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Omvoh ™ (mirikizumab-mrkz) injection
300 mg/15 mL, 100 mg/mL
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What were the results of the phase 3 clinical trials of Omvoh™ (mirikizumab-mrkz) for the treatment of ulcerative colitis in adults?
In LUCENT-1, mirikizumab met all primary and key secondary endpoints. In LUCENT-2, the primary and all secondary endpoints were met in patients who responded to mirikizumab induction therapy and received maintenance treatment with mirikizumab.
Phase 3 Studies of Mirikizumab in Patients With Ulcerative Colitis
Phase 3 Clinical Trial Program of Mirikizumab for the Treatment of Ulcerative Colitis
The safety and efficacy of mirikizumab in adult patients with moderately to severely active ulcerative colitis (UC) are being evaluated in the phase 3 studies LUCENT-1, LUCENT-2, and LUCENT-3.1
LUCENT-1
Study Design
LUCENT-1 is a 12-week, phase 3, multicenter, randomized, double-blind, parallel-arm, placebo-controlled study of mirikizumab, a p19-directed anti-interleukin-23 (anti-IL-23) antibody. The study was conducted to evaluate efficacy and safety in adult patients with moderately to severely active UC, with a modified Mayo score of 4 to 9 points and centrally read Mayo endoscopic subscore ≥2, who had an inadequate response, loss of response, or an intolerance to corticosteroids, immunosuppressants, biologic therapies, or tofacitinib.2
A total of 1281 patients were randomized in a 3:1 ratio to receive intravenous (IV) mirikizumab 300 mg or placebo every 4 weeks. Randomization was stratified by
- biologic or tofacitinib failure status
- baseline corticosteroid use
- baseline disease activity as measured by the modified Mayo score, and
- world region.2
Outcomes
The primary outcome was the proportion of patients in each treatment group who achieved clinical remission at week 12, defined as
- stool frequency subscore of 0 or 1 with ≥1-point decrease from baseline
- rectal bleeding subscore of 0, and
- endoscopic subscore of 0 or 1 excluding friability.2
Outcome |
Definition |
Alternate clinical remission |
|
Clinical response |
|
Endoscopic remission |
|
Symptomatic remission |
|
Clinical response in biologic or tofacitinib-failed patients |
|
HEMI |
|
Improvement in bowel urgency |
|
Abbreviations: HEMI = histologic-endoscopic mucosal improvement; NRS = numeric rating scale.
aAn 11-point scale that patients used to describe the severity of their daily bowel urgency (range, 0 [no urgency] to 10 [worst possible urgency), at weeks 4 and 12 in those with urgency at baseline.
Baseline Characteristics
Baseline demographics and disease characteristics were similar across treatment groups ().2
Parametera |
MIRI 300 mg |
PBO |
Age, mean years (SD) |
42.9 (13.9) |
41.3 (13.8) |
Male |
530 (61.1) |
165 (56.1) |
BMI categoryb |
||
≥18.5 to <25 kg/m2 |
451 (52.0) |
149 (50.7) |
≥25 kg/m2 |
362 (41.7) |
117 (39.8) |
Disease duration, mean years (SD) |
7.2 (6.7) |
6.9 (7.0) |
Disease extent |
||
Left-sided colitis |
544 (62.7) |
188 (64.2) |
Modified Mayo scorec category |
||
Moderate (4-6) |
404 (46.5) |
138 (47.1) |
Severe (7-9) |
463 (53.3) |
155 (52.9) |
Mayo endoscopic subscore of 3 (severe disease) |
574 (66.1) |
200 (68.3) |
Bowel urgency severity,d median (Q1, Q3) |
6.0 (5.0, 8.0) |
7.0 (5.0, 8.0) |
Fecal calprotectin, median μg/g (Q1, Q3) |
1559.0 (634.0, 3210.0) |
1471.5 (626.5, 2944.5) |
C-reactive protein, median mg/L (Q1, Q3) |
4.1 (1.5, 9.6) |
4.2 (1.2, 9.5) |
Abbreviations: BMI = body mass index; eCOA = electronic clinical outcome assessment; MIRI = mirikizumab; NRS = numeric rating scale; PBO = placebo; Q = quartile.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the eCOA transcription error in Poland and Turkey.
aData presented as n (%) unless otherwise specified.
bA total of 28 patients (9.5%) in the placebo group and 55 (6.3%) in the mirikizumab group had a BMI indicating underweight (<18.5).
cThe modified Mayo score is a sum of the Mayo stool frequency, rectal bleeding subscore, and endoscopic subscore, giving a maximum modified Mayo score of 9.
dThe urgency NRS is a patient-reported measure of the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency).
Parametera |
MIRI 300 mg |
PBO |
Prior UC treatment |
||
Failed treatment with a biologic or tofacitinib |
361 (41.6) |
118 (40.1) |
Failed TNF inhibitor treatment |
325 (37.4) |
97 (33.0) |
Failed vedolizumab treatment |
159 (18.3) |
59 (20.1) |
Failed tofacitinib treatment |
34 (3.9) |
6 (2.0) |
Number of failed biologic or tofacitinib therapies |
||
0 |
507 (58.4) |
176 (59.9) |
1 |
180 (20.7) |
65 (22.1) |
≥2 |
181 (20.9) |
53 (18.0) |
UC therapy at baseline |
||
Corticosteroids |
351 (40.4) |
113 (38.4) |
Immunomodulators |
211 (24.3) |
69 (23.5) |
Aminosalicylates |
646 (74.4) |
217 (73.8) |
Abbreviations: eCOA = electronic clinical outcome assessment; MIRI = mirikizumab; PBO = placebo; TNF = tumor necrosis factor; UC = ulcerative colitis.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the eCOA transcription error in Poland and Turkey.
aData are presented as n (%).
