▎WuXi AppTec Content Team Report

Screenshot source: CDE official website

SAM isOne of the autosomal recessive genetic diseases that causes infant mortality isDue to the survival motor neuron 1 gene (SMN1) mutation leads to the functional defect of SMN protein. Carried in the human bodySMN2Gene（SMN1Homologous gene)Although it can also express SMN protein, the incorrect mRNA splicing results in very low levels of normal SMN protein expression, which cannot compensate.SMN1SMN protein deficiency caused by gene mutations.

Risdiplam is aSMN2Gene mRNA Splicing Modulator。It achieves dual-site specific regulationSMN2Splicing, promoting the retention of exon 7, and increasing the level of functional SMN protein.The drug can also cross the blood-brain barrier, distributing both centrally and peripherally to elevate SMN protein levels across multiple systemic areas, maintaining stability.

Globally,RisdiplamReceived US FDA Approval in August 2020Approved for Marketing, used for treatmentInfants and adults aged 2 months and above with SMA, becoming the first oral therapy to receive FDA approval for the treatment of SMA. It can not only treat infants and young children with the most severe cases of SMA but also treat adolescents and adults with relatively milder symptoms. In June 2022, the FDA approved the expanded use of risdiplam to include patients agedSMA patients under 2 months of age. So far, this product has been approved for use inTreat SMA patients of all ages, including both children and adults.。

In China, risdiplam was first approved by the NMPA in June 2021 for the treatment of SMA patients aged 2 months and above, ushering in a new era of oral SMA treatment. In June 2023, the drug received another approval from the NMPA.Approved for Marketing, expanding the applicable population toSMA patients aged 16 days and above.Previously approved productsEvrysdi (risdiplam) oral solution is a liquid formulation of the drug that can be administered orally at home or given through a feeding tube in liquid form.

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Spinal muscular atrophy can be divided into Type 1, Type 2, Type 3, and Type 4 based on the age of onset, acquired motor function, and the speed of disease progression. Among them,Type 1 SMAThe most severe cases, if not treated and intervened in time, result in a median survival period of only 13.6 months for affected children, who usually do not live beyond the age of 2.Type 2 SMAMost patients will lose the ability to sit independently and become paralyzed during adolescence, often dying from complications such as respiratory failure.Type 3 SMAThe patient's motor development was normal within the first year after birth, and the ability to walk independently could be achieved. The patient's prognosis is relatively good, allowing for many years of walking; however, spinal deformities may occur later on.

According to a recent press release from Genentech, a subsidiary of Roche,RisdiplamCurrently being or already evaluated in five global multicenter trials for SMA patients, including FIREFISH (an open-label, two-part pivotal clinical trial for Type 1 SMA infants), SUNFISH (a two-part, double-blind, placebo-controlled pivotal study in Type 2 or 3 SMA patients aged 2-25), JEWELFISH (an open-label exploratory trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SMA patients aged 6 months to 60 years), and RAINBOWFISH (an open-label, single-arm, multicenter study targeting infants from birth to 6 weeks of age who are genetically diagnosed with SMA and have not yet shown symptoms).

In terms of clinical data, in March 2023, Roche announcedRisdiplamSUNFISH StudyNew long-term data.SMA patients aged 2-25Improvement in motor function was maintained for 4 years, and the overall incidence of adverse events continued to decline over 48 months.If left untreated, natural history data shows that patients with Type 2 or Type 3 SMA typically experience a decline in motor function over time.

In June 2024, Roche announced againFIREFISH StudyThe latest long-term data. The analysis shows that, by the end of the 5th year,91% acceptanceRisdiplamTreated Type 1 SMA Children Remain AliveNatural history studies show that, without treatment, children with Type 1 SMA struggle to reach such milestones and typically do not survive beyond the age of 2.

[3] Official Website of China Drug Clinical Trial and Information Disclosure Platform.