1. Spinraza™ - Nusinersen
Manufacturer: Biogen Inc.
FDA Approval Date: December 23, 2016
Jonathan Downs, PharmD Candidate

2. Spinraza™ - Nusinersen Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Spinraza™ - (Nusinersen)
Effectively educate patients on the purpose, proper use and potential adverse effects of Spinraza™ - (Nusinersen)

3. Spinraza™ - Nusinersen Clinical Application
Indications:
Treatment of spinal muscular atrophy (SMA) in pediatric and adult patients
Place in therapy:
First medication approved to treat patients with SMA
Spinraza [package insert].

4. Spinraza™ - Nusinersen Clinical Application
Contraindications:
None
Warnings/Precautions:
Thrombocytopenia and coagulation abnormalities
Nephrotoxicity
Spinraza [package insert].

5. Spinraza™ - Nusinersen Clinical Application
Pregnancy:
Adverse events not observed in animal studies
Lactation:
Unknown if excreted in breast milk
Spinraza [package insert].

6. Spinraza™ - Nusinersen Drug Facts
Pharmacology:
Antisense oligonucleotide
Increases exon 7 inclusion in SMN2 mRNA transcripts and production of full-length SMN protein
Spinraza [package insert].

7. Spinraza™ - Nusinersen Drug Facts
Spinraza [package insert].

8. Spinraza™ - Nusinersen Drug Facts
Pharmacokinetics: A
Tmax: h D
Distributes to primarily to CNS; found in skeletal muscles, liver, and kidneys M
Metabolized via exonucluase (3’- and 5’)-mediated hydrolysis E
CSF t1/ days, plasma t1/ days
Spinraza [package insert].

9. Spinraza™ - Nusinersen Drug Interactions
Drug Interactions – Object Drugs:
None
Drug Interactions – Precipitant Drugs:
Spinraza [package insert].

10. Spinraza™ - Nusinersen Adverse Effects
Common Adverse Effects: (nusinersen%)[placebo%]
Lower respiratory infection (43%) [29%
Upper respiratory infection (39%) [34%]
Constipation (30%) [22%]
Serious Adverse Effects: (nusinersen%)[placebo%]
Atelectasis (14%) [5%]
Spinraza [package insert].

11. Spinraza™ - Nusinersen Monitoring Parameters
Efficacy/Toxicity Monitoring:
Platelet count
Coagulation laboratory testing
Quantitative spot urine testing
Should be performed at baseline and prior to each dose
Spinraza [package insert].

12. Spinraza™ - Nusinersen Prescription Information
Dosing:
Initial: Four 12mg loading doses
First three doses administered 14 days apart
Fourth loading dose given 30 days after third dose
Maintenance: 12mg IT every four months
Hepatic/Renal: no adjustment needed
Cost: – $125,000/dose
FiercePharma. Accessed 01/15/2017
Spinraza [package insert].

13. Spinraza™ - Nusinersen Literature Review
Efficacy of nusinersen in symptomatic infantile-onset SMA
Study Design (N=121)
Multicenter, randomized, double-blind, sham-procedure controlled study
Patients randomized 2:1 to receive either nusinersen or sham injection
Patients were ≤ 7 months of age at the time of first dose
Interim efficacy analysis was conducted (N=82)
Interim efficacy analysis was conducted based on patients who died, withdrew, or completed at least 183 days of treatment (N=82)
Spinraza [package insert].

14. Spinraza™ - Nusinersen Literature Review
Patient Characteristics
Nusinersen (N=52)
Sham (N=30)
Female, %
56%
Caucasian, %
87%
Symptoms w/in first 12 weeks of life, %
88%
77%
Age at first dose, days
175
206
Median disease duration, weeks 14
Median length of treatment, days
261
Spinraza [package insert].

15. Spinraza™ - Nusinersen Literature Review
Primary Efficacy Endpoint
Improvement in motor milestones based on the patient’s HINE score
Assesses ability to kick, head control, rolling, sitting, crawling, standing or walking
Secondary Efficacy Endpoint
Improvement in a patient’s CHOP-INTEND score
HINE – Hammersmith Infant Neurologic Exam
This endpoint evaluates seven different areas of motor milestone development, with a maximum score between 2-4 points for each, depending on the milestone, and a total maximum score of 26. A treatment responder was defined as any patient with at least a 2-point increase (or maximal score of 4) in ability to kick (consistent with improvement by at least 2 milestones), or at least a 1-point increase in the motor milestones of head control, rolling, sitting, crawling, standing or walking (consistent with improvement by at least 1 milestone). To be classified as a responder, patients needed to exhibit improvement in more categories of motor milestones than worsening
Spinraza [package insert].

16. Spinraza™ - Nusinersen Literature Review
Endpoints
Nusinersen (N=52)
Sham (N=30)
Achievement of a motor milestone response
21 (40%)
p <
0 (0%)
CHOP-INTEND improvement ≥ 4 points from baseline
33 (63%)
1 (3%)
CHOP-INTEND worsening ≥ 4 points from baseline
2 (4%)
12 (40%)
Spinraza [package insert].

17. Spinraza™ - Nusinersen Literature Review
Conclusions
Nusinersen is an effective new option for infants diagnosed with SMA
Patients treated with nusinersen were significantly more likely to reach motor milestones compared to the sham group
Results support data from open-label studies and appear to support the need for early initiation of treatment with nusinersen
Spinraza [package insert].

18. Spinraza™ - Nusinersen Summary
Spinraza™ (nusinersen) is a novel treatment option for patients with SMA
Thrombocytopenia and nephrotoxicity are potential complications associated with nusinersen therapy
Common side effects include respiratory tract infections as well as constipation
Nusinersen does not have any significant drug-drug interactions and it does not require any dose adjustments based on hepatic or renal function

19. Spinraza™ - Nusinersen References
Spinraza [package insert]. Cambridge, MA: Biogen Inc.; 2016.
Staton T. Biogen’s $375K Spinranza price puts a Sovaldi-style spotlight on rare disease meds. FiercePharma. Published 3 Jan pharma/biogen-s- 375k-spinraza-price-puts-a-sovaldi-style- spotlight-rare-disease-meds. Accessed 15 Jan