Open-label Extension Week Research Articles

Switch to bictegravir/emtricitabine/tenofovir alafenamide from dolutegravir-based therapy.

To evaluate the efficacy and safety of 96 weeks of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) treatment in participants switching from dolutegravir (DTG)-based therapy. Studies 1489 (NCT02607930) and 1490 (NCT02607956) were phase 3 randomized, double-blind, active-controlled, first-line therapy trials in people with HIV-1. After 144 weeks of DTG-based or B/F/TAF treatment, participants could enter a 96-week open-label extension (OLE) of B/F/TAF. A pooled analysis evaluated viral suppression (HIV-1 RNA <50 copies/ml) and changes in CD4 + cell count at OLE Weeks 48 and 96, treatment-emergent resistance, safety, and tolerability after switch from a DTG-based regimen to B/F/TAF. Outcomes by prior treatment were summarized using descriptive statistics and compared by two-sided Wilcoxon rank sum test. At OLE Week 96, participants who switched to B/F/TAF ( N = 519) maintained high levels of virologic suppression (99.5 and 99.1% in those switching from DTG/abacavir/lamivudine and DTG+F/TAF, respectively) and CD4 + cell count, with no treatment-emergent resistance to B/F/TAF. Twenty-one participants experienced drug-related adverse events after switching, with diarrhea, weight gain, and headache occurring most commonly. There were no cases of proximal renal tubulopathy, drug-related Grade 4 adverse events, or serious adverse events. Two participants discontinued B/F/TAF due to treatment-related adverse events. Participants who switched from DTG/abacavir/lamivudine experienced statistically significant greater weight gain than those who switched from DTG+F/TAF; however, median weight change from the blinded phase baseline to OLE Week 96 was numerically similar across treatment groups. This medium-term analysis demonstrates the safety and efficacy of switching to B/F/TAF from a DTG-containing regimen in people with HIV-1.

P1009 Efficacy and safety of 4 years of continuous ozanimod treatment: an interim analysis of the True North open-label extension study

Abstract Background The phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod (OZA) over 52 wk in patients (pts) with moderately to severely active ulcerative colitis (UC); the ongoing TN open-label extension (OLE) is assessing long-term efficacy and safety. This interim analysis of the TN OLE assessed pts with up to ~4 y of continuous OZA treatment. Methods Clinical responders after 52 wk of continuous OZA treatment (0.92 mg/d) during TN who subsequently entered the TN OLE were included in this analysis. Data were analysed up to OLE Week (W) 142, representing up to ~4 y of continuous OZA treatment. Symptomatic response (≥1-point and ≥30% decrease from baseline [BL] in the combined 6-point rectal bleeding subscore [RBS] + stool frequency subscore [SFS] and ≥1-point decrease in RBS or absolute RBS ≤1) and symptomatic remission (RBS=0 and SFS ≤1 [and ≥1-point decrease from BL SFS]) were evaluated from OLE W5 through OLE W142. Clinical remission, clinical response, endoscopic improvement, and corticosteroid (CS)-free remission were evaluated at OLE W46, W94, and W142. Endpoints were evaluated using observed case (OC) and nonresponder imputation (NRI) analyses. Adverse events were monitored throughout TN and the OLE. Results In all, 131 pts entered the OLE after achieving clinical response on OZA at W52 in TN. At the data cutoff, 87.0% of pts completed OLE W46, 71.8% completed OLE W94, and 64.1% completed OLE W142. Most (67.9%) pts had left-sided UC disease, 23.7% had concomitant CS use at TN BL, and 32.1% had prior exposure to tumour necrosis factor inhibitors. Symptomatic response and symptomatic remission were observed in 100.0% and 84.4% of pts, respectively, at OLE W5 in the OC analysis (93.1% and 78.6%, respectively, in the NRI analysis). By OLE W142, symptomatic response and symptomatic remission rates were 98.7% and 88.3%, respectively, in the OC analysis and 58.0% and 51.9%, respectively, in the NRI analysis. Rates of clinical and endoscopic endpoints during the OLE are shown in Figure 1A (OC) and 1B (NRI). Of note, 65.3% of TN W52 clinical responders achieved clinical remission and CS-free remission at OLE W142 in the OC analysis (35.9% in the NRI analysis). With this additional year of follow-up in the OLE, there were no new cases of bradycardia, third-degree atrioventricular block, hypertension, herpes zoster, or macular oedema, and no clinically meaningful change in malignancy exposure-adjusted incidence rates (Table). No serious hepatic events occurred. Conclusion Clinical responders after 1 y on OZA sustained response for an additional 3 y and achieved clinical remission with continuous OZA exposure. OZA is a safe, tolerable, and durable therapy for pts with UC.

Bimekizumab Efficacy in Patients with Moderate to Severe Plaque Psoriasis and Hypertension, Elevated Body Mass Index, or Hyperglycemia: Results Through 3 years of Treatment in 5 Phase 3/3b Trials

