Sebelipase Alfa- Kanuma (Dec 2015)- Metabolic disorder
Drug Name:Sebelipase Alfa- Kanuma (Dec 2015)- Metabolic disorder
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
KANUMA (sebelipase alfa) injection, for intravenous use
Initial U.S. Approval: 2015
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.41
Drug Name - Sebilipase Alfa
Active Ingredient- Kanuma
Date of approval - 12/08/2015
FDA-approved use - To treat Patients with a Rare Disease known as
Lysomal Acid Lipase (LAL) deficiency
Approved by US FDA on 12/08/2015- (Ref- FDA approved List- 2015)
Adverse Reaction:
The most common adverse reactions are:
Patients with Rapidly Progressive Disease Presenting within the
First 6 Months of Life (.30%): diarrhea, vomiting, fever, rhinitis, anemia, cough,
nasopharyngitis, and urticaria.
Pediatric and Adult Patients (.8%): headache, fever, oropharyngeal pain,
nasopharyngitis, asthenia, constipation, and nausea.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions including Anaphylaxis: Observe patients during
and after the infusion. Consider interrupting the infusion or lowering the infusion rate,
based on the severity of the reaction.
If a severe hypersensitivity reaction occurs, immediately stop the infusion
and initiate appropriate treatment. Pre-treatment with antipyretics and/or
antihistamines may prevent subsequent reactions in those cases where
symptomatic treatment is required.
Hypersensitivity to Eggs or Egg Products:
Consider the risks and benefits of treatment in patients with known systemic
hypersensitivity reactions to eggs or egg products.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
KANUMA is a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific
enzyme indicated for the treatment of patients with a diagnosis of
Lysosomal Acid Lipase (LAL) deficiency. (1)
DOSAGE AND ADMINISTRATION
Patients with Rapidly Progressive LAL Deficiency Presenting within
the First 6 Months of Life:
The recommended starting dosage is 1 mg/kg as an intravenous infusion
once weekly.
For patients who do not achieve an optimal clinical response, increase
to 3 mg/kg once weekly.
Pediatric and Adult Patients with LAL Deficiency:
The recommended dosage is 1 mg/kg as an intravenous infusion once
every other week.
Administration Instructions :
Infuse over at least 2 hours.
Consider further prolonging the infusion time for the 3 mg/kg dose
or if a hypersensitivity reaction occurs.
Consider a 1-hour infusion for the 1 mg/kg dose in patients
who tolerate the infusion.
DOSAGE FORMS AND STRENGTHS
Injection: 20 mg/10 mL (2 mg/mL) solution in single-use vials.
Patient Information:
PATIENT COUNSELING INFORMATION
Hypersensitivity Reactions, including Anaphylaxis
Advise patients and caregivers that reactions related to administration and infusion may occur
during and after KANUMA treatment, including life-threatening anaphylaxis and severe
hypersensitivity reactions.
Inform patients of the signs and symptoms of anaphylaxis and hypersensitivity reactions,
and have them seek immediate medical care should signs and symptoms occur
Manufactured by:
Alexion Pharmaceuticals Inc.
Cheshire, CT 06410
US License Number: 1743
1-888-765-4747 (phone)
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
LAL deficiency is an autosomal recessive lysosomal storage disorder characterized
by a genetic defect resulting in a marked decrease or loss in activity of the lysosomal
acid lipase (LAL) enzyme.
The primary site of action of the LAL enzyme is the lysosome, where the enzyme normally
causes the breakdown of lipid particles including LDL-c. Deficient LAL enzyme activity
results in progressive complications due to the lysosomal accumulation of cholesteryl
esters and triglycerides in multiple organs, including the liver, spleen, intestine, and
the walls of blood vessels.
The resulting lipid accumulation in the liver may lead to increased liver fat content and
progression of liver disease, including fibrosis and cirrhosis. Lipid accumulation in the
intestinal wall leads to malabsorption and growth failure. In parallel, dyslipidemia
due to impaired degradation of lysosomal lipid is common with elevated LDL-c
and triglycerides and low HDL-cholesterol (HDL-c).
2. Pharmacokinetics
The pharmacokinetic profile of sebelipase alfa was nonlinear with a greater than
dose-proportional increase in exposure between 1 and 3 mg/kg based on
non-compartmental analysis of data from 26 adults. No accumulation was observed
following once weekly or once every other week dosing
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Risk Summary
There are no available data on KANUMA in pregnant women to inform any drug-associated
risk.
Animal reproductive studies conducted with sebelipase alfa showed no evidence
of embryolethality, fetotoxicity, teratogenicity, or abnormal early embryonic development
at dosages up to 164 and 526 times the human dosage of 1 mg/kg every other week
(based on AUC) in rats and rabbits, respectively
2. Lactation
Risk Summary
There are no data on the presence of sebelipase alfa in human milk, the effects on the
breastfed infant, or the effects on milk production. It is not known if sebelipase alfa is
present in animal milk.
The developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for KANUMA and any potential adverse effects on the
breastfed infant from sebelipase alfa or from the underlying maternal condition.
3. Pediatric Use
Safety and effectiveness of KANUMA have been established in pediatric patients aged
1 month and older. Clinical trials with KANUMA were conducted in 56 pediatric patients
(range 1 month to <18 years old)
4. Geriatric Use
Clinical trials of KANUMA did not include any patients aged 65 years old and older.
It is not known whether they respond differently than younger patients.
