Strensiq (asfotase alfa) / AstraZeneca - LARVOL DELTA

Adult Hypophosphatasia Presenting with Soft Tissue Heterotopic Calcific Mass Lesions. (ENDO 2025) - "The patient was started on asfotase alfa therapy with significant improvement in nonspecific myalgia, asthenia, fatigue and mobility within the intervening 1.5 months of therapy...Our patient adds heterotopic soft tissue mass calcifications to the growing profile of possible clinical presentations of adult HPP.*. .*"

Clinical • Chronic Kidney Disease • CNS Disorders • Fatigue • Genetic Disorders • Mood Disorders • Musculoskeletal Pain • Nephrology • Orthopedics • Osteoporosis • Pain • Psychiatry • Renal Calculi • Rheumatology • ALPL

Treatment Efficacy and Complications Associated with Asfotase alfa Therapy in Hypophosphatasia (ENDO 2025) - "Asfotase alfa enzyme replacement therapy not only improves the clinical symptoms and quality of life but also may be beneficial in reducing the future risk of bone and teeth complications.*. .*"

Clinical • Endocrine Disorders • Lipodystrophy • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • ALPL

Applying the Hypophosphatasia Diagnostic Criteria in a Patient Cohort at the Penn Bone Center (ENDO 2025) - "Six patients within the cohort had previous or current treatment with asfotase alfa, and FDA-approved enzyme replacement therapy used in adult patients if one of the presenting symptoms was before age 18 years...2024 Mar; 35(3):431-438.*. .*"

Clinical • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Pain • Rheumatology

Bone Mineral Density in Adults With Hypophosphatasia With or Without History of Fractures (ENDO 2025) - " Fractures occurring before asfotase alfa treatment (or at any time in untreated patients) were analyzed in younger (aged 18-≤50 y) and older (aged >50 y) adults from the Global HPP Registry (data cut: June 2023)... Median BMD T-scores were within a normal range in adults regardless of fracture history. Some patients may have concomitant osteoporosis in addition to the underlying HPP-related osteomalacia. Further analysis to distinguish fractures due to osteoporosis vs compromised mineralization is warranted.*."

Clinical • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Recurrent metatarsal, scapular and acromial fractures during Denosumab therapy in Adult-onset Hypophosphatasia with a pathogenic variant of the ALPL gene and a variant of uncertain significance of the ATRIP Gene (ENDO 2025) - "She was initially started on risedronate at age 61y but due to continued non-traumatic metatarsal fractures teriparatide was recommended...She has been offered treatment with Asfotase alfa (AA). Adult-onset HPP was recognized in a 66-yo female who presented with acromial, scapular and recurrent metatarsal fractures while on denosumab therapy for 4 y for osteoporosis...Treatment with anabolic agents such as teriparatide and romosozumab has been reported while anti-resorptives such as bisphosphonates and denosumab are contraindicated.*. .*"

Clinical • Addiction (Opioid and Alcohol) • Endocrine Disorders • Fibromyalgia • Growth Hormone Deficiency (Adult) • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoporosis • Pain • Rheumatology • ALPL • ATRIP

Delayed Diagnosis of Hypophosphatasia in a 91-year-old: An Opportunity to Improve Screening (ENDO 2025) - "His low BMD had been treated with six 5-mg doses of zoledronate (ZOL) from 2010 to 2023 and alendronate prior to 2010...Additional ZOL was held and he was evaluated for asfotase alfa... HPP may be overlooked particularly in older adults with low BMD and low ALP on long-term bisphosphonate therapy as illustrated in this case. Our patient's low ALP level was presumed secondary to longstanding suppression of bone turnover from many years of bisphosphonate exposure. Although bisphosphonates can increase risk of atypical femur fractures in HPP, our patient had no such complications."

CNS Disorders • Depression • Musculoskeletal Diseases • Orthopedics • Otorhinolaryngology • Psychiatry • Rheumatology • ALPL

Adult-Onset Hypophosphatasia with Atypical Femoral Fractures: A Diagnostic and Management Challenge (ENDO 2025) - "It is often misdiagnosed as osteoporosis, and treatment with bisphosphonates or denosumab can worsen the disease, increasing the risk of atypical femoral fractures. AHPP poses a significant diagnostic challenge, particularly in patients with long-term antiresorptive therapy. Persistently low ALP, atypical fractures, and genetic confirmation are key diagnostic markers. This case underscores the need for clinical awareness and early intervention, as asfotase alfa may play a crucial role in improving skeletal outcomes in adults with progressive disease."