Introduction: Patients with moderate to severe plaque psoriasis have a higher risk of cardiometabolic comorbidities than the general population.1,2 Here, response to bimekizumab (BKZ) in psoriasis patients with hypertension, elevated body mass index (BMI), or hyperglycemia at baseline is reported through 3 years of treatment.&#x0D; Procedure/study: Data were pooled from the following trials: BE SURE, BE VIVID, BE READY, their open-label extension (OLE) BE BRIGHT, and BE RADIANT.3–7 Included patients received BKZ 320 mg every 4 weeks (Q4W) to Week 16, then Q4W or Q8W in the maintenance period and on OLE entry. All received BKZ Q8W from Week 64 (BE RADIANT)/OLE Week 48 (BE BRIGHT) or next scheduled visit (dose groups were combined in this analysis). Psoriasis Area and Severity Index (PASI) ≤2, ≥90% improvement from baseline in PASI (PASI 90), and PASI 100 responses were evaluated in patients with psoriasis and concurrent hypertension (systolic &gt;130 mmHg or diastolic &gt;85 mmHg), elevated BMI (&gt;30 kg/m2), or hyperglycemia (≥140 mg/dL or ≥7.8 mmol/L), based on objective laboratory measurements at baseline. Data are reported using modified non-responder imputation: patients who discontinued due to lack of efficacy or treatment-related adverse events were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data.&#x0D; Results: Of 1,107 BKZ-randomized patients who entered the OLEs, 546, 493, and 81 had hypertension, elevated BMI, and hyperglycemia at baseline, respectively. At Week 16, 91.3% of all BKZ-treated patients had PASI ≤2; high response rates were also observed in patients with hypertension (88.9%), elevated BMI (87.8%), and hyperglycemia (87.7%). At Year 3 (OLE Week 96), PASI ≤2 response rates were 91.3% (all patients), 90.0% (hypertension), 89.4% (elevated BMI), and 91.1% (hyperglycemia). At Week 16, 90.9%/65.5% of all BKZ-treated patients achieved PASI 90/100; high responses were also observed in patients with hypertension (89.0%/62.8%), elevated BMI (87.6%/60.3%), and hyperglycemia (86.4%/64.2%). At Year 3, PASI 90/100 response rates were 90.7%/70.0% (all patients), 89.3%/66.3% (hypertension), 89.2%/66.2% (elevated BMI), and 87.9%/57.7% (hyperglycemia).&#x0D; Conclusion: High levels of complete/near-complete skin clearance achieved at Week 16 were durable through 3 years’ BKZ treatment in psoriasis patients, including those who had baseline hypertension, elevated BMI, or hyperglycemia.&#x0D; Funding: UCB Pharma.

Bimekizumab Efficacy Through 3 Years in Patients with Moderate to Severe Plaque Psoriasis: Long-term Pooled Analysis from BE BRIGHT

Introduction: A key factor of biologic discontinuation in plaque psoriasis patients is loss of response over time; long-term treatment efficacy is therefore important.1 Here, 3-year efficacy of bimekizumab (BKZ) from a pooled analysis of patients with moderate to severe plaque psoriasis across 3 phase 3 clinical trials and their open-label extension (OLE) is reported.&#x0D; Procedure/study: Data were pooled from the 52-week BE VIVID and 56-week BE SURE and BE READY phase 3 trials, and their common OLE BE BRIGHT.2–5 Included patients received BKZ 320 mg every 4 weeks (Q4W) then switched to Q4W or Q8W maintenance dosing from Week 16 onwards, and entered the OLE; from OLE Week 48 or the next scheduled visit, all patients received BKZ 320 mg Q8W. Proportions of patients achieving ≥90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90), PASI 100, and Dermatology Life Quality Index (DLQI) 0/1 are reported through Year 3 using modified non-responder imputation: patients who discontinued treatment due to lack of efficacy or treatment-related adverse events were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data.&#x0D; Results: 771 patients received BKZ continuously in the feeder studies and entered the OLE. Among these, at Week 16, 90.9%, 65.8%, and 71.5% achieved PASI 90, PASI 100, and DLQI 0/1, respectively. At Year 1, 93.7%, 76.6%, and 83.1% of all BKZ-treated patients achieved PASI 90 (Week 52), PASI 100 (Week 52), and DLQI 0/1 (Week 48/52), respectively. Responses were durable to Year 3 (OLE Week 96): 91.0%, 70.3%, and 82.8% of all BKZ-treated patients achieved PASI 90, PASI 100, and DLQI 0/1, respectively. Similar trends were observed in the subset of patients that received BKZ Q4W/Q8W/Q8W (initial/maintenance/OLE).&#x0D; Conclusion: High and durable clinical and health-related quality of life responses were observed over 3 years of BKZ treatment across 3 phase 3 trials and their OLE.&#x0D; Funding: UCB Pharma.

PS14 Bimekizumab response up to 3 years in patients with moderate-to-severe plaque psoriasis who responded at week 16: post hoc results from the BE BRIGHT open-label extension trial

Abstract Treatment with the interleukin-17A/F inhibitor bimekizumab (BKZ) has demonstrated maintenance of efficacy and health-related quality of life (HRQoL) outcomes over 2 years. The objective of this analysis was to assess the long-term response in patients with moderate-to-severe plaque psoriasis who achieved Psoriasis Area and Severity Index (PASI) ≤ 2, a key treat-to-target outcome, after 16 weeks of BKZ treatment over 3 years. Patients who completed a 52- (BE VIVID) or 56-week (BE SURE and BE READY) phase III feeder study were eligible to enrol in the BE BRIGHT open-label extension (OLE) (NCT03370133, NCT03412747, NCT03410992 and NCT03598790). Upon OLE entry, patients received BKZ 320 mg Q4W or Q8W based on feeder study treatment and week 52/56 PASI 90 (≥ 90% improvement in PASI) response. Patients switched from BKZ Q4W to Q8W at OLE week 24 (based on investigator discretion and PASI 90 response), or OLE week 48/next scheduled visit (all patients). Achievement of body surface area (BSA) ≤ 1% and PASI 0 (all studies), and Dermatology Life Quality Index (DLQI)0/1 (BE SURE and BE READY only due to schedule differences) is reported among week 16 PASI ≤ 2 responders through year 1 (feeder study week 52/56) and year 3 (OLE week 96). Analysed patients were randomized to BKZ, received BKZ maintenance dosing from feeder study week 16 and entered the OLE, including a subset who received BKZ Q4W through to week 16 then continuous BKZ Q8W (Q4W/Q8W/Q8W). Missing data were imputed using modified nonresponder imputation (mNRI): patients who discontinued treatment due to lack of efficacy or treatment-related adverse events were considered nonresponders; multiple imputation was used for all other missing data. The week 16 responder rate is also reported (NRI). At baseline, 989 patients were randomized to BKZ; 87.8% (n = 868) achieved PASI ≤ 2 at week 16. Of these, 694 entered the OLE. Among week 16 PASI ≤ 2 responders (n = 694), 91.9% and 82.3% achieved BSA ≤ 1% and PASI 0 after year 1 (52 weeks), and 88.6% and 74.1% after year 3, respectively. Among week 16 PASI ≤ 2 responders (n = 445), 87.8% and 86.8% achieved DLQI 0/1 after year 1 (56 weeks) and year 3, respectively. Of the week 16 PASI ≤ 2 responders who received BKZ Q4W/Q8W/Q8W (n = 189), 95.2% and 87.6% achieved BSA ≤ 1% and PASI 0 after 1 year (52 weeks), and 93.4% and 79.7% after 3 years, respectively. Among the Q4W/Q8W/Q8W patients, 94.1% and 91.2% achieved DLQI 0/1 after year 1 (56 weeks) and year 3, respectively. The BKZ provided long-term efficacy and HRQoL benefits. Among week 16 PASI ≤ 2 responders, the vast majority sustained high levels of clinical and HRQoL responses through 3 years of BKZ treatment, including those who received BKZ Q4W/Q8W/Q8W. Funding: UCB Pharma. Medical writing: Costello Medical.

