Soft Bones, the United States Hypophosphatasia Foundation, is pressing South Korean policymakers to reconsider reimbursement rules for hypophosphatasia treatment, arguing that the current framework may restrict access for people whose disease began in childhood but was diagnosed after they reached adulthood. The patient advocacy organization said on August 19 that it had submitted a formal letter on July 27 to the Office of the President of the Republic of Korea and the Speaker of the National Assembly, supporting broader access for Korean patients with hypophosphatasia, or HPP.
The intervention comes at a particularly relevant point because the disagreement is not principally about whether South Korea recognizes HPP or whether an enzyme replacement therapy exists. The Korea Disease Control and Prevention Agency currently lists HPP as a nationally managed rare disease, identifies ALPL gene variants as its underlying cause, and includes asfotase alfa enzyme replacement therapy among treatment approaches. The sharper question is how those clinical realities are translated into reimbursement eligibility.
South Korea’s Health Insurance Review and Assessment Service currently publishes reimbursement criteria for asfotase alfa, marketed as Strensiq, that require a patient with pediatric-onset HPP to satisfy several conditions. These include alkaline phosphatase below the age and sex adjusted reference range, elevated pyridoxal-5′-phosphate, characteristic HPP bone manifestations demonstrated on radiographic imaging before treatment, and initiation of therapy before age 19.
That combination creates the central policy tension behind the Soft Bones campaign. Pediatric onset of a lifelong genetic disorder and initiation of treatment during childhood are not necessarily the same event, particularly when a rare condition can remain undiagnosed for years.
Why does Korea’s age-19 rule create a gap between HPP disease onset and treatment eligibility?
Hypophosphatasia is caused by reduced activity of tissue-nonspecific alkaline phosphatase resulting from pathogenic variants in the ALPL gene. Its presentation varies widely, ranging from severe disease in infancy to less obvious skeletal, muscular and dental manifestations that may only lead to diagnosis much later. South Korea’s own rare-disease resource identifies manifestations including bone and muscle pain, pathological fractures, weakness, premature tooth loss, impaired mineralization and other systemic complications.
This variability matters because age at diagnosis does not necessarily establish age at disease onset. International HPP diagnostic work has specifically highlighted the distinction, noting that an adult can be diagnosed with childhood HPP after clinicians establish that relevant manifestations were already present earlier in life. Contemporary diagnostic frameworks therefore integrate persistently low alkaline phosphatase with combinations of clinical characteristics, elevated enzyme substrates, ALPL variants and other disease features rather than treating the patient’s age at diagnosis as a substitute for disease history.
Soft Bones is effectively arguing that South Korea’s reimbursement system can create a different outcome. A person whose HPP manifested in childhood but whose diagnosis and proposed treatment occur after age 19 can encounter the reimbursement barrier even where the historical clinical picture supports pediatric-onset disease.
That distinction is important because Strensiq’s internationally established treatment population is itself defined by disease onset rather than simply the patient’s current age. In the European Union, for example, the medicine is indicated for long-term enzyme replacement therapy in patients with pediatric-onset HPP to treat the bone manifestations of the disease. The United States indication similarly covers perinatal, infantile and juvenile-onset HPP. Adults are therefore not automatically outside the treatment population simply because they are adults, provided their disease falls within the relevant pediatric-onset indication.
Why have radiographic findings become another focus of the Korean HPP access debate?
The Korean reimbursement rule also requires characteristic HPP bone manifestations on radiographic imaging before treatment. Imaging is unquestionably important in HPP assessment, particularly where rickets, osteomalacia, fractures, pseudofractures or characteristic skeletal abnormalities are present, but modern diagnostic thinking treats HPP as a multisystem disorder whose clinical expression can extend beyond one radiographic presentation.
The International HPP Working Group’s proposed pediatric criteria illustrate that broader approach. With persistently low alkaline phosphatase as an obligate starting point, major criteria include ALPL variants, elevated natural substrates, early non-traumatic loss of primary teeth and radiographic rickets, while additional manifestations such as delayed motor development, chronic musculoskeletal pain, impaired mobility and other abnormalities contribute to the overall diagnostic assessment. The adult framework similarly includes pathogenic ALPL variants, elevated substrates, recurrent metatarsal fractures and atypical femoral fractures among major criteria, alongside several additional clinical features.
These diagnostic proposals do not themselves determine who should receive enzyme replacement therapy, and broadening diagnosis should not be confused with creating an automatic treatment entitlement. The working group itself separates the question of establishing HPP from the more complicated decision over whether a particular patient should be treated. That distinction is important for the Korean debate because a reimbursement reform could recognize a wider evidentiary picture without eliminating clinical thresholds or treatment monitoring.
