It’s a big day for Sanofi as the pharmaceutical giant welcomes two European drug approvals, both for rare enzyme deficiencies. One regulatory nod ushers in the first treatment in Europe for a particular disease. The other covers a successor to a blockbuster Sanofi drug—though that approval does not go as far as the drugmaker had hoped.
Sanofi announced Tuesday that the European Commission approved olupdase alfa, making it the first treatment authorized in Europe for acid sphingomyelinase deficiency (ASMD). Sometimes referred to as Niemann-Pick disease, the disorder leads to lipid buildup in body tissues that causes complications in various organs. The inherited enzyme deficiency is categorized according to the underlying genetic mutation. The European approval covers the treatment of children and adults with ASMD type A/B or ASMD type B.
Olupdase alfa, which is branded as Xenpoyzme, is an engineered version of the sphingomyelinase enzyme that is either deficient or defective in ASMD patients. Approval of the enzyme replacement therapy is based on the results of two clinical trials, one in children and the other in adults. Results of the placebo-controlled adult study showed that treatment with Xenpozyme improved lung function and reduced spleen size after 52 weeks, meeting the main goals of the clinical trial. The open-label pediatric study showed improvement from baseline in the measures of lung function and spleen size after one year of treatment. Regulatory approval does not cover ASMD that has manifest in the central nervous system, which was not tested in clinical trials. Xenpoyzme has also not been tested in patients with ASMD type A.
The intravenously infused therapy was well tolerated by patients. The most common adverse effects reported in the adult study included headache, an inflammatory attack of the pharynx and nasal cavities, upper respiratory tract infection, cough, and joint stiffness. In the pediatric study, adverse effects deemed serious were reported in three patients. One patient had two transient cases of elevated liver enzymes, which can be a sign of drug toxicity. Another patient had a case of hives and rash. The third patient had an anaphylactic reaction. No patients permanently discontinued treatment due to an adverse effect.
“The ASMD community has waited many years for a treatment for this rare and debilitating genetic disease,” John Reed, Sanofi executive vice president and global head of research and development said in a prepared statement. “The approval of Xenpozyme by the European Commission represents a transformational shift in what we can offer to patients, demonstrated by the clinically important improvements across major manifestations of ASMD and the sustained effects noted over longer-term treatment.”
The European approval of Xenpozyme is the drug’s second regulatory nod. Authorities in Japan approved the enzyme replacement therapy in March. The FDA is still reviewing Xenpozyme and is expected to issue a regulatory decision by October.
The second Sanofi drug approval announced Tuesday is for avalglucosidase alfa, a treatment for Pompe disease. This enzyme replacement therapy was approved by the FDA last summer. In the U.S., the drug is marketed as Nexviazyme. In Europe, it will be branded as Nexviadyme.
In Pompe disease, patients have low levels of an enzyme called acid alpha-glucosidase. This enzyme is needed to break down glycogen stored in muscle tissue. The inherited disorder leads to skeletal and cardiac muscles damage, which manifests as muscle weakness and breathing difficulty.
For years, standard Pompe treatment was a Sanofi enzyme replacement therapy called Lumizyme (marketed in Europe as Myozyme), a product that topped €1 billion (about $1.05 billion) in revenue last year. Nexviadyme is also an enzyme replacement therapy. But compared to Myozyme, the new Sanofi Pompe treatment is designed to target a particular receptor that is key for the way that cells take in the therapy. Increased cellular uptake of the enzyme replacement is intended to improve the clearance of glycogen.
The Phase 3 test of Nexviadyme compared that therapy to its predecessor. Sanofi reported that patients treated with Nexviadyme showed a 2.9% improvement from baseline in a measure of lung function, which was the main goal. While that improvement more than enough to show that Nexviadyme was roughly comparable to Myozyme, it was just shy of the change needed to demonstrate statistical superiority. A six-minute walk test was one of the secondary goals of the study. Patients treated with Nexviadyme were able to walk 32.2 meters farther compared to baseline. That’s 30 meters farther than the change reported in patients treated with Myozyme.
European approval of Nexviadyme covers both late-onset and and infantile onset Pompe disease. While the drug is new, it is apparently not novel enough. The European Commission did not recognize the therapy as a “new active substance” and an “orphan medicinal product,” designations that would have conferred 10 years of marketing exclusivity upon the drug’s approval. The FDA’s approval came with orphan drug designation, which gives the product seven years of marketing exclusivity in the U.S. Despite failing to win comparable status in Europe, Sanofi said it is positioning Nexviadyme as a new standard of care for Pompe treatment.
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