Longitudinal Clinical and MRI Outcomes in Relapsing Multiple Sclerosis (RMS) Patients After Short-term Ponesimod Treatment Interruption and Re-initiation (P6-3.007)

Longitudinal Clinical and MRI Outcomes in Relapsing Multiple Sclerosis (RMS) Patients After Short-term Ponesimod Treatment Interruption and Re-initiation (P6-3.007)

P719 Symptomatic improvement and long-term stability of ulcerative colitis symptoms over 3 years of ozanimod treatment

Abstract Background The phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod over 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). Pts completing 52 weeks of TN were eligible for the ongoing TN open-label extension (OLE) assessing the long-term efficacy and safety of ozanimod. Presented here is the interim analysis of the TN OLE focused on the symptomatic efficacy of ozanimod in pts with approximately 3 years of continuous ozanimod treatment. Methods Pts who achieved clinical response after receiving 52 weeks of continuous ozanimod during TN and subsequently entered the TN OLE were evaluated (data cutoff: 10 January 2022, at which point the OLE Week 94 disposition was available for pts). Patient-reported (rectal bleeding subscore [RBS] and stool frequency subscore [SFS]) and clinician-reported (Physician’s Global Assessment) symptomatic outcomes were determined. Symptomatic clinical response (partial Mayo score [PMS] ≥1 point and ≥30% reduction in PMS with ≥1-point decrease in RBS or absolute RBS of ≤1) and symptomatic clinical remission (RBS=0 and SFS ≤1 [and decrease of ≥1 point from baseline SFS]) were evaluated at OLE Week 5 through OLE Week 94 (146 weeks of continuous ozanimod treatment) using observed case (OC) and nonresponder imputation (NRI) analyses. PMS, RBS, and SFS were assessed from TN baseline to OLE Week 94. Results In all, 131 pts entered the OLE after achieving clinical response following 52 weeks of continuous ozanimod during TN. At data cutoff, 87.0% completed OLE Week 46 (98 weeks of continuous ozanimod) and 71.8% completed OLE Week 94 (146 weeks of continuous ozanimod). Pts had a mean age of 44 years and 52% were female. Most (68%) had left-sided UC disease, 24% had concomitant corticosteroid use at TN baseline, and 32% had prior exposure to tumor necrosis factor inhibitors. Symptomatic clinical response and symptomatic clinical remission were observed in 100.0% (Figure 1A) and 84.4% (Figure 2A) of pts, respectively, at OLE Week 5 in the OC analysis (93.1% [Figure 1B] and 78.6% [Figure 2B] in the NRI analysis). Rates of symptomatic clinical response and symptomatic clinical remission were maintained through OLE Week 94 in the OC analysis and decreased slightly over time in the NRI analysis. Reductions in mean PMS from baseline were observed during TN and sustained through OLE Week 94. Reductions from TN baseline in RBS (Figure 3) and SFS (Figure 4) were also observed through OLE Week 94. Conclusion This interim analysis of the TN OLE focusing on symptomatic endpoints found that most pts who achieved clinical response after 1 year of ozanimod sustained symptom control for another 2 years.

P687 Durability of recaptured response to ozanimod during the True North open-label extension

Abstract Background Ozanimod is approved in the EU, US, and other countries for treatment of moderately to severely active ulcerative colitis (UC) in adults. In the phase 3 True North (TN) study, ozanimod 0.92 mg once daily demonstrated efficacy and safety for up to 52 weeks in patients (pts) with moderately to severely active UC. This open-label extension (OLE) analysis evaluated the long-term durability of ozanimod based on symptomatic and clinical endpoints in pts who experienced disease relapse while on placebo during the TN maintenance period (MP) and then recaptured response to ozanimod during the OLE. Methods Responders to ozanimod 10-week induction therapy were rerandomised 1:1 to ozanimod (n=230) or placebo (n=227); this OLE interim analysis (data cutoff: January 10, 2022, at which point the OLE Week 94 disposition was available for pts) included all pts who relapsed on placebo during the MP and reinitiated ozanimod in the OLE. Endpoints included symptomatic response and remission, clinical response and clinical remission (which include endoscopy subscores), and corticosteroid (CS)-free remission (clinical remission while off CS for ≥12 weeks) evaluated using observed case (OC) and nonresponder imputation (NRI) analyses, and mean total Mayo score over time. Results A total of 77/227 pts (34%) rerandomised to placebo during MP experienced a relapse after a median of 12.7 weeks and all entered the OLE. Symptomatic response was achieved by 46/73 (63%) pts 5 weeks after restarting ozanimod in the OLE (NRI analysis: 60% at OLE Week 5) and in 32/33 (97%) by OLE Week 94 in the OC analysis. Symptomatic remission was also achieved by OLE Week 5 by 24/73 (33%) pts. Sustained efficacy of ozanimod reinitiation was also demonstrated comparing OLE Weeks 46 and 94 across clinical endpoints by OC analysis (clinical response, 76% and 86%; clinical remission, 44% and 59%; CS-free remission, 37% and 52%) and NRI analysis (clinical response, 42% and 31%; clinical remission, 25% and 22%; CS-free remission, 21% and 20%) (Figure 1). In addition, 56.3%, 52.6%, and 50% of pts who experienced clinical response, clinical remission, and CS-free remission, respectively, at OLE Week 46 continued to sustain these endpoints at OLE Week 94. Reductions in mean total Mayo score at OLE Week 46 were also sustained through OLE Week 94 (Figure 2). Conclusion Response to ozanimod was regained after temporary therapy discontinuation for most pts, and this response was durable for up to 2 years as demonstrated by both symptomatic and clinical endpoints in this interim analysis from the TN OLE study. These results suggest that pts who experienced disease relapse after temporarily holding ozanimod in clinical practice may benefit from resumption of ozanimod.

