Overview
11 DESCRIPTION Tofersen, an antisense oligonucleotide, is a 20-base residue (20-mer) 5-10-5 MOE gapmer mixed backbone oligonucleotide. Of the nineteen internucleotide linkages, fifteen are 3′-O to 5′-O phosphorothioate diesters, and four are 3′-O to 5′-O phosphate diesters. Ten of the twenty sugar residues are 2-deoxy-D-ribose and the remainder are 2′-O-(2-methoxyethyl)-D-ribose (MOE).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1. Mechanism of Action Tofersen is an antisense oligonucleotide that causes degradation of SOD1 mRNA through binding to SOD1 mRNA, which results in a reduction of SOD1 protein synthesis. 12.2. Pharmacodynamics Effect of Tofersen on Total CSF SOD1 Protein Total CSF SOD1, an indirect measure of target engagement, was evaluated in Study 1 Part C in SOD1-ALS patients [see Clinical Studies ( 14 )] . At Week 28 in Study 1 Part C, a reduction in total CSF SOD1 protein of 35% (geometric mean ratio to baseline) in the tofersen-treated group versus a 2% decrease from baseline in the corresponding placebo subjects in the ITT population was observed (difference in geometric mean ratios for tofersen to placebo: 34%; nominal p
Indications
- 1 INDICATIONS AND USAGE QALSODY is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 ( SOD1 ) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).
Common Doses
- 15 mL
- 10 mL
- 100 mg
Dosage
2 DOSAGE AND ADMINISTRATION QALSODY is administered intrathecally ( 2.1 ) Dosing Information ( 2.1 ) Recommended dose: 100 milligrams (15 mL) per administration Initiate QALSODY treatment with 3 loading doses administered at 14day intervals. A maintenance dose should be administered once every 28 days thereafter. Preparation and Administration Instructions ( 2.2 ) Allow to warm to room temperature prior to administration Administer within 4 hours of removal from vial Prior to administration, remove approximately 10 mL of cerebrospinal fluid Administer as an intrathecal bolus injection over 1...
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: Myelitis and/or Radiculitis [see Warnings and Precautions ( 5.1 )] Papilledema and Elevated Intracranial Pressure [see Warnings and Precautions ( 5.2 )] Aseptic Meningitis [see Warnings and Precautions ( 5.3 )] The most common adverse reactions ( ≥ 10% of patients treated with QALSODY and greater than placebo) were pain, fatigue, arthralgia, cerebrospinal fluid white blood cell increased, and myalgia. (Section 6.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.