Date: 2017-05-15
Type of
information: Presentation of results at a congress
phase:
Announcement: presentation of results at the European Calcified Tissue Society (ECTS) Congress
Company: Alexion Pharmaceuticals (USA - CT)
Product: Strensiq® (asfotase alfa)
Action
mechanism:
- enzyme replacement therapy (ERT). Asfotase alfa is an investigational, highly innovative, first-in-class targeted alkaline phosphatase enzyme replacement therapy. Asfotase alfa is designed to address the underlying cause of hypophosphatasia by normalizing the genetically defective metabolic process, and preventing or reversing the severe and potentially life-threatening complications of life-long dysregulated mineral metabolism.
- Strensiq™ is approved in the European Union , Japan , and Canada as a treatment for patients with HPP. The FDA has granted Breakthrough Therapy designation for Strensiq and accepted Alexion\'s Biologics License Application (BLA) for Priority Review.
Disease: hypophosphatasia
Therapeutic
area: Rare diseases - Genetic diseases - Metabolic diseases
Country:
Trial
details:
Latest
news:
- • On May 15, 2017, Alexion Pharmaceuticals announced 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 within the first 6 months were sustained through 5 years of treatment. 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 hypophosphatasia 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.
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).
Is
general: Yes
