Qalsody Drug Information

• is administered intrathecally Dosing Information 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 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 to 3 minutes 2.1. Dosing Information Recommended Dosage Administer QALSODY intrathecally using a lumbar puncture by, or under the direction of, healthcare professionals experienced in performing lumbar punctures. The recommended dosage is 100 mg (15 mL) of QALSODY per administration. Initiate QALSODY treatment with three loading doses administered at 14-day intervals. Administer a maintenance dose every 28 days thereafter. Missed Dose If the second loading dose is missed, administer QALSODY as soon as possible, and administer the third loading dose 14 days later. If the third loading dose or a maintenance dose is missed, administer QALSODY as soon as possible, and administer the next dose 28 days later. 2.2. Preparation and Administration Instructions Use aseptic technique when preparing and administering QALSODY intrathecally. Prepare and administer QALSODY according to the following steps: Preparation Vial preparation instructions Allow refrigerated QALSODY vial to warm to room temperature (25°C/77°F) prior to administration without using external heat sources . Inspect the solution in the QALSODY vial prior to administration. Do not administer if particles are observed or the liquid in the vial is not clear and colorless to slightly yellow. Do not shake the QALSODY vial. Procedural preparation instructions If indicated by the clinical condition of the patient, consider sedation. If indicated by the clinical condition of the patient, consider imaging to guide intrathecal administration of QALSODY. Prior to removing the vial's cap on the aluminum overseal, confirm readiness of the patient. An unopened QALSODY vial can be returned to the refrigerator . Evaluate patients prior to and after intrathecal injection for the presence of potential conditions related to lumbar puncture, to avoid serious procedural complications. Administration Prior to administration, remove approximately 10 mL of cerebrospinal spinal fluid (CSF) using a lumbar puncture needle. Prior to administration, remove the plastic cap and attach a needle to the syringe, for the purpose of withdrawing QALSODY from the vial. Insert the needle into the vial through the center of the overseal and withdraw the required dose of 15 mL (equivalent to 100 mg) from the vial. Do not dilute QALSODY. External filters are not required. Administer QALSODY using a lumbar puncture needle as an intrathecal bolus injection over 1 to 3 minutes. QALSODY contains no preservatives. Once drawn into the syringe, the solution should be administered immediately (within 4 hours of removal from the vial) at room temperature; otherwise, it must be discarded. Any unused contents of the single-dose vial should be discarded.

The following clinically significant adverse reactions are discussed elsewhere in the labeling: Myelitis and/or Radiculitis Papilledema and Elevated Intracranial Pressure Aseptic Meningitis 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 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1-877-725-7639 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of QALSODY cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice. The safety of QALSODY 100 mg was evaluated in 147 patients with SOD1-ALS. The median patient exposure was 119.4 weeks (range from 4 to 212 weeks). QALSODY was evaluated in the placebo-controlled Study 1 and in the open label extension Study 2. In Study 1 Part C, approximately 43% were female; 57% were male; 64% were White and 8% were Asian. The mean age at entry in Study 1 Part C was 49.8 years (range from 23 to 78 years). The most common adverse reactions (≥ 10% of patients treated with QALSODY and greater than placebo) were pain, fatigue, arthralgia, CSF white blood cell increased, and myalgia.

Table 1 shows the common adverse reactions that occurred in at least 5% of patients treated with QALSODY and at a 5% or higher frequency than placebo. Table 1: Adverse Drug Reactions That Occurred in At Least 5% of Patients Treated with QALSODY and at >5% Higher Frequency Than Placebo ‡‡ Pain includes preferred terms of pain, back pain, and pain in extremity. * CSF white blood cell increased includes preferred terms of CSF white blood cell increased and pleocytosis. Adverse Reaction Study 1 Part C QALSODY 100 mg (n = 72) % Placebo (n = 36) % Pain ‡‡ 42 22 Fatigue 17 6 Arthralgia 14 6 CSF white blood cell increased * 14 0 Myalgia 14 6 CSF protein increased 8 3 Musculoskeletal stiffness 6 0 Neuralgia 6 0 Less Common Adverse Reactions Serious adverse reactions of myelitis and radiculitis; papilledema and elevated intracranial pressure; and aseptic meningitis have occurred in patients treated with QALSODY . In the long-term extension study, nonserious adverse reactions of pyrexia have occurred with repeat administration of QALSODY.

8.1. Pregnancy Risk Summary There are no adequate data on developmental risks associated with the use of QALSODY in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data Animal Data Subcutaneous administration of tofersen (0, 3, 10, 30 mg/kg) every other day to pregnant mice during the period of organogenesis resulted in no adverse effects on embryofetal development. Plasma exposure at the highest dose tested (30 mg/kg) was approximately 4 times that in humans at the recommended human dose (RHD) of 100 mg. Subcutaneous administration of tofersen (0, 3, 10, 30 mg/kg) every other day to pregnant rabbits during the period of organogenesis resulted in no adverse effects on embryofetal development.

Plasma exposure at the highest dose tested (30 mg/kg) was approximately 20 times that in humans at the RHD. Subcutaneous administration of tofersen (0, 3, 10, or 30 mg/kg) every other day to male and female mice prior to and during mating and continuing in females throughout organogenesis resulted in no adverse effects on pre- or postnatal development. Plasma exposures at the highest dose tested (30 mg/kg) were approximately 4 times that in humans at the RHD.

8.4. Pediatric Use Safety and effectiveness in pediatric patients have not been established.