In which countries is Risdiplam approved?

Introduction to Risdiplam
Risdiplam is a ground-breaking small molecule therapeutic developed specifically for the treatment of spinal muscular atrophy (SMA), a genetic neuromuscular disorder that leads to severe muscle weakness and functional impairment. This innovative drug is notable for its novel mechanism of action that distinguishes it from traditionally administered therapies and for its potential to address unmet needs in SMA treatment. The extensive clinical development program, spanning multiple phases and geographical regions, has not only validated its efficacy and safety profile but has also paved the way for its regulatory approval across several major global markets.

Mechanism of Action
At its core, risdiplam represents a first-in-class small molecule splicing modifier. It works by targeting the pre-mRNA processing of the survival motor neuron 2 (SMN2) gene. Under normal pathological conditions, the SMN2 gene predominantly produces an unstable, truncated protein due to the exclusion of exon 7 during splicing. Risdiplam corrects this aberrant splicing, enabling inclusion of exon 7 to generate full-length SMN protein, which is crucial for motor neuron survival and function. This mechanism directly tackles the underlying protein deficiency in SMA patients, making risdiplam a transformative therapeutic option that can be administered orally—a particularly significant advantage for patient comfort and convenience.

Clinical Applications
The principal clinical application of risdiplam is in the treatment of spinal muscular atrophy, a disease that manifests in various types (most commonly types 1, 2 and 3) based on the age of onset and severity of motor impairment. Clinical trials have demonstrated that risdiplam improves motor function and extends survival, notably in infants with type 1 SMA as well as in older children and adults with later-onset forms of the disease. Its efficacy is evident in outcomes such as improved scores on motor function scales like the Bayley Scales of Infant and Toddler Development (BSID-III) for infant patients and the Motor Function Measure (MFM-32) for older populations. Moreover, as the first orally administered SMA therapy, risdiplam offers a less invasive treatment route compared to intrathecal therapies, thereby reducing the burden on patients and caregivers alike.

Regulatory Approval Process
The regulatory approval process for new drugs like risdiplam is multi-faceted and involves rigorous clinical evaluation, submission of detailed data to health authorities, and continuous collaboration between developing companies and regulators. This pathway ensures that only therapies with adequate evidence on safety, efficacy, and quality reach the market.

General Overview of Drug Approval
Globally, regulatory bodies such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), and China’s National Medical Products Administration (NMPA) follow highly structured processes to assess new candidates. These processes typically involve multiple phases of clinical trials—from early-phase exploration of safety and pharmacokinetics through to pivotal phase II/III studies that confirm efficacy. Expedited pathways, such as orphan drug designations and accelerated assessments, have been established to facilitate the rapid delivery of therapies for life-threatening or rare conditions where there is an urgent unmet need. These measures not only streamline development but also often include post-approval commitments to ensure continued safety monitoring once the product is on the market.

Specifics for Risdiplam
For risdiplam, its development was supported by extensive preclinical and clinical data that demonstrated its ability to modulate SMN2 splicing effectively. The robust clinical trials—FIREFISH, SUNFISH, JEWELFISH, and RAINBOWFISH—provided the critical evidence required for regulatory review. Key milestones included dose optimization in infants with type 1 SMA and statistically significant improvements in motor function across a broad spectrum of SMA types. These trials not only validated its safety profile—with minimal treatment-related adverse events and no withdrawals due to safety issues—but also underscored its meaningful clinical benefits. Furthermore, risdiplam’s design as an orally administered liquid means that it can be administered at home, reducing the need for hospitalization and invasive procedures—an important consideration for regulatory agencies evaluating its overall benefit–risk profile.

Global Approval Status of Risdiplam
Following its successful clinical development program, risdiplam has undergone a series of regulatory evaluations around the world. The regulatory strategies deployed by the companies involved, including Genentech, Hoffmann-La Roche, and Chugai Pharmaceutical, have led to approvals in several key territories. A multi-regional approach—tailored to meet the specific requirements of each regulatory agency—has been adopted, demonstrating both the drug’s efficacy and its favorable safety profile across different patient populations.

