The Clinical, Economic, and Ethical Imperative for Public Subsidy of Palopegteriparatide (Yorvipath) in Australia
For a powerful article by someone with lived experience of hypoparathyroidism, and the impact of not having access to Yorvipath, click here.
A Health Technology Assessment and Policy Analysis
Executive Summary
The management of chronic hypoparathyroidism in Australia currently stands at a precipice between antiquated palliation and modern physiological restoration. In February 2025, the Therapeutic Goods Administration (TGA) granted registration to Yorvipath (palopegteriparatide), a first-in-class prodrug of parathyroid hormone (PTH) designed to replace the missing endogenous hormone in adults with chronic hypoparathyroidism. This regulatory approval, which followed a Priority Review designation acknowledging the significant unmet clinical need, marked a historic milestone: Australia became the first nation following the United States to authorise this therapy, recognising its potential to mitigate the catastrophic long-term renal and neuromuscular sequelae of the disease.
However, the promise of this clinical breakthrough remains unfulfilled for Australian patients. As of late 2025, the Pharmaceutical Benefits Advisory Committee (PBAC) has twice declined to recommend palopegteriparatide for listing on the Pharmaceutical Benefits Scheme (PBS), citing uncertainties regarding cost-effectiveness, the appropriate time horizon for economic modelling, and a paucity of local epidemiological data. This reimbursement stalemate has created a profound inequity. While patients in comparable health systems—including Germany, Japan, and the United States—are transitioning to physiological replacement therapy that preserves organ function, Australians remain tethered to a high-burden regimen of calcium salts and active vitamin D metabolites. This “Standard of Care” is clinically acknowledged to be nephrotoxic, driving a significant proportion of patients toward chronic kidney disease (CKD), dialysis, and extra-skeletal calcifications.
This report provides an exhaustive clinical and health economic analysis advocating for the immediate public subsidy of palopegteriparatide. By synthesising data from the pivotal Phase 3 PaTHway trial, long-term open-label extensions, and Australian health expenditure reports, this analysis demonstrates that the PBAC’s current stance relies on a static and overly conservative interpretation of “cost-effectiveness” that fails to capture the exorbitant costs of inaction. With the direct health system expenditure on chronic kidney disease exceeding $1.9 billion annually and the cost of dialysis surpassing $85,000 per patient per year, the prevention of renal decline offered by PTH replacement presents a compelling value proposition that transcends the immediate acquisition cost of the drug.
Furthermore, this report addresses the structural barriers cited by the PBAC—specifically the lack of a national registry—proposing that these gaps are best resolved not by denial of access, but through a Managed Access Program (MAP). Drawing on successful precedents set by the listing of therapies for Cystic Fibrosis and Spinal Muscular Atrophy, we outline a robust framework for conditional listing paired with mandatory real-world data collection. This approach aligns with the Australian Government’s National Strategic Action Plan for Rare Diseases, ensuring that fiscal responsibility and equitable patient care are not mutually exclusive but rather synergistic goals.
1. Introduction: The Orphan Disease Landscape and the Access Gap
Chronic hypoparathyroidism represents a singular anomaly in the field of endocrinology. It remains the last classic hormonal deficiency state where the standard medical intervention is not the replacement of the missing hormone, but rather the aggressive supplementation of the downstream minerals that the hormone would normally regulate. For over half a century, patients have been managed with high doses of oral calcium and active vitamin D (calcitriol), a regimen that corrects serum calcium numbers on a pathology report but fails to restore the intricate physiological signalling required for long-term organ health.
1.1 The Regulatory Milestone and Subsequent Stagnation
The approval of palopegteriparatide by the TGA in February 2025 was greeted by the endocrine community as a watershed moment. The approval was based on compelling evidence from the global Phase 3 PaTHway trial, which demonstrated that the therapy could normalise serum calcium while simultaneously allowing 93% of patients to discontinue conventional therapy. The TGA’s decision to grant Orphan Drug Designation and Priority Review underscored the agency’s assessment that existing treatments were inadequate and that palopegteriparatide represented a significant therapeutic advance.
Yet, the transition from regulatory approval to patient access has stalled. The PBAC, the gatekeeper of the PBS, operates under a statutory obligation to ensure that listed medicines represent value for money. In its March 2025 and July 2025 meetings, the PBAC rejected the sponsor’s submission, creating a “valley of death” between scientific validation and practical availability. This disconnect is particularly jarring given the international context; while Australian authorities debate the granularity of utility values in economic models, the Japanese Ministry of Health, Labour and Welfare swiftly approved National Health Insurance (NHI) listing in October 2025, facilitating immediate patient access through a home-healthcare model supported by Teijin Pharma.
