Kiniksa Pharmaceuticals International, plc (KNSA) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Kiniksa announces positive data from Phase III RHAPSODY trial conference call. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions] I would now like to hand the conference over to your speaker today, Mark Ragosa, Head of Investor Relations of Kiniksa Pharmaceuticals. Thank you. Please go ahead, sir.

Thanks, Gigi. Good morning, and thank you for joining Kiniksa's call to discuss data from RHAPSODY, a pivotal Phase III trial of rilonacept in recurrent pericarditis. As you probably saw, our press release crossed the wire earlier this morning. Additionally, the data we present today can be found through the Investors and Media section of our website. Please note that we'll be making forward-looking statements today that are subject to risks and uncertainties. A review of these statements and risk factors are found on this slide as well as under the heading Risk Factors in our SEC filings. Joining me for today's call are Sanj K. Patel, Chief Executive Officer and Chairman of the Board; and John Paolini, Chief Medical Officer; Qasim Rizvi, Chief Commercial Officer and SVP of Operations; and Eben Tessari, Chief Business Officer, will also be available during the question-and-answer portion of the call. And with that, I'll turn it over to Sanj.

Thanks, Mark. Good morning, everyone. As you can imagine from seeing the press release this morning, we are obviously ecstatic to announce the data from our RHAPSODY pivotal Phase III study of rilonacept in recurrent pericarditis. The trial met its primary and all the major secondary endpoints to an extremely high level of statistical significance. In fact, the primary endpoint had a hazard ratio of 0.04 and a p-value of less than 0.0001. We believe this represents an important step forward for patients. Recurrent pericarditis is a painful and often debilitating disease, and the data from RHAPSODY highlights that treatment with rilonacept improved clinically meaningful outcomes associated with the disease. Combined with the well-tolerated safety results and a weekly dosing regimen, rilonacept has the potential to be the first FDA-approved therapy for recurrent pericarditis. We're committed to submitting an sBLA to the FDA later this year and we look forward to bringing this potential treatment to patients as fast as humanly as possible. I'll now turn the call over to our Chief Medical Officer, John Paolini, who will walk you through the data in more detail. John?

