It’s a big day for Sanofi as the pharmaceutical giant welcomes two European drug approvals, both for a rare enzyme deficiency. A regulatory nod ushered in Europe’s first treatment for a specific disease. Another covers the successor to the blockbuster Sanofi drug — although the approval fell short of the drugmaker’s expectations.
Sanofi announced on Tuesday that the European Commission Approved olupdase alfa, making it the first European-approved treatment for acid sphingomyelinase deficiency (ASMD). The disease, sometimes called Niemann-Pick disease, causes a buildup of lipids in body tissues that can lead to complications in various organs. Inherited enzyme deficiencies are classified according to the underlying genetic mutation. European approval covers the treatment of children and adults with ASMD type A/B or ASMD type B.
Olupdase alfa, branded Xenpoyzme, is an engineered version of sphingomyelinase that is either lacking or defective in ASMD patients. The approval of the enzyme replacement therapy was based on the results of two clinical trials, one in children and the other in adults. Results of a placebo-controlled adult study showed that Xenpozyme improved lung function and reduced spleen size after 52 weeks of treatment, meeting the primary goals of the clinical trial. The open-label pediatric study showed improvements from baseline in measures of lung function and spleen size after one year of treatment. Regulatory approval does not include ASMD manifested in the central nervous system that has not been tested in clinical trials. Xenpoyzme has also not been tested in patients with type A ASMD.
Intravenous infusion therapy was well tolerated by the patient. The most common adverse reactions reported in adult studies included headache, pharyngeal and nasal inflammatory attacks, upper respiratory tract infection, cough, and joint stiffness. In the pediatric study, three patients reported serious adverse reactions. One patient had two transient cases of elevated liver enzymes, which may be a sign of drug toxicity. Another patient had hives and a rash. A third patient had an allergic reaction. No patient permanently discontinued treatment due to adverse reactions.
“The ASMD community has waited years for a treatment for this rare and debilitating genetic disorder,” John Reed, executive vice president and global head of research and development at Sanofi, said in a prepared statement. “The approval of Xenpozyme by the European Commission represents a transformative shift in the services we can offer patients, reflected in clinically important improvements in key ASMD manifestations and sustained effects of long-term treatment.”
The approval of Xenpozyme in Europe is the drug’s second regulatory nod. Japanese authorities approved enzyme replacement therapy in March. The FDA is still reviewing Xenpozyme and is expected to issue a regulatory decision in October.
This Second Sanofi drug approval Announced Tuesday is avalglucosidase alfa, which is used to treat Pompe disease.This enzyme replacement therapy is Approved by the U.S. Food and Drug Administration last summer. In the United States, the drug is marketed as Nexviazyme. In Europe, it will be named Nexviadyme.
In Pompe disease, patients have low levels of an enzyme called acid alpha-glucosidase. This enzyme is necessary to break down glycogen stored in muscle tissue. Inherited disorders cause damage to the bones and heart muscle, manifesting as muscle weakness and difficulty breathing.
For years, the standard Pompe treatment was a Sanofi enzyme-replacement therapy called Lumizyme (sold as Myozyme in Europe), which generated more than 1 billion euros ($1.05 billion) in revenue last year. Nexviadyme is also an enzyme replacement therapy. But in contrast to Myozyme, the new Sanofi Pompe treatment is designed to target a specific receptor that is critical to how cells take up the treatment. Increased cellular uptake of enzyme replacements aims to improve clearance of glycogen.
Phase 3 testing of Nexviadyme compared the therapy to its predecessor. Sanofi reported that patients treated with Nexviadyme showed a 2.9% improvement from baseline in measures of lung function, the primary goal. While this improvement was sufficient to show that Nexviadyme was roughly comparable to Myozyme, it was still worse than the change required to demonstrate statistical superiority. The six-minute walk test was one of the secondary goals of the study. Compared to baseline, patients treated with Nexviadyme were able to walk 32.2 meters more. This was 30 meters higher than the change reported in patients treated with Myozyme.
European approval of Nexviadyme covers late-onset and infancy Pompe disease. While the drug is new, it’s clearly not novel enough. The European Commission does not recognize the therapy as a “new active substance” and an “orphan drug,” designations that would grant 10 years of market exclusivity after the drug is approved. FDA approval comes with orphan drug designation, which gives the product seven years of market exclusivity in the U.S. Despite failing to win a comparable position in Europe, Sanofi says it is positioning Nexviadyme as the new standard of care for Pompe treatment .
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