Omvoh

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions : Serious hypersensitivity reactions, including anaphylaxis and infusion-related reactions, have been reported. If a severe hypersensitivity reaction occurs, discontinue and initiate appropriate treatment. ( 5.1 ) Infections : OMVOH may increase the risk of infection. Do not initiate treatment with OMVOH in patients with a clinically important active infection until the infection resolves or is adequately treated. If a serious infection develops, do not administer OMVOH until the infection resolves. ( 5.2 ) Tuberculosis : Do not administer OMVOH to patients with active TB infection. Monitor patients receiving OMVOH for signs and symptoms of active TB during and after treatment. ( 5.3 ) Hepatotoxicity : Drug-induced liver injury has been reported. Monitor liver enzymes and bilirubin levels at baseline and for at least 24 weeks of treatment and thereafter according to routine patient management. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. ( 5.4 ) Immunizations : Avoid use of live vaccines. ( 5.5 ) 5.1 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis during intravenous infusion, have been reported with OMVOH administration. Infusion-related hypersensitivity reactions, including mucocutaneous erythema and pruritus, were reported during induction [see Adverse Reactions ( 6.1 )] . If a severe hypersensitivity reaction occurs, discontinue OMVOH immediately and initiate appropriate treatment. 5.2 Infections OMVOH may increase the risk of infection [see Adverse Reactions ( 6.1 )] . Do not initiate treatment with OMVOH in patients with a clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing OMVOH. Instruct patients to seek medical advice if signs or symptoms of clinically important acute or chronic infection occur. If a serious infection develops or an infection is not responding to standard therapy, monitor the patient closely and do not administer OMVOH until the infection resolves. 5.3 Tuberculosis Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with OMVOH. Do not administer OMVOH to patients with active TB infection. Initiate treatment of latent TB prior to administering OMVOH. Consider anti-TB therapy prior to initiation of OMVOH in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after OMVOH treatment. In clinical trials, subjects were excluded if they had evidence of active TB, a past history of active TB, or were diagnosed with latent TB at screening. 5.4 Hepatotoxicity A case of drug-induced liver injury (alanine aminotransferase [ALT] 18x the upper limit of normal (ULN), aspartate aminotransferase [AST] 10x ULN, and total bilirubin 2.4x ULN) in conjunction with pruritus was reported in a clinical trial subject following a longer than recommended induction regimen. OMVOH was discontinued. Liver test abnormalities eventually returned to baseline. Evaluate liver enzymes and bilirubin at baseline and for at least 24 weeks of treatment. Monitor thereafter according to routine patient management. Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction. 5.5 Immunizations Avoid use of live vaccines in patients treated with OMVOH. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with OMVOH, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or non-live vaccines in patients treated with OMVOH.

6 ADVERSE REACTIONS The following topics are also discussed in detail in the Warnings and Precautions section: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Infections [see Warnings and Precautions ( 5.2 )] Tuberculosis [see Warnings and Precautions ( 5.3 )] Hepatotoxicity [see Warnings and Precautions ( 5.4 )] Most common adverse reactions are: Ulcerative colitis (≥2%) : Induction : upper respiratory tract infections and arthralgia. ( 6.1 ) Maintenance: upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection. ( 6.1 ) Crohn's disease (≥5%) : upper respiratory tract infections, injection site reactions, headache, arthralgia, and elevated liver tests ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) 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. Ulcerative Colitis OMVOH was studied up to 12 weeks in subjects with moderately to severely active ulcerative colitis in a randomized, double-blind, placebo-controlled induction study (UC-1). In subjects who responded to induction therapy in UC-1, long term safety up to 52 weeks was evaluated in a randomized, double-blind, placebo-controlled maintenance study (UC-2) and a long-term extension study [see Clinical Studies ( 14.1 )] . In the induction study (UC-1), 1279 subjects were enrolled of whom 958 received OMVOH 300 mg administered as an intravenous infusion at Weeks 0, 4, and 8. In the maintenance study (UC-2), 581 subjects were enrolled of whom 389 received OMVOH 200 mg administered as a subcutaneous injection every 4 weeks. Table 2 summarizes the adverse reactions reported in at least 2% of subjects and at a higher frequency than placebo during UC-1. Table 2: Adverse Reactions a in Subjects with Ulcerative Colitis through Week 12 in a Placebo-Controlled Induction Study (UC-1) a Reported in at least 2% of subjects and at a higher frequency