Thank you, Sanj, and good morning, everyone. By way of background, rilonacept is a once-weekly IL-1 alpha and IL-1 beta cytokine trap, which is already approved and marketed by Regeneron in the United States for CAPS, an ultra-rare genetic autoinflammatory disease. We have been evaluating rilonacept for the treatment of recurrent pericarditis, a debilitating autoinflammatory cardiovascular disease for which there were currently no FDA-approved therapies. The FDA granted breakthrough therapy designation for rilonacept in recurrent pericarditis late last year, which we applied for on the basis of our Phase II data presented at the American Heart Association meetings last fall. We believe this speaks to the severity of the disease and the potential advance that rilonacept could represent in the management of these patients. RHAPSODY is a global pivotal Phase III study of rilonacept treatment in recurrent pericarditis, which utilizes a randomized withdrawal design, well-known in rare diseases. The co-principal investigators were Dr. Allan Klein of the Cleveland Clinic and Professor Massimo Imazio from the University of Torino in Italy. Acutely symptomatic patients who are failing their background regimen of NSAIDs, colchicines or steroids were enrolled in a 12-week single-blind run-in period, during which they received weekly rilonacept, while background pericarditis medications were tapered and discontinued. In the pivotal portion of the study, clinical responders on monotherapy rilonacept were randomized 1:1 to either continued weekly rilonacept or placebo in a double-blind, randomized withdrawal period. The primary efficacy endpoint was time to first adjudicated pericarditis recurrence during the randomized withdrawal period, the duration of which was event-driven. Patients who experienced a recurrent pericarditis event during the randomized withdrawal period could be given bailout, open-label rilonacept and remain in the study until the end of the randomized withdrawal period. Following the receipt of Breakthrough Therapy designation and based on a Type B interaction with the FDA, we expedited the time line to data by closing the randomized withdrawal period after 22 adjudicated events had accrued. Patients completing the randomized withdrawal portion of the trial were given the option to continue open-label rilonacept in the 24-month long-term extension period, allowing these patients with recurrent disease to remain on treatment, as well as helping us accrue on-drug exposure and informing optimum treatment duration. RHAPSODY was a well-balanced study and the baseline demographics of the patients upon presentation are representative of the real-world pericarditis population. In terms of prior recurrent pericarditis history, patients qualify for the trial with a mean of approximately 5 pericarditis episodes, with a mean duration of disease of 2.4 years and experiencing a mean of 4.4 episodes per year. Underlying original etiology was predominantly "idiopathic" which means usually post-viral, and there was proportional representation of post-pericardiectomy syndrome, meaning those who had, had prior cardiac surgery or percutaneous intervention. The proportions of patients receiving NSAIDs, colchicines and corticosteroids at the time of enrollment are shown here. Of note, these patients were experiencing an acute recurrence despite their standard of care treatment. 80% were on colchicine, almost half were on corticosteroids with 1/3 to 1/2 of those patients being on steroids long term. Looking at the magnitude of disease on presentation, patients were experiencing pericarditis pain on the NRS scale of just over 6 out of 10. C-reactive protein, a marker of inflammation severity, was over 6 milligrams per deciliter, with normal being 0.5 milligrams per deciliter and the minimum threshold for entry being 1 milligram per deciliter. Other objective manifestations of pericarditis listed here were represented as expected. Finally, the randomization of the study was well balanced between the rilonacept and the placebo arms. Here, you have a consort diagram detailing subject to disposition in RHAPSODY. 86 patients enrolled in the run-in period and 92% completed the run-in period. There were rapid and sustained reductions in both reported pain and inflammation as early as after the first dose. Median time to pain NRS score of 2 or less was 5 days. And median time to CRP normalization was 7 days. Median time to treatment response combining pain and CRP response was 5 days. Turning to tapering and discontinuation of standard of care treatments. Time to monotherapy rilonacept was 7.9 weeks, 2 weeks earlier than the protocol specified maximum of 10 weeks. From a randomization efficiency standpoint, only 4 patients discontinued from the run-in period for adverse experiences, and only 3 patients did not meet the NRS and CRP criteria for randomization. 61 patients were randomized, 30 to rilonacept and 31 to placebo. At the time when the randomized withdrawal portion of the trial was closed, early, as I mentioned, there were 15 patients who were still completing the run-in period. These patients were transitioned directly to the long-term extension period as shown on the right. 60 of the 61 randomized patients completed the randomized withdrawal period, and 74 of 75 eligible patients continued into the now ongoing long-term extension. The study met its primary efficacy endpoint, time to first adjudicated pericarditis recurrence in the randomized withdrawal period. This Kaplan-Meier curve shows rilonacept recipients in blue and placebo recipients in red. The hazard ratio of 0.04 means that patients randomized to rilonacept experienced a 96% reduction in the risk for a recurrent pericarditis event, with a highly statistically significant p-value of less than 0.001 (sic) [ 0.0001 ] shown here. The median time to recurrence in the rilonacept arm could not be calculated as there were not enough recurrence events in the observation period to allow for the number to be calculated.

John, I'm sorry to interrupt. You missed the 0, I know there's a lot of zeros, but you missed a 0 on the p-value. It's 0001, you said 2 0s.