Efficacy Results
Clinical Remission
Clinical remission at week 12 was achieved by
- 24.2% of patients who received mirikizumab, and
- 13.3% of patients who received placebo (p<.001, ).2
Among subgroups of patients who were biologic-naïve, clinical remission at week 12 was achieved by
- 30.9% of patients who received mirikizumab, and
- 15.8% of patients who received placebo (p<.001, ).2
Among subgroups of patients who had previously failed a biologic or tofacitinib, clinical remission at week 12 was achieved by
- 15.2% of patients who received mirikizumab, and
- 8.5% of patients who received placebo ().2
Secondary Outcomes
Alternative Clinical Remission
Alternative clinical remission at week 12 was achieved by
- 25.6% of patients who received mirikizumab, and
- 14.6% of patients who received placebo (p<.001).2
Clinical Response
Compared with placebo, a significantly greater proportion of patients who received mirikizumab achieved clinical response at week 12 (p<.00001, ).3
Among subgroups of patients who were biologic-naïve, clinical response at week 12 was achieved by
- 70.1% of patients who received mirikizumab, and
- 50.3% of patients who received placebo (p<.001, ).3
Among subgroups of patients who had previously failed a biologic or tofacitinib, clinical response at week 12 was achieved by
- 54.6% of patients who received mirikizumab, and
- 29.7% of patients who received placebo (p<.001, ).3
Endoscopic and Histologic Endpoints
Symptomatic Endpoints
Compared with placebo, a significantly greater proportion of patients who received mirikizumab reached symptomatic remission as early as week 4 and at each week thereafter through week 12 (p<.001 for each timepoint, ).3
The least-squares mean change from baseline in bowel urgency numeric rating scale was significantly greater in the mirikizumab group than in the placebo group at weeks 4 (p<.001), 8 (p<.00001), and 12 (p<.00001, ).3
Efficacy Results by Biologic Status
Efficacy results stratified by prior biologic or tofacitinib status for clinical remission and clinical response can be found in and , respectively. Additional results can be found in .
Parametersa |
Biologic or tofacitinib-failure |
Biologic and tofacitinib-naïve |
||
MIRI 300 mg IV |
PBO |
MIRI 300 mg IV |
PBO |
|
Alternate clinical remission |
59 (16.3) |
10 (8.5) |
160 (32.5) |
31 (18.1) |
Endoscopic remission |
85 (23.5) |
12 (10.2) |
226 (45.9) |
48 (28.1) |
HEMI |
56 (15.5) |
8 (6.8) |
176 (35.8) |
32 (18.7) |
Symptomatic remission |
139 (38.5) |
22 (18.6) |
248 (50.4) |
57 (33.3) |
Urgency NRS ΔBL, LSM (SE) |
-2.5 (0.13) |
-1.0 (0.23) |
-2.7 (0.10) |
-2.1 (0.17) |
Abbreviations: BL = baseline; HEMI = histologic-endoscopic mucosal improvement; IV = intravenous; LSM = least squares mean; MIRI = mirikizumab; NRS = numeric rating scale; PBO = placebo; UC = ulcerative colitis.
Note: A small group of patients were exposed, but not failed, to biologics or tofacitinib (LUCENT-1: PBO n=5, MIRI n=15).
aData presented as n (%).
Safety Results
The frequencies of treatment-emergent adverse events (TEAEs) were similar among patients who received mirikizumab (44.5%) and patients who received placebo (46.1%). A fewer percentage of patients who received mirikizumab than those who received placebo experienced serious adverse events (AEs) or discontinued from the study due to AEs. lists additional safety data.2
Parametersa |
MIRI 300 mg IV |
PBO |
TEAEs |
426 (44.5) |
148 (46.1) |
SAEs |
27 (2.8) |
17 (5.3) |
Discontinuations due to AE |
15 (1.6) |
23 (7.2) |
Death |
0b |
0 |
TEAEs occurring in ≥3% of patients in any treatment group |
||
Nasopharyngitis |
39 (4.1) |
10 (3.1) |
Arthralgia |
20 (2.1) |
4 (1.2) |
UC |
17 (1.8) |
24 (7.5) |
Anemia |
32 (3.3) |
19 (5.9) |
Headache |
32 (3.3) |
9 (2.8) |
Rash |
5 (0.5) |
2 (0.6) |
Pyrexia |
14 (1.5) |
3 (0.9) |
AEs of special interest |
||
All infections |
145 (15.1) |
45 (14.0) |
Serious infections |
7 (0.7) |
2 (0.6) |
Opportunistic infectionsc |
5 (0.5)d |
1 (0.3)e |
Cerebrocardiovascular eventsf |
1 (0.1) |
2 (0.6) |
Malignancies |
2 (0.2)g |
0 |
Depressionh |
4 (0.4) |
2 (0.6) |
Suicide/self-injuryi |
0 |
0 |
Hepatic |
15 (1.6) |
5 (1.6) |
Immediate hypersensitivitiesj |
10 (1.0) |
1 (0.3) |
Infusion reactions |
4 (0.4) |
1 (0.3) |
Abbreviations: AE = adverse event; IV = intravenous; MedDRA = Medical Dictionary for Regulatory Activities; MIRI = mirikizumab; PBO = placebo; SAE = serious adverse event; SMQ = standardized MedDRA query; TEAE = treatment-emergent adverse event; UC = ulcerative colitis.
Note: Includes the safety population which is composed of all assigned/randomized patients who received any amount of study treatment.
aData are presented as n (%).
bThere were 2 deaths during the induction follow-up period. One death was due to sudden cardiac arrest, and the other was from disseminated intravascular coagulation.
cSpecific MedDRA terms were used to identify infections considered to be opportunistic infections based on Winthrop et al. (2015).
dFor the induction period, 1 esophageal candidiasis, 2 cytomegalovirus colitis, 1 herpes zoster, and 1 intestinal tuberculosis were reported in the MIRI group; cytomegalovirus was severe in one patient. Other opportunistic infections during induction were mild to moderate, and none resulted in discontinuation of MIRI.
eFor the induction period, 1 herpes zoster was reported in the PBO group.
fThere were no reports of major adverse cardiac events in either arm.
gBoth were colon adenocarcinomas. One additional adenocarcinoma in LUCENT-1 was discovered in the post-treatment follow-up period after induction and is not included in the table.
hExcluding suicide or self-injury.
iNo instance of attempted suicide or self-injury in the induction period.
jOccurring within 24 hours of drug administration, or on the day of drug administration when time is missing. No serious hypersensitivity or anaphylactic reactions occurred during induction period. “Hypersensitivity reaction” was used as an overarching term to describe systemic events that likely had an allergic or hypersensitivity etiology - analyses for both time periods were based on narrow terms using the following SMQs: anaphylactic reaction, hypersensitivity, and angioedema.