Approved Countries
Based on information extracted from regulatory submissions and drug application details, risdiplam is currently approved in the following countries and regions:

• United States:
Risdiplam received approval from the U.S. Food and Drug Administration (FDA) for the treatment of SMA in patients 2 months of age and older. The approval is evidenced by the successful filing of the New Drug Application (NDA) that was supported by pivotal clinical trial data, including the findings from the FIREFISH and SUNFISH studies. The approval, with a documented FDA_CDER review and approval date on August 7, 2020, marks a significant milestone as risdiplam became the first oral therapy for SMA, providing a critical treatment alternative to intrathecally administered therapies.

• China (Mainland):
In China, risdiplam has been approved by the National Medical Products Administration (NMPA) under the trade names “Evrysdi” and “艾满欣.” The approval, as documented by the drug application with the number 国药准字HJ20210045, was granted based on manufacturing, quality, and clinical data demonstrating its efficacy in treating SMA. The approval date of June 16, 2021, confirms that Chinese regulatory authorities have found risdiplam to satisfy the critical safety and efficacy standards for use in the large and diverse patient population in China.

• European Union:
Risdiplam has also secured regulatory approval in the European Union, where it is marketed under the trade name “Evrysdi.” The approval process in the EU is noted for its rigorous assessment under accelerated assessment pathways. The EMA approved risdiplam based on the submission tied to the drug application number EMEA/H/C/005145 with an approval date of September 12, 2024. Prior to this formal approval, the accelerated assessment process had been activated as early as August 17, 2020, emphasizing the unmet need in the European SMA patient community and the confidence regulators had in the drug’s potential.

• Japan:
In Japan, risdiplam is approved by the Pharmaceuticals and Medical Devices Agency (PMDA). The approval is documented under the drug application number 30300AMX00294, with the product available in a dry syrup formulation under the brands “EVRYSDI Dry Syrup” and “エブリスディドライシロップ60mg.” The approval date on September 24, 2024, reflects the stringent Japanese review process and the recognition of risdiplam’s benefits in addressing SMA, particularly by providing a convenient oral administration route that circumvents the need for invasive treatment modalities.

• South Korea:
South Korea has granted an orphan drug designation for risdiplam in the treatment of SMA, with the regulatory review process culminating in an approval for its use. The drug regulatory review entry states that risdiplam was granted orphan drug status on November 2, 2020, for the treatment of spinal muscular atrophy. This designation not only confirms its clinical value in a rare disease setting but also enables expedited regulatory pathways that can facilitate wider market access in the South Korean healthcare system.

Collectively, these approvals across major markets represent a significant achievement in global SMA therapy. Each approval reflects the careful adaptation of the regulatory submission to meet local standards—whether that is the FDA’s emphasis on extensive clinical data and safety endpoints in the United States or the EMA’s accelerated processes designed for therapies addressing critical unmet needs in Europe.

Pending Approvals
In addition to the countries where risdiplam is already approved, there are several regions where regulatory filings have been made and decisions are either pending or under review. According to strategic filings and public statements by the developers, applications have been submitted in multiple other jurisdictions. For instance, Roche has filed for approval in countries such as Brazil, Chile, Indonesia, Russia, and Taiwan. While specific approval dates are not detailed in the provided references, these filings indicate the company’s commitment to expanding global access. Once the respective regulatory agencies in these regions complete their evaluations, it is expected that risdiplam may soon achieve a broader international footprint, further strengthening the global treatment network for SMA.

Implications of Approval
The regulatory approvals achieved for risdiplam have far-reaching implications—from transforming patient access to impacting the pharmaceutical market landscape and influencing treatment paradigms for spinal muscular atrophy. The multi-regional approval process and subsequent licensing strategies contribute not only to the commercial success of the drug but also to the overarching goal of improving patient outcomes internationally.

Market Impact
The approval of risdiplam in key markets such as the United States, China, the European Union, Japan, and South Korea has significant commercial and clinical ramifications. Firstly, being the first oral therapy for SMA places risdiplam in a unique market position that distinguishes it from other therapies that may require invasive administration methods. This ease of use has the potential to enhance adherence, improve patient satisfaction, and ultimately drive higher uptake across diverse age groups and SMA phenotypes.

