What is the treatment for Hypophosphatasia?

Treatment of Hypophosphatasia (HPP)

For patients with perinatal/infantile and juvenile-onset hypophosphatasia, asfotase alfa (Strensiq) is the first-line treatment, administered subcutaneously at 2 mg/kg three times per week or 1 mg/kg six times per week. 1

Disease Overview

Hypophosphatasia (HPP) is a rare inherited metabolic bone disorder caused by mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). The disease is characterized by:

• Impaired bone mineralization
• Low serum alkaline phosphatase activity
• Accumulation of TNSALP substrates
• Broad clinical manifestations ranging from life-threatening to mild forms

Classification and Diagnosis

HPP is classified based on age of onset:

• Perinatal (prenatal) benign
• Perinatal lethal
• Infantile
• Childhood
• Adult
• Odontohypophosphatasia
• Pseudohypophosphatasia

Diagnosis is based on:

• Clinical features (bone deformities, fractures, dental issues)
• Low serum alkaline phosphatase levels
• Radiological findings
• Genetic testing for definitive diagnosis

Treatment Approach

First-Line Treatment: Enzyme Replacement Therapy

For perinatal/infantile and juvenile-onset HPP:

• Asfotase alfa (Strensiq) - FDA-approved enzyme replacement therapy 1, 2
  • Dosing for perinatal/infantile-onset HPP: 2 mg/kg subcutaneously three times per week, or 1 mg/kg six times per week 1
  • Dosing for juvenile-onset HPP: 2 mg/kg subcutaneously three times per week, or 1 mg/kg six times per week 1
  • Dose may be increased to 3 mg/kg three times per week for insufficient efficacy in perinatal/infantile-onset HPP 1

Important Administration Considerations

• Do not use the 80 mg/0.8 mL vial in pediatric patients weighing less than 40 kg due to inadequate systemic exposure 1
• Rotate injection sites to prevent lipodystrophy 1
• Administer under healthcare provider supervision with appropriate medical monitoring due to risk of hypersensitivity reactions including anaphylaxis 1

Treatment for X-linked Hypophosphatemia (XLH)

For children with X-linked hypophosphatemia (a different condition from HPP):

• Burosumab is recommended for children and adolescents (aged 1-17 years) with signs of rickets 3
• When burosumab is not available, treatment with oral phosphate supplements and active vitamin D (calcitriol or alfacalcidol) is recommended 3

Monitoring During Treatment

Laboratory Monitoring

• Monitor for hypersensitivity reactions, especially during early treatment 1
• Regular assessment of biochemical markers: calcium, phosphate, PTH 3
• Monitor for ectopic calcifications with ophthalmologic examinations and renal ultrasounds 1

Clinical Monitoring

• Assess for improvement in:

  • Skeletal manifestations
  • Respiratory function
  • Growth and mobility
  • Pain reduction
  • Quality of life 4

• Evaluate for potential adverse effects:

  • Injection site reactions (most common adverse effect) 1, 5
  • Lipodystrophy 1
  • Ectopic calcifications 1
  • Hypersensitivity reactions 1

Treatment Outcomes

Clinical studies and case reports have demonstrated significant improvements with asfotase alfa treatment:

• Improved bone mineralization
• Enhanced respiratory function
• Increased survival rates in severe forms
• Better mobility and muscle strength
• Reduced pain
• Improved quality of life 2, 5, 6

Most patients report noticeable clinical improvement within approximately 3 months of starting therapy 5.

Contraindications and Precautions

• Contraindicated treatments for adults with HPP:

  • Bisphosphonates
  • Denosumab
  • Potent antiresorptive agents
  • Vitamin D (in certain cases) 7

• Precautions with asfotase alfa:

  • Monitor for hypersensitivity reactions and anaphylaxis
  • Discontinue immediately if severe hypersensitivity occurs
  • Be aware of potential drug interference with laboratory tests using alkaline phosphatase as a detection reagent 1

Multidisciplinary Approach

Due to the systemic nature of HPP, management should involve coordination among specialists:

• Endocrinologists
• Orthopedic surgeons
• Pulmonologists
• Neurologists
• Dentists
• Physical therapists
• Geneticists 4

Asfotase alfa has transformed the treatment landscape for HPP, offering significant improvements in clinical outcomes and quality of life for patients with this previously untreatable condition.