DOP37 Efficacy and safety of 3 years of continuous ozanimod treatment: an interim analysis of the True North open-label extension study

Abstract Background The phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod over 52 weeks in patients with moderately to severely active ulcerative colitis (UC). Patients completing 52 weeks of TN were eligible for the ongoing TN open-label extension (OLE) assessing the long-term efficacy and safety of ozanimod. Presented is the interim analysis of the TN OLE in patients with approximately 3 years of continuous ozanimod treatment. Methods This analysis evaluated patients who achieved clinical response after receiving 52 weeks of continuous ozanimod 0.92 mg during TN and subsequently entered the TN OLE (data cutoff: 10 January 2022, the point at which the OLE Week 94 disposition was available for patients). Patient-reported (rectal bleeding and stool frequency) and clinician-reported (Physician’s Global Assessment) outcomes were collected. Centrally read endoscopy was performed at OLE Weeks 46 and 94 (98 and 146 weeks of continuous ozanimod treatment, respectively). Efficacy data (clinical remission, clinical response, endoscopic improvement, and corticosteroid-free remission) were evaluated in the intent-to-treat population at OLE Weeks 46 and 94 using observed case (OC) and nonresponder imputation (NRI) analyses. Partial Mayo scores (PMS) were assessed from TN baseline to OLE Week 94. Adverse events were monitored throughout TN and the subsequent OLE. Results In all, 131 patients entered the OLE after achieving clinical response following 52 weeks of continuous ozanimod during TN; at data cutoff, 87.0% completed OLE Week 46 (98 weeks of continuous ozanimod) and 71.8% completed OLE Week 94 (146 weeks of continuous ozanimod). Patients had a mean age of 44 years and 52% were female. Most (68%) had left-sided UC disease, 24% had concomitant corticosteroid use at TN baseline, and 32% had prior exposure to tumour necrosis factor inhibitors. Most patients achieved clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement at OLE Week 46 in the OC (Figure 1A) and NRI (Figure 1B) analyses. At OLE Week 94, 91.4% of patients achieved clinical response in the OC analysis (NRI, 56.5%). Ozanimod was associated with a reduction in mean PMS during TN (PMS=6.2 at Week 0 and 0.9 at Week 52), and this was sustained through OLE Week 94 (PMS=0.9) (Figure 2). No new safety findings emerged from this analysis. Conclusion This interim analysis of the TN OLE found that most of the patients who achieved clinical response after 1 year of ozanimod had sustained efficacy for an additional 2 years. No new safety signals were observed with long-term ozanimod use.

P773 Extended induction in the True North open-label extension study: clinical outcomes of ~2 years of ozanimod treatment

Abstract Background Ozanimod is approved in the EU, US, and other countries for the treatment of moderately to severely active ulcerative colitis in adults. In the phase 3, 52-week, double-blind True North (TN) study, Week 10 clinical nonresponders to ozanimod could enter the open-label extension (OLE) to continue treatment. Previous analysis showed that approximately 50% of Week 10 nonresponders achieved symptomatic clinical response with extended induction during the OLE in as early as 5 weeks. The current analysis evaluated long-term clinical and symptomatic endpoints up to 2 years in this delayed responder subgroup. Methods Efficacy data were analysed for TN Week 10 ozanimod nonresponders who subsequently received open-label ozanimod in the OLE, both by whole subgroup and original study arms (double-blind [Cohort 1] and open-label ozanimod [Cohort 2]) (data cutoff: January 10, 2022). Endpoints included symptomatic clinical response, symptomatic clinical remission, total Mayo score, clinical response, clinical remission, and corticosteroid (CS)-free remission up to OLE Week 94 (104 weeks of continuous ozanimod treatment). Data were evaluated using observed case (OC) and nonresponder imputation (NRI) analyses. Results A total of 226 nonresponders at TN Week 10 entered the OLE (Cohort 1, n=150; Cohort 2, n=76). Males comprised 67% of this subgroup, and mean (SD) age was 39.6 (13.6) years. Symptomatic clinical response (Figure 1), symptomatic clinical remission, and reduction in partial Mayo scores were observed as early as OLE Week 5 and were maintained through OLE Week 94. Minimal change in total Mayo score was observed from TN Week 0 (baseline) to TN Week 10 (OLE Week 0), but significant reductions from baseline occurred by OLE Week 46 (–4.2 [2.7]) and OLE Week 94 (–5.3 [2.6]). Overall, 62% of patients achieved clinical response, 26% achieved clinical remission, and 24% achieved CS-free remission at OLE Week 46; these increased to 74%, 35%, and 33%, respectively, by OLE Week 94 in the OC analysis (Figure 2). Data were similar between Cohorts 1 and 2. Conclusion Symptomatic response in ozanimod nonresponders was observed as early as 5 weeks after extended induction with ozanimod. Delayed response to ozanimod was maintained for up to 2 years as demonstrated by both symptomatic and objective endpoints. Even in those with delayed initial response, efficacy of ozanimod was durable.

