For the past year, Xia Sheng (pseudonym), a man in his fifties living with ALS, has made a monthly pilgrimage to the neurology ward of Peking University Third Hospital to receive intrathecal injections of tofersen. His neurofilament light chain (NfL) levels, a key biomarker of nerve damage, have stabilized between 14 and 15, roughly 70% lower than before treatment, signaling that the neurodegenerative process has been substantially controlled.

His journey reflects a dramatic shift in ALS care over the past three years: from a time when no treatments were available in China, to the arrival of innovative drugs that once cost around 1.4 million yuan annually, far beyond the reach of ordinary families, to the emergence of patient assistance programs and commercial health insurance that are gradually easing the financial burden. After patient assistance, Xia Sheng's out-of-pocket costs dropped to just over 700,000 yuan in the first year and to around 400,000 yuan the following year. If Beijing's inclusive health insurance is layered on top, his personal burden could fall further to roughly 200,000 yuan.

Xia Sheng suffers from SOD1-mediated ALS, which accounts for only about 2% of all ALS cases and is the only ALS subtype with an approved targeted therapy globally. For him, this is a silver lining: multi-tiered protection has made this life-saving drug just barely within reach. But patients who can stretch to afford it remain a small minority.

Fan Dongsheng, director of neurology at Peking University Third Hospital and one of China's foremost authorities on ALS clinical research and treatment, shared data showing that while an estimated 1,000-plus patients in China carry SOD1 mutations, only about 100 are receiving treatment, roughly one in ten. Hospital accessibility and affordability remain the primary barriers keeping a significant share of patients from accessing the drug.

Yet a turning point is emerging. On November 14, the National Healthcare Security Administration released its second commercial insurance innovative drug list, which includes tofersen as the world's first and only disease-modifying therapy targeting SOD1-ALS. The list provides a clear pathway for local governments to update inclusive insurance specialty drug lists and for commercial insurance innovative drugs to enter hospitals and clinical use.

"Hospitals generally support the introduction of innovative drugs. But for these drugs to truly benefit patients, a comprehensive policy and payment environment is essential. At this stage, commercial insurance plays a particularly critical role in the rare disease field," Fan Dongsheng said.

Fan Dongsheng believes that ALS drug development and coverage is a microcosm of the broader rare disease landscape. After decades of global exploration, recent years have seen breakthroughs across disease research, new drug development, and rehabilitation. But as treatment options grow richer, the simple "one drug for all" model is increasingly inadequate for the differentiated needs of individual patients, placing higher demands on healthcare coverage.

As more rare diseases come into the purview of commercial insurance, the key to making it truly function as a risk-sharing and payment-support mechanism lies in expanding enrollment, a crucial step toward building a virtuous rare disease protection ecosystem.

Maintaining the Status Quo Is a Form of Hope

ALS, or amyotrophic lateral sclerosis, is a rare neurodegenerative disease primarily affecting the brain and spinal cord. After onset, motor neurons progressively shut down segment by segment, while consciousness remains fully intact, and the body gradually "solidifies" until the patient completely loses mobility. The annual incidence in China is about 1.62 per 100,000, with tens of thousands of existing patients, and median survival after diagnosis is typically only three to five years.

"Disease progression is like a leaking pool, with neurons gradually being lost in the process," Fan Dongsheng described. In 2023, the world's first disease-modifying ALS drug, tofersen, received accelerated approval from the U.S. FDA based on the surrogate endpoint of plasma neurofilament light chain (NfL) reduction. That same year, Xia Sheng was diagnosed with ALS.

At first, he only felt sudden weakness in his calves while walking, "a bit like stepping on cotton," with little impact on daily life. After visiting multiple hospitals without a diagnosis, he was finally confirmed as having SOD1-ALS through genetic testing at the end of that year. His condition then progressed rapidly: from walking with a cane, to depending on a cane, to using a wheelchair.

Objective indicators confirmed the worsening trend: his ALSFRS-R score, the internationally used revised ALS Functional Rating Scale, dropped by 4 points in the single year from 2024 to 2025. During the same period, blood tests showed that his NfL level had reached nearly 60 by mid-2025, indicating a high level of nerve damage.

