CLINICAL STUDIES

Clinical Studies in Plaque Psoriasis

Adults with Moderate-to-Severe Plaque Psoriasis

Four multicenter, randomized, double-blind trials (PsO1 [NCT02207231], PsO2 [NCT02207244], PsO3 [NCT02203032], and PsO4 [NCT02905331]) enrolled subjects 18 years of age and older with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy. Subjects had an Investigator's Global Assessment (IGA) score of ≥3 ("moderate") on a 5-point scale of overall disease severity, a Psoriasis Area and Severity Index (PASI) score ≥12, and a minimum affected body surface area (BSA) of 10%. Subjects with guttate, erythrodermic, or pustular psoriasis were excluded.

Trials PsO1 and PsO2

In trials PsO1 and PsO2, 1443 subjects were randomized to either TREMFYA (100 mg at Weeks 0 and 4 and every 8 weeks thereafter) administered with a prefilled syringe, placebo or U.S. licensed adalimumab (80 mg at Week 0 and 40 mg at Week 1, followed by 40 mg every other week thereafter).

Both trials assessed the responses at Week 16 compared to placebo for the two co-primary endpoints:

the proportion of subjects who achieved an IGA score of 0 ("cleared") or 1 ("minimal");
the proportion of subjects who achieved at least a 90% reduction from baseline in the PASI composite score (PASI 90).

Comparisons between TREMFYA and U.S. licensed adalimumab were secondary endpoints at the following time points:

at Week 16 (trials PsO1 and PsO2), the proportions of subjects who achieved an IGA score of 0 or 1, a PASI 90, and a PASI 75 response;
at Week 24 (trials PsO1 and PsO2), and at Week 48 (trial PsO1), the proportions of subjects achieving an IGA score of 0, an IGA score of 0 or 1, and a PASI 90 response.

Other evaluated outcomes included improvement in psoriasis symptoms assessed on the Psoriasis Symptoms and Signs Diary (PSSD) and improvements in psoriasis of the scalp at Week 16.

In both trials, subjects were predominantly men and White, with a mean age of 44 years and a mean weight of 90 kg. At baseline, subjects had a median affected BSA of approximately 21%, a median PASI score of 19, and 18% had a history of psoriatic arthritis. Approximately 24% of subjects had an IGA score of 4 ("severe"). In both trials, 23% had received prior biologic systemic therapy.

Clinical Response

Table 5 presents the efficacy results at Week 16 in trials PsO1 and PsO2.

Table 5: Efficacy Results at Week 16 in Adults with Moderate-to-Severe Plaque Psoriasis in Trials PsO1 and PsO2 (NRI NRI = Non-Responder Imputation )
Trial PsO1		Trial PsO2
Endpoint	Placebo (N=174) n (%)	TREMFYA (N=329) n (%)	Placebo (N=248) n (%)	TREMFYA (N=496) n (%)
IGA response of 0/1 Co-Primary Endpoints ^, IGA response of 0 ("cleared") or 1 ("minimal")	12 (7)	280 (85)	21 (8)	417 (84)
PASI 90 response	5 (3)	241 (73)	6 (2)	347 (70)

Table 6 presents the results of an analysis of all the North America sites (i.e., U.S. and Canada), demonstrating superiority of TREMFYA to U.S. licensed adalimumab.

Table 6: Efficacy Results in Adults with Moderate-to-Severe Plaque Psoriasis in Trials PsO1 and PsO2 (NRI NRI = Non-Responder Imputation )
Trial PsO1		Trial PsO2
Endpoint	TREMFYA (N=115) Subjects from sites in the United States and Canada n (%)	Adalimumab U.S. licensed adalimumab (N=115) n (%)	TREMFYA (N=160) n (%)	Adalimumab (N=81) n (%)
IGA response of 0/1 ("cleared" or "minimal")
Week 16	97 (84)	70 (61)	119 (74)	50 (62)
Week 24	97 (84)	62 (54)	119 (74)	46 (57)
Week 48	91 (79)	62 (54)	NA	NA
IGA response of 0 ("cleared")
Week 24	61 (53)	27 (23)	76 (48)	23 (28)
Week 48	54 (47)	28 (24)	NA	NA
PASI 75 response
Week 16	105 (91)	80 (70)	132 (83)	51 (63)
PASI 90 response
Week 16	84 (73)	47 (41)	102 (64)	34 (42)
Week 24	92 (80)	51 (44)	113 (71)	41 (51)
Week 48	84 (73)	53 (46)	NA	NA

An improvement was seen in psoriasis involving the scalp in subjects randomized to TREMFYA compared to placebo at Week 16.

Examination of age, gender, race, body weight, and previous treatment with systemic or biologic agents did not identify differences in response to TREMFYA among these subgroups.

Maintenance and Durability of Response

To evaluate maintenance and durability of response (trial PsO2), subjects randomized to TREMFYA at Week 0 and who were PASI 90 responders at Week 28 were re-randomized to either continue treatment with TREMFYA every 8 weeks or be withdrawn from therapy (i.e., receive placebo).

At Week 48, 89% of subjects who continued on TREMFYA maintained PASI 90 compared to 37% of subjects who were re-randomized to placebo and withdrawn from TREMFYA. For responders at Week 28 who were re-randomized to placebo and withdrawn from TREMFYA, the median time to loss of PASI 90 was approximately 15 weeks.

Patient Reported Outcomes

Greater improvements in symptoms of psoriasis (itch, pain, stinging, burning and skin tightness) at Week 16 in TREMFYA compared to placebo were observed in both trials based on the Psoriasis Symptoms and Signs Diary (PSSD). Greater proportions of subjects on TREMFYA compared to U.S. licensed adalimumab achieved a PSSD symptom score of 0 (symptom-free) at Week 24 in both trials.

Trial PsO3

Trial PsO3 [NCT02203032] evaluated the efficacy of 24 weeks of treatment with TREMFYA in subjects (N=268) who had not achieved an adequate response, defined as IGA ≥2 at Week 16 after initial treatment with U.S. licensed ustekinumab (dosed 45 mg or 90 mg according to the subject's baseline weight at Week 0 and Week 4). These subjects were randomized to either continue with U.S. licensed ustekinumab treatment every 12 weeks or switch to TREMFYA 100 mg at Weeks 16, 20, and every 8 weeks thereafter. Baseline characteristics for randomized subjects were similar to those observed in PsO1 and PsO2.

