Alexion Pharmaceuticals, Inc., a global pharmaceutical company, received European Commission (EC) approval for Kanuma (sebelipase alfa) for long-term enzyme replacement therapy (ERT) in patients of all ages with lysosomal acid lipase deficiency (LAL-D).

Kanuma, an innovative ERT, is the first approved treatment in the European Union for patients with LAL-D, a genetic and progressive ultra-rare metabolic disease in which patients suffer multi-organ damage and premature death. Alexion expects to begin serving patients in Germany in October and is now commencing reimbursement processes with healthcare authorities in each of the major European countries.

“Today’s approval is a crucial milestone for patients with LAL-D, a grave condition that can have devastating consequences for patients of all ages,” said Vassili Valayannopoulos, M.D., Ph.D., investigator in the Kanuma pivotal studies, Hôpital Necker-Enfants Malades and IMAGINE Institute, Paris.

“In clinical studies, 67 per cent of infants treated with Kanuma survived beyond 12 months of age, whereas without treatment, these patients would have faced a near-certain fatal outcome. In paediatric and adult patients, Kanuma was also shown to reduce the markers of liver injury and lipid accumulation, which can lead to serious and life-threatening complications.”

LAL-D is a genetic, chronic and progressive metabolic disease in which infants, children and adults suffer multi-organ damage and premature death. It is an ultra-rare disease, which is defined as a disease that affects fewer than 20 patients per one million of the general population. Patients with LAL-D often experience a rapid onset of life-threatening disease manifestations, and similar to other liver diseases, many patients may be asymptomatic until they experience a severe consequence of the disease. LAL-D is caused by genetic mutations that result in a marked decrease or loss in LAL enzyme activity in the lysosomes across multiple body tissues, leading to the chronic build-up of cholesteryl esters and triglycerides in the liver, blood vessel walls and other tissues.

“We are pleased that the European Commission has approved Kanuma for patients of all ages with LAL-D, enabling us to serve infants, children and adults in Europe with the first approved treatment for this ultra-rare, severe and life-threatening disease,” said David Hallal, chief executive officer of Alexion.

“In the absence of any effective therapy, patients with LAL-D face devastating morbidities including liver failure and premature mortality. We are grateful to the investigators, patients, and their families who participated in the clinical trials that made this approval possible and we are now commencing reimbursement processes with healthcare authorities throughout Europe to ensure that patients with LAL-D have access to Kanuma, a life-transforming treatment, as quickly as possible.”

Kanuma is a highly innovative enzyme replacement therapy (ERT) designed to address the underlying cause of LAL-D. The approval of Kanuma applies to all 28 EU member states as well as Iceland, Norway, and Lichtenstein and was granted under the accelerated assessment procedure. The decision follows the June 2015 positive opinion granted by the Committee for Medicinal Products for Human Use (CHMP). In addition, the US Food and Drug Administration granted Breakthrough Therapy designation for Kanuma for LAL deficiency presenting in infants and accepted the Kanuma BLA (Biologics License Application) for Priority Review.

The approval of Kanuma in the EU was based on data from two clinical studies and a supporting open-label extension study comprising infant, pediatric, and adult patients with LAL-D. Study results showed significant benefit in terms of survival (67 per cent, or 6 out of 9) in patients with the infant form of LAL-D beyond 12 months, compared with 0 out of 21 patients in an untreated historical cohort. Infant patients treated with Kanuma also had improvements in liver parameters, including ALT and AST, as well as weight gain within the first several weeks of treatment. In pediatric and adult patients with LAL-D, treatment with Kanuma resulted in normalization of ALT, reduction in liver fat content and other markers of liver injury compared to placebo, as well as significant improvements in lipid accumulation as measured by LDL-C and HDL-C. In patients who received Kanuma during the double-blind period and subsequently entered the open-label extension period, reductions in ALT levels were maintained and further improvements were seen in LDL-C and HDL-C.

The most serious adverse reactions experienced by 3 per cent of patients in clinical trials were signs and symptoms consistent with anaphylaxis. Signs and symptoms included chest discomfort, conjunctival injection, dyspnea, generalized and itchy rash, hyperemia, mild eyelid edema, rhinorrhea, severe respiratory distress, tachycardia, tachypnea and urticaria.

LAL-D is a genetic, chronic and progressive ultra-rare metabolic disease associated with devastating morbidities and premature mortality. In patients with LAL-D, genetic mutations result in decreased activity of the LAL enzyme. This leads to marked accumulation of cholesteryl esters and triglycerides in vital organs, blood vessels, and other tissues, resulting in progressive and multi-organ damage including fibrosis, cirrhosis, liver failure, accelerated atherosclerosis, cardiovascular disease, and other devastating consequences.

LAL-D affects patients of all ages with clinical manifestations from infancy through adulthood and may have sudden and unpredictable clinical complications. Infants experience profound growth failure, liver fibrosis, and cirrhosis with a median age of death at 3.7 months. In an observational study, approximately 50 per cent of children and adults with LAL-D progressed to fibrosis, cirrhosis, or liver transplant in 3 years.5 The median age of onset of LAL-D is 5.8 years and the disease can be diagnosed with a simple blood test.