Strensiq® (asfotase alfa) is an innovative enzyme replacement therapy approved in the United States for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).1 Strensiq is also approved in the European Union, Japan and Canada.
HPP is a genetic, chronic, progressive and life-threatening metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to debilitating or life-threatening complications.2 HPP is characterized by low alkaline phosphatase (ALP) activity and defective bone mineralization that can lead to destruction and deformity of bones and other skeletal abnormalities, as well as systemic complications such as muscle weakness and respiratory failure leading to premature death in infants.2,3,4
HPP is caused by a defect (mutation) in the gene that makes an enzyme known as tissue non-specific alkaline phosphatase (TNSALP), resulting in low levels of ALP activity.2,5,6
When ALP is functioning normally, it allows two key minerals – calcium and phosphate – to bind together to form healthy, mineralized bones.5,7 In patients with HPP, however, ALP activity is low, leading to insufficient mineralization of bone and altered calcium and phosphate metabolism.8
Many patients with HPP have weak, soft, or brittle bones, as well as skeletal deformities including HPP-related rickets and bowed legs.2-4,8 These abnormalities can impede growth in children and can continue to impair a person’s mobility.9,10
Infants and young children may experience severe symptoms of HPP, such as respiratory failure, that can lead to premature death, or severe breathing complications that require an assistive breathing device.2,10 In a retrospective natural history study of children with severe HPP, those who experienced their first symptom of HPP prior to six months of age had a very high mortality rate — 73% at five years.10
Treating Patients Who Have HPP with Strensiq
Strensiq is the first therapy to treat the underlying cause of HPP—deficient ALP. By replacing the deficient ALP, Strensiq reduces the elevated enzyme substrate levels and improves bone mineralization. Strensiq is administered via subcutaneous injection (injection under the skin).1
In clinical trials, patients with perinatal/infantile-onset HPP who were treated with Strensiq had a significant improvement in survival compared with untreated historical control patients. At 48 weeks, estimated survival was 97% for Strensiq-treated patients compared with 42% for historical control patients (Hazard Ratio [95% CI]: 0.14 [0.05, 0.39]).1
Patients treated with Strensiq also demonstrated significant radiographic improvement. In patients with perinatal/infantile-onset HPP, 74% (50/68) of Strensiq-treated patients were rated as responders on the 7-point Radiographic Global Impression of Change (RGI-C) scale at last assessment (mean 24 months). In patients with juvenile-onset HPP, 100% of Strensiq-treated patients (8/8) were rated as RGI-C responders by 54 months of treatment compared with 6% (2/32) of untreated historical control patients. The most common adverse reactions (≥10%) are injection site reactions, lipodystrophy, ectopic calcification, and hypersensitivity reactions.1
IMPORTANT SAFETY INFORMATION FOR STRENSIQ
Indications and Usage
STRENSIQ® is indicated for the treatment of patients with perinatal-, infantile- and juvenile-onset hypophosphatasia (HPP).
Warnings and Precautions
Hypersensitivity reactions, including anaphylaxis, have been reported in STRENSIQ-treated patients. Signs and symptoms consistent with anaphylaxis included difficulty breathing, choking sensation, nausea, periorbital edema, and dizziness. These reactions have occurred within minutes after subcutaneous administration of STRENSIQ and can occur in patients on treatment for more than one year. Other hypersensitivity reactions have also been reported in STRENSIQ-treated patients, including vomiting, fever, headache, flushing, irritability, chills, skin erythema, rash, pruritus and oral hypoesthesia. If a severe hypersensitivity reaction occurs, discontinue STRENSIQ treatment and initiate appropriate medical treatment. Consider the risks and benefits of re-administering STRENSIQ to individual patients following a severe reaction. If the decision is made to re-administer the product, monitor patients for a reoccurrence of signs and symptoms of a severe hypersensitivity reaction.
Localized lipodystrophy, including lipoatrophy and lipohypertrophy, has been reported at injection sites after several months in patients treated with STRENSIQ. Advise patients to follow proper injection technique and to rotate injection sites.
Patients with HPP are at increased risk for developing ectopic calcifications. In clinical trials, 14 cases (14%) of ectopic calcification of the eye including the cornea and conjunctiva, and the kidneys (nephrocalcinosis) were reported. There was insufficient information to determine whether or not the reported events were consistent with the disease or due to STRENSIQ. No visual changes or changes in renal function were reported. Ophthalmology examinations and renal ultrasounds are recommended at baseline and periodically during treatment with STRENSIQ to monitor for signs and symptoms of ophthalmic and renal ectopic calcifications and for changes in vision or renal function.
The most common adverse reactions (≥ 10%) are injection site reactions, lipodystrophy, ectopic calcifications and hypersensitivity reactions.
Strensiq [package insert]. New Haven, CT: Alexion Pharmaceuticals, Inc; 2015.
Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013; 10(suppl 2):380-388.
Fraser D. Hypophosphatasia. Am J Med. 1957;22(5):730-746.
Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;366(10):904-913.
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.
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.
Whyte MP. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci. 2010;1192:190-200.
Beck C, Morbach H, Stenzel M, et al. Hypophosphatasia — recent advances in diagnosis and treatment. Open Bone J. 2009;1:8-15.
Seshia SS, Derbyshire G, Haworth JC, et al. Myopathy with hypophosphatasia. Arch Dis Child. 1990;65(1):130-131.
Whyte MP, Leung E, Wilcox W, et al. Hypophosphatasia: a retrospective natural history study of the severe perinatal and infantile forms. Poster presented at the 2014 Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting, Vancouver, B.C., Canada, May 5, 2014. Abstract 752416.