In subjects with an inadequate response (IGA ≥2 at Week 16 to U.S. licensed ustekinumab), greater proportions of subjects on TREMFYA compared to U.S. licensed ustekinumab achieved an IGA score of 0 or 1 with a ≥2 grade improvement at Week 28 (31% vs. 14%, respectively; 12 weeks after randomization).

Trial PsO4

Trial PsO4 [NCT02905331] evaluated the efficacy, safety, and pharmacokinetics of TREMFYA administered with the One-Press injector. In this trial, 78 subjects were randomized to receive either TREMFYA (100 mg at Weeks 0 and 4 and every 8 weeks thereafter) [N=62], or placebo [N=16]. Baseline characteristics for subjects were comparable to those observed in trials PsO1 and PsO2. The co-primary endpoints were the same as those for trials PsO1 and PsO2. Secondary endpoints included the proportion of subjects who achieved an IGA score of 0 at Week 16 and the proportion of subjects who achieved a PASI 100 response at Week 16.

A greater proportion of subjects in the guselkumab group achieved an IGA score of 0 or 1 or a PASI 90 response at Week 16 (81% and 76%, respectively) than in the placebo group (0% for both endpoints). The proportion of subjects who achieved an IGA score of 0 at Week 16 was higher in the guselkumab group compared to the placebo group (56% vs. 0%). The proportion of subjects who achieved a PASI 100 response at Week 16 was higher in the guselkumab group compared to the placebo group (50% vs. 0%).

Pediatric Subjects with Moderate-to-Severe Plaque Psoriasis

Trial PsO5

One multicenter, randomized, placebo and active biological comparator-controlled trial (PsO5 [NCT03451851]) enrolled 120 subjects 6 years to 17 years of age with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy and inadequately controlled by phototherapy and/or topical therapies.

In trial PsO5, 92 subjects were randomized to receive subcutaneous injection of either TREMFYA (N=41) or placebo (N=25) at Weeks 0, 4, and 12 or an active biological comparator (N=26). An additional 28 subjects enrolled in a TREMFYA open-label arm. Subjects with a body weight of 70 kg or more received 100 mg of TREMFYA. Subjects with a body weight less than 70 kg received doses according to their weight.

Subjects had an IGA score of ≥3 ("moderate") on a 5-point scale of overall disease severity, a PASI ≥12, and a minimum affected BSA of ≥10%, and at least one of the following: 1) very thick lesions, 2) clinically relevant facial, genital, or hand/foot involvement, 3) PASI ≥20, 4) BSA >20%, or 5) IGA=4 ("severe"). Subjects with guttate, erythrodermic, or pustular psoriasis were excluded.

Of the 92 subjects in the controlled part of the trial, 55% of subjects were male, 85% were White, 4% were Asian, and 4% were Black or African American. For ethnicity, 95% of subjects identified as Not Hispanic or Latino and 5% of subjects identified as Hispanic or Latino. Subjects had a mean body weight of 57 kg, a mean age of 13 years, and a third of the subjects were less than 12 years of age. At baseline, subjects had a median affected BSA of 20%, a median PASI score of 17, and 3% had a history of psoriatic arthritis. Approximately 22% of subjects had an IGA score of 4 ("severe"). Prior phototherapy or prior conventional systemic therapy was received by 32% of subjects and prior biologic systemic therapy was received by 10% of subjects.

The responses at Week 16 were compared to placebo for the two co-primary endpoints:

the proportion of subjects who achieved an IGA score of 0 ("cleared") or 1 ("minimal");
the proportion of subjects who achieved a PASI 90 response.

Other evaluated outcomes included the proportion of subjects who achieved PASI 75, IGA score of 0 ("cleared") and PASI 100 at Week 16.

Clinical Response

Table 7 presents the efficacy results at Week 16 in trial PsO5.

Table 7: Efficacy Results at Week 16 in Pediatric Subjects 6 Years of Age and Older with Moderate-to-Severe Plaque Psoriasis in Trial PsO5 (NRI NRI = Non-Responder Imputation )
Endpoint	Trial PsO5
Placebo (N=25) n (%)	TREMFYA (N=41) n (%)	Treatment Difference (95% CI)
IGA response of 0/1 Co-primary endpoint ^, IGA response of 0 ("cleared") or 1 ("minimal")	4 (16)	27 (66)	50 (26, 69)
IGA response of 0 (cleared)	1 (4)	16 (39)	35 (11, 57)
PASI 75 response	5 (20)	31 (76)	56 (32, 74)
PASI 90 response	4 (16)	23 (56)	40 (16, 61)
PASI 100 response	0	14 (34)	34 (10, 56)

Clinical Studies in Adults with Psoriatic Arthritis

The safety and efficacy of TREMFYA were assessed in 2 randomized, double-blind, placebo-controlled trials (PsA1 [NCT03162796] and PsA2 [NCT03158285]) in 1120 adult subjects with active psoriatic arthritis (PsA) (≥3 swollen joints, ≥3 tender joints, and a C-reactive protein (CRP) level of ≥0.3 mg/dL in PsA1 and ≥5 swollen joints, ≥5 tender joints, and a CRP level of ≥0.6 mg/dL in PsA2) who had inadequate response to standard therapies (e.g., conventional DMARDs [cDMARDs]), apremilast, or nonsteroidal anti-inflammatory drugs [NSAIDs]). Subjects in these trials had a diagnosis of PsA for at least 6 months based on the Classification criteria for Psoriatic Arthritis (CASPAR) and a median duration of PsA of 4 years at baseline.

In trial PsA1, approximately 31% of subjects had been previously treated with up to 2 anti-tumor necrosis factor alpha (anti-TNFα) agents whereas in trial PsA2, all subjects were biologic naïve. Approximately 58% of subjects from both trials had concomitant methotrexate (MTX) use. Subjects with different subtypes of PsA were enrolled in both trials, including polyarticular arthritis with the absence of rheumatoid nodules (40%), spondylitis with peripheral arthritis (30%), asymmetric peripheral arthritis (23%), distal interphalangeal involvement (7%) and arthritis mutilans (1%). At baseline, over 65% and 42% of the subjects had enthesitis and dactylitis, respectively and 79% had ≥3% body surface area (BSA) psoriasis skin involvement.