P609 Impact of prior biologic exposure on durability of recaptured response to ozanimod during the True North open-label extension study

Abstract Background In the phase 3 True North (TN) study, ozanimod (OZA) 0.92 mg once daily showed efficacy and safety for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis, and is approved for adults in the EU, US, and other countries for this indication. This analysis (data cutoff: 10 January 2022) evaluated the impact of prior biologic exposure on the long-term durability of response in pts who experienced disease relapse while on placebo (PBO) during the TN maintenance period (MP) and then recaptured response to OZA during the TN open-label extension (OLE). Methods Responders to OZA 10-week induction therapy who were biologic-naive or exposed to prior biologics at baseline were rerandomised 1:1 to OZA (n=230) or PBO (n=227) during the TN MP. Pts who relapsed while on PBO subsequently entered the OLE and reinitiated open-label OZA in this interim OLE analysis. Symptomatic, clinical, endoscopic, and histologic endpoints were evaluated by observed case (OC) and nonresponder imputation (NRI) analyses. Results This analysis included 38 biologic-naive and 38 biologic-exposed pts who entered the OLE after disease relapse on PBO (median time to relapse, 13.1 and 11.2 weeks, respectively). Symptomatic clinical response based on NRI was achieved by 26/38 (68.4%) of biologic-naive and 20/38 (52.6%) of biologic-exposed pts 5 weeks after restarting OZA in the OLE. Symptomatic clinical response by OC analysis at OLE Week 5 was achieved in 72.2% (26/36) and 55.6% (20/36) of biologic-naive and -exposed pts, respectively. Although a greater proportion of biologic-naive vs -exposed pts completed OLE Week 94 (65.8% vs 39.5%), OC rates of symptomatic clinical response at OLE Week 94 were similar (biologic-naive: 95.0% [19/20] vs biologic-exposed: 100.0% [13/13]). Key clinical, endoscopic, and histologic endpoints are shown in Fig 1. Durability of response between OLE Weeks 46 and 94 was similar in biologic-naive (40%–56%) vs -exposed pts (50%–67%) but varied depending on endpoints (NRI analysis). Reductions in mean [SD] total Mayo score were similar and sustained through OLE Week 94 in biologic-naive and -exposed pts (OLE Week 0: 8.9 [1.8] and 9.3 [1.6], respectively; OLE Week 46: 2.3 [1.7] and 4.2 [2.6], respectively; OLE Week 94: 2.6 [2.0] and 2.6 [1.4], respectively) (Fig 2). Conclusion In pts who lost clinical response after OZA treatment withdrawal, symptomatic clinical response was recaptured within 5 weeks of OZA reinitiation in the majority of pts, and clinical benefit was maintained for up to 94 weeks (extent of current analysis) in biologic-naive and -exposed pts. This suggests that in clinical practice, pts who experience a disease relapse after temporarily holding OZA may benefit from resumption of OZA.

P464 Effects of ozanimod on histologic remission and mucosal healing over 3 years of continuous treatment in patients with ulcerative colitis

Abstract Background Ozanimod is approved in the European Union, United States, and other countries for the treatment of moderately to severely active ulcerative colitis in adults (UC). The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients with moderately to severely active UC. The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod. This interim analysis of the TN OLE evaluated the efficacy of ozanimod on histologic remission (HR) and mucosal healing (MH) in patients who received approximately 3 years of continuous ozanimod treatment. Methods In TN, patients were randomised to once-daily ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo (Cohort 1) or to open-label ozanimod (Cohort 2) for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo for a 42-week maintenance period (MP). Patients with clinical response to ozanimod at Week 52 in TN were eligible to continue receiving ozanimod in the ongoing OLE. This interim analysis of the OLE (data cutoff: 10 January 2022, the point at which patient disposition was available for patients until OLE Week 94) included all patients on continuous ozanimod in the TN MP who achieved clinical response at Week 52 and enrolled in the OLE (n=131). Endoscopic and histologic endpoints were evaluated at OLE Weeks 46 and 94 (98 and 146 weeks of continuous ozanimod treatment, respectively) and reported using observed case analysis. Mean Mayo endoscopy scores were evaluated from TN baseline to OLE Week 94. Results Of the 131 total patients included in this analysis, 87% completed OLE Week 46 (98 weeks of continuous ozanimod) and 72% completed OLE Week 94 (146 weeks of continuous ozanimod). Patients had a mean age of 44 years and 52% were female. Most patients (68%) had left-sided UC, 69% had prior use of corticosteroids, 99% had prior use of 5-aminosalicylic acid, and 32% had prior use of tumor necrosis factor inhibitors. Most TN Week 52 clinical responders achieved endoscopic improvement (EI), HR, and MH at OLE Weeks 46 and 94 (Figure 1). Ozanimod treatment was associated with a reduction in mean Mayo endoscopy score to 1.0 at TN Week 52; this was sustained through OLE Week 94 (Figure 2). Conclusion In this interim analysis of the TN OLE, a large proportion of clinical responders after 1 year of ozanimod who remained on ozanimod for up to 2 years thereafter, achieved EI, HR, and MH after 2 and 3 years of continuous treatment. Long-term ozanimod use may be associated with sustained endoscopic and histologic benefits in patients with UC.

P715 Achievement and maintenance of endoscopic, histologic, and combined outcomes after extended induction in Week 10 nonresponders of ozanimod: 2-year interim analysis of the True North open-label extension study

Abstract Background Ozanimod, a novel oral therapeutic option for patients with moderately to severely active ulcerative colitis, demonstrated significant improvements in clinical, endoscopic, and histologic endpoints in the phase 3, 52-week, double-blind True North (TN) study. Approximately one-third of the patients did not achieve clinical response to ozanimod after 10 weeks of TN induction therapy. However, a delayed response was observed in a subset of these nonresponders upon extended induction with ozanimod. The present analysis evaluated ozanimod efficacy on endoscopic and histologic endpoints in these delayed responders in the TN open-label extension (OLE) study. Methods Data were analysed for the overall delayed responder population and separately for the blinded (Cohort 1) and open-label (Cohort 2) cohorts (data cutoff: 10 January 2022, the point at which patient disposition was available for all patients up to OLE Week 94). Endpoints included endoscopic improvement (defined as an endoscopy subscore of ≤1 point), histologic remission (defined as Geboes index score &amp;lt;2.0), and mucosal healing (defined as endoscopy subscore of ≤1 point and Geboes index score of &amp;lt;2.0) up to OLE Week 94. The endpoints were evaluated using observed case (OC) and nonresponder imputation (NRI) analyses. Results A total of 226 patients (Cohort 1, n=150; Cohort 2, n=76) were nonresponders at Week 10 and entered the OLE (67% male; mean [standard deviation] age, 39.6 [13.6] years). At OLE entry, 24% of patients had moderate disease (Mayo endoscopic score [MES]=2) and 73% had severe disease (MES=3). Approximately half of these patients achieved symptomatic clinical response as early as 5 weeks of ozanimod open-label treatment. In OC analysis at OLE Week 46, 30% of patients achieved endoscopic improvement, 42% achieved histologic remission, and 24% achieved mucosal healing that further increased to 48%, 48%, and 39%, respectively, by OLE Week 94 (Figure 1A). In NRI analysis, the following patient proportions were observed at OLE Weeks 46 and 94: 18% and 19% (endoscopic improvement), 22% and 14% (histologic remission), and 13% and 11% (mucosal healing) (Figure 1B). Data were generally similar in Cohorts 1 and 2. Conclusion Delayed responders to ozanimod achieved and maintained mucosal healing over 2 years of continuous ozanimod treatment. Ozanimod treatment resulted in the healing of intestinal mucosal lesions, even in patients with moderate to severe disease who may have an initial delayed response to ozanimod.

