Toolkit.

• Know the Warning Signs: A series of videos that break down some of the hallmark symptoms of SMA.

• SMA CME HubSpot: Free and accredited SMA related activities.

In addition, parents also have access to an easy-to-use website that encourages parents to trust their instincts if they suspect a motor delay, because missed milestones may be a sign of a serious medical condition like SMA. On the site, parents improve their understanding of the early signs of motor delays, watch instructional videos, and download a helpful checklist to share with their doctor and help address their concerns.

EARLY ACTION, EARLY TREATMENT, SAVES LIVES.



1. Qian Y, McGraw S, Henne J, et al. Understanding the experiences and needs of individuals with Spinal Muscular Atrophy and their parents: a qualitative study. BMC Neurol. 2015;15:217.

2. Belter L, Cook S, Crawford T, et al. An overview of the Cure SMA membership database: Highlights of key demographic and clinical characteristics of SMA members. J Neuromuscul Dis. 2018;5(2):167-176.

3. Lin CW, Kalb SJ, Yeh WS. Delay in Diagnosis of Spinal Muscular Atrophy: A Systematic Literature Review. Pediatr Neurol. 2015;53(4):293-300.

4. Swoboda K, Prior T, Scott C, et al. Natural history of denervation in SMA: Relation to age, SMN2 copy number, and function. Ann Neurol. 2005;57(5):704-712.

5. Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile onset spinal muscular atrophy. N Engl J Med. 2017;377:1723-1732.

6. De Vivo DC, Hwu W-L, Reyna SP, et al. on behalf of the NURTURE Study Group. Interim efficacy and safety results from the phase 2 NURTURE study evaluating nusinersen in presymptomatic infants with spinal muscular atrophy (S46.003). Neurology. 2017;88(16 Supplement).

7. Mendell J, Al Zaidy S, Shell R, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med . 2017;377(18):1713-1722.

8. De Vivo DC, Bertini E, Swoboda KJ, et al, on behalf of the NURTURE Study Group. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Dis. (2019). doi: https://doi.org/10.1016/j.nmd.2019.09.007.

SMArt Moves start with you. Join us to save lives. Learn more at https://www.curesma.org/smartmoves/.

Cure SMA recognizes that early diagnosis and treatment occurs most effectively with universal newborn screening. SMA was added to the Recommended Uniform Screening Panel (RUSP) in July 2018. As each state works to implement SMA screening within their newborn screening panel, providers must continue to be vigilant for the early signs to optimize outcomes.

Additionally, even in states in which SMA has been added to the panel, we encourage providers to remain watchful, as approximately 3% to 5% of individuals with SMA will not be identified by newborn screening due to SMN1 point mutations. Thus, clinical evaluation and consideration of the SMA diagnosis will remain important once universal inclusion of SMA within newborn screening panels is achieved.

What About Newborn Screening?



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Newborn Screening Programs

www.cureSMA.org | 800.886.1762 | [email protected]

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www.cureSMA.org | 800.886.1762 | [email protected]

NEWBORN SCREENING UPDATE

Early diagnosis and treatment are key in the fight against SMA. The best way to do this is through screening every newborn for SMA through their state’s newborn screening program. Each state decides what conditions to screen for in these tests. Cure SMA has been working to ensure that every state screens for SMA, and thanks to the hard work of our families and advocates, we have made tremendous progress.

SMA newborn screening is being rapidly implemented throughout the U.S. As of May 1, 2020, 23 states have permanently implemented SMA newborn screening, 3 states have pilot SMA newborn screening programs, and 14 states have adopted and plan to implement SMA newborn screening programs soon. Currently, approximately 48 percent of all children with SMA are being screened for SMA.

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ESMA DRUG PIPELINE

We are funding and directing research with more breadth and depth than ever before. We know what we need to do to develop and deliver new therapies, which could also work in combination, to reach our goal of treatments for all ages and stages of SMA. And we are on the verge of further breakthroughs that will continue to change the course of SMA for everyone affected, and eventually lead to a cure.