1.2 The Structural Challenge of Rare Disease HTA
The impasse over palopegteriparatide highlights a broader systemic issue within Australian Health Technology Assessment (HTA). The PBAC’s rigorous evidentiary requirements, while effective for mass-market drugs like statins or antihypertensives, often falter when applied to rare diseases. The committee’s Public Summary Documents (PSDs) cite “uncertainty” in the economic model as a primary reason for rejection, specifically questioning the translation of surrogate endpoints (such as eGFR slope or urinary calcium reduction) into long-term “hard” outcomes like dialysis avoidance.
However, demanding 30-year randomised controlled trial (RCT) data for a rare, lifelong condition is an impossibility. It is clinically unethical to maintain a control group on a known nephrotoxic regimen (standard care) for decades to prove that they eventually develop kidney failure. This report argues that the PBAC must exercise the flexibility inherent in its mandate, leveraging the “high clinical need” provisions to accept robust surrogate markers—specifically renal function preservation—as valid predictors of long-term economic value.
2. The Clinical Reality: Pathophysiology and the Failure of Standard Care
To understand why subsidy is urgent, one must first appreciate the devastating physiological compromise imposed by the current standard of care. Chronic hypoparathyroidism is not merely a disorder of “low calcium”; it is a complex, multi-system failure of mineral homeostasis that affects the kidneys, the brain, the skeletal system, and the neuromuscular junction.
2.1 The Limitations of Calcium and Calcitriol
The parathyroid hormone (PTH) has two primary functions essential for survival:
Renal Calcium Reabsorption: It instructs the distal convoluted tubules of the kidney to reclaim calcium from the urine back into the bloodstream.
Phosphate Excretion: It promotes the excretion of phosphate into the urine (phosphaturic effect).
Vitamin D Activation: It stimulates the enzyme 1-alpha-hydroxylase in the kidney to convert inactive vitamin D into its active form (calcitriol).
In the absence of PTH, the kidneys lose the signal to reabsorb calcium. Consequently, the renal calcium threshold drops. To maintain serum calcium levels in the low-normal range required to prevent seizures and tetany, patients must ingest massive quantities of elemental calcium (often >2000mg/day) and active vitamin D.
The Pathophysiologic Trap:
Because the renal reabsorption mechanism is disabled, the massive oral calcium load “spills” directly into the urine. This results in severe hypercalciuria (high urine calcium). The kidneys are effectively bathed in a toxic concentration of calcium, leading to:
Nephrocalcinosis: The deposition of calcium salts within the kidney parenchyma.
Nephrolithiasis: The formation of recurrent kidney stones.
Tubular Damage: Progressive scarring and loss of filtration capacity, manifesting as a decline in estimated Glomerular Filtration Rate (eGFR).
Simultaneously, the loss of PTH’s phosphaturic effect leads to hyperphosphatemia. High serum phosphate, combined with the high calcium intake, raises the Calcium-Phosphate Product (Ca x P). When this product exceeds 55 mg²/dL², calcium begins to precipitate in soft tissues throughout the body, not just in the kidneys.
2.2 The “Silent” Progression to Renal Failure
The term “stable” is frequently and erroneously applied to hypoparathyroidism patients whose serum calcium levels fall within the laboratory reference range. This definition of stability masks a progressive, silent decline in organ function.
Quantifying the Risk:
Comprehensive epidemiological studies indicate a dramatically elevated risk profile for these patients compared to the general population:
Chronic Kidney Disease (CKD): A 3-fold to 17-fold increased risk of developing renal insufficiency.
Hospitalisation: A 4.8-fold increased risk of hospitalisation due to renal/urinary disorders.
Stone Disease: Up to 38% of patients develop nephrocalcinosis, often detectable only via ultrasound or CT scanning, long before creatinine levels rise.
Standard therapy is the direct driver of this pathology. By relying on “calcium loading” to maintain serum levels, clinicians are forced to sacrifice the kidneys to save the nerves. This iatrogenic damage is the central argument for the economic value of PTH replacement: the cost of the drug is an investment in preventing the inevitable, expensive destruction of the renal system.
2.3 Neurological and Soft Tissue Calcifications
The risks extend beyond the kidney. The elevated calcium-phosphate product predisposes patients to ectopic calcifications in the brain, particularly the basal ganglia. This condition, often referred to as Fahr’s Syndrome or basal ganglia calcification, is associated with movement disorders, parkinsonism, and cognitive decline.
Patients frequently report “brain fog,” executive dysfunction, and profound fatigue, which may be linked to these micro-structural changes in the brain or the constant fluctuations in serum electrolytes. A global survey of patient burden revealed that 75% of patients experienced interference with their ability to work, and 63% reported strain on family relationships due to cognitive and physical fatigue.