than placebo. b OMVOH 300 mg as an intravenous infusion at Weeks 0, 4, and 8. c Upper respiratory tract infections includes related terms (e.g., COVID-19, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection). Adverse Reactions OMVOH 300 mg Intravenous Infusion b N=958 n (%) Placebo N=321 n (%) Upper respiratory tract infections c 72 (8%) 20 (6%) Arthralgia 20 (2%) 4 (1%) In the induction study (UC-1), infusion-related hypersensitivity reactions were reported by 4 (0.4%) subjects treated with OMVOH and 1 (0.3%) subject treated with placebo. Table 3 summarizes the adverse reactions reported in at least 2% of subjects and at a higher frequency than placebo during the 40-week controlled period of UC-2. Table 3: Adverse Reactions a in Subjects with Ulcerative Colitis through Week 40 In a Placebo-Controlled Maintenance Study (UC-2) a Reported in at least 2% of subjects and at a higher frequency than placebo b OMVOH 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter for up to an additional 40 weeks. c Upper respiratory tract infections includes related terms (e.g., COVID-19, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection). d Injection site reactions includes related terms (e.g., erythema, hypersensitivity, pain, reaction, and urticaria at the injection site). e Rash is composed of several similar terms. f Herpes viral infection includes related terms (e.g., herpes zoster, herpes simplex, and oral herpes). Adverse Reactions OMVOH 200 mg Subcutaneous Injection b N=389 n (%) Placebo N=192 n (%) Upper respiratory tract infections c 53 (14%) 23 (12%) Injection site reactions d 34 (9%) 8 (4%) Arthralgia 26 (7%) 8 (4%) Rash e 16 (4%) 2 (1%) Headache 16 (4%) 2 (1%) Herpes viral infection f 9 (2%) 1 (1%) Infections In UC-1 through Week 12, infections were reported by 145 (15%) subjects treated with OMVOH 300 mg and 45 (14%) subjects treated with placebo. Serious infections were reported by less than 1% in both groups. Serious infections in the OMVOH group included intestinal sepsis, listeria sepsis, and pneumonia. In the maintenance study (UC-2) through Week 40 (a total of 52 weeks of treatment), infections were reported by 93 (24%) subjects treated with OMVOH 200 mg and 44 (23%) subjects treated with placebo. A case of COVID-19 pneumonia was reported as a serious infection in the OMVOH group. Hepatic Enzyme Elevations In UC-1 through Week 12, alanine aminotransferase (ALT) ≥5X ULN was reported by 1 (0.1%) subject treated with OMVOH 300 mg and 1 (0.3%) subject treated with placebo. Aspartate aminotransferase (AST) ≥5X ULN was reported by 2 (0.2%) subjects treated with OMVOH 300 mg and no subject treated with placebo. These elevations have been noted with and without concomitant elevations in total bilirubin. In UC-2 through Week 40 (a total of 52 weeks of treatment), 3 (0.8%) subjects treated with OMVOH 200 mg reported ALT ≥5X ULN and 3 (0.8%) subjects reported AST ≥5X ULN; with or without concomitant elevations in total bilirubin. No subjects treated with placebo experienced similar elevations [see Warnings and Precautions ( 5.4 )] . Crohn's Disease OMVOH was studied up to 52 weeks in subjects with moderately to severely active Crohn's disease in a randomized, double-blind, placebo-controlled study (CD-1). The safety population consisted of 630 subjects who received OMVOH 900 mg administered as an intravenous infusion during induction at Weeks 0, 4, and 8 followed by OMVOH 300 mg administered as a subcutaneous injection every 4 weeks and 211 subjects who received placebo [see Clinical Trials ( 14.2 )] . Eighty-five of the 211 placebo subjects in the safety population who did not achieve clinical response by patient-reported outcome at Week 12 were switched to blinded induction and maintenance treatment with OMVOH. Observed data from these 85 subjects are included in the placebo cohort up to Week 12 and in the OMVOH cohort after Week 12. In CD-1, OMVOH and placebo-treated subjects had different lengths of exposure, therefore, exposure adjusted incidence rates (EAIRs) are also displayed in Table 4 to compare adverse reactions. Common Adverse Reactions Table 4 summarizes the frequencies and EAIRs per 100 person-years (PY) for adverse reactions reported in at least 5% of subjects treated with OMVOH and at a higher frequency than placebo during CD-1. Table 4: Adverse Reactions a in Subjects with Crohn's Disease through Week 52 In a Placebo-Controlled Study (CD-1) Abbreviations: EAIR, exposure-adjusted incidence rate; PY, person-years a Reported in at least 5% of subjects and at a higher frequency than placebo b Following OMVOH 900 mg as an intravenous infusion at Week 0, Week 4, and Week 8, subjects received OMVOH 300 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter for up to an additional 40 weeks. In addition, eighty-five placebo subjects who did not achieve clinical response by patient-reported outcome at Week 12 were switched to blinded induction and maintenance treatment with OMVOH. The observed data after Week 12 from these eighty-five subjects were included in the OMVOH cohort. c EAIRs are per 100 PY. The EAIR per 100 PY can be interpreted as an estimated number