[Interview] The promise of oral SMA therapy and the flexibility gap between Korea and Japan

Treatment access for spinal muscular atrophy (SMA) in Korea remains constrained by structural barriers even as disease-modifying therapies become more widely available.

SMA is a genetic neuromuscular disease in which a lack of survival motor neuron protein leads to progressive muscle weakness, respiratory decline, and life-threatening complications.

For infants with type 1 SMA, the absence of treatment can mean a life expectancy of less than two years. As global evidence increasingly confirms that early diagnosis and early treatment change the course of the disease, Korean families still face rigid reimbursement rules that limit how and when they can receive therapy.

Roche’s Evrysdi (ingredient: risdiplam), the first oral SMA treatment that can be taken at home once a day regardless of meals, has raised expectations that patients with severe mobility issues will no longer need to rely solely on hospital-based injections.

In reality, however, strict prescription limits, one-way rules on switching between therapies, and the requirement to prove motor function improvement or maintenance every four months under the national insurance system continue to shape care in ways that do not fully reflect clinical needs.

To explore these issues, Korea Biomedical Review held a joint interview with Professor Jong-Hee Chae of the Department of Clinical Genomic Medicine at Seoul National University Hospital and Dr. Reiko Arakawa of the Department of Genomic Medicine at the National Center for Global Health and Medicine in Japan. The interview took place during the recent Fall Conference of the Korean Child Neurology Society (KCNS) at COEX Magok Convention Center in Seoul.

The two experts discussed how early diagnosis and oral therapy are changing SMA care, and how differences between Korean and Japanese reimbursement systems are translated into the daily lives of patients and caregivers.

Early treatment and oral therapy as drivers of real-world outcomes

According to Chae, the recent conference of the KCNS made it clearer than ever that the future of SMA treatment depends on how quickly patients can start therapy.

“SMA is a condition in which time is directly linked to prognosis, and the central message across sessions was that early diagnosis through newborn screening and prompt treatment initiation determine motor function and quality of life over a lifetime,” she said.

In Japan, newborn screening for SMA is already publicly funded in several municipalities, and preparations for nationwide rollout are underway.

“As screening expands and early treatment becomes the norm, severe cases that progress to advanced stages requiring intensive nursing care are expected to become increasingly rare, even if complete elimination of the disease is not realistic,” Arakawa said.

Evrysdi plays a key role in this shift.

“As an oral therapy that can be self-administered at home, it offers systemic exposure, including to the central nervous system, by increasing and maintaining levels of SMN protein throughout the body,” she said. “Clinical studies such as FIREFISH, SUNFISH, RAINBOWFISH, and JEWELFISH have shown that Evrysdi improves or stabilizes motor function from pre-symptomatic infants to adults and maintains these benefits over several years, with a safety profile that is generally manageable.”

In real-world practice, the advantage of oral therapy is less about abstract efficacy comparisons and more about the ability to deliver treatment quickly and continuously.

Chae noted that, clinically, Evrysdi is regarded as an equivalent option to intrathecal injections or gene therapy.

However, what patients feel in everyday life depends more on whether treatment can be started without delay and then maintained steadily, Evrysdi, she said, is strongest where it can be used flexibly by any patient, at any time, in any setting, without being constrained by the logistics of hospital visits.

Japan has developed this concept further through a bridging strategy.

Arakawa described how hospitals in Japan keep Evrysdi in stock so that treatment can begin immediately after an SMA diagnosis, even while preparations for gene therapy, such as securing product and checking AAV9 antibodies, are still underway.

At her own institution, there was a recent case in which Evrysdi was started within 24 hours of a positive newborn screening result. Early administration prevents further motor neuron loss during the waiting period and buys precious time to plan long-term therapy.

She added that her personal goal is to build a nationwide system in which every infant who needs it can start treatment within 14 days of birth, and that Evrysdi makes this target realistic.

In Korea, Evrysdi was approved by the Ministry of Food and Drug Safety in November 2020 and received national insurance reimbursement in October 2023, becoming the first reimbursed oral SMA therapy.

In June 2025, a tablet formulation for patients aged two years and older and weighing at least 20 kilograms was also approved, further enhancing convenience and adherence. Adults in particular tend to prefer the tablet for daily use, while both children and caregivers benefit from reduced difficulties associated with handling liquid formulations.

Despite these advances, the Korean reimbursement framework has prevented the full value of oral therapy from reaching patients.

Under current rules, Evrysdi can be prescribed only up to three bottles per visit, which amounts to roughly three to five weeks of treatment. SMA patients often have severe mobility limitations, and caregivers must accompany them to the hospital, frequently sacrificing work or school days to do so. In addition to these frequent visits for prescriptions, patients must also travel for separate assessments.