2.4 The Redefinition of Chronic Hypoparathyroidism
Significantly, the European Society of Endocrinology (ESE) released revised clinical guidelines in November 2025. A critical update in these guidelines is the redefinition of “chronic” post-surgical hypoparathyroidism. Previously defined as persisting for 6 months, the new guideline extends this window to 12 months.
This change is based on a systematic review of 14 studies involving nearly 9,000 patients, which found that approximately 7.5% of patients recover parathyroid function between month 6 and month 12. This redefinition is crucial for Australian policymakers. It ensures that any subsidy for palopegteriparatide would be targeted strictly at those with permanent, irreversible disease, thereby improving the cost-effectiveness profile by eliminating the treatment of transient cases.
3. The Pharmacological Solution: Yorvipath (Palopegteriparatide)
Yorvipath represents a sophisticated bio-engineering solution to the limitations of previous therapies. It is not simply “PTH in a syringe”; it is a prodrug designed to overcome the pharmacokinetic instability of the native peptide.
3.1 Mechanism of Action: The TransCon Technology
Native PTH has a very short half-life (minutes), which causes pulsatile levels when injected. Previous therapies like rhPTH(1-84) (Natpara) required once-daily injections that created a “peak” of hormone immediately after dosing, followed by a rapid decline to sub-therapeutic levels later in the day. This fluctuation failed to provide 24-hour control of urinary calcium.
Palopegteriparatide utilises “TransCon” (Transient Conjugation) technology. The active PTH(1-34) peptide is bound to an inert polyethylene glycol (PEG) carrier via a proprietary linker.
Controlled Release: Under physiological conditions (pH and temperature), the linker autohydrolyses at a precise, predictable rate.
Steady State: This releases fully active PTH(1-34) continuously over a 24-hour period.
Physiological Mimicry: The result is a flat, stable pharmacokinetic profile that closely mimics the continuous tonic secretion of a healthy parathyroid gland.
3.2 Clinical Efficacy: The PaTHway Phase 3 Trial
The pivotal PaTHway trial (NCT04701203) provided the evidentiary basis for global approvals. This double-blind, placebo-controlled trial randomised 84 adults to receive either palopegteriparatide or placebo (plus standard care).
Primary Composite Endpoint:
The primary endpoint was a rigorous composite requiring:
Albumin-adjusted serum calcium in the normal range (8.3–10.6 mg/dL).
Independence from active vitamin D.
Independence from therapeutic doses of calcium (≤600 mg/day).
Results:
Success Rate: 78.7% of palopegteriparatide patients met the primary endpoint compared to 4.8% of placebo patients (p < 0.0001).
Standard Care Independence: 93% of treated patients were able to completely stop active vitamin D and reduce calcium supplementation to dietary levels.
Urinary Calcium: Treatment normalised mean 24-hour urine calcium excretion, a feat that standard care rarely achieves.
3.3 Long-Term Renal Outcomes: The Economic Driver
The most critical data for the PBAC—and for the economic model—comes from the 156-week (3-year) open-label extension and post-hoc analyses.
eGFR Improvement:
In a significant finding published in 2024, palopegteriparatide treatment was associated with a statistically significant improvement in eGFR over 52 weeks. This effect was most pronounced in patients who entered the trial with impaired renal function.
Mechanism: By normalising urinary calcium and reducing the “toxic load” on the nephrons, the therapy halts the progression of nephrocalcinosis and allows functional recovery of the renal parenchyma.
Durability: Data through 3 years confirms the sustainability of this renal protection, with eGFR remaining stable or improving.
This data directly challenges the PBAC’s hesitation regarding “surrogate outcomes.” In the context of a nephrotoxic disease, a sustained improvement in eGFR is not merely a surrogate; it is a direct indicator of organ preservation and a robust predictor of delayed dialysis onset.
3.4 Quality of Life and Patient Reported Outcomes (PROs)
The PaTHway trial utilised the Hypoparathyroidism Patient Experience Scale (HPES) and the SF-36 to measure QoL.
Physical Functioning: Treated patients showed statistically significant improvements in the SF-36 Physical Functioning subscale (p = 0.0347).
Symptom Burden: Significant reductions were observed in key symptoms identified in the Hypoparathyroidism Symptom Diary, specifically physical fatigue, muscle cramps, and cognitive interference.
These PROs are vital for calculating Quality Adjusted Life Years (QALYs) in the economic model. The PBAC’s critique that the utility increments were “overestimated” suggests a disconnect between the statistical handling of the data and the profound life impact reported by patients who regain cognitive clarity and physical stamina.