Throughout this period, Xia Sheng persisted with acupuncture, traditional Chinese medicine, and rehabilitation training while continuously taking riluzole. Riluzole and edaravone are the two ALS treatments already covered by basic medical insurance, but both offer only marginal slowing of the disease. Studies show that riluzole extends survival by only two to three months, and edaravone, as an antioxidant, is effective in only about 5% of patients.

"Overall, existing treatments have some effect, but it's a bit like scratching an itch through a boot," Fan Dongsheng explained. SOD1 gene mutations cause abnormal protein production, triggering a cascade of pathological changes. Riluzole acts on excitatory signaling pathways, and edaravone scavenges free radicals, both targeting downstream links in the disease process. "It's like the water source is still leaking, and patching things up downstream has some effect, but it's hard to solve the problem at its root."

In September 2024, tofersen received conditional approval in China, and in June of the following year it was officially launched in the country. Peking University Third Hospital introduced the drug through temporary procurement the same month. On June 19, 2025, Xia Sheng completed his first dose. After more than ten injections, the results are evident: his NfL level has dropped from nearly 60 to around 14-15, indicating significantly reduced nerve damage, and the precipitous decline in his ALSFRS-R score has been "put on pause."

During an hour-long interview with Yicai, he walked slowly with a cane, accompanied by family members, speaking clearly, with no apparent impact on respiratory function. "Maintaining the status quo is a form of hope," Xia Sheng said.

According to Fan Dongsheng, since tofersen's launch in China, most early-treated patients have completed more than a dozen or even twenty-plus injections, with functional improvements observed. He looks forward to validation through longer-term and larger-sample studies. At the end of 2025, long-term results from the Phase III VALOR study and its open-label extension further demonstrated tofersen's sustained benefits in motor and respiratory function.

More definitive positive signals have also come from longer-term clinical practice abroad. Fan Dongsheng mentioned a patient in Germany who has been on tofersen for seven years and whose walking stability has improved compared to before treatment. Recently published long-term follow-up data also show that some patients experienced a degree of recovery after a period of functional decline.

Before Joining the Commercial Insurance List: Hard to Enter Inclusive Insurance, Even Harder to Enter Hospitals Routinely

Xia Sheng has calculated the costs: the first three injections were spaced 14 days apart, followed by maintenance doses every 28 days. At 14 doses per year, the annual treatment cost exceeds one million yuan, and long-term use remains an ongoing expense.

"Some patients have elderly parents and young children at home. They not only face immediate drug costs but must also consider expenses over the next five, ten, or even more years. There is currently no clear treatment duration, and it's impossible to determine whether the drug can be stopped after a few years. It may require long-term continuous use. So whether a family can bear this long-term expense is a reality patients must face, especially when many families have already lost an income source and when the next generation or other relatives may also carry the disease-causing gene," Xia Sheng said. "This long-term expense is very difficult for one family to shoulder alone."

The first cut in out-of-pocket costs came from patient assistance programs. In June 2025, the month tofersen was officially commercialized in China, the Beijing Kangmeng Charity Foundation, with corporate support, launched China's first drug assistance program for SOD1-ALS, covering loading-dose assistance (a "1+2" cycle, meaning one self-paid injection with two free), maintenance-dose assistance (two rounds of "3+3," meaning three self-paid injections with three free), and subsequent long-term "1+2" cyclical assistance. Xia Sheng was a beneficiary of this program.

Inclusive insurance has become a crucial backstop. At the end of 2025, the National Financial Regulatory Administration issued guiding opinions on promoting high-quality development of health insurance, encouraging the development of commercial medical insurance products benefiting "diseased groups and rare disease groups" and including "new medical technologies, new drugs, and new devices" in coverage. But objectively, pure commercial medical insurance products covering rare diseases remain extremely rare, and critical illness insurance reimbursement faces significant obstacles. Inclusive insurance has therefore become a decisive factor in determining patient drug accessibility, either through inclusion in specialty drug lists or coverage under inpatient out-of-pocket liability.