LUCENT-2
LUCENT-2 is a 40-week, phase 3, multicenter, randomized, double-blind, parallel-arm, placebo-controlled, maintenance study that evaluated the safety and efficacy of mirikizumab, a p19-directed anti-IL-23 antibody, conducted in adult patients with moderately to severely active UC who completed the LUCENT-1 study.2
Mirikizumab Responders From LUCENT-1
Treatment Assignment
A total of 544 patients who received mirikizumab in LUCENT-1 and achieved a clinical response were rerandomized in a 2:1 ratio to receive subcutaneous mirikizumab 200 mg or placebo every 4 weeks for 40 weeks. Randomization was stratified by
- biologic or tofacitinib failure status
- induction remission status
- baseline corticosteroid use, and
- geographic region (North America/Europe/other).2
Outcomes
The primary outcome was the achievement of clinical remission at week 40 among patients who achieved clinical response with mirikizumab during the 12-week induction period.2
Key secondary objectives were multiplicity controlled and definitions can be found in .2
Outcomes |
Definition |
Alternate clinical remission |
|
Endoscopic remission |
|
Corticosteroid-free remission |
|
HEMR |
|
Improvement in bowel urgency |
|
Bowel urgency remission |
|
Maintenance of clinical remission |
|
Abbreviations: HEMR = histologic-endoscopic mucosal remission; NRS = numeric rating scale.
aDefined as stool frequency subscore of 0, or stool frequency subscore of 1 with ≥1-point decrease from baseline and rectal bleeding subscore of 0.
bAn 11-point scale that patients used to describe the severity of their daily bowel urgency (range, 0 [no urgency] to 10 [worst possible urgency), at weeks 4 and 12 in those with urgency at baseline.
Baseline Characteristics
Baseline demographics and disease characteristics were similar across treatment groups ().2
Parameterb |
MIRI Induction Respondersc |
|
MIRI 200 mg SC |
PBO SC |
|
Age, mean years (SD) |
43.4 (14.2) |
41.2 (12.8) |
Male |
214 (58.6) |
104 (58.1) |
BMI category |
||
≥18.5 to <25 kg/m2 |
196 (53.7) |
97 (54.2) |
≥25 kg/m2 |
143 (39.2) |
74 (41.3) |
Disease duration, mean years (SD) |
6.9 (7.1) |
6.7 (5.6) |
Disease extent |
||
Left-sided colitis |
234 (64.1) |
119 (66.5) |
Modified Mayo score category |
||
Moderate (4-6) |
181 (49.6) |
77 (43.0) |
Severe (7-9) |
184 (50.4) |
102 (57.0) |
Mayo endoscopic subscore of 3 (severe disease) |
235 (64.4) |
106 (59.2) |
Bowel urgencyd severity, mean (SD) |
6.0 (2.2) |
6.2 (1.9) |
Fecal calprotectin, median μg/g (Q1, Q3) |
1482.0 (558.0, 3045.0) |
1750.0 (754.0, 3519.0) |
C-reactive protein, median mg/L (Q1, Q3) |
3.8 (1.4, 8.7) |
3.0 (1.0, 7.7) |
Abbreviations: BMI = body mass index; eCOA = electronic clinical outcome assessment; MIRI = mirikizumab; NRS = numeric rating scale; PBO = placebo; Q = quartile; SC = subcutaneous.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the eCOA transcription error in Poland and Turkey.
aRefers to induction baseline (week 0 of LUCENT-1).
bData presented as n (%) unless otherwise specified.
cDefined as patients who received 12-week mirikizumab induction therapy and achieved 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the rectal bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
dThe Urgency NRS is a patient-reported measure of the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency).
Baseline corticosteroid use was reported by 37% of patients who were rerandomized to mirikizumab and 38% of patients who were rerandomized to placebo in LUCENT-2.2
Prior biologic failure was reported by 35.1% of patients who were rerandomized to mirikizumab and 35.8% of patients who were rerandomized to placebo in LUCENT-2.2
lists baseline and prior UC therapy of mirikizumab induction responders in the LUCENT-2 clinical trial.
Parameterb |
MIRI Induction Respondersc |
|
MIRI 200 mg SC |
PBO SC |
|
Prior UC treatment |
||
Failed treatment with a biologic or tofacitinib |
128 (35.1) |
64 (35.8) |
Failed TNF inhibitor treatment |
112 (30.7) |
58 (32.4) |
Failed vedolizumab treatment |
47 (12.9) |
23 (12.8) |
Failed tofacitinib treatment |
8 (2.2) |
8 (4.5) |
Number of failed biologic or tofacitinib therapies |
||
0 |
237 (64.9) |
115 (64.2) |
1 |
77 (21.1) |
35 (19.6) |
≥2 |
51 (14.0) |
29 (16.2) |
UC therapy at baseline |
||
Corticosteroids |
135 (37.0) |
68 (38.0) |
Immunomodulators |
78 (21.4) |
39 (21.8) |
Aminosalicylates |
278 (76.2) |
134 (74.9) |
Abbreviations: eCOA = electronic clinical outcome assessment; MIRI = mirikizumab; PBO = placebo; SC = subcutaneous; TNF = tumor necrosis factor; UC = ulcerative colitis.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the eCOA transcription error in Poland and Turkey.
