Strensiq (asfotase alfa) / AstraZeneca - LARVOL DELTA

Adult patients with hypophosphatasia treated with Asfotase Alfa in real-world practice. (ASBMR 2026) - No abstract available

Clinical • Late-breaking abstract • Real-world • Real-world evidence

Evolving Therapeutic Paradigms in Pediatric Hypophosphatasia: From Survival-Driven Care to Integrated Precision Management. (PubMed, Int J Mol Sci) - "The introduction of enzyme replacement therapy (ERT) with asfotase alfa has fundamentally altered the natural history of pediatric HPP by supplementing deficient alkaline phosphatase activity at sites of active mineralization, thereby improving skeletal integrity, enhancing survival in severe forms, and supporting long-term functional gains...Growing recognition of the importance of early diagnosis has prompted exploratory efforts toward systematic identification strategies, including neonatal screening initiatives reported in selected populations, which suggest the potential for earlier therapeutic intervention during active skeletal development. Together, these considerations highlight pediatric HPP as a model of precision-oriented management in rare metabolic bone disease, where timely diagnosis and targeted enzyme replacement must be aligned with long-term, multidisciplinary care to optimize outcomes."

Journal • Review • Orthopedics • Pediatrics • Perinatal Disorders

Prevalence of clinical manifestations among patients with hypophosphatasia in Central and Eastern European countries. (PubMed, Front Endocrinol (Lausanne)) - "Most had low TN-ALP; only one received asfotase alfa...Bone-related complications, such as fractures and deformities, and joint-related conditions, particularly calcifying periarthritis, are also frequent. These findings emphasize the need for greater awareness of HPP, along with dedicated research efforts to enhance patient care and improve access to effective treatments."

Journal • CNS Disorders • Endocrine Disorders • Epilepsy • Immunology • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Pain • Renal Calculi • ALPL

A Paradoxical Complication: Calciphylaxis as a Novel Adverse Effect of Asfotase Alfa in Hypophosphatsia (ASBMR 2026) - No abstract available

Adverse events • Calciphylaxis • Rare Diseases

Effectiveness of half-dose asfotase alfa in adults with paediatric onset hypophosphatasia: UK nationally designated centre experience (ASBMR 2026) - No abstract available

Clinical • Pediatrics

Iatrogenic Pan-Craniosynostosis Due to Alkaline Phosphatase Enzyme Replacement Therapy Using Asfotase Alfa for Hypophosphatasia. (PubMed, J Plast Reconstr Surg) - "Some reports in Japan indicate that this iatrogenic complication may appear in 15.3% of cases after treatment. As craniofacial surgeons, we need to recognize this causal relationship between hypophosphatasia treatment and craniosynostosis."

Journal • Metabolic Disorders

Unexpected Adverse Reactions to Asfotase Alfa in Older Adults with Hypophosphatasia (ASBMR 2026) - No abstract available

Clinical • Unexpected adverse reaction

Seventeen-year follow-up of hypophosphatasia diagnosed in middle-aged siblings harboring a novel intronic and a rare missense ALPL gene mutation. (PubMed, Bone) - "Those harboring the maternal missense defect manifested mild hypophosphatasemia, suggesting a dominant-negative mutation effect. This experience underscores the importance of in-depth phenotyping and then clinical follow-up to characterize ALPL variant combinations, and for maintaining effective asfotase alfa treatment."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Metabolic Disorders • Muscular Dystrophy • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Pain • Renal Disease • Rheumatology • ALPL

Integrated Genetic and Biochemical Approach to Patients with Bone Disorders Exhibiting Low Alkaline Phosphatase. (PubMed, Calcif Tissue Int) - "Although clinical manifestations were comparable between monoallelic individuals without DNE and variant-negative individuals, distinct biochemical profiles were observed. Integrating genetic nosology into current diagnostic criteria may refine clinical decision-making."

Journal • Fatigue • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics

Perinatal hypophosphatasia refractory to asfotase alfa with neutralizing antibodies that affected bone mineralization: a case report. (PubMed, Clin Pediatr Endocrinol) - "Changes in bone mineralization corresponded to NAb expression, suggesting that NAbs may have influenced the therapeutic effect. The optimal AA dose may vary based on clinical findings and the NAb status."

Journal • Metabolic Disorders

Investigating for Hypophosphatasia in A Young Female Athlete with Recurrent Stress Fractures (ENDO 2026) - "Due to clinical suspicion of hypophosphatasia, supported by low ALP levels and elevated Vitamin B6, the decision was made to begin treatment with Strensiq (asfotase alfa)... This case describes a patient with recurrent fractures and persistently low levels of ALP, with other workup largely unremarkable, raising concern for hypophosphatasia. Although the genetic testing conducted was unremarkable, hypophosphatasia is still possible given the overall clinical picture. Initially, this case with a young female athlete with oligomenorrhea may have been mistaken as a presentation of hypothalamic amenorrhea."