P405 Long-term safety of 3 years of ozanimod in moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension

Abstract Background The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod in UC. This analysis evaluated the cumulative long-term safety of ozanimod in these studies, which included pts with up to ~3 years of treatment exposure. Methods In TN, pts were randomised to once-daily ozanimod 0.92 mg or placebo, or to open-label ozanimod for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo in the maintenance period through Week 52. TN pts were eligible to enrol in the OLE and receive ozanimod if they did not achieve clinical response at the end of induction (Week 10), lost response during maintenance, or completed maintenance at Week 52. This interim analysis of the TN OLE (data cutoff: 10 January 2022) included all pts who entered the OLE from TN (n=823). Safety was monitored from the first dose of ozanimod in TN and throughout the subsequent OLE. Exposure-adjusted incidence rates per 100 patient-years (PY) were calculated. Results The average age of TN OLE study participants was 41.7 years (±13.6), 41% were female, 62% had left-sided UC disease, and 35% had prior exposure to tumor necrosis factor inhibitors. Total PY exposure to ozanimod was 2219 years (mean [SD] exposure = 2.7 [1.6]). The most frequent treatment-emergent adverse events (TEAEs) reported through OLE Week 94 (up to 146 weeks of continuous treatment) are listed in the Table. Most TEAEs were nonserious; TEAEs leading to discontinuation were uncommon. Bradycardia was reported in 3 pts (0.4%; EAIR 0.1/100 PY; 2 in TN and 1 in OLE; no pts were discontinued from treatment). Macular edema was reported in 2 (0.2%; EAIR 0.1/100 PY) pts. Reductions in ALC were common (470 [57.1%] had ALC &amp;lt; 500 cells/mm3), as previously described, but ALC reductions were not associated with the occurrence of TEAEs. Malignancies were uncommon (n=13 [1.6%]; EAIR 0.6/100 PY), and included 6 basal cell carcinomas and 3 colorectal neoplasms. Two deaths were reported: 1 due to COVID-19 and 1 sudden death. Investigators deemed both to be unrelated to treatment. Ozanimod was not associated with an increased risk of ischemic heart disease or thromboembolic events. Conclusion Long-term exposure to ozanimod for up to 3 years was well tolerated in pts with moderately to severely active UC. No new safety signals were observed with long-term ozanimod use in UC (2219 PY exposure). Safety findings are consistent with previous reports from the UC and multiple sclerosis development programs (&amp;gt;16,512 PY exposure).

LBMON178 2nd Year Outcomes Of The Open-label Extension Of Chiasma Optimal, A Phase 3 Study Of Oral Octreotide Capsules In Acromegaly

Abstract Background Oral octreotide capsules (OOC) are an approved treatment option in the United States for patients with acromegaly who have previously responded to injectable somatostatin receptor ligands (iSRLs). Safety and efficacy of OOC was demonstrated in the CHIASMA OPTIMAL trial (NCT03252353), showing maintenance of response and a safety profile consistent with iSRLs. Results from the first 48 weeks of the open-label extension (OLE) of this trial suggested that this effect was durable for the long-term. Objective Report efficacy and safety through the second year of the OLE. Methods Eligible patients had the option to enroll in the OLE of CHIASMA OPTIMAL following the double-blind placebo-controlled (DPC) period. Endpoints in the second year of the OLE were exploratory, including: the proportion of patients completing week 96 of the OLE, the proportion of responders entering year 2 who remained responders of those with evaluable data (response defined as average Insulin-like growth factor I [IGF-I] ≤1. 0 × upper limit of normal [ULN] at last 2 visits between weeks 84-96), and changes in IGF-I and growth hormone (GH) from OLE baseline to OLE week 96 in those completing the DPC period on study drug. Results Thirty-two patients from the core period (DPC groups: n=14, placebo; n=18, OOC) entered year 2 of the OLE and 31 (97%) completed. OOC dose at the start of year 2 was 40 mg/d, n=3; 60 mg/d, n=8; and 80 mg/d, n=21. For patients who had non-missing data response rate at 96 weeks was 100% (17/17) for patients who entered year 2 as responders, and 93% (27/29) for patients overall. Mean IGF-I for patients from the OOC group who completed the DPC period on study drug (n=14) was 0.81 × ULN at baseline of OLE and 0.78 × ULN at week 96, (change, −0. 03 × ULN). Mean GH (n=12) was 0.43 ng/mL and 0.44 ng/mL at baseline and week 96, respectively (change, 0. 01 ng/mL). For patients who completed the DPC period on placebo (n=8), mean IGF-I was 1. 05 and 0.77 × ULN at OLE baseline and week 96, respectively (change, −0.28); mean GH (n=5) was 1. 06 and 0.34 ng/mL at OLE baseline and week 96, respectively (change, −0.72 ng/mL). Median exposure to OOC was 2.1 years, with exposure &amp;gt;3 years for 5 patients. Throughout the OLE period, 50% of patients experienced adverse events (AEs), with no serious AEs. One patient discontinued treatment due to an AE (headache). The safety profile was consistent with that reported for OOC; no new patterns were observed with increased exposure. Conclusion Maintenance of biochemical response with OOC was durable up to 96 weeks. The safety profile of OOC was consistent with that of iSRLs. No new safety signals were observed with increased exposure duration. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PBI1 Liberty Asthma Traverse Dupilumab Shows Sustained Efficacy and Improvements in Asthma Control and Health-Related Quality of Life (HRQOL) in Patients with Moderate-to-Severe Asthma