Trial PsA1 evaluated 381 subjects who were treated with placebo SC, TREMFYA 100 mg SC at Weeks 0, 4 and every 8 weeks (q8w) thereafter, or TREMFYA 100 mg SC every 4 weeks (q4w). Trial PsA2 evaluated 739 subjects who were treated with placebo SC, TREMFYA 100 mg SC at Weeks 0, 4 and q8w thereafter, or TREMFYA 100 mg SC q4w. The primary endpoint in both trials was the percentage of subjects achieving an ACR20 response at Week 24.

Clinical Response

In both trials, subjects treated with TREMFYA 100 mg q8w demonstrated a greater clinical response including ACR20, compared to placebo at Week 24 (Tables 8 and 9). Similar responses were seen regardless of prior anti-TNFα exposure in PsA1, and in both trials similar responses were seen regardless of concomitant cDMARD use, previous treatment with cDMARDs, gender and body weight.

Table 8: Percent of Adult Subjects with Active Psoriatic Arthritis with ACR Responses in Trial PsA1
Placebo (N=126)	TREMFYA 100 mg q8w (N=127)
Response Rate	Response Rate	Difference from Placebo (95% CI)
ACR 20 response Subjects with missing data at a visit were imputed as non-responders at that visit. Subjects who met escape criteria (less than 5% improvement in both tender and swollen joint counts) at Week 16 were allowed to initiate or increase the dose of the permitted concomitant medication and remained on the randomized group. Subjects who initiated or increased the dose of non-biologic DMARD or oral corticosteroids over baseline, discontinued study/study medication or initiated protocol prohibited medications/therapies for PsA prior to a visit were considered non-responders at that visit.
Week 16	25%	52%	27 (15, 38)
Week 24	22%	52%	30 (19, 41)
ACR 50 response
Week 16	13%	23%	10 (1, 19)
Week 24	9%	30%	21 (12, 31)
ACR 70 response
Week 16	6%	8%	2 (-4, 8)
Week 24	6%	12%	6 (-0.3, 13)

Table 9: Percent of Adult Subjects with Active Psoriatic Arthritis with ACR Responses in Trial PsA2
Placebo (N=246)	TREMFYA 100 mg q8w (N=248)
Response Rate	Response Rate	Difference from Placebo (95% CI)
ACR 20 response Subjects with missing data at a visit were imputed as non-responders at that visit. Subjects who met escape criteria (less than 5% improvement in both tender and swollen joint counts) at Week 16 were allowed to initiate or increase the dose of the permitted concomitant medication and remained on the randomized group. Subjects who initiated or increased the dose of non-biologic DMARD or oral corticosteroids over baseline, discontinued study/study medication or initiated protocol prohibited medications/therapies for PsA prior to a visit were considered non-responders at that visit.
Week 16	34%	55%	22 (13, 30)
Week 24	33%	64%	31 (23, 40)
ACR 50 response
Week 16	9%	29%	19 (13, 26)
Week 24	14%	32%	17 (10, 24)
ACR 70 response
Week 16	1%	14%	13 (9, 17)
Week 24	4%	19%	15 (9, 20)

The percentage of subjects achieving ACR20 response in PsA2 by visit is shown in Figure 1.

Figure 1: Percentage of Adult Subjects with Active Psoriatic Arthritis Achieving ACR 20 Response by Visit Through Week 24 in Trial PsA2

The results of the components of the ACR response criteria are shown in Table 10.

Table 10: Mean change (SD SD= standard deviation ) from Baseline in ACR Component Scores at Week 16 and 24 based on Observed Data in Trials PsA1 and PsA2
Trial PsA1		Trial PsA2
Placebo (N=126)	TREMFYA 100 mg q8w (N=127)	Placebo N=246	TREMFYA 100 mg q8w (N=248)
No. of Swollen Joints
Baseline	10.1 (7.1)	10.9 (9.3)	12.3 (6.9)	11.7 (6.8)
Mean change at Week 16	-4.2 (7.0)	-7.3 (7.0)	-5.8 (7.1)	-7.2 (6.0)
Mean change at Week 24	-5.1 (6.9)	-7.3 (8.0)	-6.4 (7.2)	-8.1 (6.1)
No. of Tender Joints
Baseline	19.8 (14.4)	20.2 (14.5)	21.6 (13.1)	19.8 (11.9)
Mean change at Week 16	-4.5 (10.8)	-10.2 (10.4)	-6.8 (10.5)	-9.0 (9.4)
Mean change at Week 24	-6.8 (13.0)	-10.5 (12.0)	-7.3 (11.2)	-10.4 (9.5)
Patient's Assessment of Pain Assessment based on Visual Analog Scale (cm) with the left end indicating "no pain" (for patient's assessment of pain), "very well" (for patient global assessment), or "no arthritis activity" (for physician global assessment) and the right end indicating "the worst possible pain" (for patient assessment of pain), "poor" (for patient global assessment), or "extremely active arthritis (for physician global assessment).
Baseline	5.8 (2.2)	6.0 (2.1)	6.3 (1.8)	6.3 (2.0)
Mean change at Week 16	-0.8 (2.3)	-1.7 (2.4)	-0.9 (2.3)	-2.2 (2.5)
Mean change at Week 24	-0.7 (2.4)	-2.2 (2.6)	-1.1 (2.4)	-2.5 (2.5)
Patient Global Assessment
Baseline	6.1 (2.2)	6.5 (2.0)	6.5 (1.8)	6.5 (1.9)
Mean change at Week 16	-1.0 (2.3)	-2.0 (2.6)	-1.0 (2.3)	-2.3 (2.6)
Mean change at Week 24	-0.9 (2.5)	-2.5 (2.7)	-1.2 (2.6)	-2.5 (2.5)
Physician Global Assessment
Baseline	6.3 (1.7)	6.2 (1.7)	6.7 (1.5)	6.6 (1.6)
Mean change at Week 16	-1.9 (2.2)	-2.9 (2.4)	-2.1 (2.2)	-3.5 (2.3)
Mean change at Week 24	-2.2 (2.3)	-3.5 (2.4)	-2.5 (2.3)	-3.8 (2.3)
Disability Index (HAQ-DI) Disability Index of the Health Assessment Questionnaire; 0 = no difficulty to 3 = inability to perform, measures the patient's ability to perform the following: dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living
Baseline	1.2 (0.7)	1.2 (0.6)	1.3 (0.6)	1.3 (0.6)
Mean change at Week 16	-0.1 (0.5)	-0.3 (0.5)	-0.1 (0.5)	-0.3 (0.5)
Mean change at Week 24	-0.1 (0.5)	-0.3 (0.6)	-0.2 (0.5)	-0.4 (0.5)
CRP (mg/dL)
Baseline	1.4 (1.9)	1.6 (2.4)	2.1 (2.7)	2.0 (2.4)
Mean change at Week 16	-0.2 (1.5)	-0.6 (2.2)	-0.6 (2.5)	-1.0 (2.2)
Mean change at Week 24	-0.0 (2.8)	-0.7 (2.1)	-0.5 (2.5)	-1.1 (2.2)

