- Patients experienced sustained improvements in physical function, speed, agility, and strength -
The results were presented at the
"The findings of this phase 2 study suggest that asfotase alfa appears
to be safe and effective long-term and reduces the debilitating burden
of HPP in adolescent and adult patients," said lead author, Priya S.
Kishnani, M.D., Division Chief, Medical Genetics,
Strensiq is approved in
Further details of the study results1
- Reductions in plasma concentrations of plasma pyridoxal 5' phosphate (PLP) and inorganic pyrophosphate (PPi) levels at 6 months were greater in patients treated with Strensiq than in the control group. PLP and PPi are substrates of the enzyme (tissue non-specific alkaline phosphatase, TNSALP) that patients with HPP lack and that Strensiq replaces. As such, PLP and PPi are biomarkers to measure reduction in HPP disease activity. Decreases from Baseline in both PLP and PPi levels were maintained through 5 years.
- Physical function, as measured by the Six Minute Walk Test (6MWT), improved from a median of 76 percent of that predicted for healthy peers at Baseline (n=15; below normal range) to a median of 85 percent predicted (n=16; within the normal range) by 6 months in patients treated with Strensiq. Results were sustained through 5 years of treatment and increased to 88 percent (n=11) at 5 years.
- Speed and agility, as measured by median change from Baseline in the BOT-2 Running Speed and Agility subscale, increased by a median of 4 points after 5 years of treatment (n=11).
- Strength, as measured by median change from Baseline in the BOT-2 Strength subscale, increased by a median of 3.5 points after 5 years of treatment (n=12).
- 1 patient withdrew because of serious AEs of injection site hypersensitivity and anaphylactoid reaction (1 episode each). This patient subsequently received Strensiq post-marketing without reaction. All patients experienced ≥1 treatment-emergent adverse event (TEAE); the majority of TEAEs were mild in intensity.
In the primary phase of this study, patients were randomized to receive no treatment (n=6), 0.3 mg/kg/day of Strensiq (n=7), or 0.5 mg/kg/day of Strensiq (n=6) for 6 months. The majority of patients (with the exception of 1 adult patient) had confirmed pediatric-onset HPP. At 6 months, all 19 patients entered the extension phase of the study and were treated with 0.5 mg/kg/day of Strensiq, then changed to 1 mg/kg/day, 6 times a week, over the next 6 to 12 months. Fourteen patients completed the study over 5 years. Data from both Strensiq dosage groups were pooled for the primary analysis.
The approved dosing regimen for patients with perinatal/infantile-onset
and juvenile-onset HPP is 2 mg/kg administered subcutaneously three
times per week, or 1 mg/kg administered six times per week. (The
About Hypophosphatasia (HPP)
HPP is a genetic, chronic, progressive, and potentially life-threatening ultra-rare metabolic disease that can affect people of all ages. HPP is characterized by defective bone mineralization that can lead to weakness and deformity of bones, fractures and other skeletal abnormalities, as well as systemic complications such as profound muscle weakness, muscle, bone and joint pain, seizures in perinatal/infantile forms of HPP, and respiratory failure leading to premature death in infants.2-6 HPP is traditionally classified by the age of the patient at the onset of symptoms of the disease, with perinatal-, infantile- and juvenile-onset HPP defined by the onset of the first symptom prior to 18 years of age.
HPP can have devastating consequences for patients at any stage of life.2 In a natural history study, infants who had their first symptom of HPP within the first 6 months of life had high mortality, with an overall mortality rate of 73 percent at 5 years.7 In these patients, mortality was primarily due to respiratory failure.2,6,8 In patients surviving and those with juvenile-onset HPP, long-term clinical sequelae include recurrent and non-healing fractures, profound muscle weakness, debilitating pain, and the requirement for ambulatory assistive devices such as wheelchairs, wheeled walkers and canes.2,5
HPP is caused by mutations in the gene encoding an enzyme known as tissue non-specific alkaline phosphatase (TNSALP). This enzyme plays a critical role in the proper mineralization of bones.2,3
About Strensiq® (asfotase alfa)
Strensiq® (asfotase alfa) is a highly innovative bone-targeted enzyme replacement therapy that treats the underlying cause of HPP by replacing the missing TNSALP enzyme. In clinical studies of patients with HPP who had their first symptom prior to the age of 18, treatment with Strensiq improved overall survival in infants, enhanced bone mineralization and improved height, weight and mobility.
Strensiq is approved in
IMPORTANT SAFETY INFORMATION
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.
Please click here for the full Prescribing Information.9
This news release contains forward-looking statements, including
statements related to potential medical benefits of Strensiq® (asfotase
alfa) for hypophosphatasia (HPP). Forward-looking statements are subject
to factors that may cause Alexion's results and plans to differ from
those expected, including, for example, risks and uncertainties of drug
development, decisions of regulatory authorities regarding the adequacy
of our research, marketing approval or material limitations on the
marketing of Strensiq for HPP, delays in arranging satisfactory
manufacturing capabilities and establishing commercial infrastructure
for Strensiq for HPP, the possibility that results of clinical trials
are not predictive of safety and efficacy results of Strensiq in broader
or different patient populations, the adequacy of our pharmacovigilance
and drug safety reporting processes, the risk that estimates regarding
the number of patients with Strensiq and observations regarding the
natural history of patients with Strensiq are inaccurate, and a variety
of other risks set forth from time to time in
1. Kishnani P, Rockman-Greenberg, C, Denker A, et al. Biochemical and
Physical Function Outcomes in Adolescents and Adults With
Hypophosphatasia Treated With Asfotase Alfa for 5 Years: Results From a
Phase 2 Study. Poster presented at the
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.
4. Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012; 366(10):904-913.
5. Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with
7. 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
8. Whyte MP,
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