4. Health Economics: The Cost of Inaction vs. The Cost of Investment
The central friction point in the PBAC’s evaluation is the Incremental Cost-Effectiveness Ratio (ICER). In the revised submission considered in July 2025, the ICER was estimated between $75,000 and $95,000 per QALY, following a significant price reduction by the sponsor. The PBAC, however, indicated that an ICER in the range of $45,000 to $55,000 would be required for a positive recommendation.
This section argues that the PBAC’s ICER calculation is artificially inflated by a conservative “base case” that ignores the massive downstream costs of renal failure.
4.1 The Burden of Chronic Kidney Disease (CKD) in Australia
CKD is one of the most expensive chronic conditions managed by the Australian healthcare system. The Australian Institute of Health and Welfare (AIHW) estimates that in 2020-21, approximately $1.9 billion of allocated health expenditure was attributed to CKD.
The Dialysis Cliff:
The transition from Stage 4 CKD to Stage 5 (End Stage Kidney Disease, ESKD) requiring dialysis represents a massive “cost cliff.”
Prevalence: Over 15,000 Australians currently receive dialysis.
Cost per Patient: The annual cost of dialysis is approximately $85,000 to $100,000 per patient in metropolitan areas.
Rural Disadvantage: For patients in remote or rural Australia, the cost of providing dialysis can exceed $120,000 per yeardue to transport and infrastructure requirements.
Household Impact: Rural households face catastrophic out-of-pocket costs, with mean spending of $1,266 per quarterrelated to CKD care, driving financial toxicity.
The Transplant Alternative:
While kidney transplantation is the gold standard for ESKD, it carries a high upfront cost of ~$105,965 in the first year, followed by ongoing immunosuppression costs of ~$14,751 annually.33 Furthermore, with over 900 new patients added to the transplant waiting list annually and demand outpacing supply, relying on transplantation as a “backup plan” for preventable hypoparathyroidism-induced failure is poor policy.
4.2 Modelling the Cost Offsets: The Time Horizon Debate
The July 2025 PBAC outcome document notes a fundamental disagreement over the economic model’s time horizon. The sponsor proposed a 51-year horizon (essentially a lifetime model), while the PBAC argued for a reduced 30-year horizon.
Critique of the 30-Year Horizon:
Restricting the model to 30 years systematically devalues the preventative nature of the drug.
Disease Timeline: A patient diagnosed with post-surgical hypoparathyroidism at age 35 will live well into their 80s.
Renal Timeline: Renal decline is cumulative. A patient may maintain adequate function for 20 years before crossing the threshold into dialysis dependency in their 60s.
The Valuation Gap: By cutting the model off at 30 years, the PBAC effectively ignores the years of dialysis avoided in the latter stages of the patient’s life—precisely when the cost savings would be realised.
If palopegteriparatide delays the onset of dialysis by even 5 years for a single patient, the health system saves approximately $425,000 ($85,000 x 5). If it prevents dialysis entirely, the lifetime savings approach $1-2 million per patient. These savings are sufficient to offset a significant portion of the drug’s acquisition cost, provided the model is allowed to run its full, clinically relevant course.
4.3 Productivity and Indirect Costs
The economic evaluation must also consider the broader societal impact, measurable in Productivity Adjusted Life Years (PALYs).
Workforce Participation: With 75% of hypoparathyroidism patients reporting work interference, effective treatment acts as a workforce enabler.
GDP Impact: Modelling of CKD prevention suggests that preventing just 10% of new kidney disease cases could save $1.1 billion in GDP through preserved productivity.
Carer Burden: The “Modified Caregiver Strain Index” scores for partners of hypoparathyroidism patients rise in correlation with symptom severity. Alleviating the patient’s burden releases caregiver capacity back into the economy.
The PBAC’s focus on direct healthcare costs (the “health system perspective”) often marginalises these productivity gains. However, for the Australian Government—which funds both the PBS and the Disability Support Pension—the “whole of government” perspective strongly favours subsidising treatment that keeps citizens employed.
Table 1: Comparative Health Economic Metrics
Comparative Health Economic Metrics
| Metric | Standard of Care (Ca + Vit D) | Yorvipath (Palopegteriparatide) | Economic Implication |
|---|---|---|---|
| Direct Drug Cost | Low (<$500/year) | High (Requires Subsidy) | Immediate budget impact. |
| Renal Event Risk | High (Hypercalciuria driven) | Low (Physiological restoration) | Long-term cost driver. |
| Dialysis Cost Risk | High ($85k – $120k/year) | Minimal | Major cost offset. |
| Hospitalisation | Frequent (Renal/Electrolyte) | Reduced | Reduced acute care spend. |
| Productivity | Impaired (Brain fog/Fatigue) | Restored | GDP/Tax revenue gain. |
| Monitoring | Frequent (pathology/specialist) | Routine | Efficiency in specialist usage. |
5. The Regulatory and Reimbursement Impasse: Analysis of PBAC Outcomes
The path to PBS listing has been obstructed by HTA processes that struggle to accommodate the nuances of this condition.