aRefers to induction baseline (week 0 of LUCENT-1).
bData presented as n (%).
cDefined as patients who received 12-week mirikizumab induction therapy and achieved 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the rectal bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
Efficacy Results
Clinical Remission
Clinical remission at week 40 was achieved by
- 49.9% of patients who were rerandomized to mirikizumab, and
- 25.1% of patients who were rerandomized to placebo (p<.001, ).2
Of the patients who received mirikizumab during the induction and maintenance treatment period and achieved clinical remission at the end of week 52 of LUCENT-2, 97.8% of those patients were corticosteroid-free.2
Secondary Outcomes
Alternate clinical remission at week 40 was achieved by
- 54.9% of patients who were rerandomized to mirikizumab, and
- 27.0% of patients who were rerandomized to placebo (p<.001).2
In addition, patients who received mirikizumab achieved all other key secondary endpoints at week 40 (p<.001, ).2
Parametersb |
MIRI Induction Respondersc |
|
MIRI 200 mg SC (N=365) |
PBO SC (N=179) |
|
Clinical remissiond |
182 (49.9)e |
45 (25.1) |
Common risk differencef for MIRI vs placebo (95% CI) |
23.2 (15.2, 31.2) |
|
Corticosteroid-free clinical remissiong |
164 (44.9)e |
39 (21.8) |
Common risk difference for MIRI vs placebo (95% CI) |
21.3 (13.5, 29.1) |
|
Endoscopic remissionh |
214 (58.6)e |
52 (29.1) |
Common risk difference for MIRI vs placebo (95% CI) |
28.5 (20.2, 36.8) |
|
HEMRi |
158 (43.3)e |
39 (21.8) |
Common risk difference for MIRI vs placebo (95% CI) |
19.9 (12.1, 27.6) |
|
Bowel urgency improvement, LSM (SE)j |
-3.80 (0.14)e |
-2.74 (0.20) |
LSM difference for MIRI vs placebo (SE) |
-1.06 (0.23) |
|
Bowel urgency remission, n/N (%)k |
144/336 (42.9)e |
43/172 (25.0) |
Common risk difference for MIRI vs placebo (95% CI) |
18.1 (9.8, 26.4) |
|
Maintenance of clinical remission, n/N (%)l |
91/143 (63.6)e |
24/65 (36.9) |
Common risk difference for MIRI vs placebo (95% CI) |
24.8 (10.4, 39.2) |
Abbreviations: eCOA = electronic clinical outcome assessment; HEMR = histologic-endoscopic mucosal remission; LSM = least squares mean; MIRI = mirikizumab; mITT = modified intent-to-treat; NRS = numeric rating scale; PBO = placebo; SC = subcutaneous; UC = ulcerative colitis.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the eCOA transcription error in Poland and Turkey.
aThe mITT population comprised all assigned/randomized patients who received any amount of study treatment excluding patients impacted by the eCOA transcription error in Poland and Turkey.
bData presented as n (%) unless otherwise specified.
cDefined as patients who received 12-week mirikizumab induction therapy and achieved 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the rectal bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
dDefined as 1) stool frequency=0 or SF=1 with a ≥1-point decrease from baseline, 2) rectal bleeding=0, and 3) endoscopic subscore=0 or 1 (excluding friability).
ep<.001 vs placebo.
fThe common risk difference is the difference in proportions adjusted for the stratification factors (biologic failure status, baseline corticosteroid use, geographic region, and induction remission status).
gDefined as 1) clinical remission at week 40, 2) symptomatic remission at week 28, and 3) no corticosteroid use for ≥12 weeks prior to week 40.
hDefined as endoscopic subscore=0 or 1 (excluding friability).
iHistologic remission with absence of mucosal neutrophils, defined using the Geboes scoring system with subscores of 0 for grades: 2b (lamina propria neutrophils); 3 (neutrophils in epithelium); 4 (crypt destruction); 5 (erosion or ulceration), and endoscopic remission.
jChange from induction baseline in Urgency NRS. The Urgency NRS is a patient-reported measure of the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency).
kDefined as Urgency NRS=0 or 1 among patients induced into clinical response with mirikizumab in LUCENT-1 and had Urgency NRS ≥3 at induction baseline.
lDefined as clinical remission at week 40 among patients induced into clinical remission with mirikizumab in LUCENT-1.
Efficacy Results by Biologic Status
The proportion of patients who achieved clinical remission and endoscopic remission at the end of the 40-week maintenance period of LUCENT-2 was significantly greater in the mirikizumab group than in the placebo group regardless of prior biologic or tofacitinib use or failure (p<.001, ).2
Parametersa |
MIRI Induction Respondersb |
|||
Biologic or tofacitinib-failure |
Biologic and tofacitinib-naïve |
|||
MIRI 200 mg SC |
PBO |
MIRI 200 mg SC |
PBO |
|
Clinical remission |
59 (46.1) |
10 (15.6) |
118 (51.5) |
35 (30.7) |
Alternate clinical remission |
60 (46.9) |
10 (15.6) |
124 (54.1) |
37 (32.5) |
CS-free clinical remission |
52 (40.6) |
9 (14.1) |
107 (46.7) |
30 (26.3) |
Maintenance of clinical remission, n/Nc (%) |
24/36 (66.7) |
2/18 (11.1) |
65/104 (62.5) |
22/47 (46.8) |
Endoscopic remission |
65 (50.8) |
13 (20.3) |
143 (62.4) |
39 (34.2) |
Clinical response |
91 (71.1) |
26 (40.6) |
194 (84.7) |
62 (54.4) |
HEMR |
46 (35.9) |
9 (14.1) |
108 (47.2) |
30 (26.3) |
Bowel urgency remission, n/Nd (%) |
43/122 (35.2) |
12/63 (19.0) |
96/206 (46.6) |
31/108 (28.7) |
Abbreviations: CS = corticosteroid; HEMR = histologic-endoscopic mucosal remission; MIRI = mirikizumab; PBO = placebo; SC = subcutaneous; UC = ulcerative colitis.
