Empaveli

WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA EMPAVELI, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae type B [see Warnings and Precautions (5.1) ] . Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, unless the risks of delaying therapy with EMPAVELI outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor. See Warnings and Precautions (5.1) for additional guidance on the management of the risk of serious infections caused by encapsulated bacteria. Patients receiving EMPAVELI are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected. Because of the risk of serious infections caused by encapsulated bacteria, EMPAVELI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the EMPAVELI REMS [see Warnings and Precautions (5.2) ] . WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA See full prescribing information for complete boxed warning. EMPAVELI increases the risk of serious and life-threatening infections caused by encapsulated bacteria including Streptococcus pneumoniae , Neisseria meningitidis and Haemophilus influenzae type B. Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, unless the risks of delaying EMPAVELI outweigh the risks of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor. ( 5.1 ) Patients receiving EMPAVELI are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected. ( 5.1 ) EMPAVELI is available only through a restricted program called EMPAVELI REMS.

5 WARNINGS AND PRECAUTIONS Serious infections caused by encapsulated bacteria. ( 5.1 ) Infusion-Related Reactions: Monitor patients for infusion-related reactions and institute appropriate medical management as needed. ( 5.3 ) Interference with Laboratory Tests: Use of silica reagents in coagulation panels may result in artificially prolonged activated partial thromboplastin time (aPTT). ( 5.5 ) 5.1 Serious Infections Caused by Encapsulated Bacteria EMPAVELI, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria including Streptococcus pneumoniae , Neisseria meningitidis (caused by any serogroup, including non-groupable strains), and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initation of EMPAVELI treatment is contraindicated in patients with unresolved serious infection caused by encapsulated bacteria. Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to administration of the first dose of EMPAVELI, according to the most current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI. Note that, ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent EMPAVELI therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including EMPAVELI. The benefits and risks of treatment with EMPAVELI, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by encapsulated bacteria. Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of EMPAVELI in patients who are undergoing treatment for serious infections. EMPAVELI is available only through a restricted program under a REMS [see Warnings and Precautions (5.2) ]. 5.2 EMPAVELI REMS EMPAVELI is available only through a restricted program under a REMS called EMPAVELI REMS, because of the risk of serious infections caused by encapsulated bacteria [see Warnings and Precautions (5.1) ] . Notable requirements of the EMPAVELI REMS include the following: Prescribers must enroll in the REMS. Prescribers must counsel patients about the risk of serious infections caused by encapsulated bacteria. Prescribers must provide the patients with the REMS educational materials. Prescribers must assess patient vaccination status for encapsulated bacteria and vaccinate if needed according to current ACIP recommendations two weeks prior to the first dose of EMPAVELI. Prescribers must provide a prescription for antibacterial drug prophylaxis if treatment must be started urgently, and the patient is not up to date with vaccinations against encapsulated bacteria according to current ACIP recommendations at least two weeks prior to the first dose of EMPAVELI. Pharmacies that dispense EMPAVELI must be certified in the EMPAVELI REMS and must verify prescribers are certified. Patients must receive counseling from the prescriber about the need to receive vaccinations against encapsulated bacteria per ACIP recommendations, the need to take antibiotics as directed by the prescriber, and the signs and symptoms of serious infections. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 2 months following treatment discontinuation with EMPAVELI. Further information is available at www.empavelirems.com or 1-888-343-7073 5.3 Infusion-Related Reactions Systemic hypersensitivity reactions (e.g., facial swelling, rash, urticaria, pyrexia) have occurred in patients treated with EMPAVELI, which may resolve after treatment with antihistamines. Cases of anaphylaxis leading to treatment discontinuation have been reported. If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue EMPAVELI infusion immediately, institute appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved. 5.4 Monitoring PNH Manifestations after Discontinuation of EMPAVELI After discontinuing treatment with EMPAVELI, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH levels along with sudden decrease in PNH clone size or hemoglobin, or reappearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues EMPAVELI for at least 8 weeks to detect hemolysis and other reactions. If hemolysis, including elevated LDH, occurs after discontinuation of EMPAVELI, consider restarting treatment with EMPAVELI. 5.5 Interference with Laboratory Tests There may be interference between silica reagents in coagulation panels and EMPAVELI that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, avoid the use of silica reagents in coagulation panels.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Serious Infections Caused by Encapsulated Bacteria [see Warnings and Precautions (5.1) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] The most common adverse reactions in patients with PNH (incidence ≥10%) were injection site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, pain in extremity, hypokalemia, fatigue, viral infection, cough, arthralgia, dizziness, headache, and rash. ( 6.1 ) The most common adverse reactions in patients with C3G or primary IC-MPGN (incidence ≥10%) were infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apellis Pharmaceuticals, Inc. at 1-833-866-3346 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 a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Paroxysmal Nocturnal Hemoglobinuria Study in Complement-Inhibitor Experienced Adult Patients with PNH (Study APL2-302) The data described below reflect the exposure in 80 adult patients with PNH who received EMPAVELI (n=41) or eculizumab (n=39) at the recommended dosing regimens for 16 weeks. Serious adverse reactions were reported in 7 (17%) patients with PNH receiving EMPAVELI. The most common serious adverse reaction in patients treated with EMPAVELI was infections (5%). The most common adverse reactions (≥10%) with EMPAVELI were injection-site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, viral infection, and fatigue. Table 2 describes the adverse reactions that occurred in ≥5% of patients treated with EMPAVELI in Study APL2-302. Table 2: Adverse Reactions Reported in ≥5% of Patients Treated with EMPAVELI in Study APL2-302 Adverse Reaction EMPAVELI (N=41) n (%) Eculizumab (N=39) n (%) General disorders and administration site conditions Injection-site reaction Grouped terms Term includes injection-site erythema, injection-site reaction, injection-site swelling, injection-site induration, injection-site bruising, injection-site pain, injection-site pruritus, vaccination site reaction, administration site swelling, injection-site hemorrhage, injection -site edema, injection-site warmth, administration site pain, application site pain, injection-site mass, injection-site rash, vaccination site pain 16 (39) 2 (5) Fatigue 5 (12) 9 (23) Chest pain 3 (7) 1 (3) Infections and infestations Infections 12 (29) 10 (26) Respiratory tract infection 6 (15) 5 (13) Viral Infection 5 (12) 3 (8) Gastrointestinal disorders Diarrhea 9 (22) 1 (3) Abdominal pain 8 (20) 4 (10) Musculoskeletal disorders Back pain 3 (7) 4 (10) Nervous system disorders Headache 3 (7) 9 (23) Vascular disorders Systemic hypertension 3 (7) 1 (3) Clinically relevant adverse reactions in less than 5% of patients include: Intestinal ischemia Biliary sepsis Hypersensitivity pneumonitis After the randomized control period, 77 patients continued the study, and all were treated with EMPAVELI monotherapy at the recommended dosing regimen for up to 48 weeks. Serious adverse reactions were reported in 18 patients (23%). Additional adverse reactions reported in >5% of patients treated with EMPAVELI during the open-label part of the study compared to the randomized controlled part in Table 1 were cough (12%), arthralgia (8%), oropharyngeal pain (8%), pyrexia (8%), pain in extremity (7%), thrombocytopenia (7%), abdominal distension (5%), acute kidney injury (5%), anxiety (5%), and myalgia (5%). One patient (1%) died due to COVID-19 infection. Description of Select Adverse Reactions Injection-Site Reactions Injection/infusion-site reactions (e.g., erythema, swelling, induration, pruritus, and pain) have been reported during Study APL2-302. These reactions were mild or moderate in severity. Diarrhea Seventeen cases of diarrhea have been reported during the 48 weeks. Fifteen of the cases were mild and two were moderate. Study in Complement-Inhibitor Naïve Adult Patients with PNH (Study APL2-308) The data described below reflect the exposure in adult patients with PNH who received EMPAVELI (n=46) or the control arm (supportive care excluding complement inhibitors) (n=18) in Study APL2-308 [see Clinical Studies (14.1) ] . One patient (2%) who received EMPAVELI died due to septic shock. Serious adverse reactions were reported in 6 (13%) patients with PNH receiving EMPAVELI. The most common adverse reaction (≥10%) in patients treated with EMPAVELI were injection site reactions, infections, viral infection, pain in extremity, hypokalemia, arthralgia, dizziness, abdominal pain, rash, and headache. Table 3 describes the adverse reactions that occurred in ≥5% of patients treated with EMPAVELI in Study APL2‑308. Table 3: Adverse Reactions Reported in ≥5% of Patients Treated with EMPAVELI in Study APL2-308 Adverse Reaction EMPAVELI (N=46) n (%) Control Arm Control Arm = supportive care (excluding complement inhibitors) (N=18) n (%) Exposure Adjusted Rate (per 100 pt yrs) Exposure Adjusted Rate (per 100 pt yrs) EMPAVELI (N=46) group includes patients who received EMPAVELI at any point during the study, including patients randomized to EMPAVELI (N=35) and patients randomized to the control arm and crossed over to EMPAVELI treatment (N=11). General disorders and administration site conditions Injection-site reaction Grouped terms Term includes injection-site bruising, injection-site hemorrhage, injection-site swelling, application site reaction, infusion-site pruritus, injection-site erythema, injection-site rash, puncture site reaction. 12 (26) 42 0 0 Pyrexia 4(9) 14 0 0 Peripheral edema 3 (7) 11 0 0 Infections and Infestations Infections 9 (20) 32 4 (22) 74 Viral infection 6 (13) 21 2 (11) 37 Musculoskeletal and connective tissue disorders Pain in extremity 6 (13) 21 0 0 Arthralgia 5 (11) 18 0 0 Musculoskeletal pain 3 (7) 11 0 0 Metabolism and nutrition disorders Hypokalemia 6 (13) 21 2 (11) 37 Nervous system disorders Dizziness 5 (11) 18 0 0 Headache 5 (11) 18 0 0 Somnolence 3 (7) 11 0 0 Gastrointestinal disorders Abdominal pain 5 (11) 18 1 (6) 18 Skin and subcutaneous tissue disorders Rash 5(11) 18 0 0 Ecchymosis 3 (7) 11 0 0 Erythema 3 (7) 11 0 0 Blood and lymphatic system disorders Thrombocytopenia 3 (7) 11 1 (6) 18 Respiratory, thoracic and mediastinal disorders Cough 4 (9) 14 0 0 Epistaxis 3 (7) 11 0 0 Investigations Blood creatinine increased 3 (7) 11 0 0 C3 Glomerulopathy or Primary IC-MPGN Study in Adult and Pediatric Patients 12 Years of Age and Older with C3G or Primary IC-MPGN (Study APL2-C3G-310) The data described below reflects the exposure in adult (n=35) and pediatric patients 12 years of age and older (n=28) with native kidney C3G (n=46), native kidney primary IC-MPGN (n=12), or recurrent C3G following kidney transplant (n=5) who received EMPAVELI at the recommended dosing regimens during the 26-week placebo-controlled period of Study APL2-C3G-310. Serious adverse reactions due to viral infections resulting in hospitalizations occurred in 2 (3%) patients with C3G or primary IC-MPGN receiving EMPAVELI and 1 (2%) patient on placebo. One patient (2%) on EMPAVELI with native kidney C3G died because of respiratory failure due to COVID-19 pneumonia; there were no deaths in the placebo arm. Table 4 describes the adverse reactions that were reported in ≥5% of patients (adults and pediatric patients 12 years of age and older) treated with EMPAVELI and at a greater incidence than placebo in Study APL2-C3G-310. Adverse reactions in pediatric patients were similar to those seen in adults. Following the 26-week placebo-controlled period in Study APL2-C3G-310, 118 patients were treated with EMPAVELI at the recommended dosing regimen for a 26-week open-label period. The safety profile was consistent with that observed during the 26-week placebo-controlled period. During the open-label period, one patient with native kidney C3G had a serious adverse event of pneumonia secondary to Streptococcus pneumoniae , and one patient with recurrent C3G following kidney transplant developed herpes zoster meningoencephalitis while on concomitant immunosuppression, leading to treatment discontinuation. Table 4: Adverse Reactions Reported in ≥5% of Patients (adult and pediatric) Treated with EMPAVELI and Greater than Placebo in Study APL2-C3G-310 Adverse Reaction EMPAVELI (N=63) n (%) Placebo (N=61) n (%) General disorders and administration site conditions Infusion-site reactions Term includes the following reactions at the infusion site: erythema, pruritus, swelling, bruising, induration, pain, hemorrhage, discomfort, oedema, rash, and hypoaesthesia. 16 (25) 14 (23) Pyrexia 12 (19) 6 (10) Fatigue 4 (6) 1 (2) Infections and infestations Nasopharyngitis 11 (18) 7 (12) Influenza 7 (11) 3 (5) Gastrointestinal disorders Nausea 6 (10) 4 (7) Respiratory, thoracic and mediastinal disorders Cough 6 (10) 1 (2) Study in Adult Recurrent C3G or Primary IC-MPGN Following Kidney Transplant (Study APL2-C3G-204) In a study in 13 adults with recurrent C3G or primary IC-MPGN after kidney transplant (NCT#04572854), one patient with primary IC-MPGN experienced a serious adverse event of Pneumocystis jirovecii pneumonia while on EMPAVELI and concurrent immunosuppressive medications. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of EMPAVELI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to EMPAVELI exposure. Anaphylaxis and urticaria [see Warnings and Precautions (5.3) ]