5.1 The July 2025 PBAC Resubmission
Following an initial rejection in March 2025, the sponsor resubmitted in July with a revised proposal.
Price Reduction: The sponsor offered a price reduction (redacted in PSD, but implied to be significant) to lower the ICER.
Anniversary Reductions: The sponsor agreed to remove anniversary price reductions, simplifying the pricing structure.
Sticking Points: The sponsor did not accept the PBAC’s recommendation to reduce the time horizon to 30 years or to halve the utility increments (QoL gains).
The PBAC maintained that without these structural changes to the model, the ICER remained too high and the uncertainty too great. This negotiation dynamic reveals a fundamental disagreement: the sponsor believes the drug transforms lives and saves kidneys over a lifetime; the PBAC is sceptical of the magnitude of that transformation given the “surrogate” nature of the trial data.
5.2 The Circular Data Problem
A recurring theme in the PBAC’s rejection is the “lack of Australian data” regarding prevalence and outcomes.
The Paradox: Australia has no national registry for hypoparathyroidism. Consequently, we lack precise data on how many patients progress to renal failure.
The Catch-22: The PBAC refuses to list the drug because there is no data; yet without a listed treatment to incentivise patient enrolment and clinician engagement, a registry cannot be effectively established.
This is a structural failure. It is unreasonable to penalise patients for the absence of data that the health system has failed to collect. The solution, successfully employed for other rare diseases, is to use the listing of the drug as the catalyst for data collection.
5.3 International Benchmarking: Australia Falling Behind
While Australia deliberates, other jurisdictions have found ways to value the therapy.
Germany: The Federal Joint Committee (G-BA) granted reimbursement, recognising the “additional benefit” inherent in its orphan drug status.
Japan: Teijin Pharma successfully listed Yorvipath on the NHI price list in October 2025. The Japanese system’s willingness to reimburse focused on the high unmet need and the clear mechanism of action.
United Kingdom: NICE is currently evaluating the drug (expected 2026), but the MHRA approval has paved the way for individual funding requests.
Australia’s TGA approval was world-leading in speed; its reimbursement process is now lagging, creating a disparity where Australian patients are clinically eligible but financially excluded.
6. The Solution: A Managed Access Program (MAP) via Risk Sharing
To bridge the gap between the PBAC’s evidentiary requirements and the urgent clinical need, we propose a specific policy framework: A Managed Access Program (MAP) underpinned by a rigorous Risk Sharing Arrangement (RSA). This approach has been successfully used in Australia for conditions like Spinal Muscular Atrophy (SMA) and Cystic Fibrosis (CF).
6.1 Precedents for Managed Access
Cystic Fibrosis (Ivacaftor): When first listed, long-term survival data was unavailable. The government implemented a “Pay for Performance” scheme where rebates were tied to patient response, ensuring funding was only provided for effective use.
Spinal Muscular Atrophy (Nusinersen): Listing included strict starting and stopping criteria and mandatory data collection to verify motor milestone achievements.
6.2 Proposed Framework for Yorvipath
Component 1: Targeted Eligibility (The “High Need” Cohort)
Access should initially be restricted to patients with the highest risk of complications, aligning with the “Inadequately Controlled” definition in the ESE 2025 guidelines.
Criteria:
Confirmed chronic hypoparathyroidism (>12 months duration).
Evidence of renal complication (nephrocalcinosis, stones, or eGFR <60 mL/min/1.73m²).
OR uncontrollable hypercalciuria (>7.5 mmol/24h) despite optimised standard care.
OR severe symptomatic instability (hospital admissions for hypocalcemia).
Component 2: The Australian Hypoparathyroidism Registry
The government should mandate participation in a national registry as a condition of subsidy (Deed of Agreement).
Data Points: Baseline and longitudinal eGFR, 24-hour urine calcium, hospitalisation rates, and SF-36 QoL scores.
Funding: Co-funded by the sponsor and the government, similar to the cystic fibrosis registry model.
Objective: To generate the local epidemiological data the PBAC requested within 3-5 years, allowing for a review of the economic model based on real-world Australian evidence.
Component 3: Financial Risk Sharing (RSA)
To mitigate the budget impact and “uncertainty,” the RSA should include:
Expenditure Caps: A hard cap on the total PBS subsidy per year. If volume exceeds the cap, the sponsor rebates 100% of the excess cost.
Stopping Rules: Explicit criteria for weaning patients off the drug if they do not achieve a defined response (e.g., normalisation of urinary calcium or 50% reduction in oral calcium intake) by 26 weeks. This ensures the government does not pay for non-responders.
