SPINRAZA

What it is

SPINRAZA (nusinersen heptadecasodium) is a solution for injection containing 12 mg of nusinersen in each 5 mL single-use vial. SPINRAZA is a sterile, preservative-free clear to colourless isotonic solution for injection in a single use vial, practically free from visible particles, with a pH of approximately 7.2. SPINRAZA is an antisense oligonucleotide (ASO) specifically designed to treat Spinal Muscular Atrophy (SMA), an autosomal recessive progressive neuromuscular disease due to mutations in the chromosome 5q. Nusinersen increases the proportion of exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts by binding to an intronic splice silencing site (ISSN1) found in intron 7 of the SMN2 pre-mRNA.

Approved indications

— Treatment of 5q Spinal Muscular Atrophy (SMA)

Dosing overview

The recommended dosage is 12 mg (5 mL) per administration. SPINRAZA treatment should be initiated as early as possible after diagnosis with 4 loading doses on Days 0, 14, 28, and 63. A maintenance dose should be administered once every 4 months thereafter. Treatment should be administered by health care professionals experienced in performing lumbar punctures. SPINRAZA is for intrathecal use by lumbar puncture.

Key safety warnings

Thrombocytopenia and coagulation abnormalities, including acute severe thrombocytopenia, have been observed after administration of other subcutaneously or intravenously administered antisense oligonucleotides. If clinically indicated, platelet and coagulation laboratory testing is recommended prior to administration of SPINRAZA. Renal toxicity has been observed after administration of other subcutaneously and intravenously administered antisense oligonucleotides. In a combined analysis of the sham-controlled studies for patients with infantile-onset and later-onset SMA, 71 of 123 (58%) of SPINRAZA-treated patients had elevated urine protein, compared to 22 of 65 (34%) sham-controlled patients. If clinically indicated, urine protein testing (preferably using a first morning urine specimen) is recommended. For persistent elevated urinary protein, further evaluation should be considered. There have been reports of communicating hydrocephalus not related to meningitis or bleeding in patients treated with nusinersen in the post-market setting. In patients with decreased consciousness, an evaluation for hydrocephalus should be considered. The benefits and risks of nusinersen treatment in patients with a ventriculo-peritoneal shunt are unknown at present and the maintenance of treatment needs to be carefully considered. Adverse events associated with the administration of SPINRAZA by lumbar puncture, such as headache, back pain, vomiting, procedure-related haematoma and post lumbar puncture syndrome, have been observed. The incidence and severity of these events were consistent with events expected to occur with lumbar puncture.

Contraindications

SPINRAZA is contraindicated in patients who have a history of hypersensitivity reactions to the active ingredient or its excipients.

PBS listing

SPINRAZA solution for injection 12 mg in 5 mL is listed on the PBS with 19 items under authority required restriction at an ex-manufacturer price of A$104,500.00.

Regulatory history

Nusinersen (SPINRAZA) was approved by the TGA on 2 November 2017 for the treatment of 5q Spinal Muscular Atrophy (SMA). The PBAC recommended SPINRAZA in November 2017 for the treatment of spinal muscular atrophy Type 1, Type 2 and Type 3a in eligible patients. In March 2018, the PBAC recommended a Section 100 Authority Required listing for Type I, II and IIIa SMA, with further negotiations on price required. In July 2020, the PBAC recommended a change to add pre-symptomatic initiation to the listing. In March 2022, the PBAC recommended extension of the listing to adult patients older than 18 years of age diagnosed with 5q spinal muscular atrophy with symptom onset prior to 19 years of age (primarily SMA Types II and III). In July 2023, the PBAC recommended the listing for pre-symptomatic spinal muscular atrophy.