Moreover, the broader therapeutic label—spanning multiple SMA types—ensures that a wide range of patients can benefit from risdiplam. The extensive data from pivotal clinical trials that demonstrated improvements in motor function directly support its market potential, as clinicians and healthcare providers are increasingly looking for treatments that offer both effectiveness and convenience. The positive clinical outcomes, coupled with favorable safety findings across multiple studies, signal a robust market demand and contribute to a competitive landscape that challenges the existing standard of care.

Financially, the global acceptance of risdiplam is poised to drive significant revenue for the companies involved. Expanding into multiple regions not only mitigates the risks associated with market concentration but also underscores the potential for high sales volumes. The oral administration route further reduces associated treatment costs, such as those incurred during hospital visits or invasive procedures, making risdiplam an attractive option for healthcare systems keen to optimize resource allocation while improving patient care.

Accessibility and Distribution
The multi-regional approval of risdiplam enhances its accessibility and broadens the spectrum of distribution channels. In the United States, the drug is marketed by Genentech, a member of the Roche Group, which has established robust distribution networks to ensure that the product reaches patients conveniently—often via home delivery mechanisms that are particularly critical for patients with limited mobility. Similarly, in the European Union, the EMA approval facilitates standardized marketing and reimbursement negotiations across member states, which is crucial for ensuring that patients across different countries have equitable access.

In Japan, the formulation as a dry syrup is specifically designed to cater to the needs of pediatric patients and caregivers, providing ease of use and dosing flexibility. In China, the availability of a powder formulation that can be reconstituted as needed reflects an approach tailored to local manufacturing and distribution practices, ensuring consistency in product quality while meeting the demands of a vast and diverse patient population.

The orphan drug designation in South Korea also plays an important role in optimizing accessibility, as it paves the way for cost-effective pricing strategies, dedicated funding mechanisms, and specific reimbursement policies tailored for rare diseases. This regulatory incentive is intended to support the commercialization and distribution of treatments for conditions that might otherwise struggle to attract competitive market interest.

In terms of global distribution, the comprehensive approval in major markets is likely to create a ripple effect, encouraging regulatory agencies in pending jurisdictions to expedite their reviews. As awareness grows regarding the therapeutic benefits of risdiplam, stakeholders—including patient advocacy groups, clinicians, and policymakers—are increasingly supportive of ensuring that its access is prioritized, ultimately contributing to a more unified and patient-centric approach to SMA management.

Conclusion
In summary, risdiplam has achieved regulatory approval in several key regions: it is approved in the United States by the FDA (with an approval date of August 7, 2020) as the first oral therapy for SMA; in China by the NMPA (approval date June 16, 2021) under the trade names “Evrysdi” and “艾满欣”; in the European Union by the EMA (approval date September 12, 2024) under the trade name “Evrysdi”; in Japan by the PMDA (approval date September 24, 2024) as a dry syrup formulation; and it has received orphan drug designation and subsequent approval in South Korea (approval date November 2, 2020). These approvals, supported by robust clinical trial data that demonstrate improved motor function and a favorable safety profile, represent a transformative milestone in the treatment of SMA.

The multi-layered regulatory strategy—which involved navigating distinct requirements, leveraging accelerated review pathways, and tailoring product formulations for local markets—has not only expedited patient access to this critical therapy but has also set a new benchmark for the development of oral treatments for neuromuscular disorders. Furthermore, with pending filings in additional markets such as Brazil, Chile, Indonesia, Russia, and Taiwan, the global footprint of risdiplam is poised to expand further.

From a market perspective, the approval of risdiplam translates into a substantial impact on treatment paradigms by providing a convenient, home-administered alternative to more invasive approaches. This, in turn, is expected to significantly enhance patient adherence and quality of life while also generating considerable revenue for its developers. Access and distribution are supported by the establishment of dedicated commercial networks and tailored product formulations that address the specific needs of diverse patient populations, thereby ensuring that the benefits of risdiplam reach as many patients as possible around the globe.

Overall, the regulatory success across multiple jurisdictions underscores the therapeutic’s robust benefit–risk profile and highlights the potential of innovative, patient-friendly therapies to revolutionize treatment landscapes for rare and debilitating conditions like spinal muscular atrophy. Risdiplam’s achievement in obtaining global approvals is not just a victory in regulatory terms but also a significant stride toward improving the lives of patients with SMA worldwide.