Achieving asthma control and improving HRQoL are important long-term asthma management goals. Dupilumab, a monoclonal antibody targeting IL-4/IL-13, is approved for management of moderate-to-severe asthma. We report effects of long-term use of dupilumab on asthma control and HRQoL outcomes from the TRAVERSE open-label extension (OLE) study (NCT02134028) in patients who completed a previous dupilumab asthma study. 5-item Asthma Control Questionnaire (ACQ-5) and overall Asthma Quality of Life Questionnaire (AQLQ) scores up to 48 weeks of OLE in patients with moderate-to-severe asthma who had participated in the DRI (24-week) or QUEST (52-week) studies and received add-on dupilumab 300 mg q2w during the OLE were evaluated in the overall ITT population and type 2 asthma population (defined as blood eosinophils ≥150 cells/mL or FeNO ≥25 ppb at parent study baseline [PSBL]). A within-patient change of ≥0.5 in ACQ-5 or AQLQ score was considered clinically meaningful. 2,062 patients from DRI and QUEST were enrolled. ACQ-5 and AQLQ scores improved throughout the OLE. Mean (SD) ACQ-5 scores at PSBL for placebo-dupilumab/dupilumab-dupilumab patients in DRI and QUEST were 2.63(0.77)/2.74(0.80) and 2.73(0.74)/2.76(0.79), respectively; at Week 48 of OLE, mean (SD) change from baseline was −1.33(1.07)/−1.57(1.11) and −1.64(1.08)/−1.69(1.08). Mean (SD) AQLQ scores at PSBL for placebo-dupilumab/dupilumab-dupilumab patients in DRI and QUEST were 4.27(1.12)/3.98(1.10) and 4.25(1.01)/4.29(1.08), respectively; at Week 48 of OLE, mean (SD) change from baseline was 1.07(1.13)/1.40(1.19) and 1.39(1.17)/1.40(1.18). Similar efficacy was observed in DRI/QUEST patients with type 2 asthma. The safety profile during the OLE was similar to that observed in the overall populations of the parent studies. Asthma control and HRQoL in patients with moderate-to-severe asthma continued to improve with dupilumab and were sustained over the long-term treatment duration of the OLE study.

POS1038 THE EFFECT OF FILGOTINIB ON ENTHESITIS: 100-WEEK DATA FROM AN OPEN-LABEL EXTENSION STUDY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

Background:Filgotinib (FIL), a novel preferential Janus kinase 1 inhibitor, was assessed in patients with active psoriatic arthritis (PsA) in the 16-week, Phase 2, EQUATOR trial (NCT03101670).1 EQUATOR2 (NCT03320876) is the open-label extension (OLE). As previously reported, an interim analysis of the OLE showed that the majority of patients had clinical resolution of enthesitis by Week 52.2Objectives:This post-hoc analysis evaluated the effect of FIL on clinical enthesitis after 100 weeks of treatment in the OLE, as assessed using the Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index, and evaluated the discriminatory capacity of the two indices. In addition, we assessed which of the sites included in LEI and SPARCC were most frequently involved and whether treatment effect was consistent across sites.Methods:In EQUATOR, patients with active moderate-to-severe PsA (≥5 swollen joints and ≥5 tender joints, fulfilling Classification for PsA criteria) were randomised 1:1 to receive oral FIL 200 mg or placebo (PBO) once daily (QD) for 16 weeks. At Week 16, all patients could continue into the OLE, receiving FIL 200 mg QD for up to an additional 304 weeks. We compared changes from core baseline in LEI and SPARCC measures, the effect on enthesitis at sites included in LEI and SPARCC assessments and the discriminatory capacity of both enthesitis indices.Results:Of 131 patients randomised to EQUATOR, 122 entered the OLE. There was strong agreement between LEI and SPARCC at baseline. While most patients had enthesitis at baseline according to either index (76/131 [58.0%] by LEI; 85/131 [64.9%] by SPARCC), a minority had enthesitis at a large number of sites (6.9% with 5–6 LEI sites; 12.2% with ≥9 SPARCC sites). The sites most frequently involved at baseline were the lateral epicondyle humerus and Achilles tendon, sites common to both LEI and SPARCC. There was greater variability in the change from baseline to Week 16 in SPARCC compared with LEI (Table 1). LEI showed a greater discriminatory capacity than SPARCC when change from baseline was compared for FIL vs PBO at Week 16, as shown by higher absolute standardised mean difference: −0.70 (LEI) and −0.30 (SPARCC) (observed cases; Table 1). Subgroup analyses indicated that the treatment effect of FIL vs PBO at Week 16 for all sites was consistent with the overall treatment effect seen for LEI or SPARCC, and indicative of an improvement with FIL vs PBO for nearly all sites. The proportion of patients with enthesitis decreased from baseline up to OLE Week 100 (Figure 1). There were no major differences in long-term effect on enthesitis between sites.Conclusion:FIL improved enthesitis consistently across sites compared with PBO. Rapid improvement in enthesitis was seen up to Week 16 of the core study and improvements continued up to Week 52, after which responses were generally stable up to Week 100. LEI assesses fewer locations than SPARCC, but reassuringly captured the sites most commonly affected by enthesitis; LEI also had greater discriminatory capacity.

