Date: 2016-03-28
Type of information: Granting of a Market Authorisation in Japan
Product name: Kanuma™
Compound: sebelipase alfa - recombinant human lysosomal acid lipase
Therapeutic area: Rare diseases - Genetic diseases - Metabolic diseases
Action mechanism: enzyme replacement therapy. Sebelipase alfa (SBC-102) is a recombinant form of the human lysosomal acid lipase (LAL) enzyme under development by Synageva as an enzyme replacement therapy for LAL Deficiency. LAL Deficiency is a rare autosomal recessive lysosomal storage disease (LSD) caused by a marked decrease in LAL enzyme activity that results in the buildup of fatty material in the liver, blood vessel walls, and other tissues and organs. In May 2015, Alexion Pharmaceuticals and Synageva BioPharma have entered into a definitive agreement pursuant to which Alexion will acquire Synageva.
Company: Synageva BioPharma (USA - MA), now Alexion Pharmaceuticals (USA - CT)
Disease: lysosomal acid lipase deficiency (LAL Deficiency)
Latest news: On March 28, 2016, Alexion Pharmaceuticals announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Kanuma® (sebelipase alfa) for the treatment of patients of all ages in Japan with lysosomal acid lipase deficiency. Alexion expects that initial patients with LAL-deficiency in Japan will start commercial treatment with Kanuma in Q3 2016. * On December 8, 2015, Alexion Pharmaceuticals announced that the 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™ is the first therapy approved in the U.S. 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. 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. Patients, caregivers, and healthcare providers in the U.S. can call 1-888-765-4747 to speak with a OneSource nurse case manager. Alexion is preparing to serve patients in the U.S. with Kanuma and expects that Kanuma will become available commercially during the first week of January 2016. The Company's expanded access program will remain open to enable patients with LAL-D in the U.S. 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 Pediatric Disease Priority Review Voucher, which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. The rare pediatric 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 U.S. 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%, 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. * On September 1, 2015, Alexion Pharmaceuticals announced that the European Commission (EC) has approved Kanuma™ (sebelipase alfa) for long-term enzyme replacement therapy (ERT) in patients of all ages with lysosomal acid lipase deficiency (LAL-D). Kanuma 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. Clinical Data: 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%, 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% 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. * On June 26, 2015, the European Medicines Agency (EMA) announced that the Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation for Kanuma® (sebelipase alfa), for the treatment of lysosomal acid lipase (LAL) deficiency. There is currently no approved therapy for this condition. Due to the lack of treatment and the high death rate in infants under the age of one, the CHMP decided to speed up the evaluation of this medicine and recommended marketing authorisation following an accelerated assessment. This mechanism is one of the Agency’s tools to speed up patient access to new medicines where there is an unmet medical need. Kanuma® is indicated for long-term enzyme replacement therapy (ERT) in infants, children and adult patients. The CHMP based its recommendation on four studies which provided evidence on the safety and efficacy in infants (under six months of age), children and adults. LAL is a rare disease; therefore the number of participants in these studies was small. Across all four studies, a total of 106 patients with LAL deficiency received treatment with sebelipase alfa, including 14 infants. In the clinical trials significant improvements were observed for a number of disease parameters. There was an improvement in survival of infants with LAL deficiency for which no treatment was available up until now. Collection of long-term efficacy data will continue through an ongoing study in infants with LAL deficiency. The most common side effects with Kanuma® were potential allergic reaction (hypersensitivity), high levels of fatty material in the blood (transient hyperlipidemia) and development of anti-drug antibodies (ADAs) which can hamper treatment as it might induce hypersensitivity and/or make treatment potentially less effective. The CHMP recommended that hypersensitivity, which appears to be more frequent in infants, should be further monitored following authorisation in all age groups. CHMP also required that long-term monitoring of ADAs in infants and in older populations be carried out. Following this positive CHMP opinion, the COMP will assess whether the orphan designation should be maintained. * On March 30, 2015, Synageva BioPharma announced the submission to the Comisión Federal para la Protección contra Riesgos Sanitarios (Cofepris) in Mexico for Kanuma® as a treatment for patients with lysosomal acid lipase deficiency. The submission to Cofepris for Kanuma® included previously reported data from the global, randomized, double-blind, placebo controlled Phase 3 trial in children and adults with LAL Deficiency, and the Phase 2/3 trial of Kanuma in infants with LAL Deficiency. * On February 23, 2015, Synageva BioPharma announced that the FDA has accepted for review the Biologics License Application (BLA) for Kanuma™ (sebelipase alfa) for the treatment of lysosomal acid lipase deficiency (LAL Deficiency). The FDA granted the company's