Alexion Pharmaceuticals, Inc., a global biopharmaceutical company, announced that the US Food and Drug Administration (FDA) has approved Kanuma (sebelipase alfa) for the treatment of patients of all ages with a diagnosis of lysosomal acid lipase deficiency (LAL-D). Kanuma, an innovative enzyme replacement therapy (ERT), is the first therapy approved in the US for the treatment of patients with LAL-D, a genetic and progressive ultra-rare metabolic disease in which patients suffer multi-organ damage and premature death.

“We are pleased with the FDA approval of Kanuma, a transformative treatment for patients with LAL-D, a devastating, ultra-rare disease that causes premature death in infants and multi-organ damage in those who survive,” said David Hallal, chief executive officer of Alexion.

“Importantly, the label includes a survival benefit in infants and reductions in important markers of liver disease, including ALT and liver fat content, as well as significant improvements in lipid parameters, in children and adults. This approval also strengthens Alexion’s global leadership in rare diseases as we broaden our product portfolio to transform the lives of more patients with severe and life-threatening disorders. We look forward to bringing Kanuma to patients with LAL-D and their physicians in the United States.”

“I am delighted that patients with LAL-D now have the first approved therapy that treats the underlying cause of the disease,” said Barbara K. Burton, M.D., lead clinical trial investigator, professor of paediatrics at the Northwestern University Feinberg School of Medicine and Attending Physician at the Ann and Robert H. Lurie Children’s Hospital of Chicago.

“In the absence of treatment, LAL-D is nearly always fatal in infants and puts pediatric and adult patients at high risk of vital organ damage and premature mortality. In clinical studies, 67 per cent of infants who received enzyme replacement therapy survived beyond 12 months of age, and children and adults had meaningful improvements in multiple disease-related liver and lipid abnormalities.”

LAL-D is a genetic, chronic, and progressive metabolic disease associated with significant morbidity and premature mortality. 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 can experience a rapid onset of life-threatening disease manifestations, and without treatment, the youngest patients with LAL-D face rapid disease progression that is typically fatal within a matter of months. In addition, 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 organs.

“Patients with LAL-D often suffer for years from a delayed diagnosis, only to be further devastated once properly diagnosed because there have been no approved treatments for this disease,” said Brett Billmeyer, Board of Directors, LAL Solace. “Today, we are thrilled to welcome the FDA approval of Kanuma, providing an approved and effective treatment to patients with LAL-D and their families for the first time and, with it, bringing much-needed awareness to this often overlooked and devastating disease.”

Alexion will offer support to patients with LAL-D through its OneSource program. OneSource provides each patient and family with personalized support from a dedicated Alexion nurse case manager, who can help patients understand their insurance benefits and receive reimbursement assistance. Through OneSource, patients and families can obtain further information regarding third-party foundations and co-pay assistance programs that help patients meet out-of-pocket expenses related to the treatment of LAL-D. For uninsured patients who have no access to insurance, the Alexion Access Foundation, a charitable entity, provides Kanuma free of charge for patients.

Alexion is preparing to serve patients in the US with Kanuma and expects that Kanuma will become available commercially during the first week of January 2016. The company’s expanded access programme will remain open to enable patients with LAL-D in the US to access Kanuma until commercial product is available.

The FDA approved Kanuma under Priority Review, and had previously granted Breakthrough Therapy designation for Kanuma for LAL-D presenting in infants. With this approval, the FDA also issued a Rare Paediatric Disease Priority Review Voucher, which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. The rare paediatric disease review voucher program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases. Kanuma is also approved in the European Union, and a New Drug Application for Kanuma has been submitted to Japan’s Ministry of Health, Labour and Welfare.

The approval of Kanuma in the US 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. In pediatric and adult patients with LAL-D (ages 4 to 58 years), treatment with Kanuma resulted in larger reductions from baseline in ALT values and liver fat content, as measured by MRI, compared to treatment with placebo. Reduced ALT values were generally seen within 2 weeks. In addition, treated patients had significant improvements in lipid parameters, including LDL-C, HDL-C, non-HDL-C, and triglycerides, compared to placebo. The significance of these findings as they relate to cardiovascular morbidity and mortality or progression of liver disease in LAL deficiency has not been established. Continued improvements in ALT, LDL-C and HDL-C were seen in patients treated with Kanuma for up to 36 weeks.

The most commonly reported adverse events observed in clinical trials in infants were diarrhea, vomiting, fever, rhinitis, anemia, cough, nasopharyngitis, and urticaria. The most commonly reported adverse events observed in clinical trials in paediatric and adult patients were headache, fever, oropharyngeal pain, nasopharyngitis, asthenia, constipation, and nausea.