Treatment with TREMFYA resulted in an improvement in the skin manifestations of psoriasis in subjects with PsA.

Treatment with TREMFYA resulted in improvement in dactylitis and enthesitis in subjects with pre-existing dactylitis or enthesitis.

Physical Function

TREMFYA treated subjects in the TREMFYA 100 mg q8w group in both trials PsA1 and PsA2 showed greater mean improvement from baseline in physical function compared to subjects treated with placebo as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 16 and 24. In both trials, the proportion of HAQ-DI responders (≥0.35 improvement in HAQ-DI score) was greater in the TREMFYA q8w dose group compared to placebo at Weeks 16 and 24.

Other Health-Related Outcomes

General health status was assessed by the Short Form health survey (SF-36). At Week 24, subjects in the TREMFYA 100 mg q8w dose group in both trials PsA1 and PsA2 showed greater improvement from baseline in the SF-36 physical component summary (PCS) compared with placebo. There was not a statistically significant improvement observed in the SF-36 MCS. At Week 24, there was numerical improvement in the physical functioning, role-physical, bodily-pain, general health, social-functioning and vitality domains but not in the role-emotional and mental health domains. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue score (FACIT-F) in trials PsA1 and PsA2. Treatment with TREMFYA resulted in improvement in fatigue as measured by FACIT-F.

Clinical Studies in Adults with Ulcerative Colitis

The efficacy and safety of TREMFYA was assessed in three randomized, double-blind, placebo-controlled trials (UC1, UC2, and UC 4) that enrolled adult subjects with moderately to severely active ulcerative colitis. Disease activity was assessed by the modified Mayo score (mMS), a 3-component Mayo score (0 –9) which consists of the following subscores (0 to 3 for each subscore): stool frequency (SFS), rectal bleeding (RBS), and findings on centrally reviewed endoscopy (ES). An ES of 2 was defined by marked erythema, lack of vascular pattern, friability, and/or erosions; an ES of 3 was defined by spontaneous bleeding and ulceration. Enrolled subjects with a mMS between 5 and 9 and an ES of 2 or 3 were classified as having moderately to severely active ulcerative colitis. Subjects with inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine), biologic therapy (TNF blockers, vedolizumab), and/or Janus kinase (JAK) inhibitors were enrolled. In UC4, subjects with inadequate response, loss of response, or intolerance to sphingosine-1-phosphate receptor modulators (S1PRM) were also enrolled.

Induction Trial: UC1

In the 12-week induction trial (UC1; NCT04033445), 701 adult subjects with moderately to severely active ulcerative colitis were randomized 3:2 to receive either TREMFYA 200 mg or placebo by intravenous infusion at Week 0, Week 4, and Week 8.

At baseline in trial UC1, the median mMS was 7, 64% of subjects had severely active disease (mMS ≥7), and 68% of subjects had an ES of 3. In trial UC1, 49% of subjects had previously failed (inadequate response, loss of response, or intolerance) treatment with at least one biologic therapy and/or JAK inhibitor, 48% were biologic and JAK inhibitor naïve, and 3% had previously received but not failed a biologic or JAK inhibitor. The median age was 39 years (ranging from 18 to 79 years); 43% were female; and 72% identified as White, 21% as Asian, 1% as Black or African American, <1% as American Indian or Alaskan Native, and <1% as multiple racial groups.

Enrolled subjects were permitted to use stable doses of oral aminosalicylates, immunomodulators (azathioprine, 6-mercaptopurine, methotrexate), and/or oral corticosteroids (up to 20 mg/day prednisone or equivalent). At baseline, 72% of subjects were receiving aminosalicylates, 21% of subjects were receiving immunomodulators, and 43% of subjects were receiving corticosteroids. Concomitant biologic therapies or JAK inhibitors were not permitted.

In trial UC1, the primary endpoint was clinical remission at Week 12 as defined by the mMS. Secondary endpoints at Week 12 included endoscopic improvement, clinical response, and histologic endoscopic mucosal improvement (see Table 11 ).

Table 11: Proportion of Adult Subjects with Moderately to Severely Active Ulcerative Colitis Meeting Efficacy Endpoints at Week 12 in Trial UC1
Endpoint	Placebo	TREMFYA 200 mg Intravenous Infusion TREMFYA 200 mg as an intravenous infusion at Week 0, Week 4, and Week 8	Treatment Difference (95% CI)
Clinical remission A stool frequency subscore of 0 or 1 and not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability
Total Population	N=280 8%	N=421 23%	15% (10%, 20%) p <0.001, adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method (adjusted for stratification factors: biologic and/or JAK-inhibitor failure status and concomitant use of corticosteroids at baseline)
Prior biologic and/or JAK inhibitor failure Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) and/or a Janus kinase (JAK) inhibitor for ulcerative colitis	N=136 4%	N=208 13%
Without prior biologic or JAK inhibitor failure Includes subjects that were biologic and/or JAK inhibitor naïve and subjects with biologic and/or JAK inhibitor exposure who did not meet criteria for failure. Of these, 7 subjects in the placebo group and 11 subjects in the TREMFYA group were previously exposed to, but did not fail, a biologic or JAK inhibitor	N=144 12%	N=213 32%
Endoscopic improvement An endoscopy subscore of 0 or 1 with no friability
Total Population	N=280 11%	N=421 27%	16% (10%, 21%)
Prior biologic and/or JAK inhibitor failure	N=136 5%	N=208 15%
Without prior biologic or JAK inhibitor failure	N=144 17%	N=213 38%
Clinical response Decrease from induction baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1 point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1
Total Population	N=280 28%	N=421 62%	34% (27%, 41%)
Prior biologic and/or JAK inhibitor failure	N=136 20%	N=208 51%
Without prior biologic or JAK inhibitor failure	N=144 35%	N=213 71%
Histologic endoscopic mucosal improvement (HEMI) An endoscopy subscore of 0 or 1 with no friability and Geboes score ≤3.1 (indicating neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue)
Total Population	N=280 8%	N=421 24%	16% (11%, 21%)
Prior biologic and/or JAK inhibitor failure	N=136 4%	N=208 13%
Without prior biologic or JAK inhibitor failure	N=144 10%	N=213 33%