of first occurrences of the adverse reaction of interest if 100 subjects were treated for one year. d Upper respiratory tract infections includes related terms (e.g., COVID-19, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection). e Injection site reactions includes related terms (e.g., erythema, hematoma, induration, pain, pruritus, and reaction at the injection site). f Headache includes related terms (i.e., headache and migraine). g Elevated liver tests include related terms (e.g., ALT increased, AST increased, alkaline phosphatase increased, bilirubin increased, and GGT increased) Adverse Reactions OMVOH b N=715, PY=655 n (%) [EAIR c ] Placebo N=211, PY=120 n (%) [EAIR c ] Upper respiratory tract infections d 199 (28) [37] 47 (22) [47] Injection site reactions e 69 (10) [11] 8 (4) [7] Headache f 45 (6) [7] 9 (4) [8] Arthralgia 44 (6) [7] 11 (5) [10] Elevated liver tests g 36 (5) [6] 8 (4) [7] Hepatic Enzyme Elevations Of the subjects with reported adverse reactions of elevated liver tests ( see Table 4 ), 3 subjects treated with OMVOH reported ALT ≥5X ULN and 2 subjects reported AST ≥5X ULN. Neither subject had a concomitant elevation in total bilirubin. No subjects treated with placebo experienced similar elevations. Less Common Adverse Reactions (<5%) In CD-1 through Week 52, urticaria was reported by 13 (2%, 2 per 100 PY) subjects treated with OMVOH and no subjects treated with placebo. Infections In CD-1 through Week 52, infections were reported by 282 (39%, 58 per 100 PY) subjects treated with OMVOH and 73 (35%, 81 per 100 PY) subjects treated with placebo. Serious infections in the OMVOH group included abscess (including abdominal abscess, anal abscess, gluteal abscess, and perineal abscess), cellulitis, pneumonia, and sepsis.

<table ID="t2" width="100%"><caption>Table 2: Adverse Reactions^a in Subjects with Ulcerative Colitis through Week 12 in a Placebo-Controlled Induction Study (UC-1) </caption><col width="33.333%" align="left"/><col width="33.400%" align="left"/><col width="33.267%" align="left"/><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^a Reported in at least 2% of subjects and at a higher frequency than placebo. </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^b OMVOH 300 mg as an intravenous infusion at Weeks 0, 4, and 8. </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^c Upper respiratory tract infections includes related terms (e.g., COVID-19, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection). </paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="middle" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Adverse Reactions</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">OMVOH</content> <content styleCode="bold">300 mg Intravenous Infusion</content><content styleCode="bold">^b</content> <content styleCode="bold">N=958</content> <content styleCode="bold">n (%)</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Placebo</content> <content styleCode="bold">N=321</content> <content styleCode="bold">n (%)</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Upper respiratory tract infections^c</td><td align="center" valign="top" styleCode="Botrule Rrule">72 (8%) </td><td align="center" valign="top" styleCode="Botrule Rrule">20 (6%) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Arthralgia </td><td align="center" valign="top" styleCode="Botrule Rrule">20 (2%) </td><td align="center" valign="top" styleCode="Botrule Rrule">4 (1%) </td></tr></tbody></table>

<table ID="t3" width="100%"><caption>Table 3: Adverse Reactions^a in Subjects with Ulcerative Colitis through Week 40 In a Placebo-Controlled Maintenance Study (UC-2) </caption><col width="33.333%" align="left"/><col width="33.400%" align="left"/><col width="33.267%" align="left"/><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^a Reported in at least 2% of subjects and at a higher frequency than placebo </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^b OMVOH 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter for up to an additional 40 weeks. </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^c Upper respiratory tract infections includes related terms (e.g., COVID-19, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection). </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^d Injection site reactions includes related terms (e.g., erythema, hypersensitivity, pain, reaction, and urticaria at the injection site). </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^e Rash is composed of several similar terms. </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^f Herpes viral infection includes related terms (e.g., herpes zoster, herpes simplex, and oral herpes). </paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="middle" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Adverse Reactions</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">OMVOH</content> <content styleCode="bold">200 mg Subcutaneous Injection</content><content styleCode="bold">^b</content> <content styleCode="bold">N=389</content> <content styleCode="bold">n (%)</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Placebo</content> <content