Biogen
Treatment for: Spinal Muscular Atrophy
Spinraza (nusinersen) is a survival motor neuron-2 (SMN2)-directed antisense oligonucleotide indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
WWW.SPINRAZA.COM
SPINRAZA- nusinersen injection, solution
Biogen
1 INDICATIONS AND USAGE
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Information
SPINRAZA is administered intrathecally by, or under the direction of, healthcare professionals experienced in performing lumbar punctures.
Recommended Dosage
The recommended dosage is 12 mg (5 mL) per administration.
Initiate SPINRAZA treatment with 4 loading doses. The first three loading doses should be administered at 14-day intervals. The 4th loading dose should be administered 30 days after the 3rd dose. A maintenance dose should be administered once every 4 months thereafter.
DOSAGE FORMS AND STRENGTHS
Injection: 12 mg/5 mL (2.4 mg/mL) nusinersen as a clear and colorless solution in a single-dose vial.
DESCRIPTION
SPINRAZA contains nusinersen, which is a modified antisense oligonucleotide, where the 2′-hydroxy groups of the ribofuranosyl rings are replaced with 2′-O-2-methoxyethyl groups and the phosphate linkages are replaced with phosphorothioate linkages. Nusinersen binds to a specific sequence in the intron downstream of exon 7 of the SMN2 transcript. The structural formula is:
Structural Formula
(click image for full-size original)
SPINRAZA is supplied as a sterile, preservative-free, colorless solution for intrathecal use in a single-dose glass vial. Each 1 mL solution contains 2.4 mg of nusinersen (equivalent to 2.53 mg of nusinersen sodium salt). Each 1 mL also contains calcium chloride dihydrate (0.21 mg) USP, magnesium chloride hexahydrate (0.16 mg) USP, potassium chloride (0.22 mg) USP, sodium chloride (8.77 mg) USP, sodium phosphate dibasic anhydrous (0.10 mg) USP, sodium phosphate monobasic dihydrate (0.05 mg) USP, and Water for Injection USP. The product may contain hydrochloric acid or sodium hydroxide to adjust pH. The pH is ~7.2.
The molecular formula of SPINRAZA is C234 H323 N61 O128 P17 S17 Na17 and the molecular weight is 7501.0 daltons.
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
SPINRAZA is an antisense oligonucleotide (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in transgenic animal models of SMA, SPINRAZA was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein.
