Rare metabolic disorder now has new treatment

FDA approved Strensiq (asfotase alfa) as the first approved treatment for perinatal, infantile and juvenile-onset hypophosphatasia (HPP).   

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HPP is a rare, genetic, progressive, metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to severe disability and life-threatening complications. It is characterized by defective bone mineralization that can lead to rickets and softening of the bones that result in skeletal abnormalities. It can also cause complications such as profound muscle weakness with loss of mobility, seizures, pain, respiratory failure and premature death.

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Severe forms of HPP affect an estimated 1 in 100,000 newborns, but milder cases, such as those that appear in childhood or adulthood, may occur more frequently.

“For the first time, the HPP community will have access to an approved therapy for this rare disease,” said Amy G. Egan, MD, deputy director of the Office of Drug Evaluation in FDA’s Center for Drug Evaluation and Research (CDER). “Strensiq’s approval is an example of how the Breakthrough Therapy Designation program can bring new and needed treatments to people with rare diseases.”

Here are the top 5 ways Strensiq helps combat HPP:

• Strensiq, manufactured by Alexion Pharmaceuticals in Cheshire, Conn., is administered via injection 3 or 6 times per week. Strensiq works by replacing the enzyme (known as tissue-nonspecific alkaline phosphatase) responsible for formation of an essential mineral in normal bone, which has been shown to improve patient outcomes.

• The safety and efficacy of Strensiq were established in 99 patients with perinatal (disease occurs in utero and is evident at birth), infantile- or juvenile-onset HPP who received treatment for up to 6.5 years during 4 prospective, open-label studies. Study results showed that patients with perinatal- and infantile-onset HPP treated with Strensiq had improved overall survival and survival without the need for a ventilator (ventilator-free survival). Ninety-seven percent of treated patients were alive at aged 1 year compared to 42% of control patients selected from a natural history study group. Similarly, the ventilator-free survival rate at aged 1 year was 85% for treated patients compared to less than 50% for the natural history control patients.  

• Patients with juvenile-onset HPP treated with Strensiq showed improvements in growth and bone health compared to control patients selected from a natural history database.  All treated patients had improvement in low weight or short stature or maintained normal height and weight. In comparison, approximately 20% of control patients had growth delays over time, with shifts in height or weight from the normal range for children their age to heights and weights well below normal for age. Juvenile-onset patients also showed improvements in bone mineralization, as measured on a scale that evaluates the severity of rickets and other HPP-related skeletal abnormalities based on x-ray images. All treated patients demonstrated substantial healing of rickets on x-rays while some natural history control patients showed increasing signs of rickets over time.

• Strensiq received a breakthrough therapy designation because it is the first and only treatment for perinatal, infantile and juvenile-onset HPP. FDA granted Strensiq orphan drug designation because it treats a disease affecting fewer than 200,000 patients in the United States, along with priority review.

• Alexion was granted a rare pediatric disease priority review voucher by FDA– a provision intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. Development of this drug was also in part supported by the FDA Orphan Products Grants Program, which provides grants for clinical studies on safety and/or effectiveness of products for use in rare diseases or conditions.

The most common side effects in patients treated with Strensiq include injection site reactions, hypersensitivity reactions (such as difficulty breathing, nausea, dizziness and fever), lipodystrophy (a loss of fat tissue resulting in an indentation in the skin or a thickening of fat tissue resulting in a lump under the skin) at the injection site, and ectopic calcifications of the eyes and kidney.

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