The Cure SMA Drug Pipeline is one of the primary ways we evaluate the success of our research program. It identifies the major drug programs in development and tracks their progress from basic research through FDA approval and beyond. The Cure SMA Drug Pipeline identifies several possible treatment targets:

• Replacement or correction of the faulty SMN1 gene.

• Modulation of the low functioning SMN2 “back-up gene.”

• Muscle protection to prevent or restore the loss of muscle function in SMA.

• Neuroprotection of the motor neurons affected by loss of SMN protein.

• Newer approaches that identify additional systems and pathways affected by SMA.

BASIC RESEARCH SEED IDEAS PRECLINICAL: DISCOVERY CLINICAL DEVELOPMENT FDA

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IDENTIFICATION OPTIMIZATION SAFETY & MANUFACTURING PHASE 1 PHASE 2 PHASE 3

Roche-Genentech/PTC/SMAF-Risdiplam

Cytokinetics/Astellas-CK-2127107

Novartis-LMI070

Scholar Rock – SRK-015 (Muscle Drug)

AveXis/Novartis – AVXS-101 (IT)

Biogen – BIIB110 (Muscle Ehancing Agent)

Biogen-Gene Therapy

Columbia/NU-p38aMAPK Inhibitor

MU/ Shift Pharmaceuticals-E1 ASO

Genzyme/Voyager Therapeutics – CNS Gene Therapy

AurimMed Pharma – Small Molecule

Calibr-Small Molecule

Indiana U/Brigham & Women’s - Small Molecule

Biogen / Ionis 2nd Generation ASO

Harvard-Small Molecule

Long Non-Coding RNA Project

Patten-Zebrafish Screen

Monani-Modifier Program

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SMA DRUG PIPELINE We’re funding and directing research with more breadth and depth than ever before. We know what we need to do to develop and deliver new therapies, which could also work in combination, to reach our goal of treatments for all ages and types. And we’re on the verge of further breakthroughs that will continue to change the course of SMA for everyone affected, and eventually lead to a cure.

Praxis Biotech-Protein Synthesis Enhancers

Biogen/Ionis-Spinraza

AveXis/Novartis – Zolgensma (IV)


Cure SMA AdvertisementLet’s hold this page for a Conference update; either a cancellation/next steps or talking about the excitement to come.

If the unexpected circumstances of 2020 have shown us anything, it is how impactful this one week of the year is for families, individuals, researchers, and medical professionals in the SMA community. We cannot wait to welcome you back as we gather next June in Texas. The JW Marriott Austin will host the 2021 Annual SMA Conference and SMA Research & Clinical Care Meeting. The hotel is centrally located in Austin’s lively downtown neighborhood with a variety of restaurants, live music, and entertainment venues.

Cure SMA is excited to reunite the SMA community for the 2021 Annual SMA Conference in Austin, Texas from Thursday, June 10 – Sunday, June 13, 2021. Additional conference details will be announced in the upcoming months and registration will launch in the fall of 2020.

If you have any questions, please contact [email protected].

2021 ANNUAL SMA CONFERENCE

to the Cure SMA website for more details on the 2021 Annual SMA Conference as they become available.

JOIN US IN AUSTIN, TEXAS!THURSDAY, JUNE 10 – SUNDAY, JUNE 13, 2021

Stay Tuned

We look forward to seeing you in Austin next June!


Mary Schroth MD Mary is the Chief Medical Officer for Cure SMA. She brings 25 years of experience as a Pediatric Pulmonologist to Cure SMA and is Professor Emeritus at the University of Wisconsin School of Medicine and Public Health. As a specialist in SMA respiratory care and an educator, Dr. Schroth is a leader in the SMA community and with Cure SMA.

Vanessa Battista, RN, MS, CPNP – Palliative Care and Quality of Life Subcommittee ChairPalliative Care Pediatric Nurse Practitioner at Children's Hospital of Philadelphia in Philadelphia, PA.

William Bell, BS Pharm, MBA, MSCC, RPhDirector of Clinical Client Services in Chalfont, PA.

