July 6, 2020 CORD and Cure SMA gene Therapy webinar

1. (How) Will Canadians Access
Once-in-a-Lifetime Gene Therapy?
What If You Can’t Wait
CELL & GENE THERAPY WEBINAR
MONDAy JULY 6 @ 12 PM

2. URGENT CASE
FOR TIMELY ACCESS TO GENE THERAPY
Question: Will Canada provide timely access to gene therapy for
infants with Spinal Muscular Atrophy?
The Breakthrough: Unlike conventional therapies that treat symptoms or slow down disease progression,
gene therapy replaces a faulty gene with a healthy functional one. So, the body functions as if there were no disease.
The Challenge: The healthy gene cannot repair damage already done. So, the earlier the gene therapy, the better
the outcomes. And sometimes there is a limit as to when it can be given.
The Opportunity: The first two gene therapies to be submitted to Health Canada are awaiting approval. We need
a plan for funding so patients can access as soon as possible.
Why Now: Spinal Muscular Atrophy is a progressive neuromuscular disorder; infants with the most severe type will die
before the age of two. The gene therapy Zolgensma has been approved in the USA for almost two years, in Europe since May, and will
hopefully be approved in Canada by the end of 2020. But it will not be available in time for some Canadian babies if the Canadian approval
follows the American approval in restricting access to infants under the age of two years old.
The MOST URGENT Case: Kaysen has Type 1 SMA and turns two on July 17th. Unlike two other Canadian babies, he was not “randomly selected” to
receive the drug through Novartis’ global compassionate access program. His only chance is to appeal to the provincial drug program (Alberta Health)
to provide early compassionate funding.

3. SPEAKERS
Dr. Alex MacKenzie
Children's Hospital of Eastern Ontario (Ottawa, Ontario)
Dr. Hernan Gonorazky
The Hospital for Sick Children (Toronto, Ontario)
Durhane Wong-Rieger, PhD (Moderator)
President & CEO, Canadian Organization for Rare Disorders
Doug Earle
President & CEO, Fighting Blindness Canada

4. PANELISTS
Lana Bernardin
SMA parent, Alberta
Laura Franzese
SMA parent, Ontario
Scott Van Doormaal
SMA parent, British Columbia
Christine Vasey
SMA parent, Ontario

5. Gene therapy
in SMA
Hernan D. Gonorazky M.D.
Assistant Professor, Faculty of Medicine
University of Toronto
Division of Neurology, The Hospital for Sick Children
hernan.gonorazky@sickkids.ca

6. Disclosures
I have had the following financial
relationships with the manufacturers of
commercial products or providers of
commercial services
Consultant: Biogen, Roche

7. Kolb and Kissel, Arch Neurol 2011
Spinal Muscular Atrophy
NIH targets SMA
SOC GuidelinesSMN genes
identified
2016
6 drugs in clinical
development

8. • Is the drug effective?
• Who, when should we treat?
• Access to medication?
• Cost?
• Ethics?
• Impact in public health?

9. Spinal muscular
atrophy (SMA)
• Autosomal recessive disorder
• Incidence 1 in 10 000 live births, carrier rate
1/50
• Second most common AR disorder
• Degeneration of anterior horn motor neurons
• Leads to muscle weakness and atrophy
resulting into permanent disability and/ or
death

10. Classification
of childhood
proximal SMA

11. By Sponk, Tryphon, Magnus Manske, User:Dietzel65, LadyofHats

14. Gene splicing
C
Exon 6 Exon 7 Exon 8
T
Exon 6 Exon 7 Exon 8
C
C
C
C
C
DNA
RNA
SMN PROTEIN
SMN 1 SMN 2
T
~20% of SMN protein is produced by SMN2
T
T
T
T
T
T

15. Correlation of Type of SMA and SMN2 copies
E. Tizzano Ferrari

17. D.C. Schorling et al. / Advances in Treatment of Spinal Muscular Atrophy
Therapeutic approaches to SMA

18. Spinal muscular atrophies: Emerging therapies
>45 countries
Approved: Not yet approved
Dr. Hugh McMillan

19. Increase SMN2 derivated proteins
HUMAN GENE THERAPY 24:489–498 (May 2013)
T
T
T
T
T

20. Gene therapy replacement

21. AAV (Adeno associated viruses)
• This are not Adenovirus
• Its not know to be disease causing
Low immune response
Target different organs

22. Previous immune status to AAV
AAV (Adeno associated viruses) challenges
Carry small genes only
Transduction of non target cells

23. • (scAAV9) can infect 40-60% of motor neurons when injected intravenously
into neonatal mice.
• At day 1, delivery rescues motor function, neuromuscular physiology and life
span.
Foust et al. 2010
Dominguez et al. 2011
• At day 5, partial correction
• At day 10, treatment has little effect
Foust et al. 2010
Rescue of the spinal muscular atrophy phenotype in a mouse model by
early postnatal delivery of SMN
Mackenzie A. Nature Biotech. 2010: 28: 235-7

25. Omnasemnogene parvovec
• Key inclusion criteria
• “Pre-symptomatic infants”, < 6 weeks at first dose
• Genetic diagnosis of SMA (SMN2: 2 or 3 copies)
• Primary outcome
• 2xSMN2 copies – independent sitting > 30 sec
• 3xSMN2 copies – independent standing > 3 sec
• Key secondary outcomes
• Survival. Motor milestones
Kindly provided by Dr. H. McMillan

26. Omnasemnogene parvovec
Presented @ Child Neurology Society – Oct 2019
Kindly provided by Dr McMillan

27. Omnasemnogene parvovec
Presented @ Child Neurology Society – Oct 2019
Kindly provided by Dr McMillan

28. • Omnasemnogene parvovec
Potential
benefits
Potential
risks
• Single dose IV treatment
• Non-integrating
• Early data – marked
improvement in motor
outcome
• Effects sustained 4-5+ years
• Risk of liver injury
• Risk of bleeding
• Risks associated with respiratory illness
• Risk of SMN to non-nerve cells
• Risk of gene disruption
Kindly provided by Dr McMillan

29. Ramos DM, d'Ydewalle C, Gabbeta V, et al. J Clin
Invest. 2019;129(11):4817–4831.
SMN expression

31. Summary
• Gene therapy is a promising therapeutic option
• Its not a cure (does not infect all motorneurons and it does not restored
lost ones)
• Well tolerated, single time infusion.
• Major impact if given earlier
• We do not know long term effects and we do not know how long it is going
to last

32. NEUROMUSCULAR DISORDERS
Neurology
Jennifer Boyd
Eugenia Law
Jiri Vajsar
Jim Dowling
Fatema Al-Amrani
Hebah Qashqari
Respirology
Reshma Amin
Jackie Chiang
Physiotherapy
Lauren Weinstock
Renne Haldenby
IGT
Prakash Muthusami
G- tube Clinic
Silvana Oppesidiano
Sonica Fracassa
Orthopaedics Surgery
David Lebel
Reinhard Zeller
Orthothist
Samantha Lam-Bellisimo
Boorview Rehablilitation Center
Laura McAdam
Melissa Dermody
Pediatrics
Anaesthesiology
Tobias Everet
4C Infusion center
New Born Screening Sickkids

33. 37

34. JULY
9
Federal Price Controls and Access
to Medicines Webinar Series
38
JULY
16at 1pm at noon
An invitation for the Board
of the PMPRB to hear
directly from patients
Sharing and comparing feedback
for the PMPRB Guidelines