Strensiq, an innovative enzyme replacement therapy ( ERT ), is the first therapy approved in the U.S. for the treatment of patients with HPP, a genetic, chronic, and progressive ultra-rare metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to debilitating or life-threatening complications.
Asfotase alfa can effectively replace in the skeleton the deficient enzyme called tissue non-specific alkaline phosphatise. Without treatment, many newborns and infants with HPP fail to develop a normal rib cage and die from respiratory failure, and young children with HPP can suffer from rickets and muscle weakness.
In clinical studies, 97% of severely affected newborns or infants were alive at age 1 year with Asfotase alfa treatment compared to 42% of historical control patients.
Treatment with Asfotase alfa, now for up to seven years, often markedly improved overall health.
In young children with HPP, now treated for five years with Asfotase alfa, significant corrections of the skeletal complications were documented, and all had better mobility and function.
Hypophosphatasia is characterized by low alkaline phosphatase ( ALP ) activity and defective bone mineralization that can lead to deformity of bones and other skeletal abnormalities, as well as systemic complications such as profound muscle weakness, seizures, pain, and respiratory failure leading to premature death in infants. hypophosphatasia is an ultra-rare disease, which is defined as a disease that affects fewer than 20 patients per one million in the general population.
The FDA approved Strensiq under Priority Review, and had granted Breakthrough Therapy designation for Strensiq.
The approval of Strensiq in the U.S. was based on data from four clinical trials and supporting extension trials comprising patients with perinatal-, infantile- and juvenile-onset hypophosphatasia who received treatment with Strensiq for up to 6.5 years.
In patients ( ages 1 day to 6.5 years ) with perinatal/infantile-onset hypophosphatasia, treatment with Strensiq resulted in a significant survival benefit compared to historical control patients with similar clinical characteristics.
At week 48, the Kaplan-Meier estimate of overall survival was 97% for treated patients ( n=68 ) compared to 42% for historical control patients ( n=48 ).
In addition, estimated invasive ventilator-free survival was 96% for treated patients ( n=54 ) compared to 31% for historical control patients ( n=48 ).
Study results have also demonstrated substantial improvements in the skeletal manifestations of hypophosphatasia, as assessed by the Radiographic Global Impression of Change ( RGI-C ) scale, and improvements in height and weight, as measured by z-scores, in patients treated with Strensiq.
In patients ( ages 6 to 12 years ) with juvenile-onset hypophosphatasia, treatment with Strensiq resulted in significant improvements in the skeletal manifestations of hypophosphatasia at 24 weeks, as measured by RGI-C, compared to historical controls.
By month 54, 100% of Strensiq-treated juvenile-onset patients were responders to treatment ( n=8 ), as measured by substantial bone healing, compared to 6% of patients in the historial control group ( n=32 ) at last assessment.
In addition, patients treated with Strensiq had improvements in height and weight, as measured by z-scores, compared with untreated historical controls, as well as improvements in gait and mobility.
By 4 years of treatment, 100% of patients assessed ( n=6 ) achieved the 6 Minute Walk Test within the normal range for age-, sex- and height-matched peers, whereas no patients were in the normal range at baseline.
The most commonly reported adverse events observed in clinical trials were injection site reactions. Other common adverse reactions included lipodystrophy, ectopic calcifications, and hypersensitivity reactions.
Hypophosphatasia is a genetic, chronic, progressive, and life-threatening ultra-rare metabolic disease characterized by low alkaline phosphatase activity and defective bone mineralization.
Hypophosphatasia is caused by mutations in the gene encoding an enzyme known as tissue non-specific alkaline phosphatase ( TNSALP ).
The genetic deficiency in hypophosphatasia can affect people of all ages. Hypophosphatasia is traditionally classified by the age of the patient at the onset of symptoms of the disease, with perinatal-, infantile- and juvenile-onset hypophosphatasia defined as patients who have their first symptom prior to 18 years of age.
Hypophosphatasia can have devastating consequences for patients at any stage of life. In a natural history study, infants who had their first symptom of hypophosphatasia within the first 6 months of life had high mortality, with an overall mortality rate of 73% at 5 years. In these patients, mortality is primarily due to respiratory failure. In patients surviving and those with juvenile-onset hypophosphatasia, 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. ( Xagena )
Source: Alexion, 2015