Alison Ballard, RN, MSNPediatric Nurse Practitioner and Neuromuscular Care Coordinator at Children's Hospital Colorado in Denver, CO.

John Brandsema, MD specializes in Pediatric Neuromuscular Neurology at Children's Hospital of Philadelphia, associated with the Perelman School of Medicine at The University of Pennsylvania in Philadelphia, PA.

Medical Advisory Council (MAC)

Jin Yun (Helen) Chen, MS, CGC Genetic Counselor at Massachusetts General Hospital in Boston, MA.

Bakri Elsheikh, MBBS, FRCP specializes in Neurology, Neuromuscular Medicine, and Clinical Neurophysiology at The Ohio State University Wexner Medical Center in Columbus, OH.

Albert Freedman, PhD specializes in Psychology in independent practice in Philadelphia, PA.

Thomas Crawford, MD specializes in Pediatric Neurology at Johns Hopkins Hospital, associated with Johns Hopkins University in Baltimore, MD.

Tina Duong, MPT, PhDcPhysical Therapist at Stanford University in Stanford, CA.

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Melissa Gibbons, MS, CGC Genetic Counselor at Children's Hospital Colorado, associated with the University of Colorado in Denver, CO.

Jennifer Hubbell, OTR/L Occupational Therapist at Cincinnati Children's Hospital Medical Center in Cincinnati, OH.

Becky Hurst Davis MS, RD, CSP, CD Pediatric Nutritionist at Intermountain Healthcare in Salt Lake City, UT.

Chamindra Konersman, MD Neurologist at Rady Children's Hospital, associated with the University of California San Diego in San Diego, CA.

Richard M. Kravitz, MD Pediatric Pulmonologist and Sleep Medicine Physician at Duke University in Durham, NC.

Kristin J. Krosschell, PT, DPT, MA, PCS Pediatric Physical Therapist at Northwestern University in Chicago, IL.

Oren Kupfer, MD Pediatric Pulmonologist at Children's Hospital Colorado, associated with the University Of Colorado School Of Medi-cine in Denver, CO.

Khalida Liaquat, MS, LCGC Genetic Counselor at Athena Diagnostics in Marlborough, MA.

Diane Murrell, LCSW – Care Coordination, Case Management, & Nursing Subcommittee Chair Social Worker at Texas Children's Hospital in Houston, TX.

Leslie Nelson, PT, PhDc, OCS Pediatric Neuromuscular Physical Therapist at Children’s Health, associated with the University of Texas Southwestern in Dallas, TX.

Julie Parsons, MD – Neurology Subcommittee ChairPediatric Neurologist at Children's Hospital Colorado, associated with the University of Colorado in Denver, CO.

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Silvana Ribaudo, MD – Genetics, OB/GYN, & Family Planning Subcommittee Chair Obstetrician and Gynecologist at Columbia University in New York City, NY.

Samuel Rosenfeld, MD Orthopedic Surgeon at CHOC Children's Hospital in Orange, CA.

Peter Schochet, MD Pediatric Pulmonologist at Children’s Health, associated with the University of Texas Southwestern in Dallas, TX.

Perry Shieh, MD, PhD – Adult Care Subcommittee Chair Neurologist at UCLA Medical Center in Los Angeles, CA.

Anne Stratton, MD Pediatric Physiatrist at Children's Hospital Colorado, associated with the University of Colorado in Denver, CO.

Edward C. Smith, MD Pediatric Neurologist at Duke University in Durham, NC.

Stacey Tarrant, BS, RD, LDN Nutritionist at Boston Children's Hospital in Boston, MA.

Fred W. Troutman, PhD, RN Nurse Educator, Professor Emeritus at Walla Walla University in Portland, OR.

Jane B. Taylor, MD, MsCR Pediatric Pulmonologist at the the UPMC Children's Hospital of Pittsburgh, associated with the University of Pittsburgh School of Medicine in Pittsburgh, PA.

Laura Watne, MS RD CSP Nutritionist at Children's Hospital Colorado, associated with the University of Colorado in Denver, CO.

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SMA CLINICAL CARE

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Transcript of SMA CLINICAL CARE