Thank you. Specifically, there were only 2 recurrence events in the rilonacept arm, and these occurred after brief temporary study drug interruptions of 3 or fewer weekly doses. The median time to first recurrence in the placebo arm was 8.6 weeks after randomization, consistent with the expected washout pharmacokinetics of once-weekly rilonacept at steady state. Almost half of the placebo patients who went on to suffer a recurrence event did so within the first month after randomization, underscoring the tenacity of recurrent pericarditis. These data demonstrate that in this study, remaining on continued rilonacept therapy resulted in continued clinical response. Finally, for those patients who received open-label bailout rilonacept after their primary efficacy endpoint, there were no pericarditis recurrences for the remainder of the study. Major secondary efficacy endpoints in the randomized withdrawal period were also highly statistically significant. Following the receipt of Breakthrough Therapy designation and based on a Type B interaction with the FDA to expedite the primary analysis of the study, these major secondary efficacy endpoints were calculated in those patients who had, had at least 16 weeks of participation in the randomized portion of the study with week 8 and week 24 data being reported as a sensitivity analysis. On the left-hand side of the slide, using the objective study criteria of maintaining an NRS of less than or equal to 2 and CRP of less than or equal to 0.5 milligrams per deciliter while on monotherapy and without a recurrence, 81% of rilonacept recipients maintained clinical response at week 16 of the randomized withdrawal period compared to 20% of placebo recipients with a p-value of 0.0002. Consistent results were observed as early as at week 8 and at the longer time point of week 24. And these results were also highly statistically significant. In the middle panel, this endpoint was taken from a patient quality of life perspective, utilizing a patient-reported pericarditis symptom survey and we see a consistent result. 81% of rilonacept patients experienced absent or minimal pericarditis symptoms at week 16 at the randomized withdrawal period compared to 25% of placebo recipients, p equals 0.0006. Consistent results were observed as early as at week 8 and at the longer time point of week 24, and these results were also highly statistically significant. Finally, in the far right panel, also from the patient perspective, we looked at the percent of trial days through week 16 that patients reported no or minimal pericarditis pain. For rilonacept recipients, that was 95% of trial days being pain-free or at most, experiencing minimal pain versus 47% of trial days for placebo recipients with a p-value of less than 0.0001. Consistent results were observed at weeks 8 and 24, and these were also highly statistically significant. Rilonacept was well tolerated in the study with adverse events consistent with the FDA-approved label for the treatment of cryopyrin-associated periodic syndromes, or CAPS. In the left panel is the summary of adverse events. The safety data during the run-in period while all patients were receiving rilonacept are shown in the left-most column, and the data from the randomized withdrawal period are shown in the right 2 columns. There were no deaths or SUSARs. Serious adverse events were unrelated to study drug. The most common adverse events were injection site reactions and an increase in infections predominantly in the upper respiratory tract, such as URIs and nasopharyngitis shown in the right panel, as expected and consistent with the ARCALYST label. It should be pointed out that because of the randomized withdrawal design and the switch to open-label bailout rilonacept until the end of the randomized withdrawal period in patients in the placebo arm who experienced a recurrence, the median exposure time on rilonacept of 25.14 weeks was therefore almost fourfold greater than the exposure time on placebo of 6.71 weeks, possibly introducing a potential bias, if anything, in favor of placebo. Given the efficacy outcomes shown in the prior slides, we believe that the benefit/risk in this trial favors rilonacept. On behalf of the Kiniksa team, I would like to thank the co-principal investigators, Dr. Allan Klein and Professor Massimo Imazio, and acknowledge the significant contributions of the global trial investigators, study coordinators and nurses in the United States, Italy, Israel and Australia, who worked tirelessly on this study. And of course, the patients suffering from recurrent pericarditis who gave of their time to participate in RHAPSODY. Thank you. With that, I will turn it back over to you, Sanj.

Thanks, John. Based on our ongoing market research and preparations to commercialization, we continue to be excited with the opportunity in recurrent pericarditis. There are approximately 40,000 recurrent pericarditis patients that are seeking medical treatment in the U.S. and approximately 14,000 of those are in 3 main subgroups. These include the refractory, multiple relapsing and steroid-dependent patients, and they could benefit the most from rilonacept treatment. We'll focus on these patients first as they all have multiple unmet medical needs. And physicians have indicated an interest to treat across all of these subgroups. In summary, and as I mentioned earlier, we are obviously very happy with these data and believe rilonacept has the potential to have a transformational impact on patients suffering from recurrent pericarditis. We look forward to next steps, which include the transfer of the BLA for rilonacept from Regeneron to Kiniksa and to submitting the sBLA to the FDA later this year. We also plan to continue to execute across our entire portfolio in the second half of 2020 and beyond. And we're excited to continue with the passion and the drive that we have and to bring life-changing therapies to patients in need. And with that, I'll hand it back to the operator, Gigi, to begin the Q&A portion of the call. Thank you.