<table width="75%"><caption>Table 2: Adverse Reactions Reported in &#x2265;5% of Patients Treated with EMPAVELI in Study APL2-302</caption><col width="50%" align="left" valign="top"/><col width="20%" align="center" valign="top"/><col width="30%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule" valign="middle">Adverse Reaction</th><th styleCode="Rrule">EMPAVELI (N=41) n (%)</th><th styleCode="Rrule">Eculizumab (N=39) n (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">General disorders and administration site conditions</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Injection-site reaction<footnote ID="t1ft1">Grouped terms</footnote><footnote>Term includes injection-site erythema, injection-site reaction, injection-site swelling, injection-site induration, injection-site bruising, injection-site pain, injection-site pruritus, vaccination site reaction, administration site swelling, injection-site hemorrhage, injection -site edema, injection-site warmth, administration site pain, application site pain, injection-site mass, injection-site rash, vaccination site pain</footnote></td><td styleCode="Rrule">16 (39)</td><td styleCode="Rrule">2 (5)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Fatigue<footnoteRef IDREF="t1ft1"/></td><td styleCode="Rrule">5 (12)</td><td styleCode="Rrule">9 (23)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Chest pain<footnoteRef IDREF="t1ft1"/></td><td styleCode="Rrule">3 (7)</td><td styleCode="Rrule">1 (3)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Infections and infestations</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Infections<footnoteRef IDREF="t1ft1"/></td><td styleCode="Rrule">12 (29)</td><td styleCode="Rrule">10 (26)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Respiratory tract infection<footnoteRef IDREF="t1ft1"/></td><td styleCode="Rrule">6 (15)</td><td styleCode="Rrule">5 (13)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Viral Infection<footnoteRef IDREF="t1ft1"/></td><td styleCode="Rrule">5 (12)</td><td styleCode="Rrule">3 (8)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Diarrhea</td><td styleCode="Rrule">9 (22)</td><td styleCode="Rrule">1 (3)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Abdominal pain<footnoteRef IDREF="t1ft1"/></td><td styleCode="Rrule">8 (20)</td><td styleCode="Rrule">4 (10)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Musculoskeletal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Back pain<footnoteRef IDREF="t1ft1"/></td><td styleCode="Rrule">3 (7)</td><td styleCode="Rrule">4 (10)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Nervous system disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">3 (7)</td><td styleCode="Rrule">9 (23)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Vascular disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Systemic hypertension<footnoteRef IDREF="t1ft1"/></td><td styleCode="Rrule">3 (7)</td><td styleCode="Rrule">1 (3)</td></tr></tbody></table>

<table width="75%" ID="tab2"><caption>Table 3: Adverse Reactions Reported in &#x2265;5% of Patients Treated with EMPAVELI in Study APL2-308</caption><col width="45%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="30%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule" valign="middle" rowspan="2">Adverse Reaction</th><th styleCode="Rrule">EMPAVELI (N=46) n (%)</th><th styleCode="Rrule">Control Arm<footnote>Control Arm = supportive care (excluding complement inhibitors)</footnote> (N=18) n (%)</th></tr><tr><th styleCode="Rrule" align="center">Exposure Adjusted Rate (per 100 pt yrs)</th><th styleCode="Rrule" align="center">Exposure Adjusted Rate (per 100 pt yrs)</th></tr></thead><tfoot><tr><td colspan="3" align="left">EMPAVELI (N=46) group includes patients who received EMPAVELI at any point during the study, including patients randomized to EMPAVELI (N=35) and patients randomized to the control arm and crossed over to EMPAVELI treatment (N=11).</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">General disorders and administration site conditions</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Injection-site reaction<footnote ID="foot1">Grouped terms</footnote><footnote>Term includes injection-site bruising, injection-site hemorrhage, injection-site swelling, application site reaction, infusion-site pruritus, injection-site erythema, injection-site rash, puncture site reaction.