Trial UC1 was not designed to evaluate the relationship of histologic endoscopic mucosal improvement at Week 12 to disease progression and long-term outcomes.

Rectal Bleeding and Stool Frequency Subscores

Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 4 in subjects treated with intravenous TREMFYA compared to placebo.

Endoscopic Assessment

Normalization of the endoscopic appearance of the mucosa (endoscopic remission) was defined as ES of 0. At Week 12 of UC1, a greater proportion of subjects treated with TREMFYA compared to placebo-treated subjects achieved endoscopic remission (15% vs 5%).

Fatigue Response

In trial UC1, subjects treated with TREMFYA experienced a clinically meaningful improvement in fatigue, assessed by the PROMIS-Fatigue Short form 7a, at Week 12, compared to placebo-treated subjects. The effect of TREMFYA to improve fatigue after 12 weeks of induction has not been established.

Maintenance Trial: UC2

The maintenance trial (UC2) evaluated 568 subjects who received one of two intravenous TREMFYA induction regimens, including the recommended 200 mg regimen, for 12 weeks in trials UC1 or UC3 (induction dose-finding study) and demonstrated clinical response per mMS after 12 weeks. Subjects were re-randomized to receive a subcutaneous maintenance regimen of either TREMFYA 100 mg every 8 weeks, TREMFYA 200 mg every 4 weeks, or placebo for up to an additional 44 weeks.

In trial UC2, 42% of subjects had failed (inadequate response, loss of response, or intolerance) treatment with one or more biologics or JAK inhibitors.

The primary endpoint was clinical remission at Week 44 defined by mMS. Secondary endpoints included corticosteroid-free clinical remission, endoscopic improvement, histologic endoscopic mucosal improvement, all at Week 44 and maintenance of clinical remission at Week 44 in subjects who achieved clinical remission 12 weeks after intravenous TREMFYA induction treatment (see Table 12 ).

Table 12: Proportion of Adult Subjects with Moderately to Severely Active Ulcerative Colitis Meeting Efficacy Endpoints at Week 44 in Trial UC2
Endpoint	Placebo	TREMFYA 100 mg Every 8 Weeks Subcutaneous Injection TREMFYA 100 mg as a subcutaneous injection every 8 weeks after the induction regimen	TREMFYA 200 mg Every 4 Weeks Subcutaneous Injection TREMFYA 200 mg as a subcutaneous injection every 4 weeks after the induction regimen	Treatment Difference vs Placebo (95% CI)
Endpoint	Placebo			TREMFYA 100 mg	TREMFYA 200 mg
Clinical remission A stool frequency subscore of 0 or 1 and not increased from induction baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability
Total population Subjects who achieved clinical response 12 weeks following the intravenous administration of TREMFYA in either induction trial UC1 or induction dose-finding trial UC4	N=190 19%	N=188 45%	N=190 50%	25% (16%, 34%) p <0.001, adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for randomization stratification factors	30% (21%, 38%)
Prior biologic and/or JAK inhibitor failure Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) and/or a Janus kinase (JAK) inhibitor for ulcerative colitis	N=75 8%	N=77 40%	N=88 40%
Without prior biologic or JAK inhibitor failure Includes subjects that were biologic and/or JAK inhibitor naïve and subjects with biologic and/or JAK inhibitor exposure who did not meet criteria for failure. Of these, 7 subjects in the placebo group, 6 subjects in the TREMFYA 100 mg group, and 6 subjects in the TREMFYA 200 mg group were previously exposed to, but did not fail, a biologic or JAK inhibitor	N=115 26%	N=111 49%	N=102 59%
Corticosteroid-free clinical remission Not requiring any treatment with corticosteroids for at least 8 weeks prior to week 44 and also meeting the criteria for clinical remission at week 44
Total population	N=190 18%	N=188 45%	N=190 49%	26% (17%, 34%)	29% (20%, 38%)
Prior biologic and/or JAK inhibitor failure	N=75 7%	N=77 40%	N=88 40%
Without prior biologic or JAK inhibitor failure	N=115 26%	N=111 49%	N=102 57%
Endoscopic improvement An endoscopy subscore of 0 or 1 with no friability
Total population	N=190 19%	N=188 49%	N=190 52%	30% (21%, 38%)	31% (22%, 40%)
Prior biologic and/or JAK inhibitor failure	N=75 8%	N=77 45%	N=88 42%
Without prior biologic or JAK inhibitor failure	N=115 26%	N=111 52%	N=102 60%
Histologic endoscopic mucosal improvement (HEMI) An endoscopy subscore of 0 or 1 with no friability and Geboes score ≤3.1 (indicating neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue)
Total population	N=190 17%	N=188 44%	N=190 48%	26% (17%, 34%)	30% (21%, 38%)
Prior biologic and/or JAK inhibitor failure	N=75 8%	N=77 38%	N=88 39%
Without prior biologic or JAK inhibitor failure	N=115 23%	N=111 48%	N=102 56%
Maintenance of Clinical Remission at Week 44 in subjects who achieved clinical remission after 12 weeks of induction
Total population Subjects who achieved clinical remission 12 weeks following intravenous administration of TREMFYA in either induction trial UC1 or induction dose-finding trial UC4	N=59 34%	N=66 61%	N=69 72%	26% (9%, 43%) p <0.01, adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for randomization stratification factors	38% (23%, 54%)
Prior biologic and/or JAK inhibitor failure	N=15 27%	N=20 60%	N=18 56%
Without prior biologic or JAK inhibitor failure Includes subjects that were biologic and/or JAK inhibitor naïve and subjects with biologic and/or JAK inhibitor exposure who did not meet criteria for failure. Of these, 3 subjects in the placebo group, 3 subjects in the TREMFYA 100 mg group, and 3 subjects in the TREMFYA 200 mg group were previously exposed to, but did not fail, a biologic or JAK inhibitor.	N=44 36%	N=46 61%	N=51 78%

Trial UC2 was not designed to evaluate the relationship of histologic endoscopic mucosal improvement at Week 44 to disease progression and long-term outcomes.