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

Severe Hypercalcemia Associated With Perinatal Hypophosphatasia While Receiving Enzyme Replacement Therapy. (PubMed, JCEM Case Rep) - "Hypercalcemia is more common in the perinatal and infantile forms and may be mitigated or prevented with enzyme replacement therapy asfotase alfa (AA)...This case underscores the significance of vigilant monitoring of calcium levels and dietary intake in infants diagnosed with HPP. While calcitonin is typically not considered as a sustained treatment for hypercalcemia, the present case illustrates the efficacy of adjunct calcitonin therapy, in conjunction with restricted calcium intake and maximum AA dosing, in managing severe hypercalcemia in an infant with perinatal HPP."

Journal • Endocrine Disorders • Metabolic Disorders • ALPL

HICKORY: Phase 3 Study of ALXN1850 Versus Placebo in Adolescent and Adult Participants With HPP Who Have Not Previously Been Treated With Asfotase Alfa (clinicaltrials.gov) - P3 | N=124 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Mar 2028 ➔ May 2029

Trial completion date • ALPL

Patient-Reported Outcomes and Quality of Life in Children and Adults With HPP Treated With Asfotase Alfa (ESPE-ESE 2025) - No abstract available

Clinical • HEOR • Patient reported outcomes

Effects of asfotase alfa on fracture healing of adult patient with hypophosphatasia and literature review. (PubMed, Orphanet J Rare Dis) - "Adult HPP patients mainly present with recurrent or poorly healing fractures, bone pain, and early loss of teeth. AA replacement therapy can effectively promote fracture healing, relieve bone pain, and enhance mobility."

Journal • Review • Genetic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • ALPL

Mobility and Quality of Life in Adults with Paediatric-Onset Hypophosphatasia Treated with Asfotase Alfa: Results from UK Managed Access Agreement. (PubMed, Adv Ther) - "Asfotase alfa treatment improved mobility, physical function, pain, and HRQoL and was well tolerated. These data show the benefit of asfotase alfa in adults with paediatric-onset HPP."

HEOR • Journal • Musculoskeletal Diseases • Orthopedics • Pain • Pediatrics • Rare Diseases

Hypophosphatasia (HPP) Patient & Caregiver Disease Burden, Quality of Life & Treatment Experience: A Mixed Methods Study Concept (ISPOR 2025) - "A mix of caregivers of patients from different age, severity levels, asfotase alfa treatment status and country income levels (and correspondingly healthcare systems) will be targeted. Quantitative analysis of survey data will present demographic data of caregivers and patients as well as information on current patient clinical manifestations. To the best of our knowledge, this is the first study measuring HPP caregiver quality of life. It is expected to contribute to better understanding of the wider disease impact beyond patients and to help decision making with regards to resource allocation for treatments that reduce the burden of HPP patients and, correspondingly, their caregivers."

Clinical • HEOR • Genetic Disorders • Musculoskeletal Diseases

Safety and efficacy of long term asfotase alfa treatment in childhood hypophosphatasia. (PubMed, Ital J Pediatr) - "Pediatricians should consider HPP in children presenting with a suggestive clinical phenotype. Calcium-phosphorus metabolism, ALP, and vitamin B6 should always be investigated in suspected cases. Moreover, asfotase alfa represents a safe, well-tolerated, and effective drug in children with HPP."

Journal • Genetic Disorders • Pediatrics • ALPL

Effectiveness and safety of asfotase alfa for people with hypophosphatasia: a plain language summary of three studies. (PubMed, J Comp Eff Res) - "Treatment can improve quality of life for people with HPP. The findings from these studies support the continued use and further development of asfotase alfa as a treatment for people with HPP."