</footnote></td><td styleCode="Rrule">12 (26) 42</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Pyrexia</td><td styleCode="Rrule">4(9) 14</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Peripheral edema<footnoteRef IDREF="foot1"/></td><td styleCode="Rrule">3 (7) 11</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Infections and Infestations</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Infections<footnoteRef IDREF="foot1"/></td><td styleCode="Rrule">9 (20) 32</td><td styleCode="Rrule">4 (22) 74</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Viral infection<footnoteRef IDREF="foot1"/></td><td styleCode="Rrule">6 (13) 21</td><td styleCode="Rrule">2 (11) 37</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Pain in extremity</td><td styleCode="Rrule">6 (13) 21</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Arthralgia</td><td styleCode="Rrule">5 (11) 18</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Musculoskeletal pain</td><td styleCode="Rrule">3 (7) 11</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Metabolism and nutrition disorders</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Hypokalemia</td><td styleCode="Rrule">6 (13) 21</td><td styleCode="Rrule">2 (11) 37</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Nervous system disorders</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Dizziness</td><td styleCode="Rrule">5 (11) 18</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Headache</td><td styleCode="Rrule">5 (11) 18</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Somnolence</td><td styleCode="Rrule">3 (7) 11</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Abdominal pain<footnoteRef IDREF="foot1"/></td><td styleCode="Rrule">5 (11) 18</td><td styleCode="Rrule">1 (6) 18</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Rash<footnoteRef IDREF="foot1"/></td><td styleCode="Rrule">5(11) 18</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Ecchymosis</td><td styleCode="Rrule">3 (7) 11</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Erythema</td><td styleCode="Rrule">3 (7) 11</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Blood and lymphatic system disorders</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Thrombocytopenia</td><td styleCode="Rrule">3 (7) 11</td><td styleCode="Rrule">1 (6) 18</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Cough<footnoteRef IDREF="foot1"/></td><td styleCode="Rrule">4 (9) 14</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Epistaxis</td><td styleCode="Rrule">3 (7) 11</td><td styleCode="Rrule">0 0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule"><content styleCode="bold">Investigations</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Blood creatinine increased</td><td styleCode="Rrule">3 (7) 11</td><td styleCode="Rrule">0 0</td></tr></tbody></table>

<table width="75%"><caption>Table 4: Adverse Reactions Reported in &#x2265;5% of Patients (adult and pediatric) Treated with EMPAVELI and Greater than Placebo in Study APL2-C3G-310</caption><col width="45%" align="left" valign="top"/><col width="25%" align="left" valign="top"/><col width="30%" align="left" valign="top"/><thead><tr styleCode="botrule"><th styleCode="Lrule Rrule" valign="middle">Adverse Reaction</th><th styleCode="Rrule">EMPAVELI (N=63) n (%)</th><th styleCode="Rrule">Placebo (N=61) n (%)</th></tr></thead><tbody><tr styleCode="botrule"><td styleCode="Lrule"><content styleCode="bold">General disorders and administration site conditions</content></td><td/><td styleCode="Rrule"/></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule">Infusion-site reactions<footnote>Term includes the following reactions at the infusion site: erythema, pruritus, swelling, bruising, induration, pain, hemorrhage, discomfort, oedema, rash, and hypoaesthesia.</footnote></td><td styleCode="Rrule">16 (25)</td><td styleCode="Rrule">14 (23)</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule">Pyrexia </td><td styleCode="Rrule">12 (19)</td><td styleCode="Rrule">6 (10)</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule">Fatigue</td><td styleCode="Rrule">4 (6)</td><td styleCode="Rrule">1 (2)</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Infections and infestations</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule">Nasopharyngitis</td><td styleCode="Rrule">11 (18)</td><td styleCode="Rrule">7 (12)</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule">Influenza</td><td styleCode="Rrule">7 (11)</td><td styleCode="Rrule">3 (5)</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule">Nausea </td><td styleCode="Rrule">6 (10)</td><td styleCode="Rrule">4 (7)</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Cough </td><td styleCode="Rrule">6 (10)</td><td styleCode="Rrule">1 (2)</td></tr></tbody></table>