Endoscopic Assessment

Normalization of the endoscopic appearance of the mucosa (endoscopic remission) was defined as ES of 0. In UC2, greater proportions of subjects treated with TREMFYA 100 mg every 8 weeks or TREMFYA 200 mg every 4 weeks achieved endoscopic remission at Week 44 compared to placebo-treated subjects (35% and 34%, respectively, vs. 15%).

Trial UC4

In trial UC4 (NCT05528510), subjects with moderately to severely active ulcerative colitis were randomized 1:1:1 to receive TREMFYA 400 mg subcutaneous induction at Weeks 0, 4, and 8 followed by TREMFYA 200 mg subcutaneous maintenance every 4 weeks beginning at Week 12; TREMFYA 400 mg subcutaneous induction at Weeks 0, 4, and 8 followed by TREMFYA 100 mg subcutaneous maintenance every 8 weeks beginning at Week 16; or placebo. Efficacy was evaluated in 395 randomized subjects.

At baseline in trial UC4, the median mMS was 7; 65% of subjects had severely active disease (mMS ≥7), and 59% of subjects had an ES of 3. A total of 41% of subjects had previously failed treatment with at least one biologic therapy, JAK inhibitor, and/or S1PRM, 57% were biologic, JAK inhibitor, and S1PRM naïve, and 2% had previously received but had not failed a biologic, JAK inhibitor, or S1PRM. The median age of subjects was 40 years (ranging from 18 to 80 years); 39% were female; and 64% identified as White, 30% as Asian, and 3% as Black or African American.

Enrolled subjects were permitted to use stable doses of oral aminosalicylates, immunomodulators (azathioprine, 6-mercaptopurine, methotrexate), and/or oral corticosteroids (up to 20 mg/day prednisone or equivalent). At baseline, 78% of subjects were receiving aminosalicylates, 21% of subjects were receiving immunomodulators, and 33% of subjects were receiving corticosteroids. Concomitant biologic therapies, JAK inhibitors, or S1PRMs were not permitted.

In trial UC4, the primary endpoint was clinical remission at Week 12 as defined by the mMS. Secondary endpoints at Week 12 included endoscopic improvement, clinical response, and histologic-endoscopic mucosal improvement. Secondary endpoints at Week 24 included clinical remission and endoscopic improvement. The results of analyses of multiplicity-controlled efficacy endpoints in trial UC4 are shown in Table 13.

Table 13: Proportion of Adult Subjects with Moderately to Severely Active Ulcerative Colitis Meeting Efficacy Endpoints at Week 12 and Week 24 in Trial UC 4
Endpoint	Placebo	TREMFYA 400 mg Subcutaneous Injection at Weeks 0, 4, and 8 At baseline, subjects were randomized 1:1:1 to receive subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg every 8 weeks; subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 200 mg every 4 weeks; or placebo. Because dosing is identical through Week 12, subjects in both TREMFYA groups are combined for the analysis of the Week 12 endpoints		Treatment Difference vs Placebo (95% CI) The adjusted treatment difference and the CIs were based on the common risk difference calculated using Mantel-Haenszel stratum weights and Sato variance estimator. The stratification variables used were prior biologic, JAK inhibitor, and/or S1PRM failure status (Yes or No), and Mayo endoscopy subscore at baseline (moderate [2] or severe [3]).
Week 12
Clinical remission A stool frequency subscore of 0 or 1 and not increased from induction baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability
Total Population	N=130 7%	N=265 26%		19% (12%, 26%) p <0.001
Prior biologic, JAK inhibitor, and/or S1PRM failure Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab), a Janus kinase (JAK) inhibitor, and/or S1PRM for ulcerative colitis	N=55 4%	N=107 14%
Without prior biologic, JAK inhibitor, or S1PRM failure Includes subjects that were biologic, JAK inhibitor, and S1PRM naïve and subjects with biologic, JAK inhibitor, and/or S1PRM exposure, who did not meet criteria for failure. Of these, 3 subjects in the placebo group and 3 subjects in the TREMFYA group were previously exposed to, but did not fail, a biologic, JAK inhibitor, or S1PRM	N=75 9%	N=158 35%
Endoscopic improvement An endoscopy subscore of 0 or 1 with no friability
Total Population	N=130 12%	N=265 36%		24% (17%, 32%)
Prior biologic, JAK inhibitor, and/or S1PRM failure	N=55 5%	N=107 22%
Without prior biologic, JAK inhibitor, or S1PRM failure	N=75 16%	N=158 46%
Clinical response Decrease from baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1 point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1
Total population	N=130 35%	N=265 66%		30% (21%, 40%)
Prior biologic, JAK inhibitor, and/or S1PRM failure	N=55 25%	N=107 56%
Without prior biologic, JAK inhibitor, or S1PRM failure	N=75 43%	N=158 73%
Histologic endoscopic mucosal improvement An endoscopy subscore of 0 or 1 with no friability and Geboes score ≤3.1 (indicating neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue)
Total Population	N=130 10%	N=265 30%		20% (13%, 27%)
Prior biologic, JAK inhibitor, and/or S1PRM failure	N=55 5%	N=107 19%
Without prior biologic, JAK inhibitor, or S1PRM failure	N=75 13%	N=158 38%
Week 24
Endpoint	Placebo	TREMFYA 100 mg Subcutaneous Injection every 8 weeks starting at Week 16	TREMFYA 200 mg Subcutaneous Injection every 4 weeks starting at Week 12	Treatment difference vs Placebo (95% CI)
				TREMFYA 100 mg	TREMFYA 200 mg
Clinical remission
Total Population	N=130 10%	N=134 34%	N=131 34%	23% (14%, 33%)	24% (15%, 34%)
Prior biologic, JAK inhibitor, and/or S1PRM failure	N=55 5%	N=55 13%	N=52 25%
Without prior biologic, JAK inhibitor, or S1PRM failure	N=75 13%	N=79 48%	N=79 41%
Endoscopic improvement
Total Population	N=130 12%	N=134 39%	N=131 44%	27% (17%, 37%)	32% (22%, 41%)
Prior biologic, JAK inhibitor, and/or S1PRM failure	N=55 5%	N=55 16%	N=52 35%
Without prior biologic, JAK inhibitor, or S1PRM failure	N=75 16%	N=79 54%	N=79 49%

