Enzyme Replacement Therapy (Hypophosphatasia — Tissue Non-specific Alkaline Phosphatase)

Asfotase Alfa

Brand names: Strensiq

Adult dose

Dose: Paediatric-onset hypophosphatasia: 2 mg/kg 3 times per week OR 1 mg/kg 6 times per week, subcutaneously. (Adult-onset disease: 1 mg/kg 3 times/week — see SmPC)

Route: Subcutaneous injection

Frequency: 3 or 6 times weekly

Clinical pearls

Enzyme replacement for hypophosphatasia (HPP) — rare inherited metabolic disorder with deficient tissue non-specific alkaline phosphatase (TNSALP)
NICE TA467 (2017): recommended for perinatal, infantile, and juvenile-onset hypophosphatasia
Perinatal-onset is life-threatening (respiratory failure from hypomineralised ribcage)
Clinical features: bone pain, fractures, premature deciduous tooth loss, seizures (pyridoxine-responsive in neonates), short stature
Diagnose by low serum ALP + elevated PLP (pyridoxal phosphate), PPi, and PEA; confirm by gene sequencing
Approved for use in NHS England via Highly Specialised Technology (HST10) pathway
Significant cost — patient must meet criteria for HST10

Contraindications

Hypersensitivity to asfotase alfa
Ectopic calcification syndromes not related to hypophosphatasia

Side effects

Injection site reactions (erythema, bruising, induration — very common; rotate sites)
Ectopic calcification (nephrocalcinosis, ophthalmological) — monitor
Lipodystrophy at injection sites
Hypersensitivity/anaphylaxis
Pyrexia

Interactions

No clinically significant drug interactions documented
Vitamin B6 supplementation may be required in some patients (pyridoxine-responsive seizures in neonates with HPP)

Monitoring

Alkaline phosphatase (ALP) — target gradual normalisation
Renal ultrasound (nephrocalcinosis) every 6 months
Ophthalmology (ectopic ocular calcification) annually
Bone radiographs every 6–12 months
Height, weight, motor development (children)
Injection sites

Reference: BNF; NICE TA467 (Asfotase alfa for treating paediatric-onset hypophosphatasia, 2017); NHS England HST10; ESPE Hypophosphatasia Guidelines; https://bnf.nice.org.uk/drugs/asfotase-alfa/. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways