-If a loading dose is delayed or missed, administer it as soon as possible, with at least 14-days between doses and continue dosing as prescribed. -If a maintenance dose is delayed or missed, administer it as soon as possible and continue dosing every 4 months. Use: For the treatment of spinal muscular atrophy (SMA)
Full Answer
How often do you take nusinersen for muscle atrophy?
Nusinersen dosing information. Usual Adult Dose for Spinal Muscular Atrophy: Loading dose: 12 mg intrathecally every 14 days for 3 doses, then 12 mg intrathecally 30 days after the 3rd dose. Maintenance dose: 12 mg intrathecally once every 4 months.
What is nusinersen used to treat?
Data synthesis: It is a novel modified antisense oligonucleotide designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron protein deficiency. Nusinersen has been studied for safety, pharmacokinetics, and efficacy in both open-label and randomized controlled trials.
Does nusinersen need to be refrigerated?
*Based on Clinical Practice Guideline at CS Mott Hospital, Michigan Medicine, Ann Arbor, MI. Each vial of nusinersen is intended for a single administration.8Nusinersen vials should be stored in their cartons and in the refrigerator until the time of use. The medication should be protected from light until the time of use.
What is the dosing schedule for nusinersen (norepinephrine)?
This dosing schedule is based on manufacturer recommendations, but no other schedules were tested or have been published. Maintenance therapy can begin once the loading doses have been completed. In maintenance, patients receive a dose of nusinersen every 4 months. Table 3summarizes the dosing schedule and routine monitoring for nusinersen.
How effective is nusinersen?
Results from the probabilistic sensitivity analyses found that nusinersen had a zero likelihood of achieving a cost-effective ratio of less than $500,000 per QALY gained.
Does nusinersen cure SMA?
Spinraza (nusinersen), marketed by Biogen, was the first FDA-approved therapy to treat SMA. It is an SMN-enhancing therapy that works by targeting the SMN2 gene, causing it to make more complete protein.
How often is nusinersen administered?
The first three loading doses should be administered at 14-day intervals. The 4th loading dose should be administered 30 days after the 3rd dose. A maintenance dose should be administered once every 4 months thereafter.
Is nusinersen the same as Spinraza?
Nusinersen (SPINRAZATM) is the first drug developed specifically to treat 5q SMA. The most common form of SMA is known as '5q SMA' due to its genetic cause. 5q SMA includes the different 'Types' or clinical classifications Types 1, 2, 3 and 4.
How quickly does SPINRAZA work?
How long does it take to work? Spinraza starts working to treat SMA as soon as it's injected. In clinical studies, more than half of the people who were given Spinraza showed a decrease in their SMA symptoms within 15 months of their first dose.
Can SPINRAZA reverse SMA?
“Spinraza changed the entire course of history in SMA,” said Dr. Jill Jarecki, Chief Scientific Officer of Cure SMA, a patient organization that has invested $75 million in research since 1984. That research included early studies on the unique genetics of SMA.
How is nusinersen administered?
SPINRAZA is an intrathecal injection administered by, or under the direction of, healthcare professionals experienced in performing lumbar punctures. The recommended dosage is 12 mg (5 mL) per administration. Treatment with SPINRAZA begins with 4 loading doses. The first 3 doses are administered at 14-day intervals.
Is nusinersen a biologic?
Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder....Nusinersen.Clinical dataMolar mass7500.86 g·mol−127 more rows
What is nusinersen used for?
Nusinersen injection is used to treat children and adults with spinal muscular atrophy (SMA).
Is Risdiplam better than nusinersen?
Overall, it was established that Risdiplam leads to higher survivability rates and had better performance on motor milestone response of the infants of over 85 percent if the treatment is administered early. As such, it is a treatment that gets a higher recommendation as compared to Nusinersen.
How does nusinersen Spinraza work?
Spinraza is a synthetic anti-sense oligonucleotide (a type of genetic material) that enables the SMN2 gene to produce full length protein, which is able to work normally. This replaces the missing protein, thereby relieving the symptoms of the disease.
How long do you take Spinraza for?
The first 3 loading doses of SPINRAZA are administered every 14 days. The fourth and final loading dose is administered 30 days later. Maintenance doses are then administered every 4 months thereafter.
How long does it take to get a Nusinersen injection?
The nusinersen injection takes about 1 to 3 minutes to complete. You may be given a sedative to help you relax and keep you comfortable during the injection.
What is nusinersen?
Nusinersen works by helping the body produce a protein essential to the function of nerves that control muscle movement. This protein is lacking in people with an inherited disorder called spinal muscular atrophy caused by a mutation in a specific gene.
What other drugs will affect nusinersen?
Other drugs may interact with nusinersen, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.
What tests are done to check for nusinersen?
Your doctor will perform blood and urine tests to make sure you do not have conditions that would prevent you from safely receiving nusinersen.
Can you take Nusinersen if you are allergic to it?
You should not be treated with nusinersen if you are allergic to it.
Does Nusinersen cause rash?
a red skin rash; or. kidney problems--foamy urine; red or brown colored urine; swelling in your face, stomach, hands, or feet. Nusinersen may affect growth in children. Tell your doctor if your child is not growing at a normal rate while using nusinersen. Common side effects may include: headache; back pain;
How long does nusinersen stay in the body?
Metabolism and elimination of nusinersen is via exonuclease hydrolysis and urinary excretion.8,10To date, nusinersen has no known interaction with the cytochrome P450 enzymes, indicating limited drug interactions.10The manufacturer estimates that the terminal elimination half-life for nusinersen is 135 to 177 days in the CSF and approximately 63 to 87 days in the plasma .8The prolonged half-life of nusinersen is estimated to be due to the distribution of the medication from the CSF to the CNS tissues and a slow elimination phase of clearance back to the CSF and then systemic circulation.12
Where is Nusinersen administered?
