Domestic approval of high-dose 'Spinraza' imminent

A high-dose therapy has secured data showing improvement in motor function assessment

Increased loading and maintenance dosage…highlighted as a treatment that maximized treatment response

SMA treatment 'Spinraza'

Ahead of the introduction of 'Spinraza,' a high-dose regimen of the spinal muscular atrophy (SMA) treatment, to Korea following global approvals, the possibility of a shift in treatment strategy is being raised.

The trend of improving effectiveness through dose optimization is evident, moving away from the existing low-dose (12mg) treatment.

According to industry sources on the 8th, the domestic approval of Biogen Korea's Spinraza (nusinersen) high-dose formulations (50mg/5mL, 28mg/5mL) is imminent. An approval decision is expected within this month.

Previously, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the high-dose regimen. The strategy involves administering 50mg twice at 14-day intervals during the initial loading phase, followed by a 28mg maintenance therapy at 4-month intervals, thereby maximizing therapeutic effects by increasing the drug concentration compared to the existing regimen.

Spinraza is an antisense oligonucleotide (ASO) that continuously increases SMN protein levels. To deliver treatment to the cause of the disease, it can be administered directly into the central nervous system, where motor neurons are located, via intrathecal injection. Since Spinraza allows multiple administrations, it can demonstrate differentiation in its administration method.

Spinraza has confirmed a consistent effect and safety profile across all ages and types based on clinical research data and real-world evidence (RWE) accumulated over more than 8 years of treatment.

The efficacy of the high-dose Spinraza was confirmed through the Phase 2/3 DEVOTE study. In the primary cohort analysis, the treatment-naïve symptomatic infant patient group showed a statistically significant improvement in motor function assessment (CHOP-INTEND).

The treatment group recorded an average increase of +15.1 points, while the comparison group (untreated group) showed -11.1 points, resulting in a mean difference of 26.19 points. While motor function improved in the high-dose regimen group, it worsened in the untreated group, proving a distinct therapeutic effect compared to the natural course of the disease.

Regarding safety, a profile similar to the existing low-dose regimen was confirmed. However, pneumonia, aspiration pneumonia, and malnutrition were reported as major adverse reactions in infant SMA patients.

The high-dose drug can also be used in patients already receiving treatment. Patients who were maintaining low-dose treatment can continue maintenance therapy at the same 4-month intervals after a single high-dose loading, allowing for a dose increase while maintaining treatment continuity.

This high-dose strategy is seen as a variable that can change the SMA treatment paradigm beyond simply adding an option. The approach to maximize treatment response is considered to have begun, given that dose optimization was pursued based on long-term (over 10 years) data from the existing treatment.

In particular, as approvals have already been granted in major countries such as the U.S., Europe, and Japan, attention is focused on the timing of introduction and the reimbursement strategy in Korea. If the high-dose drug becomes a differentiated option compared to existing treatments, its impact on the overall SMA treatment landscape is expected to be significant.

More treatment options…treatment choice based on mechanisms of action·administration methods·reimbursement 

The domestic SMA treatment includes Spinraza, Roche's 'Evrysdi (risdiplam)', and Novartis' 'Zolgensma (onasemnogene abeparvovec)'. All share the common goal of improving SMN protein deficiency but differ in their mechanisms of action and administration methods.

Spinraza is an ASO-based treatment that acts on the central nervous system via direct intrathecal administration and has dominated the market based on long-term clinical data and prescribing experience. Evrysdi is an oral small-molecule treatment that regulates SMN2 splicing, characterized by its ability to cross the blood-brain barrier and act systemically.

Zolgensma is a gene therapy that directly delivers the SMN1 gene, with therapeutic effects expected after a single administration.

Recently, with the expansion of reimbursement criteria for Evrysdi, the flexibility of treatment strategies has greatly improved. The introduction of the tablet form, the extension of the prescription period (up to approximately 2 months), and the allowance of bidirectional switching with injections are evaluated as having made treatment choices based on patient conditions much more flexible.

Ultimately, the SMA treatment trend is shifting away from a single, treatment-centered approach toward a customized strategy that considers the mechanism, administration method, and reimbursement criteria.