Strensiq in HPP


HPP is a life-threatening, systemic, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene, resulting in a deficiency of the alkaline phosphatase (ALP) enzyme. This deficiency leads to debilitating or life-threatening consequences.1-5

Regardless of age, patients with HPP face a range of devastating skeletal and other systemic consequences.1, 6-11 The signs and symptoms of HPP can vary from patient to patient, and can include problems in the bones, brain, muscles, joints, lungs, teeth, and kidneys.1,4 Many patients with HPP have weak or soft bones, leading to frequent fractures, as well as skeletal deformities.1,2,12 Like many genetic diseases, underlying biochemical abnormalities and pathological disease processes of HPP are pervasive throughout life—though symptoms may not manifest or be recognized until later.1

HPP can be misdiagnosed because its clinical presentation can overlap with other more common skeletal disorders.1,13 A widely available, routine blood test can detect low ALP.1,13 Patients with HPP typically have ALP activity below the age-adjusted lower limit of normal.1,13 It is critical to get an accurate diagnosis as early as possible to ensure that appropriate care is provided.1,13

Treating Patients who have HPP with Strensiq

Strensiq™ (asfotase alfa) is a first-in-class enzyme replacement therapy designed to address the underlying cause of HPP—deficient alkaline phosphatase (ALP). By replacing deficient ALP, treatment with Strensiq aims to improve the elevated enzyme substrate levels and improve the body's ability to mineralize bone.
 
Strensiq is approved in Canada as an enzyme replacement therapy for patients with confirmed diagnosis of paediatric-onset hypophosphatasia under the NOC/c policy. In clinical studies, patients with infantile-onset HPP (ages ≤5 years at enrollment) treated with Strensiq demonstrated rapid and sustained improvements in bone mineralization. Patients with juvenile-onset HPP treated with Strensiq demonstrated significant improvements in bone health compared to a control group of HPP patients selected from a natural history database, as well as improvements in physical function and growth.

More Information

See the Strensiq Product Monograph

References

1. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013; 10(suppl 2):380-388.
2. Fraser D. Hypophosphatasia. Am J Med. 1957;22(5):730-746.
3. Whyte MP. Hypophosphatasia: nature’s window on alkaline phosphatase function in humans. In: Bilezikian JP, Raisz LG, Martin TJ, eds. Principles of Bone Biology. Vol 1. 3rd ed. San Diego, CA: Academic Press; 2008:1573-1598.
4. Whyte MP. Hypophosphatasia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 4. 8th ed. New York, NY: McGraw-Hill; 2001:5313-5329.
5. Greenberg CR, Taylor CLD, Haworth JC, et al. A homoallelic Gly317→ Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian Mennonites. Genomics. 1993;17(1):215-217.
6. Baumgartner-Sigl S, Haberlandt E, Mumm S, et al. Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene. Bone. 2007;40(6):1655-1661.
7. Eade AWT, Swannell AJ, Williamson N. Pyrophosphate arthropathy in hypophosphatasia. Ann Rheum Dis. 1981;40(2):164-170.
8. Balasubramaniam S, Bowling F, Carpenter K, et al. Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary to reduced co-factor pyridoxal-5-phosphate availability. J Inherit Metab Dis. 2010;33(3):25-33.
9. Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with hypophosphatasia. Arch Dis Child. 1990;65(1):130-131.
10. Whyte MP, Murphy WA, Fallon MD. Adult hypophosphatasia with chondrocalcinosis and arthropathy: variable penetrance of hypophosphatasemia in a large Oklahoma kindred. Am J Med. 1982;72(4):631-641.
11. Fallon MD, Teitelbaum SL, Weinstein RS, Goldfischer S, Brown DM, Whyte MP. Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms. Medicine. 1984;63(1):12-24.
12. Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012; 366(10):904-913.
13. Mornet E, Nunes ME. Hypophosphatasia. In: Pagon RA, Bird TD, Dolan CR, Stephen K, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993.