Rectal Bleeding and Stool Frequency Subscores

Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 3 in subjects treated with subcutaneous TREMFYA compared to placebo.

Endoscopic Assessment

Normalization of the endoscopic appearance of the mucosa (endoscopic remission) was defined as ES of 0. At Week 12 of UC4, a greater proportion of subjects treated with TREMFYA compared to placebo-treated subjects achieved endoscopic remission (16% vs 2%). Greater proportions of subjects treated with TREMFYA 100 mg every 8 weeks or TREMFYA 200 mg every 4 weeks achieved endoscopic remission at Week 24 compared to placebo-treated subjects (20% and 27%, respectively, vs 3%).

Clinical Studies in Adults with Crohn's Disease

The efficacy and safety of TREMFYA were assessed in three randomized, double-blind, placebo-controlled trials that enrolled adult subjects with moderately to severely active Crohn's disease who had a history of inadequate response, loss of response, or intolerance to oral corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, methotrexate), and/or biologic therapy (TNF blockers or vedolizumab). Moderately to severely active Crohn's disease was defined as a Crohn's Disease Activity Index (CDAI) score of ≥220 and a Simple Endoscopic Score for Crohn's Disease (SES-CD) of ≥6 (or ≥4 for subjects with isolated ileal disease). Subjects were permitted to use stable doses of oral corticosteroids (prednisone ≤40 mg/day or equivalent), immunomodulators (azathioprine, 6-mercaptopurine, methotrexate), and/or aminosalicylates.

Trials CD1 and CD2

In trial CD1 (NCT03466411), 361 subjects were randomized to receive intravenous TREMFYA 200 mg at Weeks 0, 4, and 8 (N = 285) or placebo (N = 76). The median age of subjects enrolled into trial CD1 was 33 years (range: 18 – 83 years); 46% were female; and 75% identified as White, 22% as Asian, 1% as Black or African American, <1% as Native Hawaiian or Pacific Islander, and 2% did not report their racial group. The median baseline CDAI score was 285 (range: 220 – 442), and the median baseline SES-CD score was 11 (range: 4 – 39). Of the randomized subjects, 52% of subjects had previously failed (inadequate response, loss of response, or intolerance) treatment with at least one biologic therapy, 43% were biologic-naïve, and 6% had previously received but had not failed a biologic. At baseline, 37% of subjects were receiving oral corticosteroids and 30% of subjects were receiving immunomodulators (azathioprine, 6-mercaptopurine, methotrexate).

In trial CD2 (NCT03466411), 360 subjects were randomized to receive intravenous TREMFYA 200 mg at Weeks 0, 4, and 8 (N = 288) or placebo (N = 72). The median age of subjects enrolled into trial CD2 was 33 years (range:18 – 72 years); 39% were female; and 73% identified as White, 23% as Asian, 1% as Black or African American, <1% as Native Hawaiian or Pacific Islander, and 2% did not report their racial group. The median baseline CDAI score was 286 (range: 220 – 442) and the median baseline SES-CD score was 11 (range: 4 – 42). Of the randomized subjects, 52% of subjects had previously failed (inadequate response, loss of response, or intolerance) treatment with at least one biologic therapy, 41% were biologic-naïve, and 7% had previously received but had not failed a biologic. At baseline, 36% of the subjects were receiving oral corticosteroids and 31% of the subjects were receiving immunomodulators (azathioprine, 6-mercaptopurine, methotrexate).

The results of efficacy endpoints at Week 12 for CD1 and CD2 trials are shown in Table 14.

Table 14: Proportion of Adult Subjects with Moderately to Severely Active Crohn’s Disease Meeting Efficacy Endpoints at Week 12 in Trials CD1 and CD2
Trial CD1			Trial CD2
Endpoint	Placebo	TREMFYA 200 mg Intravenous Infusion TREMFYA 200 mg as an intravenous infusion at Weeks 0, 4, and 8.	Treatment Difference vs Placebo (95% CI) The adjusted treatment difference and the confidence intervals (CIs) were based on the common risk difference test using Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification variables used were baseline CDAI score (≤300 or >300), baseline SES-CD score (≤12 or >12), BIO-Failure status (Yes or No), and baseline corticosteroid use (Yes or No).	Placebo	TREMFYA 200 mg Intravenous Infusion	Treatment Difference vs Placebo (95% CI)
Clinical remission Clinical remission is defined as CDAI score <150. at Week 12
Total population	N=76 20%	N=285 47%	27% (17%, 38%) p <0.001	N=72 15%	N=288 47%	31% (21%, 41%)
Prior biologic failure Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) for Crohn's disease.	N=39 21%	N=147 44%	N=39 15%	N=148 47%
Without prior biologic failure Includes subjects that were biologic naïve and subjects with prior biologic exposure who did not meet criteria for failure. In CD1, 3 subjects in the placebo group and 18 subjects in the intravenous TREMFYA 200 mg group were previously exposed to but did not fail a biologic therapy. In CD2, 6 subjects in the placebo group and 19 subjects in the intravenous TREMFYA 200 mg group were previously exposed to but did not fail a biologic therapy.	N=37 19%	N=138 49%	N=33 15%	N=140 48%
Endoscopic response Endoscopic response is defined as >50% improvement from baseline in SES-CD score. at Week 12
Total population	N=76 9%	N=285 36%	27% (19%, 35%)	N=72 13%	N=288 34%	21% (11%, 30%)
Prior biologic failure	N=39 3%	N=147 26%	N=39 8%	N=148 28%
Without prior biologic failure	N=37 16%	N=138 47%	N=33 18%	N=140 40%
Clinical remissionat Week 12 and endoscopic responseat Week 12
Total population	N=76 3%	N=285 20%	17% (11%, 23%)	N=72 3%	N=288 21%	18% (12%, 24%)
Prior biologic failure	N=39 3%	N=147 14%	N=39 3%	N=148 19%
Without prior biologic failure	N=37 3%	N=138 26%	N=33 3%	N=140 24%

Stool Frequency and Abdominal Pain

Greater reductions in stool frequency and abdominal pain were observed as early as Week 4 in subjects treated with intravenous TREMFYA compared to placebo.

