QALSODY

5 WARNINGS AND PRECAUTIONS Myelitis and/ or Radiculitis: Serious events of myelitis and radiculitis have been reported. Monitor for symptoms; diagnostic workup and treatment should be initiated according to the standard of care. ( 5.1 ) Papilledema and Elevated Intracranial Pressure: Serious events of papilledema and elevated intracranial pressure have been reported. Monitor for symptoms; diagnostic workup and treatment should be initiated according to standard of care. ( 5.2 ) Aseptic Meningitis: Serious events of aseptic meningitis have been reported. Monitor for symptoms; diagnostic workup and treatment should be initiated according to standard of care. ( 5.3 ) 5.1. Myelitis and/or Radiculitis Serious adverse reactions of myelitis and radiculitis have been reported in patients treated with QALSODY. Six patients treated with QALSODY experienced myelitis or radiculitis in the clinical studies. Two patients discontinued treatment with QALSODY and required symptomatic management with full resolution of symptoms. In the remaining 4 patients, symptoms resolved without discontinuation of QALSODY. If symptoms consistent with myelitis or radiculitis develop, diagnostic workup and treatment should be initiated according to the standard of care. Management may require interruption or discontinuation of QALSODY. 5.2. Papilledema and Elevated Intracranial Pressure Serious adverse reactions of papilledema and elevated intracranial pressure have been reported in patients treated with QALSODY. Four patients developed elevated intracranial pressure and/or papilledema. All patients received treatment with standard of care with resolution of symptoms, and no events led to discontinuation of QALSODY. If symptoms consistent with papilledema or elevated intracranial pressure develop, diagnostic workup and treatment should be initiated according to the standard of care. 5.3. Aseptic Meningitis Serious adverse reactions of aseptic meningitis (also called chemical meningitis or drug-induced aseptic meningitis) have been reported in patients treated with QALSODY. One patient experienced a serious adverse reaction of chemical meningitis, which led to discontinuation of QALSODY. One patient experienced a serious adverse reaction of aseptic meningitis, which did not lead to discontinuation of QALSODY. In addition, nonserious adverse drug reactions of CSF white blood cell increased, and CSF protein increased have also been reported with QALSODY [see Adverse Reactions ( 6.1 )]. If symptoms consistent with aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care.

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 6.1 ) 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 [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . In the long-term extension study, nonserious adverse reactions of pyrexia have occurred with repeat administration of QALSODY.

<table ID="t1" width="100%"><caption>Table 1: Adverse Drug Reactions That Occurred in At Least 5% of Patients Treated with QALSODY and at &gt;5% Higher Frequency Than Placebo </caption><col width="35.579%" align="left"/><col width="29.943%" align="left"/><col width="34.478%" align="left"/><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^{&#x2021;&#x2021;} Pain includes preferred terms of pain, back pain, and pain in extremity. </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^* CSF white blood cell increased includes preferred terms of CSF white blood cell increased and pleocytosis. </paragraph></td></tr></tfoot><tbody><tr><td rowspan="2" align="center" valign="bottom" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Adverse Reaction</content></td><td colspan="2" align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Study 1 Part C</content></td></tr><tr><td align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">QALSODY</content> <content styleCode="bold">100 mg</content> <content styleCode="bold">(n = 72)</content> <content styleCode="bold">%</content></td><td align="center" valign="bottom" styleCode="Botrule Rrule"><content styleCode="bold">Placebo</content> <content styleCode="bold">(n = 36)</content> <content styleCode="bold">%</content></td></tr><tr><td align="center" valign="middle" styleCode="Botrule Lrule Rrule">Pain^{&#x2021;&#x2021;}</td><td align="center" valign="middle" styleCode="Botrule Rrule">42 </td><td align="center" valign="middle" styleCode="Botrule Rrule">22 </td></tr><tr><td align="center" valign="middle" styleCode="Botrule Lrule Rrule">Fatigue </td><td align="center" valign="middle" styleCode="Botrule Rrule">17 </td><td align="center" valign="middle" styleCode="Botrule Rrule">6 </td></tr><tr><td align="center" valign="middle" styleCode="Botrule Lrule Rrule">Arthralgia </td><td align="center" valign="middle" styleCode="Botrule Rrule">14 </td><td align="center" valign="middle" styleCode="Botrule Rrule">6 </td></tr><tr><td align="center" valign="middle" styleCode="Botrule Lrule Rrule">CSF white blood cell increased^*</td><td align="center" valign="top" styleCode="Botrule Rrule">14 </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td></tr><tr><td align="center" valign="middle" styleCode="Botrule Lrule Rrule">Myalgia </td><td align="center" valign="middle" styleCode="Botrule Rrule">14 </td><td align="center" valign="middle" styleCode="Botrule Rrule">6 </td></tr><tr><td align="center" valign="middle" styleCode="Botrule Lrule Rrule">CSF protein increased </td><td align="center" valign="middle" styleCode="Botrule Rrule">8 </td><td align="center" valign="middle" styleCode="Botrule Rrule">3 </td></tr><tr><td align="center" valign="middle" styleCode="Botrule Lrule Rrule">Musculoskeletal stiffness </td><td align="center" valign="middle" styleCode="Botrule Rrule">6 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0 </td></tr><tr><td align="center" valign="middle" styleCode="Botrule Lrule Rrule">Neuralgia </td><td align="center" valign="middle" styleCode="Botrule Rrule">6 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0 </td></tr></tbody></table>