7. Policy Alignment and Ethical Obligations
7.1 The National Strategic Action Plan for Rare Diseases
The Australian Government launched the National Strategic Action Plan for Rare Diseases in 2020, with Rare Voices Australia (RVA) playing a central role in its implementation.
Pillar 1 (Awareness and Education): Recognises the need for accurate diagnosis.
Pillar 2 (Care and Support): Calls for equitable access to treatments.
Pillar 3 (Research and Data): Prioritises the collection of data to inform policy.
Rejecting Yorvipath contradicts Pillar 2 and Pillar 3. By denying access, the government fails to provide equitable care for a rare condition and misses the opportunity to build the data infrastructure envisioned by the plan. The RVA’s advocacy emphasises that “systems are often not fit for purpose for rare disease,” and the Yorvipath case is a prime example of this systemic misalignment.
7.2 Equity and Rural Health
Chronic hypoparathyroidism disproportionately affects rural patients due to the intense monitoring requirements of standard care. Rural patients incur higher out-of-pocket costs and face greater barriers to accessing emergency care for hypocalcaemic crises.
Home Care Model: Leveraging the Teijin Pharma model from Japan—where home nursing support aids adherence—could be adapted for rural Australia to ensure safe initiation of Yorvipath without requiring relocation to major cities.
7.3 The Human Cost
Behind the ICERs and p-values are human lives. The current system forces these patients to live with a ticking clock on their kidney function. The ethical principle of non-maleficence (do no harm) suggests that continuing to prescribe a known nephrotoxic regimen (standard care) when a safer alternative exists is morally defensible only if the alternative is impossible to procure. With TGA approval, it is now procurable; it is only the funding model that stands in the way.
8. Conclusion and Recommendations
The Australian Government is currently saving money on the pharmaceutical budget at the expense of the hospital budget. The refusal to subsidise palopegteriparatide saves the PBS the cost of the drug today, but commits the state and federal health budgets to millions in dialysis and renal care costs tomorrow.
The clinical evidence for palopegteriparatide is robust: it restores physiology, normalises urinary calcium, and preserves renal function. The economic “uncertainty” cited by the PBAC is a function of the disease’s rarity and duration, not a flaw in the therapy itself. This uncertainty can be managed—not by rejection, but by a well-designed Managed Access Program.
Recommendation 1: Conditional PBS Listing via Section 100
Action: The PBAC should recommend listing Yorvipath as a Section 100 (Highly Specialised Drug) with “Authority Required (Written)” status.
Condition: Access restricted to patients with “inadequately controlled” disease as defined by the ESE 2025 guidelines (renal risk, hypercalciuria, or severe symptoms).
Recommendation 2: Implementation of a Registry-Based RSA
Action: The Department of Health and Aged Care should execute a Deed of Agreement requiring the establishment of the “Australian Hypoparathyroidism Registry.”
Mechanism: Continued subsidy after 3 years should be contingent on the registry demonstrating renal protection (stable eGFR) in the treated population.
Recommendation 3: Re-evaluation of the Economic Time Horizon
Action: The PBAC Economics Sub-Committee should accept a 50-year time horizon for the base case analysis, acknowledging that chronic hypoparathyroidism is a lifelong condition and that truncating the model at 30 years artificially excludes the primary value driver (dialysis avoidance in later life).
Recommendation 4: Rural Support Integration
Action: In line with the National Strategic Action Plan for Rare Diseases, the listing should include provisions for telehealth initiation or home-nurse support (similar to the Japanese rollout) to ensure equitable access for rural Australians who face the highest burden from the current standard of care.
Australia has the regulatory framework, the fiscal capacity, and the ethical obligation to solve this problem. By moving from a passive “rejection” stance to an active “managed access” stance, the government can deliver life-changing therapy to its citizens while safeguarding the health budget against inefficiency.
