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Omvoh ™ (mirikizumab-mrkz) injection
300 mg/15 mL, 100 mg/mL
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What are the effects of Omvoh™ (mirikizumab-mrkz) on histologic and histologic-endoscopic endpoints in patients with ulcerative colitis?
Compared with placebo, a significantly greater proportion of patients who received mirikizumab achieved HEMI and HEMR at week 12, and the effect was sustained after 40 additional weeks of treatment with mirikizumab (p<.001 for all).
Histologic and Histologic-Endoscopic Improvement and Remission in the LUCENT‑1 and LUCENT‑2 Clinical Trials
Definitions of Histologic and Histologic-Endoscopic Endpoints in the LUCENT Clinical Trial Program lists definitions of the histologic and histologic-endoscopic endpoints in the LUCENT-1 and LUCENT-2 clinical trials.
Endpoint |
Definition |
Histologic improvement |
Geboes ≤3.1 |
Histologic remission |
Geboes ≤2B.0 |
HEMI |
ES=0 or 1 (excluding friability) plus Geboes ≤3.1 |
HEMR |
ES=0 or 1 (excluding friability) plus Geboes ≤2B.0 |
Abbreviations: ES = Endoscopic Subscore; HEMI = histologic-endoscopic mucosal improvement; HEMR = histologic-endoscopic mucosal remission.
In patients with moderately to severely active ulcerative colitis, at the end of the 12-week induction period of LUCENT-1, a greater proportion of patients who received mirikizumab than patients who received placebo achieved
- histologic improvement
- histologic remission
- histologic-endoscopic mucosal improvement (HEMI), and
- histologic-endoscopic mucosal remission (HEMR) (p<.001 for all) (Histologic and Histologic-Endoscopic Outcomes at Week 12 of LUCENT-1 and at Week 40 of LUCENT-2).1
In LUCENT-2, patients who achieved a clinical response to treatment with mirikizumab 300 mg infused intravenously during the induction period (LUCENT-1) were rerandomized to receive either mirikizumab 200 mg or placebo injected subcutaneously (SC) every 4 weeks for an additional 40 weeks (for a total of 52 weeks of continuous therapy).1
At week 40, significantly more patients who continued maintenance treatment with mirikizumab achieved histologic and histologic-endoscopic mucosal remission with absence of neutrophils in the mucosa than did patients who received placebo (p<.001 for both) (Histologic and Histologic-Endoscopic Outcomes at Week 12 of LUCENT-1 and at Week 40 of LUCENT-2).1
Outcome |
LUCENT-1 |
LUCENT-2 |
||
Week 12 |
Week 40 |
|||
MIRI 300 mg IV Q4W (N=868) |
PBO IV Q4W |
MIRI 200 mg SC Q4W |
PBO SC Q4W |
|
Histologic improvement,a n (%) |
340 (39.2) |
61 (20.7) |
200 (54.8) |
46 (25.7) |
Treatment difference, % (95% CI)b |
18.5 (12.9, 24.0)c |
28.0 (19.9, 36.1)c |
||
Histologic remission,d n (%) |
254 (29.3) |
46 (15.6) |
177 (48.5) |
44 (24.6) |
Treatment difference, % (95% CI)b |
13.7 (8.6, 18.7)c |
22.5 (14.5, 30.5)c |
||
HEMI,e n (%) |
235 (27.1) |
41 (13.9) |
174 (47.7) |
40 (22.3) |
Treatment difference, % (95% CI)b |
13.4 (5.5, 21.4)c |
23.9 (16.1, 31.7)c |
||
HEMR,f n (%) |
193 (22.2) |
33 (11.2) |
158 (43.3) |
39 (21.8) |
Treatment difference, % (95% CI)b |
11.3 (6.7, 15.8)c |
19.9 (12.1, 27.6)c |
||
Abbreviations: ES = Endoscopic Subscore; HEMI = histologic-endoscopic mucosal improvement; HEMR = histologic-endoscopic mucosal remission; IV = intravenous; MIRI = mirikizumab; MMS = Modified Mayo Score; PBO = placebo; Q4W = every 4 weeks; SC = subcutaneous.
aGeboes ≤3.1.
bThe common risk difference is the difference in proportions adjusted for the following stratification factors: prior biologic or tofacitinib failure (yes or no), baseline corticosteroid use (yes or no), baseline disease activity (MMS: 4-6 or 7-9), and geographic region (North America, Europe, or other). The confidence intervals are calculated using the Mantel-Haenszel-Sato method.
cp<.001.
dGeboes ≤2B.0.
eDefined as (1) Mayo ES=0 or 1 excluding friability, and (2) Geboes ≤3.1.
fDefined as (1) Mayo ES=0 or 1 excluding friability, and (2) Geboes ≤2B.0.