One-Year Outcomes of the Open-Label Extension of CHIASMA OPTIMAL, a Phase 3 Study of Oral Octreotide Capsules in Acromegaly

Background: Based on the CHIASMA OPTIMAL study, oral octreotide capsules (OOC) were recently approved in the US as a long-term maintenance therapy for patients with acromegaly previously responding to injectable octreotide or lanreotide, somatostatin receptor ligands (SRLs). Results on longer-term efficacy and safety of OOC from the first 48 weeks of the open-label extension (OLE) of this study are presented here. Methods: Eligible patients had the option to enroll in the OLE of CHIASMA OPTIMAL following the double-blind placebo-controlled (DPC) period; 90% of patients who received OOC in the DPC period enrolled. All patients entering the OLE were initiated on a 60 mg/day dose of OOC and titrated up or down based on insulin-like growth factor I (IGF-I) level and/or acromegaly signs or symptoms. End points in the OLE were exploratory and included the proportion of patients who completed week 48 of the OLE, the proportion who completed as responders (defined as average IGF-I ≤1.0 × upper limit of normal [ULN] at weeks 46/48), and changes in IGF-I from baseline of DPC and OLE until week 48 of the OLE; multiple imputation (MI) was used for missing data. Results: Forty patients entered the OLE (n=20 each; OOC and placebo). Median exposure to OOC in the OLE was > 1 year for those who had been on placebo in the DPC and ≤ 21 months for those who had been on OOC. Dosing of OOC at the end of their participation in the OLE was 40 mg, n=3; 60 mg, n=10; and 80 mg, n=27. In those who received OOC during the DPC, 90% (n=18) completed 48 weeks of the OLE. Of responders at the end of the DPC period (n=14), 92.6% maintained response at OLE week 48. In patients from the OOC group who completed the DPC on study drug, average IGF-I using MI was 0.91 and 0.90 × ULN at OLE baseline and week 48, respectively. The mean change in IGF-I from the baseline of the DPC to OLE week 48 was 0.06 × ULN in patients who completed the DPC on OOC (n=19). In those who received placebo during the DPC, 70% (n=14) completed 48 weeks of the OLE. Of responders at the end of the DPC (n=5), 100% maintained response at OLE week 48. In patients from the placebo group who completed the DPC and did not revert to prior injectable therapy (n=9), the average IGF-I values were 1.09 and 0.87 × ULN at OLE baseline and week 48 respectively, using MI. The mean change in IGF-I from the baseline of the DPC to OLE week 48 was 0.08 × ULN in patients who completed the DPC on placebo (n=9). The most common treatment-emergent adverse events (TEAEs) were gastrointestinal; most were mild or moderate. The incidence of TEAEs was similar between patients who were on OOC or placebo during the DPC. The safety profile during the OLE did not show new concerns with increased duration of drug exposure. Conclusion: Long term maintenance of biochemical response to OOC is durable as assessed following ≤ 21 months of treatment. The OOC safety profile in the extension study is consistent with that of injectable SRLs but without injection-related AEs.

Efficacy results of pimavanserin from a multi-center, open-label extension study in Parkinson's disease psychosis patients

IntroductionPimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved for hallucinations and delusions associated with Parkinson's disease psychosis (PDP). We present durability of response with pimavanserin in patients with PDP for an additional 4 weeks of treatment. MethodsThis was an open-label extension (OLE) study in patients previously completing one of three double-blind, placebo-controlled (Core) studies. All patients received pimavanserin 34 mg once daily. Efficacy assessments included the Scale for the Assessment of Positive Symptoms (SAPS) PD and H + D scales, Clinical Global Impression (CGI) Improvement and Severity scales and Caregiver Burden Scale (CBS), through 4 weeks in the OLE. Safety assessments were conducted at each visit. ResultsOf 459 patients, 424 (92.4%) had a Week 4 efficacy assessment. At Week 4 (10 weeks total treatment), SAPS-PD mean (standard deviation) change from OLE baseline was −1.8 (5.5) and for SAPS-H + D was −2.1 (6.2) with pimavanserin 34 mg. Patients receiving placebo during the Core studies had greater improvements (SAPS-PD -2.9 [5.6]; SAPS-H + D −3.5 [6.3]) during the OLE. For participants treated with pimavanserin 8.5 or 17 mg during the Core studies, further improvement was observed during the OLE with pimavanserin 34 mg. The mean change from Core Study baseline for SAPS-PD score was similar among prior pimavanserin 34 mg and prior placebo-treated participants (−7.1 vs. −7.0). The CGI-I response rate (score of 1 or 2) at Week 4 was 51.4%. Adverse events were reported by 215 (46.8%) patients during the first 4 weeks of OLE. The most common AEs were fall (5.9%), hallucination (3.7%), urinary tract infection (2.8%), insomnia (2.4%), and peripheral edema (2.2%) ConclusionsPatients previously on pimavanserin 34 mg during three blinded core studies had durability of efficacy during the subsequent 4 week OLE SAPS-PD assessment. Patients previously on blinded placebo improved after 4 weeks of OL pimavanserin treatment. These results in over 400 patients from 14 countries support the efficacy of pimavanserin for treating PDP.

Long-Term Safety and Efficacy of Risankizumab in Patients with Moderate-to-Severe Chronic Plaque Psoriasis: Results from a Phase 2 Open-Label Extension Trial.

IntroductionAlthough many biologic therapies are effective for clearing skin of patients with psoriasis, some lose effectiveness over time. This phase 2 open-label extension (OLE) trial was designed to investigate the long-term safety and efficacy of risankizumab.MethodsIn the phase 2, double-blind, active comparator, predecessor trial (NCT02054481), patients with moderate-to-severe chronic plaque psoriasis were treated for 24 weeks with subcutaneous (SC) risankizumab or ustekinumab, followed by a 24-week follow-up without treatment administration. Patients could enroll in the OLE (NCT02203851) when they experienced loss of treatment response (< 50% improvement in the Psoriasis Area Severity Index [PASI 50]) during follow-up) or at the end of follow-up if treatment response was ongoing. In the OLE, patients were treated every 12 weeks for at least 48 weeks with SC risankizumab 90 or 180 mg, beginning at week 12 (OLE visit 2), if the patient had not achieved PASI 90. Efficacy endpoints included the proportions of patients who achieved PASI 50/75/90/100 and static Physician’s Global Assessment (sPGA) of clear or almost clear skin at week 48 (sPGA 0/1; OLE visit 5).ResultsOf the 110 enrolled patients, 99 (90.0%) completed the OLE. No patients discontinued the study because of adverse events. At week 48, 74.1% of patients achieved PASI 90, whereas 98.1, 91.7, 53.7, and 67.6% achieved PASI 50/75/100 and sPGA 0/1, respectively. All efficacy results were consistent or slightly increased at OLE week 48 compared with week 12. No new safety findings were observed.ConclusionRisankizumab treatment was well tolerated with sustained clinical efficacy for at least 48 weeks.Trial RegistrationClinicalTrials.gov identifier; NCT02203851.