Nusinersen is administered into the cerebrospinal fluid (CSF) because ASOs do not penetrate the blood brain barrier and all studies to date have relied on intrathecal drug delivery.11The pharmacokinetics of nusinersen is best described as a 4-compartment model.12The central nervous system (CNS) tissue is the primary site of action for nusinersen.10,12The CNS tissues and CSF are distinct pharmacokinetic compartments when considering the pharmacokinetics of nusinersen. However, at steady-state, the CSF concentration should be proportional to the CNS tissue concentration of the medication.12Once nusinersen is in the CNS, it is estimated that there is a redistribution into the CSF before the medication is cleared into the systemic circulation.12Although the clinical trials used dosing based on age-to-CSF volume relationships, post hoc CSF half-life values from the pharmacokinetic analysis showed that the CSF half-life of nusinersen was not age or body-weight dependent.10,12Therefore, although the trials used age-based dosing, a fixed dose for all ages and weights was recommended for commercial use because there was no dose-limiting toxicity documented for any trial participants.12Dosing for nusinersen was based solely on the pharmacokinetics of the CSF owing to the need to distribute nusinersen throughout the CNS to all tissues containing the targeted SMN neurons.12
What is Nusinersen used for?
Nusinersen: A Novel Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy
How many trials are there for Nusinersen?
Two phase 2/3 trials to evaluate nusinersen efficacy in SMA-1 patients have been published as of April 2018 (PubMed search; April 10, 2018). As of this date, 11 trials have been listed in Clinicaltrials.gov, one of which is the extended access program. The first trial was an open-label, dose-escalation study for 20 type-1 patients. Infants included were between 3 weeks and 7 months of age at start of trial and most had 2 copies of SMN2.13Four of the 20 participants were given loading doses of 6 mg each, on days 1, 15, and 85, followed by 12-mg maintenance doses on day 253 and every 4 months after this. The next 16 participants received 12-mg loading and maintenance doses on the same schedule as the smaller-dose group.13This, and all other clinical trials for nusinersen, was sponsored by Ionis Pharmaceuticals/Biogen (Cambridge, MA). The outcome measures used included the Hammersmith Infant Neurological Exam–Part 2 (HINE-2) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). The study was conducted at 4 US sites with enrollment occurring between May 2013 and July 2014. This trial demonstrated safety and tolerability as well as divergence from the Kaplan-Meier survival curve created from a preceding natural history study.14In addition, there were improvements in motor function scores (CHOP INTEND and HINE-2) and achievement of motor milestones, compared with the known natural course of SMA-1.13
What should be routinely evaluated for SMA?
Nutrition. Children with SMA should be routinely evaluated for aspiration, constipation, feeding, and swallowing. These complications are universally experienced by those with SMA-1, increasingly seen with SMA-2 as they near late childhood or adolescence, and are uncommonly part of the course of SMA-3. Caloric intake, nutrition supplementation, and required food consistency should be regularly evaluated. If poor oral intake or aspiration is identified in a patient, management with a nasogastric tube or percutaneous gastric tube is recommended.
How long does it take for SMA-1 to become symptomatic?
Patients with SMA-1 may appear normal at birth but become symptomatic within the first 6 months of life.
When do SMA-2 babies die?
They generally die by age 2 years, unless they are supported with continuous mechanical ventilation. SMA-2 is less severe and initial symptoms begin between the ages of 6 and 18 months. Children with SMA-2 are able to sit, but typically never walk independently.
How long does Spinraza last?
Part C will test adults on Spinraza for more than one year, with these patients getting a single 50 mg dose four months after their most recent treatment, followed by 28 mg maintenance doses four and eight months later. Researchers expect to finish the DEVOTE study in July 2023.
Where is Spinraza administered?
Spinraza is administered as an intrathecal injection, or an injection directly into the spinal canal. Treatment must take place in hospitals or at centers whose staff are trained in performing lumbar punctures. The most common side effects of Spinraza are respiratory infections and constipation.
How does Spinraza work?
Spinraza is a type of RNA-based molecule, called antisense oligonucleotide (ASO), designed to increase the levels of the survival motor neuron (SMN), a protein essential for motor neuron and muscle health and whose production in impaired in people with SMA. Motor neurons are the specialized nerve cells that control voluntary movement.
What is Spinraza used for?
Spinraza became the first therapy approved by the U.S. Food and Drug Administration (FDA) to treat SMA type 1, type 2, and type 3 — covering both infants and adults — in December 2016, under a priority review program for rare diseases.
What is the second trial of Spinraza?
Results from the second trial (NCT01703988) , called CS2, and its extension CS12 (NCT02052791) indicated that children treated with Spinraza over three years showed improvements in motor function and stable disease activity. These results were a marked departure from SMA’s known course in untreated patients (SMA’s natural history).
When will the SMA end?
It is due to conclude in August 2023. Interim findings released in May 2020 and reaching out for some participants to 6.5 years of treatment, showed sustained benefits — from motor skill gains to disease stabilization — across a range of SMA patients who were at ages now ranging from toddlers to young adults.
Does Spinraza produce SMN?
Spinraza increases the ability of cells to produce functional SMN protein from the SMN2 gene. It does so by binding to the SMN2 mRNA and “patching” this signal. This allows the SMN2 mRNA to be full length, just like the SMN1 mRNA.