Subgroup Analyses Among Patients Who Previously Failed or Did Not Fail a Biologic or Tofacitinib
The efficacy of mirikizumab in resolving active histologic inflammation in the LUCENT-1 induction and LUCENT-2 maintenance trials was demonstrated regardless of prior biologic or tofacitinib exposure or failure (Histologic and Histologic-Endoscopic Outcomes at Week 12 of LUCENT-1 Among Prior Biologic or Tofacitinib Failed and Not Failed Subgroups and Histologic and Histologic-Endoscopic Outcomes at Week 40 of LUCENT-2 Among Prior Biologic or Tofacitinib Failed and Not Failed Subgroups).2
Outcome |
Not Biologic or Tofacitinib Failed |
Biologic or Tofacitinib Failed |
||
MIRI 300 mg IV Q4W (N=507) |
PBO IV Q4W |
MIRI 300 mg IV Q4W |
PBO IV Q4W |
|
Histologic improvement,a n (%) |
235 (46.4) |
45 (25.6) |
105 (29.1) |
16 (13.6) |
Treatment difference, % (95% CI) |
20.8 (13.0, 28.6)b |
15.5 (7.8, 23.3)b |
||
Histologic remission,c n (%) |
183 (36.1) |
35 (19.9) |
71 (19.7) |
11 (9.3) |
Treatment difference, % (95% CI) |
16.2 (9.0, 23.4)b |
10.3 (3.7, 17.0)d |
||
HEMI,e n (%) |
179 (35.3) |
33 (18.8) |
56 (15.5) |
8 (6.8) |
Treatment difference, % (95% CI) |
16.6 (9.4, 23.7)b |
8.7 (2.9, 14.6)f |
||
HEMR,g n (%) |
149 (29.4) |
25 (14.2) |
44 (12.2) |
8 (6.8) |
Treatment difference, % (95% CI) |
15.2 (8.7, 21.7)b |
5.4 (-0.2, 11.1) |
||
Abbreviations: ES = Endoscopic Subscore; HEMI = histologic-endoscopic mucosal improvement; HEMR = histologic-endoscopic mucosal remission; IV = intravenous; MIRI = mirikizumab; PBO = placebo; Q4W = every 4 weeks.
aGeboes ≤3.1.
bp<.001.
cGeboes ≤2B.0.
dp=.011.
eDefined as (1) Mayo ES=0 or 1 excluding friability, and (2) Geboes ≤3.1.
fp=.018.
gDefined as (1) Mayo ES=0 or 1 excluding friability, and (2) Geboes ≤2B.0.
Outcome |
Not Biologic or Tofacitinib Failed |
Biologic or Tofacitinib Failed |
||
MIRI 200 mg SC Q4W (N=237) |
PBO SC Q4W |
MIRI 200 mg SC Q4W |
PBO SC Q4W |
|
Histologic improvement,a n (%) |
141 (59.5) |
34 (29.6) |
59 (46.1) |
12 (18.8) |
Treatment difference, % (95% CI) |
29.9 (19.5, 40.4)b |
27.3 (14.5, 40.2)b |
||
Histologic remission,c n (%) |
124 (52.3) |
33 (28.7) |
53 (41.4) |
11 (17.2) |
Treatment difference, % (95% CI) |
23.6 (13.2, 34.1)b |
24.2 (11.6, 36.8)b |
||
HEMI,d n (%) |
125 (52.7) |
31 (27.0) |
49 (38.3) |
9 (14.1) |
Treatment difference, % (95% CI) |
25.8 (15.5, 36.1)b |
24.2 (12.2, 36.2)b |
||
HEMR,e n (%) |
112 (47.3) |
30 (26.1) |
46 (35.9) |
9 (14.1) |
Treatment difference, % (95% CI) |
21.2 (10.9, 31.4)b |
21.9 (10.0, 33.8)b |
||
Abbreviations: ES = Endoscopic Subscore; HEMI = histologic-endoscopic mucosal improvement; HEMR = histologic-endoscopic mucosal remission; MIRI = mirikizumab; PBO = placebo; Q4W = every 4 weeks; SC = subcutaneous.
aGeboes ≤3.1.
bp<.001.
cGeboes ≤2B.0.
dDefined as (1) Mayo ES=0 or 1 excluding friability, and (2) Geboes ≤3.1.
eDefined as (1) Mayo ES=0 or 1 excluding friability, and (2) Geboes ≤2B.0.
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
A key secondary endpoint of LUCENT-1 was histologic-endoscopic mucosal improvement (Proportion of Patients With Ulcerative Colitis Meeting HEMI Efficacy Endpoint in LUCENT-1 at Week 12).3
Endpoint |
Mirikizumab 300 mg IV Q4Wa |
PBO IV Q4W |
Treatment Differenceb |
HEMIc |
|||
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; 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.
cHEMI 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).
dThe endpoint was tested at an alpha level of 0.00125, with a p-value <0.001.
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.
LUCENT-1 was not designed to evaluate the relationship of histologic-endoscopic mucosal improvement at week 12 to disease progression and long-term outcomes.3
LUCENT-2
Among patients who achieved clinical response at week 12 in LUCENT-1, a key secondary endpoint at week 40 was histologic-endoscopic mucosal improvement (Proportion of Patients With Ulcerative Colitis Meeting HEMI Efficacy Endpoint at Week 40 in LUCENT-2).3
Endpoint |
Mirikizumab 200 mg SC Q4Wb |
PBO SC Q4Wc |
Treatment Differenced |
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; 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.
fHEMI 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).
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.
LUCENT-2 was not designed to evaluate the relationship of histologic-endoscopic mucosal improvement at week 40 to disease progression and long-term outcomes.3
Enclosed Prescribing Information
References
1Magro F, Pai RK, Kobayashi T, et al. Efficacy of mirikizumab in resolving active histologic inflammation in ulcerative colitis in LUCENT-1 induction and LUCENT-2 maintenance trials. Abstract presented at: United European Gastroenterology Week (UEGW); October 8-11, 2022.
2Magro F, Pai RK, Kobayashi T, et al. Efficacy of mirikizumab in resolving active histologic inflammation in ulcerative colitis in LUCENT-1 induction and LUCENT-2 maintenance trials. Poster presented at: United European Gastroenterology Week (UEGW); October 8-11, 2022.
3Omvoh [package insert]. Indianapolis, IN: Eli Lilly and Company; 2023.
4D'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;388:2444-2455. https://doi.org/10.1056/NEJMoa2207940
5US National Library of Medicine. ClinicalTrials.gov. February 29, 2000. Accessed August 31, 2023. https://clinicaltrials.gov/
6US 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.4,5
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-2.3,4,6
Date of Last Review: October 11, 2022