[Operator Instructions] Our first question comes from the line of Paul Choi from Goldman Sachs.

Let me offer my congratulations on the solid data. A few from us, please. Maybe just with regard to the placebo patients who were offered rescue therapy with rilonacept. Could you maybe comment on any symptomatic improvement that you've seen in terms of the follow-up? I know it's early in terms of the extension data, but any sort of recovery in those patients that you could comment on would be great. And then second, on the commercial side, as you think about the duration here, I think you've talked a little bit about perhaps a real-world range of 6 to 12 months. Based on what you're seeing also here in the extension data, do you think that's maybe a little conservative? And then third, on the commercial side as well. Could you maybe just talk a little bit about where you are with regards to supply and the relationship with Regeneron?

Sure. Thank you, Paul, and good morning. And I'll maybe take the first question and then pass it over to Q and to Sanj. So with regard to the placebo patients, yes, after a documented recurrent pericarditis event, these patients were offered bailout. And what we know from that period, because they were continued in their follow-up through the end of the randomized withdrawal period, is that there were no further recurrences while on bailout rilonacept. And Q, over to you.

Great. Thank you, John. So your question, Paul, around the duration. Obviously, the market research we had done was before we had seen these data. And at that point, the market research did suggest initially, patients being treated 6 to 9 months with potentially up to 12 months. We will have to go back and do additional market research to see if these data change physicians' perception. I think what I can say is there are going to be patients that will need to stay on treatment for longer. And there's still going to be more data coming out of the long-term extension, which hopefully we'll address in more clarity, the duration question. So yes, and I think your second point about the supply. So yes, we're working very closely with the Regeneron, putting in a commercial supply agreement, and we don't anticipate any issues there.

Our next question comes from the line of Geoff Meacham from Bank of America.

Congrats on the data. I don't think we've ever seen a hazard ratio that low. So I have 2 questions. The first one is just given the rapid onset of action and the effect size, maybe just talk about the upstream opportunity in less severe patients. Is that a future development indication for you guys? And then just a follow-up on the duration of therapy. The number of patients in the long-term extension, I was just curious to see if that could be something that could ultimately be on the label as well? Or would you have to run another study that looks at more chronic dosing?

Geoff, this is Q. To your question about upstream, so much of it's going to depend on what our final label looks like. I think what you heard from Sanj is that there are 40, 4-0, 40,000 patients that are seeking treatment for recurrent pericarditis. We believe that the highest unmet need initially is going to be within that 14,000 patient population. And then the rest of it will come down to what our final label actually looks like, to what we can promote to. And then your question on duration, again, we'd have to see how those discussions go with the FDA in terms of including data from the long-term extension. That data is going to be coming on a kind of a rolling basis. So we'll get more of that information over the coming months. But I think these data are just so compelling and so overwhelming. They certainly impressed us, and I'm confident they're going to play out very favorably with our key stakeholders.

Our next question comes from the line of Anupam Rama from JPMorgan.

Congrats on the data. Just what scientific forum or medical conference are you guys aiming for the full RHAPSODY data? And how do you think about medical education overall here in the virtual world that we live in? And then just a quick reminder on the size and scope of the sales infrastructure you think you're going to need for recurrent pericarditis.