Note: A small group of patients were exposed, but not failed, to biologics or tofacitinib (LUCENT-1: PBO n=5, MIRI n=15; LUCENT-2: PBO n=0, MIRI n=3).
aData presented as n (%) unless otherwise specified.
bDefined as patients who received 12-week mirikizumab induction therapy and achieved 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the rectal bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
cDenominator is patients who achieved clinical remission at week 12 of LUCENT-1.
dDenominator is patients who had urgency numeric rating scale ≥3 at induction baseline.
Safety Results
The frequency of TEAEs was similar between patients who received mirikizumab and patients who received placebo. In addition, the percentage of patients who received mirikizumab and experienced a serious AE or discontinued from the study due to an AE was less than the percentage of patients who received placebo. See for additional safety data.2
Parametersa |
MIRI Induction Respondersb |
|
MIRI 200 mg SC |
PBO SC |
|
TEAE |
251 (64.5) |
132 (68.8) |
SAE |
13 (3.3) |
15 (7.8) |
Most commonly reported TEAEsc |
||
Nasopharyngitis |
28 (7.2) |
11 (5.7) |
Arthralgia |
26 (6.7) |
8 (4.2) |
UC |
26 (6.7) |
40 (20.8) |
Injection site pain |
17 (4.4) |
6 (3.1) |
Headache |
16 (4.1) |
2 (1.0) |
Rash |
14 (3.6) |
0 |
Pyrexia |
13 (3.3) |
5 (2.6) |
Anemia |
8 (2.1) |
9 (4.7) |
AEs of special interest |
||
All infections |
93 (23.9) |
44 (22.9) |
Serious infections |
3 (0.8) |
3 (1.6) |
Opportunistic infectionsd |
5 (1.3)e |
0 |
Cerebrocardiovascular events |
0 |
1 (0.5)f |
Malignancies |
1 (0.3)g |
1 (0.5)h |
Depressioni |
4 (1.0) |
0 |
Suicide/self-injury |
1 (0.3)j |
0 |
Hepatic |
12 (3.1) |
4 (2.1) |
Immediate hypersensitivitiesk |
7 (1.8) |
2 (1.0) |
Injection site reactions |
34 (8.7) |
8 (4.2) |
Death |
0 |
1 (0.5)l |
Discontinuation due to AE |
6 (1.5) |
16 (8.3) |
Abbreviations: AE = adverse event; COVID-19 = coronavirus disease 2019; MedDRA = Medical Dictionary for Regulatory Activities; MIRI = mirikizumab; PBO = placebo; SAE = serious adverse event; SC = subcutaneous; SMQ = standardized MedDRA query; TEAE = treatment-emergent adverse event; UC = ulcerative colitis.
Note: Includes the safety population which is composed of all assigned/randomized patients who received any amount of study treatment.
aData presented as n (%).
bDefined as patients who received 12-week mirikizumab induction therapy and achieved 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the rectal bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
cDefined as AEs reported by at least 3% of patients in either treatment group.
dSpecific MedDRA terms were used to identify infections considered to be opportunistic infections based on Winthrop et al. (2015).
eFour cases of herpes zoster infections and one case of oral candidiasis; herpes zoster was severe in one patient.
fOne adjudicated event of ischemic stroke.
gGastric cancer.
hBasal cell carcinoma.
iExcluding suicide or self-injury.
jAttempted suicide not considered related to study drug by investigator.
kOccurring within 24 hours of drug administration, or on the day of drug administration when time is missing. No serious hypersensitivity or anaphylactic reactions occurred during induction period. “Hypersensitivity reaction” was used as an overarching term to describe systemic events that likely had an allergic or hypersensitivity etiology - analyses for both time periods were based on narrow terms using the following SMQs: anaphylactic reaction, hypersensitivity, and angioedema.
lDue to COVID-19 infection.
Mirikizumab Nonresponders From LUCENT-1
Treatment Assignment
A total of 272 patients who received mirikizumab or placebo in LUCENT-1 and did not achieve clinical response were entered into an open-label extended induction treatment arm. Patients received an additional three doses of 300-mg intravenous mirikizumab every 4 weeks for 12 weeks. Patients who achieved clinical response at week 12 (representing week 24 of the overall 52-week period) of LUCENT-2 were then eligible to continue on to open-label 200-mg subcutaneous mirikizumab every 4 weeks through week 40 of LUCENT-2.2
Baseline Characteristics
Parameterb |
MIRI Induction Nonrespondersc |
OL MIRI 300 mg IV |
|
Age, mean years (SD) |
44.0 (14.2) |
Male |
182 (66.9) |
BMI category |
|
≥18.5 to <25 kg/m2 |
134 (49.3) |
≥25 kg/m2 |
122 (44.8) |
Disease duration, mean years (SD) |
7.62 (6.8) |
Disease extent |
|
Left-sided colitis |
154 (56.6) |
Modified Mayo score category |
|
Moderate (4-6) |
117 (43.0) |
Severe (7-9) |
154 (56.6) |
Mayo endoscopic subscore of 3 (severe disease) |
197 (72.4) |
Bowel urgencyd severity, mean (SD) |
6.2 (2.2) |
Fecal calprotectin, median μg/g (Q1, Q3) |
1546.0 (650.0, 2912.0) |
C-reactive protein, median mg/L (Q1, Q3) |
5.5 (2.5, 13.6) |
Abbreviations: BMI = body mass index; eCOA = electronic clinical outcome assessment; IV = intravenous; MIRI = mirikizumab; NRS = numeric rating scale; OL = open label; Q = quartile.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the eCOA transcription error in Poland and Turkey.
aRefers to induction baseline (week 0 of LUCENT-1).
bData presented as n (%) unless otherwise specified.
cDefined as patients who received 12-week mirikizumab induction therapy and did not achieve 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the rectal bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
dThe Urgency NRS is a patient-reported measure of the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency).
lists the baseline and prior UC therapy of mirikizumab induction nonresponders in the LUCENT-2 clinical trial.
