$ALXN Long-term Data Confirm Benefits of Treatment with Strensiq®

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Long-term Data Confirm Benefits of Treatment with Strensiq® (asfotase alfa) in Adolescents and Adults with Hypophosphatasia (HPP) Through Five Years

Alexion Pharmaceuticals, Inc. (ALXN) announced today that researchers presented data showing that the rapid benefits of Strensiq® (asfotase alfa) achieved in adolescents and adults (ages 13-66 years at study entry) with hypophosphatasia (HPP) within the first 6 months were sustained through 5 years of treatment.1 These are the final data from the extension phase of a randomized, open-label, dose-ranging Phase 2 trial of Strensiq and they confirm previously presented interim results.

The results were presented at the European Calcified Tissue Society (ECTS) Congress in Austria and demonstrate a reduction in two key biomarkers of HPP disease activity, as well as improvements in physical function in patients treated with Strensiq, as observed in tests to measure walking distance, running speed and agility, and muscle strength. Strensiq was generally well-tolerated. The most common treatment-related adverse events were mild to moderate injection-site reactions.1

“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, Duke University School of Medicine, Durham, North Carolina. “Patients with HPP can suffer multiple fractures, deformities, short stature, impaired mobility, pain, and limited activities of daily living.”

Strensiq is approved in the United States as a treatment for patients with perinatal-, infantile- or juvenile-onset HPP. Strensiq is also approved in Australia, Canada, the European Union, Israel, Japan, South Korea, and Switzerland.

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 U.S. Prescribing Information recommends increasing the dose to 3 mg/kg three times per week in patients with infantile-onset HPP in cases of insufficient efficacy).

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)

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