The US FDA has designated Alexion’s drug for the inherited metabolic disorder hypophosphatasia (HPP) as a breakthrough, potentially speeding up its approval.
The drug, called asfotase alfa, is an enzyme replacement therapy designed to address the underlying cause of HPP and prevent the progressive organ and bone damage caused by the disease.
Created by the 2012 FDA Safety & Innovation Act (FDASIA), breakthrough status means the FDA considers a drug shows substantial improvement over existing therapies for serious and unmet medical needs. The designation reduces the requirements for registration, for example by reducing the size and duration of pivotal trials.
Alexion has already started phase II clinical trials of asfotase alfa in HPP patients whose symptoms start early in life (prior to 18 years of age) and will consult with the FDA on the measures that will be needed to support its approval.
The disease is described as “ultra-rare”, so trials are likely to be very small, and Alexion indicated earlier this year that it hopes to file for approval of asfotase alfa in both the US and EU in 2014.
HPP is characterised by defective phosphate and calcium regulation in the body resulting from a deficiency in the enzyme tissue non-specific alkaline phosphatase (TNSALP), and can develop at any age. Currently, there is no treatment available, and mortality rates are very high.
If HPP starts in the womb the consequences are almost invariably fatal, while around half of infants who develop it in the first six months of life also die. For those who develop symptoms later fare a little better, but suffer from severe respiratory difficulties, bone fractures and muscle weakness. Preliminary clinical results with asfotase alfa suggest the drug can improve bone development, muscle strength and respiratory function.
Alexion focuses its attention on rare diseases, and has already chalked up one success with its Soliris (eculizumab) product, a first-in-class terminal complement inhibitor that is approved for the treatment of patients with paroxysmal nocturnal haemoglobinuria (PNH).
Soliris sales topped $1.1bn in 2012, a 45 per cent increase over the previous year, and analysts have suggested that asfotase alfa could give the company a second big-selling product. Alexion acquired rights to asfotase alfa (formerly ENB-0040) when it bought Enobia Pharma last year for $610m in cash plus $470m in potential milestone payments.