Parameterb |
MIRI Induction Nonrespondersc |
OL MIRI 300 mg IV |
|
Prior UC treatment |
|
Failed treatment with a biologic or tofacitinib |
147 (54.0) |
Failed TNF inhibitor treatment |
135 (49.6) |
Failed vedolizumab treatment |
81 (29.8) |
Failed tofacitinib treatment |
18 (6.6) |
Number of failed biologic or tofacitinib therapies |
|
0 |
125 (46.0) |
1 |
56 (20.6) |
≥2 |
91 (33.5) |
UC therapy at baseline |
|
Corticosteroids |
118 (43.4) |
Immunomodulators |
77 (28.3) |
Aminosalicylates |
202 (74.3) |
Abbreviations: eCOA = electronic clinical outcome assessment; IV = intravenous; MIRI = mirikizumab; OL = open label; TNF = tumor necrosis factor; UC = ulcerative colitis.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the eCOA transcription error in Poland and Turkey.
aRefers to induction baseline (week 0 of LUCENT-1).
bData presented as n (%).
cDefined as patients who received 12-week mirikizumab induction therapy and did not achieve 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the rectal bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
Efficacy Results
At the end of the 12-week (representing week 24 of the overall 52-week period) extended induction period of LUCENT-2, 272 mirikizumab induction nonresponders received a total of three additional doses of open-label intravenous mirikizumab 300 mg administered every 4 weeks. Of these patients, 53.7% achieved clinical response and 11.4% achieved clinical remission.2
Starting at week 12 of LUCENT-2 and lasting through week 40 of LUCENT-2, 144 mirikizumab induction nonresponders received open-label subcutaneous mirikizumab 200 mg administered every 4 weeks. Of these patients, 72.2% achieved clinical response and 36.1% achieved clinical remission.2
Safety Results
Safety results for the mirikizumab induction nonresponders during the open-label induction and open-label maintenance periods of LUCENT-2 can be found in .
Parametersa |
MIRI Induction Nonresponders |
|
LUCENT-2 Week 12b |
LUCENT-2 Week 40c |
|
OL Induction MIRI 300 mg IV |
OL Maintenance MIRI 200 mg SC |
|
TEAE |
120 (38.3) |
99 (57.9) |
SAE |
17 (5.4) |
6 (3.5) |
Most commonly reported TEAEsd |
||
Nasopharyngitis |
8 (2.6) |
9 (5.3) |
Arthralgia |
14 (4.5) |
13 (7.6) |
UC |
8 (2.6) |
11 (6.4) |
Injection site pain |
NA |
6 (3.5) |
Headache |
5 (1.6) |
7 (4.1) |
Diarrhea |
2 (0.6) |
6 (3.5) |
Anemia |
6 (1.9) |
8 (4.7) |
AEs of special interest |
||
All infections |
40 (12.8) |
31 (18.1) |
Serious infections |
5 (1.6) |
2 (1.2) |
Opportunistic infectionse |
2 (0.6)f |
1 (0.6)g |
Cerebrocardiovascular events |
2 (0.6) |
1 (0.6) |
Malignancies |
4 (1.3)h |
1 (0.6)i |
Depressionj |
0 |
2 (1.2) |
Suicide/self-injury |
0 |
0 |
Hepatic |
6 (1.9) |
3 (1.8) |
Immediate hypersensitivitiesk |
2 (0.6) |
1 (0.6) |
Infusion/Injection site reactionsl |
1 (0.3) |
13 (7.6) |
Death |
0m |
0 |
Discontinuation due to AE |
10 (3.2) |
4 (2.3) |
Abbreviations: AE = adverse event; COVID-19 = coronavirus disease 2019; IV = intravenous; MedDRA = Medical Dictionary for Regulatory Activities; MIRI = mirikizumab; NA = not applicable; OL = open label; SAE = serious adverse event; SC = subcutaneous; SMQ = standardized MedDRA query; TEAE = treatment-emergent adverse event; UC = ulcerative colitis.
Note: Includes the safety population which is composed of all assigned/randomized patients who received any amount of study treatment.
aData presented as n (%).
bRepresenting 24 weeks of continuous treatment.
cRepresenting 52 weeks of continuous treatment.
dDefined as AEs reported by at least 3% of patients in either treatment group.
eSpecific MedDRA terms were used to identify infections considered to be opportunistic infections based on Winthrop et al. (2015).
fOne case of gastrointestinal candidiasis and one case of cytomegalovirus esophagitis.
gOne case of herpes simplex virus.
hTwo malignancies were squamous cell carcinoma, one was adenocarcinoma of the colon, and one was rectal cancer.
iThe one malignancy was Kaposi's sarcoma.
jExcluding suicide or self-injury.
kOccurring within 24 hours of drug administration, or on the day of drug administration when time is missing. No serious hypersensitivity or anaphylactic reactions occurred during induction period. “Hypersensitivity reaction” was used as an overarching term to describe systemic events that likely had an allergic or hypersensitivity etiology - analyses for both time periods were based on narrow terms using the following SMQs: anaphylactic reaction, hypersensitivity, and angioedema.
lInduction AE of interest is infusion-site reaction; maintenance AE of interest is injection-site reaction.
mOne death occurred during the post-treatment follow-up period due to COVID-19 infection after patient discontinued from the study and withdrew consent.
Patient Population With Modified Mayo Score of 5 to 9
The United States Prescribing Information (USPI) presents data that differs from the information in data disclosures, reflecting adjustments made in accordance with FDA guidance on inclusion criteria and endpoints for ulcerative colitis clinical studies. Supplementary details can be found in the Appendix. The information below originates from the USPI.
