Arena Pharmaceuticals Inc (ARNA) Q1 2019 Earnings Call Transcript

So with that, I will turn the call over to Preston Klassen to walk through the Phase 3 ELEVATE UC program. Preston?

Preston Klassen -- Executive Vice President, Research and Development and Chief Medical Officer

Thanks, Amit. As a reminder, last year, we delivered highly positive results from our Phase 2 OASIS trial of etrasimod for the treatment of moderate to severely active ulcerative colitis, or UC in a patient population where high proportion of patients, 40%, had already failed the previous biologic therapy.

We believe these Phase 2 data demonstrates that etrasimod has the potential to be a best-in-disease product for UC, and IBD continues to have a large unmet need, highlighting the opportunity for etrasimod to make a real difference to patients. And we are pleased today to provide additional detail on the Phase 3 clinical program in UC, which will be branded as the ELEVATE UC program.

Before I walk through the details, we developed the ELEVATE UC program with the following goals in mind. A trial design that is appropriate to meet global regulatory requirements for approval, effective use of enrolled patients to speed time-to-market and targeted endpoints and other design elements to produce a competitive label for payers and providers, ultimately delivering a product that offers sustained and market meaningful, long-term safety and efficacy for patients in a once-daily oral therapy.

We believe that etrasimod and the ELEVATE UC program will allow us to meet these imperatives. The etrasimod global Phase 3 ELEVATE UC registrational program will consist of two key trials to evaluate etrasimod 2-milligram, once-daily in subjects with moderately to severely active ulcerative colitis.

The first trial is ELEVATE UC 52, a treat-through trial design with a 12-week induction period, seamlessly followed by 40 weeks of maintenance for a total 52-week exposure, and the second trial is ELEVATE UC 12, which is a confirmatory 12-week induction period trial.

We plan to conduct additional studies to provide direct evidence of differentiation and value for healthcare providers and payers. These trials will elucidate the safety, efficacy and convenience benefits of etrasimod, particularly in the context of biologic and broadly immunosuppressive oral treatments.

For competitive reasons, we will not go into specific details on these additional trials at this time, but we will provide those details when we are closer to initiation. Across each of the two pivotal studies, we will target a population that includes both patients who are naive to prior biologics or JAK inhibitor therapy and patients who had previously been on and failed, or are intolerant to prior therapy with a biologic or JAK inhibitor.

We will ensure that the program enrolls adequate representation from both biologic or JAK naive patients and patients with prior exposure to get prescribing physicians important guidance on what to expect when etrasimod is used either ahead of these other therapies or after other therapies have failed. We believe this program will maximize our speed to filing and provide a robust dataset to exhibit the potential benefits of etrasimod .

And with that, I'll provide some additional detail on these two trials within the ELEVATE UC program. ELEVATE UC 52 will be a 2:1 randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of etrasimod 2-milligram once-daily in subjects with moderately to severely active UC, defined as a baseline of three-domain, modified Mayo Score of four to nine, with an endoscopic score of two or more and a rectal bleeding score of one or more. This is a one-year trial, examining both clinical remission at 12 weeks, which is typically referred to as induction and clinical remission at 52 weeks.

The trial consists of a 28-day screening period, a 12-week treatment period, a 40-week treatment period and a two week follow-up period. We plan to enroll approximately 370 subjects. The primary objective of this trial is to assess the safety and efficacy of etrasimod on clinical remissions after both 12 weeks and 52 weeks.

But the primary endpoint is the FDA required three-domain, modified Mayo Score, which is similar to the primary endpoint in the Phase 2 OASIS study. And the trial is appropriately powered to achieve significance on the 12 week and 52-week remission endpoints as co-primary endpoints at a population level.

In addition, we will be assessing several key secondary measures, including the efficacy of etrasimod on clinical response, symptomatic response in remission, endoscopic changes, corticosteroid-free remission and mucosal healing in these subjects at time points up to 52-weeks of treatment.

Other objectives include evaluation of etrasimod pharmacokinetics and a variety of exploratory biomarkers, and the effect of etrasimod on health-related, patient reported outcome measures. We continue to expect to initiate the ELEVATE UC 52 trial by mid-year, and we plan to have data in 2021. The ELEVATE UC program will be conducted in approximately 450 sites across more than 40 countries. And I will provide additional color on our plans to execute the program and meet these timelines in a moment.

The second pivotal Phase 3 trial is ELEVATE UC 12, also a 2:1 randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of etrasimod 2-milligram once-daily in subjects with moderately to severely active UC, using the same baseline disease severity definition.

This trial is a confirmatory 12-week induction study, and consists of the 28-day screening period, a 12-week treatment period and a two-week follow-up period. ELEVATE UC 12 will enroll approximately 330 subjects to assess the efficacy that etrasimod when administered for 12 weeks on clinical remission, again using the same three-domain modified Mayo Score endpoint for remission.

Secondary measures in this study are similar to those I mentioned as part of the ELEVATE UC 52 trial. We plan to conduct the ELEVATE UC 12 trial across the same global trial site network of approximately 450 sites developed for the ELEVATE UC 52 trial, and we plan to stagger enrollment to optimize conduct of the one-week trial and ensure that the confirmatory 12-week trial is not rate limiting to completion of the program to enable NDA submission.

I will speak to additional aspects of the trial execution in a moment. Importantly for both studies, after participation in the main trial, enrolled patients will have the opportunity to move into an open-label extension trial from which we will gather additional long-term safety and efficacy information.

We have discussed in prior calls and presentations that in multiple quantitative market research surveys, providers and patients strongly prefer the Phase 2 generated profile of etrasimod's safety and efficacy and the convenience of once-daily oral therapy over alternatives, including biologics and JAK inhibitors. These two pivotal Phase 3 trials are intended to confirm this highly advantageous profile and upon approval, have established an label (ph).

I want to point out that the primary endpoint of clinical remission used in the three domain, modified Mayo Scores, the current FDA standard and requirement for approval of products in ulcerative colitis. In the Phase 2 OASIS trial, using this three-domain, modified Mayo Score endpoint, etrasimod demonstrated a placebo-corrected 25.4% clinical remission proportion over 12 weeks, which is an even greater separation from placebo than the 18.7% delta observed for the four-domain, total Mayo Score endpoint in that study.

And by way of contrast, four-domain, total Mayo Score endpoints in the Phase 3 from approved products or in Phase 2 from products still in development in ulcerative colitis, have shown only approximately 7% to 11% placebo-corrected remission rates.

Furthermore, our experience from the Phase 2 open-label extension leads us to believe that remission rates will increase over time in contrast to biologic therapies, which also have a waning affect over time in part due to the presence of neutralizing antibodies.

Our Phase 2 data are extremely strong, highly competitive and critically, it represents a direct read through to the planned Phase 3 trials, providing us confidence and enthusiasm that address and will demonstrate clinically meaningful and market-leading evidence of efficacy and safety. It is clear that IBD generally and ulcerative colitis specifically has a competitive landscape into the trial recruitment, and we are taking a proactive and broad approach trough recruiting patients into the ELEVATE UC program.