Journal • Review • Pain

Medical Management of Hypophosphatasia: Review of Data on Asfotase Alfa. (PubMed, Curr Osteoporos Rep) - "Alternatives to asfotase alfa remain limited, but a derivative, efzimfotase alfa, currently undergoes clinical testing. Studies in larger HPP patient populations suggest efficacy of enzyme replacement therapy independent of patient age and time of disease onset."

Journal • Review • Fatigue • Orthopedics • Pain • Pediatrics

CHESTNUT: Phase 3 Study of ALXN1850 in Pediatric Participants With HPP Previously Treated With Asfotase Alfa (clinicaltrials.gov) - P3 | N=42 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Pediatrics

Hypophophatasia: the importance of knowing in advance. (PubMed, Minerva Endocrinol (Torino)) - "Recently, asfotase alfa, a bone targeted recombinant TNSALP has been used to treat HPP with significant success, highlighting the importance of early diagnosis and intervention. This review describes our current knowledge of HPP, reporting on the epidemiology, classification, clinical presentation and main diagnostic features of the disease, as well as more recent therapeutic approaches."

Journal • CNS Disorders • Epilepsy • Genetic Disorders • Osteoporosis • Respiratory Diseases • Rheumatology

Long-Term Outcomes of Early Enzyme Replacement Therapy With Asfotase Alfa in Perinatal Benign Hypophosphatasia: Amelioration of Bone Deformities in a Young Child. (PubMed, Cureus) - "Shortening and bowed limbs improved, and his body height increased from -3.48 SD (at the age of two years and three months) to -1.71 SD (at the age of nine years and eight months) after starting ERT. Hence, early ERT effectively improves motor development, bone deformity, and short stature in patients with perinatal benign HPP."

Journal • Developmental Disorders • Musculoskeletal Diseases • Orthopedics • ALPL

Diagnosis and Treatment of Hypophosphatasia. (PubMed, Calcif Tissue Int) - "Asfotase alfa as first-in-class enzyme replacement therapy (ERT) for HPP has been shown to improve survival, rickets, and functional outcomes in severely affected children, but further research is needed to refine how enzyme replacement can also address emerging manifestations of the disease. Prospectively, further elucidating the pathophysiology behind the diverse clinical manifestations of HPP is instrumental for improving diagnostic concepts, establishing novel means for substituting enzyme activity, and developing integrative, multimodal care."

Journal • Review • CNS Disorders • Epilepsy • Fatigue • Gastrointestinal Disorder • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Psychiatry • ALPL

HICKORY: Phase 3 Study of ALXN1850 Versus Placebo in Adolescent and Adult Participants With HPP Who Have Not Previously Been Treated With Asfotase Alfa (clinicaltrials.gov) - P3 | N=124 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • ALPL

Novel therapeutic options for hypophosphatasia. (PubMed, J Bone Miner Res) - No abstract available

Journal

Efficacy of asfotase alfa in a patient with adult-onset hypophosphatasia without obvious bone lesions: a case report with review of literature. (PubMed, Endocr J) - "This case highlights the potential of asfotase alfa in effectively alleviating symptoms in patients with adult-onset HPP without bone lesions, emphasizing the importance of patient selection and outcome monitoring. We also discuss the key considerations for future treatment, supported by a literature review of asfotase alfa in adult patients with HPP."

Journal • Endocrine Disorders • Fatigue • Grave’s Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain

Adult hypophosphatasia presenting with recurrent acute joint pain. (PubMed, Endocrinol Diabetes Metab Case Rep) - "Some cases of adult HPP have arthralgia as the only presenting symptom. At one-year follow-up, enzyme replacement therapy with asfotase alfa might lead to a reduction in arthralgia attacks due to HPP."

Journal • Genetic Disorders • Immunology • Inflammation • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rheumatology • ALPL

A Case of Hypophosphatasia Started Enzyme Replacement Therapy Since Babyhood Stage. (PubMed, Children (Basel)) - "This report suggests that early enzyme replacement therapy may prevent traditional tooth loss in patients with HPP. It also highlights the new challenges posed for dental professionals in providing infection control in large pulp cavities and receding periodontal tissue."

Journal • Genetic Disorders • Infectious Disease • Musculoskeletal Diseases • Orthopedics