LUCENT-1
In LUCENT-1, efficacy was evaluated in 1062 patients who were randomized 3:1 at week 0 to receive 300 mg mirikizumab or placebo by intravenous infusion at weeks 0, 4, and 8.6
Patients had a mean age of 43 years (range 18 to 79 years); 40% were female; and 71% identified as White, 25% as Asian, 1% as American Indian or Alaska Native, 1% as Black or African American, and <2% as another racial group or did not report their racial group.6
Patients were permitted to use stable doses of
- aminosalicylates (5-ASAs)
- immunomodulators, such as
- 6-mercaptopurine (6-MP)
- azathioprine (AZA), or
- methotrexate (MTX), and
- oral corticosteroids, such as
- prednisone ≤20 mg/day or equivalent
- extended-release budesonide 9 mg/day, or
- beclomethasone dipropionate 5 mg/day.6
At induction baseline,
- 41% of patients were receiving oral corticosteroids
- 24% were receiving immunomodulators, and
- 75% were receiving 5-ASAs.6
At baseline, patients had a modified Mayo score (MMS) of 5 to 9, including a centrally read endoscopy subscore of 2 or 3.6
An endoscopy subscore of 2 was defined by
- marked erythema
- absent vascular pattern
- friability, and
- erosions.6
An endoscopy subscore of 3 was defined by
- spontaneous bleeding, and
- ulceration.6
At LUCENT-1 baseline,
- the median MMS was 7, and
- 58% of patients had severely active disease (MMS of 7-9).6
At LUCENT-1 baseline,
- 57% were biologic- and Janus Kinase (JAK) inhibitor-naïve
- 41% had failed at least one biologic
- 3% had failed a JAK inhibitor, and
- 2% had previously received but had not failed a biologic or JAK inhibitor.6
The LUCENT-1 primary endpoint was clinical remission at week 12.6
The secondary endpoints were
- clinical response
- endoscopic improvement, and
- histologic-endoscopic mucosal improvement ().6
Endpoint |
mirikizumab 300 mg IV Q4Wa |
PBO IV Q4W |
Treatment Differenceb |
Clinical remissionc |
|||
Total population |
N=795 |
N=267 |
10% (5, 15) d |
Biologic- and JAKi-naïve |
N=450 |
N=155 |
N/A |
Prior biologic or JAKi failuree |
N=331 |
N=107 |
N/A |
Clinical responsef |
|||
Total population |
N=795 |
N=267 |
22% (15, 28)d |
Biologic- and JAKi-naïve |
N=450 |
N=155 |
N/A |
N=331 |
N=107 |
N/A |
|
Endoscopic improvementg |
|||
Total population |
N=795 |
N=267 |
14% (8, 20)d |
Biologic- and JAKi-naïve |
N=450 |
N=155 |
N/A |
Prior biologic or JAKi failuree |
N=331 |
N=107 |
N/A |
HEMIh |
|||
Total population |
N=795 |
N=267 |
11% (6, 16)d |
Biologic- and JAKi-naïve |
N=450 |
N=155 |
N/A |
Prior biologic or JAKi failuree |
N=331 |
N=107 |
N/A |
Abbreviations: HEMI = histologic-endoscopic mucosal improvement; IV = intravenously; JAKi = Janus Kinase inhibitor; mMS = Modified Mayo Score; N/A = not available; PBO = placebo; Q4W = every 4 weeks; TNF = tumor necrosis factor.
aOmvoh (mirikizumab) 300 mg as an IV infusion at weeks 0, 4, and 8.
bAdjusted treatment difference based on Cochran-Mantel-Haenszel method adjusted for randomization stratification factors.
cClinical remission based on MMS is defined as: stool frequency subscore = 0 or 1, rectal bleeding subscore = 0, and centrally read endoscopy subscore = 0 or 1 (excluding friability).
dThe endpoint was tested at an alpha level of 0.00125, with a p-value <.001.
ePrior biologic or JAKi failure includes loss of response, inadequate response, or intolerance to one or more biologic therapy (TNF blocker or vedolizumab), or tofacitinib.
fClinical response is defined as a decrease in the mMS of ≥2 points with ≥30% decrease from baseline, and either a decrease of ≥1 point in the rectal bleeding subscore from baseline or a rectal bleeding subscore of 0 or 1.
gEndoscopic improvement is defined as a centrally read endoscopy subscore of 0 or 1 (excluding friability).
hHEMI is defined as achieving both endoscopic improvement (centrally read endoscopy subscore of 0 or 1, excluding friability) and histologic improvement (neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue based on the Geboes scoring system).
LUCENT-2
LUCENT-2 is the maintenance study that evaluated 506 patients who achieved clinical response at week 12 in the LUCENT-1 study. These patients were randomized 2:1 to receive either 200 mg mirikizumab or placebo subcutaneously every 4 weeks for 40 weeks in LUCENT-2. The total length of treatment for LUCENT-1 and LUCENT-2 was 52 weeks.6
Among patients who achieved clinical response at week 12 in LUCENT-1, the primary endpoint was the proportion of patients in clinical remission at week 40 (52 weeks of continuous treatment in LUCENT-1 and LUCENT-2).6
Among patients who achieved clinical response at week 12 in LUCENT-1, the secondary endpoints at week 40 included
- endoscopic improvement
- maintenance of clinical remission in patients who achieved clinical remission at week 12
- corticosteroid-free clinical remission, and
- histologic-endoscopic mucosal improvement ().6
Endpoint |
mirikizumab 200 mg SC Q4Wb |
PBO SC Q4Wc |
Treatment Differenced |
Total population |
N=337 |
N=169 |
22% (14, 31)g |
Biologic- and JAKi-naïve |
N=208 |
N=109 |
N/A |
Prior biologic or JAKi failedh |
N=121 |
N=59 |
N/A |
Total population |
N=337 |
N=169 |
27% (19, 36)g |
Biologic- and JAKi-naïve |
N=208 |
N=109 |
N/A |
Prior biologic or JAKi failedh |
N=121 |
N=59 |
N/A |
Maintenance of clinical remission in patients who achieved clinical remission at week 12j |
|||
Total population |
N=128 |
N=62 |
23% (8, 38)k |
Biologic- and JAKi-naïve |
N=91 |
N=48 |
N/A |
Prior biologic or JAKi failedh |
N=34 |
N=14 |
N/A |
Total population |
N=337 |
N=169 |
22% (13, 30)g |
Biologic- and JAKi-naïve |
N=208 |
N=109 |
N/A |
Prior biologic or JAKi failedh |
N=121 |
N=59 |
N/A |
Total population |
N=337 |
N=169 |
19% (11, 27)g |
Biologic- and JAKi-naïve |
N=208 |
N=109 |
N/A |
Prior biologic or JAKi failedh |
N=121 |
N=59 |
N/A |
Abbreviations: HEMI = histologic-endoscopic mucosal improvement; JAKi = Janus Kinase inhibitor; mMS = Modified Mayo Score; N/A = not available; PBO = placebo; Q4W = every 4 weeks; SC = subcutaneous; TNF = tumor necrosis factor.