Soft Bones said the Korean Hypophosphatasia Patient Association is seeking precisely that kind of change, including greater recognition of clinical manifestations beyond radiographic findings, consideration of genetic testing together with characteristic symptoms, and revision of the age restriction for patients with confirmed childhood-onset disease who continue to have a clinical need for treatment. The organization said a proposal to expand the criteria was submitted to Korean authorities in April 2026 and remains under review.
What does the evidence show about asfotase alfa treatment in adults with HPP?
The treatment evidence makes the age question more nuanced rather than eliminating it. Asfotase alfa is an enzyme replacement therapy designed to replace deficient tissue-nonspecific alkaline phosphatase activity, and the strongest regulatory precedent remains centered on pediatric-onset HPP. The evidence base in adults is considerably smaller than would be expected for common metabolic or musculoskeletal diseases, reflecting the rarity and heterogeneity of HPP.
A multinational study involving 19 adolescents and adults aged 13 to 66 evaluated asfotase alfa in an initial randomized, open-label period followed by extended treatment. The study found pharmacodynamic changes and reported improvements in several functional measures over prolonged follow-up, but its small population and open-label design limit the conclusions that can be drawn from it.
A much larger observational analysis published in 2024 used data from the Global HPP Registry and included 190 adults who had received asfotase alfa for at least six months. Importantly for the Korean policy question, 91.1% of those adults were classified as having pediatric-onset HPP, while the median age when treatment started was 45.5 years. The study reported improvements across measures including walking distance, pain, disability and health-related quality of life among patients with available follow-up, although its observational design means it cannot provide the same level of causal certainty as a large randomized controlled trial.
Those data do not establish that every adult with HPP should receive asfotase alfa, nor do they settle questions surrounding adult-onset disease. They do, however, demonstrate why a reimbursement system based partly on treatment initiation before a specific birthday can produce a different patient population from a system based primarily on documented pediatric disease onset, current disease burden and treatment suitability.
Could South Korea broaden HPP access without abandoning reimbursement controls?
Expanding eligibility would not necessarily require South Korea to move from restrictive coverage to unrestricted access. The existing HIRA framework already contains mechanisms intended to evaluate treatment after initiation, including clinical assessments at treatment start, three months, six months and every six months thereafter, covering parameters such as growth, respiratory function, motor development, walking ability and pain. HIRA also calls for annual evaluation against discontinuation criteria.
That creates room for a more clinically nuanced policy design. Authorities could potentially reconsider whether treatment must begin before age 19 or whether radiographic abnormalities should remain an absolute gatekeeper while retaining biochemical confirmation, documentation of pediatric onset, relevant clinical manifestations, specialist assessment and continuing evaluation of treatment response. Whether Korean authorities ultimately choose such a framework remains uncertain, but the existing monitoring architecture means eligibility reform and utilization control are not necessarily opposing objectives.
South Korea has also modified the administration of Strensiq reimbursement before. HIRA’s April 2024 revision removed provisions related to prior review as the treatment shifted toward post-review arrangements, while the substantive biochemical, radiographic and age criteria remained in the published reimbursement standard. That history suggests policymakers have already been willing to adjust the mechanics of access without dismantling oversight of this expensive and highly specialized rare-disease therapy.
What will determine whether the 2026 Korean HPP reimbursement review changes treatment access?
The next material development is not another advocacy statement but the Korean authorities’ decision on the reimbursement expansion proposal that Soft Bones says has been under consideration since April. As of August 20, the currently published HIRA standard still contains the requirement for characteristic radiographic bone findings and treatment initiation before age 19, so the Soft Bones letter should be viewed as part of an ongoing policy campaign rather than evidence that Korean coverage has already changed.
For clinicians and rare-disease policymakers, the central test will be whether reimbursement criteria can distinguish between a patient whose HPP genuinely began only in adulthood and an adult whose pediatric-onset disease went unrecognized or untreated for years. For the Korean Hypophosphatasia Patient Association, the outcome will determine whether clinical history, genetic evidence and current functional burden can carry more weight when a patient does not fit the existing age and imaging requirements.
For Alexion Pharmaceuticals and the wider rare-disease industry, the commercial impact of any single Korean reimbursement revision would be constrained by the extremely small HPP population. The broader significance lies in how health systems handle a growing class of lifelong genetic disorders where regulatory indications, diagnostic timing and reimbursement rules can define patient populations in subtly different ways.
The Korean HPP review therefore reaches beyond a simple request to remove an age limit. It asks whether reimbursement should remain tied to when treatment happened to begin or evolve toward a framework that more closely follows when the disease began, how confidently that history can be established, how severely the patient is currently affected and whether continued treatment can demonstrate measurable clinical value. That is the policy decision Korean authorities now have to resolve.