9. Appendix: Data Tables
Table 2: PaTHway Phase 3 Trial Key Outcomes (Week 26)
PaTHway Phase 3 Trial Key Outcomes (Week 26)
| Endpoint | Yorvipath (Palopegteriparatide) | Placebo (Standard of Care) | P-Value |
|---|---|---|---|
| Primary Composite Endpoint | 78.7% | 4.8% | < 0.0001 |
| Independence from Active Vit D | 93% | N/A | - |
| Independence from Therapeutic Calcium | 93% | N/A | - |
| Normal 24-hr Urine Calcium | Yes (Mean Normalised) | No (Remained Elevated) | - |
| SF-36 Physical Functioning | Significant Improvement | No Change | 0.0347 |
Table 3: Comparative Annual Cost Analysis (Estimates)
Comparative Annual Cost Analysis (Estimates)
| Cost Driver | Standard of Care Scenario | Yorvipath Scenario | Note |
|---|---|---|---|
| Medication | ~$500 (Calcium/Calcitriol) | High (Market Price – Confidential) | The primary upfront cost. |
| Monitoring | ~$2,000 (Pathology/Endo) | ~$1,500 (Routine) | Reduced crisis management. |
| Hospitalisation | ~$5,000 (Weighted Avg Risk) | <$1,000 (Reduced Risk) | Based on 4.8x risk reduction. |
| Dialysis (If Needed) | $85,000 – $120,000 | $0 (Prevented) | The critical offset. |
| Productivity Loss | High (Fatigue/Brain Fog) | Low (Restored Function) | Indirect economic gain. |
References
1. Australian public assessment report for YORVIPATH - Therapeutic Goods Administration (TGA), accessed on November 22, 2025, https://www.tga.gov.au/sites/default/files/2025-08/auspar-yorvipath-250801.pdf
2. First and Only Treatment for Chronic Hypoparathyroidism Approved in Australia - Specialised Therapeutics, accessed on November 22, 2025, https://stabiopharma.com/first-and-only-treatment-for-chronic-hypoparathyroidism-approved-in-australia/
3. Australia Grants First Global Market Approval for YORVIPATH® to Treat Chronic Hypoparathyroidism - BioPharma APAC, accessed on November 22, 2025, https://biopharmaapac.com/news/57/5995/australia-grants-first-global-market-approval-for-yorvipath-to-treat-chronic-hypoparathyroidism.html
4. m.pbs.gov.au, accessed on November 22, 2025, https://m.pbs.gov.au/industry/listing/elements/pbac-meetings/psd/2025-07/files/palopegteriparatide-psd-july-2025.docx
5. 1 Palopegteriparatide (chronic hypoparathyroidism, parathyroid hormone (PTH) replacement therapy) Resolution of: 20 June 2024, accessed on November 22, 2025, https://www.g-ba.de/downloads/91-1455-1045/2024-06-20_Current-Version_Palopegteriparatide_D-1010_EN.pdf
6. Teijin Pharma Launches YORVIPATH, a First of its Kind Treatment in Japan for the Rare Disease Hypoparathyroidism, accessed on November 22, 2025, https://firstwordpharma.com/story/6516605
7. Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26‐Week Results From the Phase 3 PaTHway Trial - PMC, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10099823/
8. Risk of Chronic Kidney Disease and Estimated Glomerular Filtration Rate Decline in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study - NIH, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8004481/
9. Renal complications in patients with chronic hypoparathyroidism receiving conventional therapy: A systematic literature review - Endocrine Abstracts, accessed on November 22, 2025, https://www.endocrine-abstracts.org/ea/0070/ea0070aep212
10. Australian facts, Expenditure on chronic kidney disease, accessed on November 22, 2025, https://www.aihw.gov.au/reports/chronic-kidney-disease/chronic-kidney-disease/contents/impact-of-chronic-kidney-disease/expenditure-on-chronic-kidney-disease
11. New hope for kidney patients around the world with investment into Australian dialysis device manufacture | The George Institute for Global Health, accessed on November 22, 2025, https://www.georgeinstitute.org/news-and-media/news/new-hope-for-kidney-patients-around-the-world-with-investment-into-australian-dialysis-device
12. National Strategic Action Plan for Rare Diseases - Department of Health, Disability and Ageing, accessed on November 22, 2025, https://www.health.gov.au/sites/default/files/documents/2020/03/national-strategic-action-plan-for-rare-diseases.pdf
13. Implementing Outcomes-Based Managed Entry Agreements for Rare Disease Treatments: Nusinersen and Tisagenlecleucel - PubMed Central, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8260322/
14. Chuikyo Clears Listing for Yorvipath and More Drugs; Zero Premium Rule Weighs Yet Again, accessed on November 22, 2025, https://pj.jiho.jp/article/253954
15. Revised European Society of Endocrinology Clinical Practice Guideline: Treatment of Chronic Hypoparathyroidism in Adults - Oxford Academic, accessed on November 22, 2025, https://academic.oup.com/ejendo/article/193/5/G49/8321487
16. Epidemiology and Financial Burden of Adult Chronic Hypoparathyroidism - Pure, accessed on November 22, 2025, https://pure.au.dk/ws/files/346314838/Epidemiology_and_Financial_Burden_of_Adult_Chronic_Hypoparathyroidism.pdf
