SMA Treatments and Clinical Trials. Kenneth Hobby, President Mary Schroth, MD, Chief Medical Officer Jill Jarecki, PhD, Chief Scientific Officer

Transcription

1 SMA Treatments and Clinical Trials Kenneth Hobby, President Mary Schroth, MD, Chief Medical Officer Jill Jarecki, PhD, Chief Scientific Officer

2 Agenda Introduction Kenneth Hobby, President Spinraza Update Mary Schroth, MD, Chief Medical Officer Zolgensma Update Kenneth Hobby, President Clinical Trial Update Jill Jarecki, PhD, Chief Scientific Officer Making Treatment Decisions Jill Jarecki, PhD, Chief Scientific Officer Q & A

3 SMA Drug Pipeline

4 Current Treatment: Spinraza 1 st Approved Treatment Expectations: Not a cure Not for everyone Impact Timing and Type of Impact Baseline 6 months 12 months 18 months 24 months IMPROVEMENTS Increase Maintain Slow Progression Natural History

5 Spinraza Treated Patients October 2018: ~2700 patients dosed in US Including extension trials and support programs ~50% of children < 2 yo with SMA receiving Spinraza Increasing number of adults ~30% of all in US ~6,000 Globally US Patients Dosed Q1 Q2 Q3 Q4 18Q1 Q2 Q3

6 Treatment Sites and Capacity Website Directory of New Treatment Network: Spinraza: 159 sites in 44 states and DC with at least one site/state ~100 more sites dosing US Sites Dosing 50 0 US Sites Public Listing Q1 Q2 Q3 Q4 18Q1 Q2 Q3 Contact: treatments@curesma.org

7 Coverage and Payors % Coverage: Types I, II, III 2, 3 copies SMN2 Pediatric 76-80% Coverage: 4 copies SMN2 Adult Non-invasive ventilation Restrictive: Types 0, IV 1 copy SMN2 Tracheostomy or permanent ventilation

8 New Therapies and Care Standard of Care - critically important to optimize function Breathing Close monitoring Coughing support and clearing secretions Breathing support during sleep as needed Nutrition Growing and gaining weight is key to optimizing motor function and strength Monitoring swallow Physical and Occupational Therapy Optimize function and impact of new treatments /educational-resources/

9 2 years of Spinraza Improved Access More adults are receiving Spinraza, ~15% of all adults (>18 years old) Increasing experience with techniques to safely deliver treatment ~ 50% of pediatric patients (birth to 17 years) are receiving therapy Impact: Increased infant survival Earlier treatment in infants results in the best outcomes regardless of treatment Changing care needs with careful monitoring

10 Gene Therapy - Zolgensma Replacing missing SMN1 gene - One time treatment Two Delivery Approaches: Same therapeutic, but different delivery approaches Intravenous (IV) and Intrathecal (IT) IV: Now with FDA BLA IT Ongoing clinical trials Results are very good in young Type I: Don t know yet in other types and older Don t wait on approval: Time more important Unknowns and narrow label

11 IV Gene Therapy Timing: FDA date of May 2019 Expectations: Approval for close to clinical trial criteria: Type I and under 8.5kg (maybe under 9 months) Maybe also presymptomatic Insurance will strictly follow label Switch or both unlikely: Costs and data and label

12 IT Gene Therapy Timing: Possibly 2020 Expectations: Approval for older and other types Will FDA go broader here than trial criteria: Type II to 5 years Other trials needed

13 Why Different This Time Will not be same as Spinraza, with rapid approval and label for all very unusual Have a treatment approved New technology Limits to IV approach Normal is to match the trial criteria

14 Why Two Approaches IV: Throughout whole body IT: Just to central nervous system Older and Bigger: Need more virus and this may not be safe when given IV everywhere Greater chance of AAV antibodies

15 Recruiting Clinical Trials A Study of RO (Risdiplam) in Adult and Pediatric Participants with SMA (Clinicaltrials.gov Identifier: NCT ) Also Known By: JEWELFISH General Criteria*: Children, teens and adults age who have previously been exposed to an SMN2- targeting therapy. Phase: Phase 2, with sites in NYC, Italy, Switzerland Ongoing

16 Recruiting Clinical Trials Pre-Symptomatic Study of Intravenous AVXS-101 in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2 (SPR1NT) ClinicalTrials.gov Identifier: NCT AVXS gene therapy with one-time IV infusion International trial in pre-symptomatic patients with SMA Types 1, 2, 3 44 patients with 2, or 3 copies of SMN2, under six weeks of age and pre-symptomatic Ongoing

17 Recruiting Clinical Trials Spinraza in Adult Spinal Muscular Atrophy (SAS) ClinicalTrials.gov Identifier: NCT Safety, tolerability, and effectiveness of SPINRAZA (nusinersen) in ambulatory and non-ambulatory adult patients with SMA,18 years to 60 years of age. 73 participants. Study visits including standardized assessments of strength and function will occur at baseline, day 15 after treatment initiation, day 30, day 60, and then 4-month intervals through month 30. Multi-center

18 Recruiting Clinical Trials Study of Intrathecal Administration of AVXS-101 for Spinal Muscular Atrophy (STRONG) Clinicaltrials.gov Identifier: NCT Up to 60 months of age and three copies of SMN2 and symptoms < 12 months of age - Sit independently and not standing or walking independently - Currently fully-enrolled at the low- and mid-dose cohorts. - Enrollment starting for higher dose cohort is to explore whether it will provide the opportunity for additional efficacy. - Phase 1 Trial for 51 subjects at multiple sites in the US

19 Planned Clinical Trials Scholar Rock SRK-015 (myostatin inhibitor) to improve muscle strength Safety trial on health volunteers by Q Proposed patient trials for SMA patients who are on therapies to up-regulating SMN levels and as monotherapy in certain populations Phase 2 proof-of-concept study in the first quarter of 2019 REACH AVXS gene therapy with one-time IT injection Multi-national trial expected in early 2019 in SMA Types 1, 2, and 3 Likely 50 patients between six months and 18 years of age Timeline TBD Phase III trial of Reldesemtiv (CK ) in Patients with SMA Muscle function drug acting as fast skeletal muscle troponin activator TBD for enrollment criteria Timeline TBD RO (Risdiplam) in pre-symptomatic infants with SMA Also called Rainbowfish Timeline TBD

20 Considerations to be Discussed with Neurologist on Approved Treatment vs. Trials Recommended not to wait for future trials to open, if other options available now Delays in opening trials are common and can t be predicated Changes in inclusion and exclusion are common until formally announced Earliest possible administration of SMN enhancing drugs yield best results Timing is one of biggest factor in degree of response to SMN!

21 Considerations to be Discussed with Neurologist on Approved Treatment vs. Trials Evaluate available safety and efficacy data Evaluate possibility of placebo Small molecule versus other drug modality Type I enrollment versus other SMA types Evaluate route and timing of administration Understand inclusion and exclusion criteria Determine whether previous drug exposure allowed and when Most trials today will prohibit co-utilization with Spinraza Particularly if another SMN enhancer Increased motor function must be detected for FDA approval Much harder when already another SMN enhancer to detect signal

22 Considerations for Combination Therapies: Combinations Must be Chosen Carefully General Are they safe when used together? Is there additive clinical benefit? Does that benefit outweigh the risk of using together? Does one drug reduce efficacy or availability of the other? Can they readily be co-administered? Combining Two SMN Enhancers Do they work by different biological mechanisms? Are SMN levels increased together over either drug alone? Do they target different cells? Do they provide longer duration of effect together? Readouts in trials with two combination therapies more challenging.

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24 Resources Cure SMA website: Social Media