Zolgensma
Zolgensma Uses, Dosage, Side Effects, Food Interaction and all others data.
Zolgensma is an adeno-associated virus vector-based gene therapy that has been approved by the FDA in May 2019 for the treatment of infant patients (less than 2 years of age) with spinal muscular atrophy (SMA) and a specific mutation in the survival motor neuron 1 (SMN1) gene. SMA is a rare genetic disease that affects the survival and function of motor neurons, leading to debilitating and often fatal muscle weakness. As there is no cure for SMA, onasemnogene abeparvovec is a disease-modifying agent that decelerates the disease progression, improves motor function, and manages the symptoms. The use and effectiveness of onasemnogene abeparvovec in patients with advanced SMA, such as those with complete paralysis of the limbs and permanent dependence on ventilators, has not been evaluated. Zolgensma is the first gene therapy that was approved for this indication in the USA. Nusinersen is another gene therapy that is currently approved by the FDA for the treatment of SMA in pediatric and adult patients.
Developed by AveXis, a Novartis company, onasemnogene abeparvovec is commonly marketed as Zolgensma®, which is available as a single-dose intravenous infusion. Zolgensma for therapeutic use and marketing is currently being assessed by the EU and an intrathecal formulation of the drug is currently undergoing clinical development in the USA.
Zolgensma is a gene therapy that restores the levels of SMN protein in the spinal cord to promote the survival and function of motor neurons. Acute serious liver injury and elevated aminotransferases were observed with the treatment of onasemnogene abeparvovec in clinical trials.
| Trade Name | Zolgensma |
| Generic | Onasemnogene abeparvovec |
| Onasemnogene abeparvovec Other Names | Onasemnogene abeparvovec, onasemnogene abeparvovec-xioi |
| Type | Infusion, Intravenous |
| Protein binding | There is limited pharmacokinetic information on onasemnogene abeparvovec. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | Novartis Gene Therapies |
| Available Country | United Kingdom, United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Zolgensma is a gene therapy used to treat neonatal and infant patients with spinal muscular atrophy caused by bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
Zolgensma is indicated for the treatment of pediatric patients less than 2 years of age (neonatal and infant patients) with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
Zolgensma is also used to associated treatment for these conditions: Spinal Muscular Atrophy (SMA)
How Zolgensma works
Spinal muscular atrophy is a genetic disorder caused by mutations in the SMN gene, which encodes the SMN protein. SMN protein is found ubiquitously but it is highly expressed in the spinal cord where it is responsible for the survival and maintenance of specialized nerve cells called motor neurons. SMN1 and SMN2 genes encode the SMN protein but many mutations in the SMN1 gene have been found to cause spinal muscular atrophy, as SMN1 is the primary gene responsible for functional production of SMN protein. A common mutation that causes spinal muscular atrophy involves a bi-allelic deletion of exon 7 in the SMN1 gene. The number of copies of the SMN2 gene varies among individuals: while higher number of SMN2 gene copies may protect against SMN protein deficiency caused by SMN1 gene mutations, it is generally proposed that the bi-allelic mutation in the SMN1 gene cannot be compensated by the SMN2 gene. The mutation results in insufficient SMN protein expression and inefficient assembly of the machinery needed to process pre-mRNA for motor neuron development and survival. Spinal muscular atrophy involves a progressive degeneration and loss of lower motor neurons, leading to muscle weakness and atrophy.
Zolgensma is gene therapy that consists of a recombinant self-complementary adeno-associated virus serotype 9 (AAV9) as a gene delivery vector, which contains a transgene encoding the human survival motor neuron (SMN) protein. AAV9 is commonly used in gene therapy applications because it is capable of crossing the blood-brain barrier and transducing neurons in the CNS. After administration, this viral vector is shed and a copy of the gene encoding the human SMN protein is delivered, leading to cell transduction and expression of the SMN protein.
Toxicity
The LD50 and information on overdose have not been evaluated with onasemnogene abeparvovec. In mice toxicology studies, dose-dependent cardiac and hepatic toxicities were observed following intravenous administration. Cardiac toxicity was characterized by mononuclear cell inflammation accompanied by edema, slight to mild fibrosis, and scattered myocardial cell degeneration/regeneration, as well as atrial thrombosis and dilation. Hepatotoxicity was characterized by hepatocellular hypertrophy, Kupffer cell activation, perinuclear vacuolation, and scattered hepatocellular necrosis.
Food Interaction
No interactions found.Volume of Distribution
There is limited pharmacokinetic information on onasemnogene abeparvovec. When biodistribution was evaluated in autopsy studies, the highest levels of vector DNA were found in the liver. Vector DNA was also detected in the spleen, heart, pancreas, inguinal lymph node, skeletal muscles, peripheral nerves, kidney, lung, intestines, spinal cord, brain, and thymus.
Elimination Route
There is limited pharmacokinetic information on onasemnogene abeparvovec.
Half Life
There is limited pharmacokinetic information on onasemnogene abeparvovec.
Clearance
There is limited pharmacokinetic information on onasemnogene abeparvovec.
Elimination Route
There is limited pharmacokinetic information on onasemnogene abeparvovec.
Innovators Monograph
You find simplified version here Zolgensma