However, most inclusive insurance products impose a single-drug reimbursement cap under inpatient liability, which is typically lower than specialty drug reimbursement. Not to mention that routine hospital entry for rare disease drugs itself faces numerous challenges.

Fan Dongsheng noted that patients using the drug are currently concentrated in economically developed coastal regions such as Zhejiang and Guangdong, with fewer in northern and western regions, closely tied to hospital accessibility and patients' economic foundations. When patients from central and western regions travel to Beijing for treatment, family expenses are further driven up. Moreover, whether in Beijing or nationally, the drug typically enters hospitals through temporary procurement, making routine entry extremely difficult.

According to the latest data provided by Biogen, the company behind the drug, tofersen's drug network currently covers 18 provinces. Although the drug has obtained specialty drug access qualifications from 17 inclusive insurance products, the vast majority are prefecture-level products. Compared to the more than 200 active inclusive insurance products nationwide, there remains substantial room for expanded access.

"For the company, participating in this commercial insurance innovative drug list negotiation was a decision made after comprehensive evaluation based on multiple factors including patient accessibility, innovation value, and sustainable development," Biogen said. Although the discount rebate mechanism was not smooth when the first commercial insurance list was implemented, leading to a significant reduction in the number of drugs applying for the list this year, Biogen told Yicai: "The commercial insurance innovative drug list is a new exploration requiring coordination among pharmaceutical companies, insurance institutions, medical institutions, and other parties. Currently, policies such as the 'three exclusions' have created better conditions for innovative drugs to enter medical institutions and clinical use. We look forward to further clarification and improvement of related policies and supporting mechanisms to truly translate policy support into patient access."

After Joining the Commercial Insurance Innovative Drug List, What Next?

After tofersen enters the commercial insurance innovative drug list, what Fan Dongsheng hopes for is systemic change. He proposed several ideas: Since genetically mutated ALS carries significant hereditary risk, can clinical application of new drugs drive early genetic testing, early diagnosis, and early treatment for at-risk populations? What is tofersen's replacement effect on "old drugs" like riluzole and edaravone already covered by basic medical insurance? Can existing standard treatment regimens be further optimized based on real-world studies? And can a reasonable payment mechanism guide more corporate resources toward rare disease research and development?

Fan Dongsheng used the "leaking pool" metaphor to explain the significance of early intervention: disease progression is like a pool continuously leaking water, with neurons gradually being lost. If problems can be identified early and intervened promptly, it may be possible to plug the leak and preserve as much "water in the pool" as possible. Conversely, if diagnosis is delayed by three to five years, a large amount of water has already been lost, and remediation cannot restore the original state.

The reason more real-world studies are still needed, Fan Dongsheng said, is that observations of current patients show two trends: on one hand, patients' NfL biomarker levels generally show a significant downward trend, especially in patients with higher pre-treatment levels, who typically also face higher disease progression risk. On the other hand, patients' function may continue to decline for a period, much like a high-speed train that doesn't stop immediately after braking but needs time to gradually decelerate. These findings require more thorough verification.

Ding Weibo, Asia-Pacific president of Biogen, also mentioned in an interview with Yicai that the company places great importance on accumulating real-world evidence from Chinese patients, which is valuable for further understanding SOD1-ALS and optimizing clinical practice. He revealed that Biogen is currently supporting domestic ALS experts in conducting real-world studies of tofersen, planning to rely on multiple ALS centers to systematically evaluate biomarker changes, clinical function, and safety in Chinese patients.

Ding Weibo also noted that this year, the Chinese ALS expert consensus has been updated, separately listing tofersen and clearly identifying it as an antisense oligonucleotide (ASO) drug targeting SOD1-mutated ALS, recommending that patients confirmed to carry SOD1 pathogenic variants consider using it.

This year, a rare disease drug from the first commercial insurance innovative drug list successfully achieved an "identity transformation," newly becoming a nationally negotiated drug. When asked whether the company would further pursue basic medical insurance coverage after accumulating real-world evidence, Ding Weibo told Yicai: "We maintain an open attitude toward all pathways that can improve drug accessibility."