“Because patients need to come back every three to five weeks just to renew their medication, the supposed advantages of oral therapy, continuity and accessibility, are not being realized,” Chae explained.

She pointed out that long-term treatment costs for Evrysdi and nusinersen are not dramatically different after one to two years, and that the gap is not large enough to justify such rigid controls.

The restriction on switching between therapies adds another layer of difficulty.

In Korea, switching from intrathecal Nusinersen to oral Evrysdi under reimbursement is allowed only once, and there is no possibility of returning to the original therapy.

According to Chae, this one-way rule effectively means that once a family chooses an option, there is no going back, even if the patient’s condition changes.

SMA symptoms can fluctuate, and some patients may respond differently over time, so clinicians need the flexibility to change strategies based on age, mobility, caregiver capacity, and treatment response.

In Japan, by contrast, physicians can freely decide whether to switch between Nusinersen and Evrysdi, and can adjust treatment plans as circumstances evolve.

Arakawa commented that there have been virtually no reports of reduced efficacy or safety problems related to switching.

Instead, accumulated data show that the earlier treatment starts, the better the outcomes, regardless of which specific therapy is used at a given time.

She described Japan’s approach as one that prioritizes patient-centered, individualized care, giving medical teams the authority to select and change therapies without being bound by administrative one-way rules.

Four-month motor function reassessment rule fuels anxiety in Korea

If prescription volume limits and switching restrictions shape the logistics of care, the four-month motor function evaluation rule influences the emotional and psychological landscape for Korean SMA families.

Under current national insurance criteria, patients must undergo standardized motor function assessments every four months. Continued reimbursement is contingent on demonstrating improvement or at least maintenance of function at each evaluation. If scores fall below a set level, treatment can be stopped.

For a progressive neuromuscular disease that is rarely cured in the conventional sense, this framework is particularly harsh.

SMA therapies aim to maintain function for as long as possible and slow progression rather than reverse damage in all patients. Yet, even temporary worsening caused by surgery, infection, or an acute illness can lower scores and trigger the risk of losing reimbursement.

Chae emphasized that these rules place patients and caregivers under constant stress.

Families live with the fear that therapy could be cut off, not because it has truly failed, but because a score dropped during a difficult period.

“Repeated motor function assessments every four months are a major psychological burden,” she said. “Parents worry every time that the result might not meet the criteria, and that their child’s treatment could be stopped.”

This anxiety is added on top of the everyday challenges of living with SMA, she added.

She also pointed out that the rule burdens clinicians and the rare disease care system itself.

Conducting comprehensive motor assessments at such frequent intervals demands significant time and resources from specialists, in addition to routine clinical care. In a field where medical personnel and clinic capacity are limited, this administrative workload can crowd out other essential activities.

Japan has taken a fundamentally different approach.

“There are no government regulations linking motor function test results directly to treatment continuation,” the Japanese physician said. “Instead, physicians are given full discretion to judge whether therapy should be maintained and the priority is to ensure that once a patient with SMA is diagnosed, the patient can continue to receive appropriate treatment without interruption.”

In Japan, stopping therapy is regarded as an extreme decision given the biology of SMA, where ongoing production and maintenance of SMN protein are required over the long term, she added.

From a clinical standpoint, Arakawa further explained that imposing routine motor assessments every four months, on top of standard care, would be extremely burdensome.

“The added pressure of knowing that treatment might be discontinued if measurable improvement is not seen would also weigh heavily on clinicians,” she said. “Such requirements, in her view, are not compatible with the management of a chronic progressive rare disease that requires sustained therapy.”

A call for patient-centered policy reform

Both experts concluded with a strong call for policy adjustments in Korea to maximize the benefits of oral therapy and ensure patient-centered care.

Chae noted that the treatment environment has evolved significantly, with many patients now diagnosed early and receiving timely treatment.

She suggested that conducting research that differentiates outcomes between early and late treatment groups and quantitatively assesses the caregiving and societal burdens would provide the necessary evidence to advocate for a more flexible treatment environment.

To meaningfully improve the SMA treatment environment in Korea, she recommended expanding newborn screening (NBS) for early diagnosis, increasing flexibility in switching between SMA therapies; extending prescription intervals for oral treatments, and easing regulatory requirements related to motor function assessments.

Arakawa expressed hope that Korea, like Japan, would continue its journey toward a more patient-centered environment, enabling children with rare diseases to experience a healthy and fulfilling childhood.