Anupam, this is John. Nice to talk with you. So with regard to the Scientific Congress, so we'll obviously be working with our co-principal investigators at putting together the complete package to be presented at an upcoming Scientific Congress. We're working through those details now as well as potential publication in a major medical journal. And as far as medical education goes, obviously, this information, as it enters into the literature, will become part of the knowledge of cardiologists. And of course, we'll look to the authors of guidelines and other recommendations in terms of how that then works its way into the education of new physicians and cardiologists. But of course, we're very excited about the data and what this represents in terms of a transformational advance for patients.

And on the question of the commercial infrastructure. What we like about the opportunity within recurrent pericarditis -- this is Sanj, is that it does require a relatively limited commercial infrastructure. We believe around 30 sales reps should cover the -- also the high-volume specialists. And we'll also have a digital -- efficient digital marketing effort to support some of the more lower-volume prescribers. We do have an existing MSL, Medical Science Liaison team in place. So we're very much seeing this as a rare disease drug log. But maybe I'll hand it over to Qasim, who's our head of commercial, and he can sort of elaborate further where we think this is a nice opportunity for us.

Yes, Sanj. I think, Sanj, you know that -- and maybe, Anupam, your question around given the current environment, how do we ensure we get the information out appropriately at the right time. So obviously, the MSL will be reacting to any questions that we may receive on the data. They're already in place. And as we're building out the commercial organization, we're making sure that all of our CRMs and technology platforms do enable us to do remote calling, digital detailing. So if there are any access concerns or restrictions at the time of launch, we're going to be well positioned in one place to do as much as is necessarily remotely and digitally to get this information out.

Our next question comes from the line of David Nierengarten from Wedbush Securities.

Congrats on the data. Maybe to ask a question that was previously asked a different way in terms of looking at earlier line patients. Is it possible -- or when you think about the treatment paradigm to have -- or for physicians to treat a perhaps less severe patient on a, I guess, to say, PRN basis, but on 1 or 2 treatments because it does act so quickly, and then the patient essentially recovers? Or, in addition, are you thinking about any additional post-approval studies based on that? And a quick follow-up. You kind of -- what's left in terms of filing that sBLA, what do you need to do if there's any unusual mechanics or anything additional there that you need to you have for that sBLA?

So maybe I could kind of take a crack at potentially moving in earlier lines. And honestly, David, I think it would be dangerous for us to kind of speculate what physicians might do. And so I wouldn't want to say yes or no. So I think it's dangerous to speculate on that. In terms of other indications, obviously, life cycle management is important for us, especially with data like these. I think it's showing the potential that rilonacept that could have in other IL-1 alpha-, beta-driven diseases. So we will continue to evaluate life cycle extension opportunities there. And then in terms of the sBLA filing, I think the -- nothing unusual. I think Sanj mentioned it in his comments was actually we will be having the BLA transfer over [indiscernible]. So that happens all the time, nothing unusual. So we don't expect anything untoward.

And David, maybe I could add one more thing, just about the question that you asked about the duration -- treating briefly, if I understood your question correctly. So understanding that these patients presented with an acute pericarditis episode and then were treated for 12 weeks in the run-in period before the randomized withdrawal period. And then during that randomized withdrawal period, then the events then began to occur with 50% of the placebo patients having an event within the first month, I think, speaks to the fact that these patients certainly needed a substantial period of time with evidence of ongoing inflammation. And so what we know for the duration of the entire trial is that continued rilonacept therapy resulted in continued control of the disease, at least for that study period.

At this time, I am showing no further questions. I would like to turn the call back over to Sanj K. Patel for closing remarks.

Thanks, operator, and thank you, everybody, for dialing in and for the questions today. Obviously, this is a great moment for patients, and we're all very excited. I'm going to echo John's comments and thanking the patients for their participation in the trial. And obviously, all the brilliant Kiniksa team members who have just worked tirelessly in quite a difficult environment. And they've just done so well. So we've got a lot more work to do. We're very excited, and thanks, everybody, and back to work. Thanks.

Ladies and gentlemen, this concludes today's conference call. Thanks for participating. You may now disconnect.