Trial CD3

In trial CD3, 340 subjects were randomized in a 1:1:1 ratio to receive subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg every 8 weeks (with the first dose given at Week 16); subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 200 mg every 4 weeks (with the first dose given at Week 12); or placebo. The median age of subjects enrolled into trial CD3 was 36 years (range: 18 – 83 years); 41% were female; and 66% identified as White, 22% as Asian, 3% as Black or African American, and 9% did not report their racial group. The median baseline CDAI score was 291 (range: 220 – 447), and the median baseline SES-CD score was 10 (range: 4 – 40). Of the randomized subjects, 46% of subjects had previously failed (inadequate response, loss of response, or intolerance) treatment with at least one biologic therapy, 47% were biologic naïve, and 7% had previously received but had not failed a biologic. At baseline, 30% of the subjects were receiving oral corticosteroids and 29% of the subjects were receiving immunomodulators (azathioprine, 6-mercaptopurine, methotrexate).

In trial CD3, the coprimary endpoints were clinical remission at Week 12 and endoscopic response at Week 12 compared to placebo. Additional efficacy endpoints included clinical response at Week 12, clinical remission at Week 24, clinical remission at Week 48, and endoscopic response at Week 48. The results of analyses of multiplicity-controlled efficacy endpoints in trial CD3 are shown in Table 15.

Table 15: Proportion of Adult Subjects with Moderately to Severely Active Crohn's Disease Meeting Efficacy Endpoints in Trial CD3
Endpoint	Placebo	TREMFYA 400 mg Subcutaneous Injection at Weeks 0, 4, and 8 At baseline, subjects were randomized 1:1:1 to receive subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg every 8 weeks; subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 200 mg every 4 weeks; or placebo. Because dosing is identical through Week 12, subjects in both TREMFYA groups are combined for the analysis of the Week 12 endpoints.		Treatment Difference vs Placebo (95% CI) The adjusted treatment difference and the CIs were based on the common risk difference test using Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification variables used were baseline CDAI score (≤300 or >300), baseline SES-CD score (≤12 or >12), BIO-Failure status (Yes or No). CI = confidence interval
Week 12
Clinical Remission Clinical remission is defined as CDAI score <150.
Total population	N=115 22%	N=225 56%		34% (24%, 44%) p<0.001
Prior biologic failure Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) for Crohn's disease.	N=53 17%	N=104 60%
Without prior biologic failure Includes subjects that were biologic naïve and subjects with prior biologic exposure who did not meet criteria for failure. Of these, 8 subjects in the placebo group and 17 subjects in the subcutaneous TREMFYA 400 mg group, were previously exposed to but did not fail a biologic therapy.	N=62 26%	N=121 52%
Endoscopic Response Endoscopic response is defined as >50% improvement from baseline in SES-CD score.
Total population	N=115 15%	N=225 34%		19% (10%, 28%)
Prior biologic failure	N=53 11%	N=104 27%
Without prior biologic failure	N=62 18%	N=121 40%
Clinical Response Clinical response is defined as ≥100-point decrease from baseline in CDAI total score.
Total population	N=115 33%	N=225 72%		39% (29%, 50%)
Prior biologic failure	N=53 28%	N=104 76%
Without prior biologic failure	N=62 37%	N=121 69%
Weeks 24 and 48
Endpoint	Placebo	TREMFYA 100 mg Subcutaneous Injection every 8 weeks starting at Week 16	TREMFYA 200 mg Subcutaneous Injection every 4 weeks starting at Week 12	Treatment difference vs Placebo (95% CI)
Endpoint	Placebo			TREMFYA 100 mg	TREMFYA 200 mg
Clinical Remissionat Week 24
Total population	N=115 21%	N=114 61%	N=111 58%	39% (28%, 51%)	37% (25%, 48%)
Prior biologic failure	N=53 19%	N=54 63%	N=50 52%
Without prior biologic failure Includes subjects that were biologic naïve and subjects with prior biologic exposure who did not meet criteria for failure. Of these, 8 subjects in the placebo group, 7 subjects in the subcutaneous TREMFYA 100 mg group, and 10 subjects in the subcutaneous TREMFYA 200 mg group were previously exposed to but did not fail a biologic therapy.	N=62 23%	N=60 58%	N=61 62%
Clinical Remissionat Week 48
Total population	N=115 17%	N=114 59%	N=111 65%	41% (30%, 52%)	47% (36%, 58%)
Prior biologic failure	N=53 9%	N=54 56%	N=50 60%
Without prior biologic failure	N=62 24%	N=60 62%	N=61 69%
Endoscopic Responseat Week 48
Total population	N=115 5%	N=114 39%	N=111 48%	34% (24%, 44%)	42% (32%, 53%)
Prior biologic failure	N=53 0%	N=54 33%	N=50 52%
Without prior biologic failure	N=62 10%	N=60 45%	N=61 44%

Stool Frequency and Abdominal Pain

Greater reductions in stool frequency and abdominal pain were observed as early as Week 4 in subjects treated with subcutaneous TREMFYA 400 mg compared to placebo.

Endoscopic Remission at Week 48

Endoscopic remission was defined as an SES-CD score ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component. In trial CD3, a greater proportion of subjects treated with either TREMFYA regimen (i.e., subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg at Week 16 and every 8 weeks thereafter or subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 200 mg at Week 12 and every 4 weeks thereafter) achieved endoscopic remission, compared to placebo-treated subjects (31% and 40%, respectively, vs. 6%).

Tremfya | Agrace Pharma