request for Priority Review, which shortens the regulatory review period and is reserved for investigational therapies that treat serious conditions and, if approved, would provide a significant improvement in safety or effectiveness compared to available therapies. The FDA established a target action date of September 8, 2015 under the Prescription Drug User Fee Act (PDUFA). The BLA for Kanuma™ included previously reported data from the global, randomized, double-blind, placebo controlled Phase 3 trial in children and adults with LAL Deficiency, and the Phase 2/3 trial of Kanuma in infants with LAL Deficiency. Patients in these trials, combined with patients in other ongoing clinical trials with Kanuma™, represent the largest patient population studied to date for this rare, devastating disease. * On December 2, 2014, Synageva BioPharma announced the completion of the rolling submission of a Biologics License Application (BLA) to the FDA for sebelipase alfa as a treatment for patients with lysosomal acid lipase deficiency (LAL Deficiency). Included in the submission is a request for Priority Review which, if granted and the BLA is accepted for review, would shorten the FDA's anticipated regulatory review time from approximately 12 to 8 months. The company also announced the submission of a Marketing Authorization Application (MAA) in the European Union for sebelipase alfa for LAL Deficiency, which is subject to the validation process by the European Medicines Agency (EMA). The EMA recently granted the company's request for accelerated assessment, which has the potential to shorten the EMA's regulatory review time. The BLA and MAA include previously reported data from the global, randomized, double-blind, placebo controlled Phase 3 trial of sebelipase alfa in children and adults with LAL Deficiency, and the Phase 2/3 trial of sebelipase alfa in infants with LAL Deficiency. Patients in these trials, combined with patients in other ongoing clinical trials with sebelipase alfa, represent the largest patient population studied to date for this rare, devastating disease. Positive results from the global, Phase 3, double-blind, placebo-controlled trial evaluating sebelipase alfa in children and adults with LAL Deficiency were presented during the American Association for the Study of Liver Diseases (AASLD ) on November 10, 2014 . The trial met the primary endpoint of ALT normalization (a marker of liver injury) and multiple secondary endpoints, and demonstrated significant improvements in multiple disease-related parameters of dyslipidemia and liver injury compared with placebo. Most adverse events during the double-blind treatment period were mild and unrelated to sebelipase alfa. Positive results were also previously reported from the ongoing, open-label Phase 2/3 trial of sebelipase alfa in infants with LAL Deficiency. Six infants met the primary endpoint of survival at 12 months of age and five infants continue on treatment with sebelipase alfa. Three infants died shortly after the start of the study, unrelated to sebelipase alfa, and one infant who met the primary endpoint of survival at 12 months of age subsequently died at 15 months of age considered unlikely related to treatment with sebelipase alfa. Adverse events with sebelipase alfa were mostly mild to moderate. * On October 21, 2014, Synageva BioPharma announced the start of a rolling submission of a Biologics License Application (BLA) to the FDA for sebelipase alfa as a treatment for patients with lysosomal acid lipase deficiency (LAL Deficiency). A rolling submission allows completed portions of the application to be submitted and reviewed by the FDA on an ongoing basis. The company anticipates completing the rolling submission of the BLA to the FDA and submitting the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) by the end of January 2015. The BLA and MAA will include data from the global, randomized, double-blind, placebo controlled Phase 3 trial of sebelipase alfa in children and adults with LAL Deficiency, and the Phase 2/3 trial of sebelipase alfa in infants with LAL Deficiency. * On May 20, 2013, Synageva BioPharma announced that the FDA granted Breakthrough Therapy designation to sebelipase alfa for the treatment of early onset lysosomal acid lipase deficiency (LAL Deficiency), also known as Wolman disease. The designation was based on data generated from clinical trials with sebelipase alfa in patients with early onset LAL Deficiency. * On June 23, 2011, Synageva BioPharma announced that their lead program, SBC-102, an enzyme replacement therapy for Lysosomal Acid Lipase (LAL) Deficiency, currently in clinical trials, has been granted fast track designation by the FDA.
Patents: * On February 18, 2015, Synageva BioPharma announced that the European Patent Office issued European Patent No. EP2613798 B1 relating to the treatment of lysosomal acid lipase deficiency (LAL Deficiency). This patent provides protection until 2031, not including any patent term extension. In March 2014, the U.S. Patent and Trademark Office issued U.S. Patent No. 8,663,631 relating to methods of treating LAL Deficiency. The U.S. patent also provides protection until 2031, not including any patent term extension. These patents complement existing and planned global patent portfolios covering the company's LAL Deficiency program, which includes intellectual property directed to compositions of matter, methods of use and manufacturing.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2015-12-08
UE authorization: 2015-09-01
Favourable opinion UE: 2015-06-25
Favourable opinion USA:
Orphan status USA: 2010-01-07
Orphan status UE: 2010-12-17
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