Genetic Disorders • Gynecology • Musculoskeletal Diseases • Orthopedics • Women's Health

Multigenerational Hypophosphatasia Due to A Pathogenic ALPL Frameshift Variant: Diagnostic Challenges and Therapeutic Implications in Adult-Onset Disease (ENDO 2026) - "Both individuals began enzyme replacement therapy with recombinant mineral-targeted alkaline phosphatase (asfotase alfa), a manufactured form of the missing enzyme used as treatment since 2015 for pediatric-onset HPP... This family case series underlines the broad clinical spectrum and diagnostic challenges of adult-onset hypophosphatasia. Preserved or elevated bone mineral density does not rule out HPP and may delay diagnosis. Persistently low alkaline phosphatase, even in adults with normal or elevated bone mineral density, should prompt evaluation for hypophosphatasia and ALPL genetic testing."

Clinical • CNS Disorders • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • ALPL

Pyridoxic Acid Measurement Improves Interpretation of Pyridoxal-5′-Phosphate in the Evaluation of Suspected Hypophosphatasia (ENDO 2026) - "Importantly, PA remains interpretable in patients receiving asfotase alfa, supporting its utility for assessing vitamin B6 status during enzyme replacement therapy. Normal PLP and PA in some HPP patients may reflect variant-specific ALPL effects, supporting future studies incorporating paired PLP, pyridoxal, and PA measurements."

MON-746 - Keep It in the Dark: Importance of Proper B6 Tubing for Hypophosphatasia Diagnosis (ENDO 2026) - "Given a persistent clinical suspicion for HPP, despite the normal B6, genetic testing was pursued and revealed a heterozygous pathogenic variant in ALPL, confirming HPP and prompting initiation of asfotase alfa...In patients with high clinical suspicion for HPP, a normal PLP result should prompt repeat testing with confirmation of light protection through collection and processing, or consideration of genetic testing. For clinicians, awareness of this pre-analytical issue is essential to avoid a missed or delayed HPP diagnosis."

Acromegaly • Alzheimer's Disease • Cardiovascular • CNS Disorders • Endocrine Disorders • Endometriosis • Gynecology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoporosis • Women's Health • ALPL

Keep It in the Dark: Importance of Proper B6 Tubing for Hypophosphatasia Diagnosis (ENDO 2026) - "Given a persistent clinical suspicion for HPP, despite the normal B6, genetic testing was pursued and revealed a heterozygous pathogenic variant in ALPL, confirming HPP and prompting initiation of asfotase alfa...In patients with high clinical suspicion for HPP, a normal PLP result should prompt repeat testing with confirmation of light protection through collection and processing, or consideration of genetic testing. For clinicians, awareness of this pre-analytical issue is essential to avoid a missed or delayed HPP diagnosis."

Acromegaly • Alzheimer's Disease • Cardiovascular • CNS Disorders • Endocrine Disorders • Endometriosis • Gynecology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoporosis • Women's Health • ALPL

A Rare Coexistence of Bone Metabolism Disorders: Hypophosphatasia in the Setting of Primary Hyperparathyroidism (ENDO 2026) - "A positive HPP panel confirmed the diagnosis, and enzyme replacement therapy with asfotase alfa was started... This case highlights the importance of maintaining clinical suspicion of HPP in patients who present with hyperparathyroidism and a low to normal ALP, as delaying diagnosis can lead to inappropriate management. Additionally, typical osteoporosis pharmacological agents such as bisphosphonates are contraindicated in HPP and may worsen skeletal outcomes if started."

Chronic Kidney Disease • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Osteoporosis • Renal Calculi • Renal Disease • ALPL

Treatment of Adult-Onset Hypophosphatasia with Anabolic Therapy (ENDO 2026) - "CASE PRESENTATION 65-year-old man with a history of ankylosing spondylitis, hyperlipidemia, chronic compression fracture of C7 was referred for evaluation of severe osteoporosis (T-score of -3.7 to -4) being treated with alendronate. This case highlights the importance of considering alternative diagnoses in adults presenting with osteoporosis and decreased alkaline phosphatase. Additionally, we describe the use of anabolic agents such as teriparatide and abaloparatide in patients when treatment with asfotase alfa is unavailable or inaccessible to patients."