styleCode="bold">N=192</content> <content styleCode="bold">n (%)</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Upper respiratory tract infections^c</td><td align="center" valign="top" styleCode="Botrule Rrule">53 (14%) </td><td align="center" valign="top" styleCode="Botrule Rrule">23 (12%) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Injection site reactions^d</td><td align="center" valign="top" styleCode="Botrule Rrule">34 (9%) </td><td align="center" valign="top" styleCode="Botrule Rrule">8 (4%) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Arthralgia </td><td align="center" valign="top" styleCode="Botrule Rrule">26 (7%) </td><td align="center" valign="top" styleCode="Botrule Rrule">8 (4%) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Rash^e</td><td align="center" valign="top" styleCode="Botrule Rrule">16 (4%) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (1%) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Headache </td><td align="center" valign="top" styleCode="Botrule Rrule">16 (4%) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (1%) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Herpes viral infection^f</td><td align="center" valign="top" styleCode="Botrule Rrule">9 (2%) </td><td align="center" valign="top" styleCode="Botrule Rrule">1 (1%) </td></tr></tbody></table>

<table ID="t4" width="100%"><caption>Table 4: Adverse Reactions^a in Subjects with Crohn&apos;s Disease through Week 52 In a Placebo-Controlled Study (CD-1) </caption><col width="30.157%" align="left"/><col width="29.424%" align="left"/><col width="40.420%" align="left"/><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">Abbreviations: EAIR, exposure-adjusted incidence rate; PY, person-years </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^a Reported in at least 5% of subjects and at a higher frequency than placebo </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^b Following OMVOH 900 mg as an intravenous infusion at Week 0, Week 4, and Week 8, subjects received OMVOH 300 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter for up to an additional 40 weeks. In addition, eighty-five placebo subjects who did not achieve clinical response by patient-reported outcome at Week 12 were switched to blinded induction and maintenance treatment with OMVOH. The observed data after Week 12 from these eighty-five subjects were included in the OMVOH cohort. </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^c EAIRs are per 100 PY. The EAIR per 100 PY can be interpreted as an estimated number of first occurrences of the adverse reaction of interest if 100 subjects were treated for one year. </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^d Upper respiratory tract infections includes related terms (e.g., COVID-19, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection). </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^e Injection site reactions includes related terms (e.g., erythema, hematoma, induration, pain, pruritus, and reaction at the injection site). </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^f Headache includes related terms (i.e., headache and migraine). </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^g Elevated liver tests include related terms (e.g., ALT increased, AST increased, alkaline phosphatase increased, bilirubin increased, and GGT increased) </paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="middle" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Adverse Reactions</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">OMVOH</content><content styleCode="bold">^b</content> <content styleCode="bold">N=715, PY=655</content> <content styleCode="bold">n (%) [EAIR</content><content styleCode="bold">^c</content><content styleCode="bold">]</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Placebo</content> <content styleCode="bold">N=211, PY=120</content> <content styleCode="bold">n (%) [EAIR</content><content styleCode="bold">^c</content><content styleCode="bold">]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Upper respiratory tract infections^d</td><td align="center" valign="top" styleCode="Botrule Rrule">199 (28) [37] </td><td align="center" valign="top" styleCode="Botrule Rrule">47 (22) [47] </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Injection site reactions^e</td><td align="center" valign="top" styleCode="Botrule Rrule">69 (10) [11] </td><td align="center" valign="top" styleCode="Botrule Rrule">8 (4) [7] </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Headache^f</td><td align="center" valign="top" styleCode="Botrule Rrule">45 (6) [7] </td><td align="center" valign="top" styleCode="Botrule Rrule">9 (4) [8] </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Arthralgia </td><td align="center" valign="top" styleCode="Botrule Rrule">44 (6) [7] </td><td align="center" valign="top" styleCode="Botrule Rrule">11 (5) [10] </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Elevated liver tests^g</td><td align="center" valign="top" styleCode="Botrule Rrule">36 (5) [6] </td><td align="center" valign="top" styleCode="Botrule Rrule">8 (4) [7] </td></tr></tbody></table>