17. Kidney Complications and Hospitalization in Patients With Chronic Hypoparathyroidism: A Cohort Study in Sweden - PubMed Central, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9516192/
18. Renal complications in patients with chronic hypoparathyroidism on conventional therapy: a systematic literature review - NIH, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8087595/
19. Long-term complications of permanent hypoparathyroidism in adults: prevalence and associated factors - PubMed, accessed on November 22, 2025, https://pubmed.ncbi.nlm.nih.gov/38460072/
20. Burden of illness in not adequately controlled chronic hypoparathyroidism: Findings from a 13‐country patient and caregiver survey - NIH, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC7027891/
21. (PDF) Burden of Illness in Not Adequately Controlled Chronic Hypoparathyroidism: Findings From a 13‐Country Patient and Caregiver Survey - ResearchGate, accessed on November 22, 2025, https://www.researchgate.net/publication/337214637_Burden_of_Illness_in_Not_Adequately_Controlled_Chronic_Hypoparathyroidism_Findings_From_a_13-Country_Patient_and_Caregiver_Survey
22. Press release: ESE announces Revised Clinical Practice Guideline: Treatment of Chronic Hypoparathyroidism in Adults, accessed on November 22, 2025, https://www.ese-hormones.org/news/press-release-ese-announces-revised-clinical-practice-guideline-treatment-of-chronic-hypoparathyroidism-in-adults/
23. ENDO 2025 PaTHway 3-Year Data - Ascendis Pharma, accessed on November 22, 2025, https://investors.ascendispharma.com/static-files/76489af0-563c-4503-adc8-4faf69450323
24. Study Details | NCT04701203 | A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With Hypoparathyroidism | ClinicalTrials.gov, accessed on November 22, 2025, https://www.clinicaltrials.gov/study/NCT04701203
25. Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial - PubMed, accessed on November 22, 2025,https://pubmed.ncbi.nlm.nih.gov/38691316/
26. New 3-Year Phase 3 Data Confirmed Sustained Response to TransCon® PTH (Palopegteriparatide) Therapy in Adults with Hypoparathyroidism, Including Improvements in Biochemistries, Kidney Function, and Quality of Life | Ascendis Pharma, accessed on November 22, 2025, https://investors.ascendispharma.com/news-releases/news-release-details/new-3-year-phase-3-data-confirmed-sustained-response-transconr
27. OR10-05 Efficacy and Safety of Palopegteriparatide Treatment in Adults With Hypoparathyroidism: 3-Year Results From The Phase 3 PaTHway Trial - NIH, accessed on November 22, 2025,https://pmc.ncbi.nlm.nih.gov/articles/PMC12544390/
28. Dialysis care in Australia: a call for reform and innovation, accessed on November 22, 2025,https://www.mja.com.au/journal/2025/223/2/dialysis-care-australia-call-reform-and-innovation
29. Dialysis system - NSW Health & Medical Research, accessed on November 22, 2025, https://www.medicalresearch.nsw.gov.au/projects/dialysis-system/
30. Estimating the cost of chronic kidney disease in Australia - PMC - NIH, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11590276/
31. THE FINANCIAL BURDEN OF CHRONIC KIDNEY DISEASE FOR RURAL AUSTRALIAN FAMILIES - ANZSN Congress, accessed on November 22, 2025, https://anzsnevents.com/12639/
32. Cost-Effectiveness and Budget Impact Analysis of Implementing a ‘Soft Opt-Out’ System for Kidney Donation in Australia - NIH, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9385789/
33. The Preventable Productivity Burden of Kidney Disease in Australia - PMC - NIH, accessed on November 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8017534/
34. Results for orphan drug early benefit assessments in Germany - AMNOG-Monitor, accessed on November 22, 2025, https://www.amnog-monitor.com/overview/indication-areas/orphan-drugs/
35. Yorvipath - Parathyroid UK, accessed on November 22, 2025, https://parathyroiduk.org/clinical-trials/current-trials/yorvipath-pth/
36. Access to cystic fibrosis medication expanded - RACGP, accessed on November 22, 2025, https://www1.racgp.org.au/newsgp/clinical/access-to-cystic-fibrosis-medication-expanded
37. IP14. MANAGED ENTRY SCHEMES: HYPE VS REALITY - ISPOR, accessed on November 22, 2025, https://www.ispor.org/docs/default-source/conference-ap-2018/managed_entry_schemes_sept_3rd.pdf?sfvrsn=bf86dca7_0
38. palopegteriparatide-psd-march-2025.docx - PBS, accessed on November 22, 2025, https://m.pbs.gov.au/industry/listing/elements/pbac-meetings/psd/2025-03/files/palopegteriparatide-psd-march-2025.docx
39. Rare Voices Australia - Healthdirect, accessed on November 22, 2025, https://www.healthdirect.gov.au/partners/rare-voices-australia
40. Advocacy in rare disease - Rare Voices Australia, accessed on November 22, 2025, https://rarevoices.org.au/taking-action-together-toolkit/section-3-approaches-and-tools-to-support-effective-advocacy/advocacy-in-rare-disease/