Clinical • Ankylosing Spondylitis • Dyslipidemia • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoporosis • Rare Diseases • Seronegative Spondyloarthropathies • ALPL

Beyond Guidelines: Osteoporosis Management in Adult-Onset Hypophosphatasia (ENDO 2026) - "She had previously been treated with alendronate for three years, completed eight years prior to her current presentation and later received two doses of denosumab...Asfotase alfa, a recombinant TNSALP enzyme, is approved for pediatric HPP and has demonstrated improvements in fracture healing, pain, and functional outcomes in adults; however, clinical trials have not shown substantial improvements in bone mineral density...Limited case reports suggest potential benefits of teriparatide, though prospective trials are lacking. This case underscores the limitations of DEXA in assessing bone quality in HPP and highlights the need for individualized, mechanism-based osteoporosis management."

Clinical • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Perinatal Disorders • Rheumatology • ALPL

Diagnostic Delay in Hypophosphatasia: Juvenile-Onset Disease Recognized in Adulthood after Endocrine Evaluation for Progressive Weakness (ENDO 2026) - "Pain management and vitamin D repletion were initiated, and the patient was referred for weight-based asfotase alfa therapy to address longstanding symptoms and reduce future complications...Appropriate treatment may prevent complications such as dental abnormalities, kidney stones, nephrocalcinosis, and atypical femur fractures. Early diagnosis can reduce unnecessary evaluations, avoid potentially harmful treatments, optimize mineral metabolism, and identify candidates for enzyme replacement therapy, ultimately improving long-term outcomes and quality of life."

Clinical • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Renal Calculi • ALPL

Experiences with the use of asfotase alfa in three patients with childhood-onset hypophosphatasia. (PubMed, Endocrinol Diabetes Metab Case Rep) - "Monitoring treatment response requires a comprehensive clinical evaluation beyond DXA measurements. Real-world clinical experience is crucial for optimizing treatment strategies for HPP."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Pediatrics • ALPL

Effects of comorbid chronic kidney disease on late-onset hypophosphatasia mice under treatment with asfotase alfa. (PubMed, JBMR Plus) - "Gene expression profiling in the kidney revealed that AA treatment modulates the immune and mineral metabolism pathways, while CKD superimposition induces a shift toward pro-inflammatory and pro-fibrotic responses, compromising renal and skeletal homeostasis. These findings underscore the importance of carefully evaluating HPP patients under treatment with mineral-targeted TNAP at risk of developing comorbid conditions associated with ectopic calcification."

Journal • Preclinical • Chronic Kidney Disease • Nephrology • Orthopedics • Renal Disease • ALPL

PATIENT SUPPORT AND REAL-WORLD EVIDENCE GENERATION IN RARE DISEASE: A CASE STUDY IN HYPOPHOSPHATASIA (ISPOR 2026) - "Collecting data from consenting patients through a manufacturer‑sponsored support program, combined with the centralized visibility provided by an exclusive rare‑disease pharmacy, creates a scalable mechanism for generating RWE that is otherwise difficult to obtain while also supporting timely and appropriate patient access to therapy."

Case study • Clinical • HEOR • Real-world • Real-world evidence • Metabolic Disorders • Rare Diseases

Successful treatment using asfotase alfa for delayed healing of a metatarsal stress fracture in an adolescent girl with hypophosphatasia. (PubMed, Osteoporos Int) - "Here we present, to the best of our knowledge, the first pediatric case in which treatment with AA supported healing of a delayed union stress fracture in the context of clinically diagnosed and genetically supported HPP. Our findings support considering AA initiation in pediatric patients diagnosed with HPP who present delayed fracture healing despite standard conservative management."

Journal • Musculoskeletal Diseases • Orthopedics • Pediatrics • ALPL

Lunch Product Theater: Get Straight to the Source of Hypophosphatasia Sponsored by Alexion, AstraZeneca Rare Disease (AACE 2026) - "In addition, the phase 3 efficacy and safety data for STRENSIQ will be examined. Objectives:- Explore the connection between low levels of alkaline phosphatase (ALP) and one or more clinical signs and symptoms of hypophosphatasia.- Understand the highly variable nature of HPP presentation and how it can affect the different systems of the body.- Recognize the signs, symptoms, and burden of HPP, as well as the importance of a timely diagnosis. This program is sponsored by Alexion, AstraZeneca Rare Disease."

Rare Diseases

ALXN1850-HPP-301: Phase 3 Study of ALXN1850 versus Placebo in Adolescent and Adult Participants with HPP who have not previously been treated with Asfotase Alfa (clinicaltrialsregister.eu) - P2/3 | N=34 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • ALPL