Sanofi’s Genzyme unit has been awarded breakthrough status in the US for rare and life-threatening metabolic disorder called Niemann-Pick disease type B.
The FDA gave the coveted status to olipudase alfa, which is designed to replace the enzyme that is deficient in the inherited disease, also known as acid sphingomyelinase deficiency (ASMD). The enzyme deficiency causes harmful quantities of a fatty substance called sphingomyelin to build up in the body’s organs.
Genzyme is developing olipudase alfa (GZ402665) for the type B variant of the disease, in which the build-up occurs mainly in the liver, spleen and lungs. The drug is not being developed for the type A form of ASMD, in which sphingomyelin accumulation takes place mainly in the central nervous system.
“Supplementing the defective or deficient native enzyme with olipudase alfa allows for the breakdown of sphingomyelin,” according to Sanofi, which has started enrolling patients in a phase I/II paediatric study of the drug, which is a recombinant form of the human enzyme. A second, phase II/III trial in adults is due to start before the end of the year, it added.
ASMD is in a class of around 50 diseases known as lysosomal storage disorders (LSDs), a group which also includes Gaucher and Fabry disease.
Genzyme has built the core of its business by focusing on this group, developing big-selling brands such as Gaucher therapy Cerezyme (imiglucerase alfa), Fabrazyme (agalsidase beta) for Fabry disease and Pompe disease therapies Myozyme and Lumizyme (both alglucosidase alfa).
At the moment the company is essentially on its own developing a therapy for ASMD type B, and while stem cell transplantation has shown some promise it carries risks such as graft-versus-host disease.
“There is tremendous unmet need in the ASMD… type B community, and we are hopeful that olipudase alfa can be developed into a meaningful treatment for patients,” said Genzyme’s global head of rare diseases Richard Peters.
“We appreciate FDA’s support for this important program giving us the opportunity to utilize an important expedited drug development pathway for olipudase alfa and providing hope for patients affected with a chronic and progressively debilitating disease,” he added.
Therapeutic candidates may be thin on the ground for ASMD type B, but there have however been some therapeutic advances for the type C variant, which is caused by a protein rather than an enzyme deficiency.
Actelion has approval for its Zavesca (miglustat) drug in ASMD type C, while other candidates are coming through development including Orphazyme’s arimoclomol (rhHSP70), which is due to start a phase II/III trial shortly.
The pharma industry has been ramping up its investment in rare and orphan disease therapies in recent years, in part because their small target populations are offset by high-prices and lower reimbursement obstacles that provide a return on investment, as well as longer periods of market exclusivity.