aRepresenting a total of 52 weeks of continuous therapy.
bOmvoh (mirikizumab) 200 mg as a SC injection at week 12 and every 4 weeks thereafter for up to an additional 40 weeks.
cThe placebo arm includes subjects who received Omvoh (mirikizumab) during the induction study (LUCENT-1) and were randomized to receive placebo through week 40.
dAdjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for randomization stratification factors.
eAmong patients who achieved clinical response at week 12 in LUCENT-1 with Omvoh (mirikizumab) induction treatment.
fClinical remission based on mMS is defined as: stool frequency subscore = 0 or 1, rectal bleeding subscore = 0, and centrally read endoscopy subscore = 0 or 1 (excluding friability).
gp<.001.
hPrior biologic or JAKi failure includes loss of response, inadequate response, or intolerance to one or more biologic therapy (TNF blocker or vedolizumab), or tofacitinib.
iEndoscopic improvement is defined as a centrally read endoscopy subscore of 0 or 1 (excluding friability).
jAmong subjects who achieved clinical remission at week 12 in LUCENT-1 with Omvoh (mirikizumab) induction treatment.
kp<.01.
lCorticosteroid-free clinical remission is defined as clinical remission at week 40 and no corticosteroid use for ≥12 weeks prior to week 40 assessment.
mHEMI is defined as achieving both endoscopic improvement (centrally read endoscopy subscore of 0 or 1, excluding friability) and histologic improvement (no neutrophils in crypts or lamina propria, no crypt destruction, and no erosions, ulcerations, or granulation tissue based on the Geboes scoring system).
Bowel Urgency
Bowel urgency was assessed during LUCENT-1 and LUCENT-2 with an Urgency Numeric Rating Scale (NRS) of 0 to 10.6
A greater proportion of subjects with a baseline Urgency NRS weekly average score ≥3 treated with mirikizumab compared to placebo reported an Urgency NRS weekly average score of 0 or 1 (39% versus 23%) at week 40.6
Urgency NRS weekly average scores of 0 to 1 were also observed in a greater proportion of subjects treated with mirikizumab compared to placebo at Week 12.6
Endoscopic Assessment
Normalization of endoscopic appearance of the mucosa (endoscopic remission) was defined as a Mayo endoscopic subscore of 0. At week 40 of LUCENT-2, endoscopic remission was observed in a greater proportion of subjects treated with mirikizumab compared to placebo (22% versus 14%).6
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1US National Library of Medicine. ClinicalTrials.gov. February 29, 2000. Accessed April 18, 2023. https://clinicaltrials.gov/
2D'Haens G, Dubinsky M, Kobayashi T, et al; LUCENT Study Group. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2023;388(26):2444-2455. https://doi.org/10.1056/NEJMoa2207940
3D'Haens G, Kobayashi T, Morris N, et al. Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-1 study. Poster presented at: 17th Congress of the European Crohn’s and Colitis Organisation (ECCO Virtual); February 16-19, 2022.
4Winthrop KL, Novosad SA, Baddley JW, et al. Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015;74(12):2107-2116. http://dx.doi.org/10.1136/annrheumdis-2015-207841
5Dubinsky MC, Irving PM, Li X, et al. Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study. Poster presented at: Digestive Disease Week; May 24, 2022; San Diego, CA.
6Omvoh [package insert]. Indianapolis, IN: Eli Lilly and Company; 2023.
7US National Library of Medicine. ClinicalTrials.gov. February 29, 2000. Accessed August 31, 2023. https://clinicaltrials.gov/
8US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Ulcerative colitis: developing drugs for treatment. Guidance for industry. April 2022. Accessed August 31, 2023. https://www.fda.gov/media/158016/download
Appendix
The mirikizumab clinical development program for ulcerative colitis began in 2015 with specific criteria for eligible patients: those with moderately to severely active ulcerative colitis, defined by a modified Mayo score (MMS) of 4 to 9 and an endoscopic subscore (ES) of at least 2, based on endoscopy within 14 days before baseline. Throughout data disclosures, this patient group has consistently been used.2,7
In April 2022, the FDA issued draft guidance, stipulating that clinical studies evaluating drug candidates for moderately to severely active ulcerative colitis treatment should involve patients with an MMS of 5 to 9, including an ES of at least 2. As a result, the United States prescribing information contains data only from patients meeting this revised criteria. This adjustment led to 100 fewer patients evaluated in LUCENT-1 and 38 fewer mirikizumab induction responders evaluated in LUCENT-2.2,6,8
The FDA draft guidance also defined endoscopic remission as an ES) of 0 and endoscopic improvement as an ES of 0 or 1 (excluding friability). This differs from the LUCENT program where endoscopic remission is defined as an ES of 0 or 1 (excluding friability). To reconcile these differences, the mirikizumab USPI reports endoscopic improvement defined an ES of 0 or 1 (excluding friability) when detailing LUCENT-1 and -2 efficacy results.3,5,6,8
Date of Last Review: May 30, 2023