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Intercept Pharmaceuticals Inc (NASDAQ:ICPT)
Q1 2021 Earnings Call
May 6, 2021, 8:30 a.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Welcome to the Q1 2021 Intercept Pharmaceuticals Earnings Call. My name is Anette, and I'll be your operator for today's call. [Operator Instructions]

I will now turn the call over to Lisa DeFrancesco. Lisa, you may begin.

Lisa DeFrancesco -- Senior Vice President of Investor Relations and Corporate Affairs

Thank you. Good morning, and thank you for joining us on today's call. This morning, we issued a press release announcing our first quarter 2021 results and financial position, which is available on our website at www.interceptpharma.com. Before we begin our discussion, I'd like to note that during our call, we will be making forward-looking statements, including statements regarding our approved product and clinical development program; certain regulatory matters; and our strategy, prospects, financial guidance and future commercial and financial performance. Listeners are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this call. And we undertake no obligation to update such statements, except as required by law. Forward-looking statements are based on estimates and assumptions that, although believed to be reasonable, are inherently uncertain and subject to a number of risks and uncertainties. Some, but not necessarily all, of the risk factors that could cause our actual results to differ materially from our historical results or those anticipated or predicted by our forward-looking statements are discussed in this morning's press release and in our periodic public filings with the SEC.

Today's call will begin with prepared remarks from our President and Chief Executive Officer, Jerry Durso; our Chief Accounting Officer, Acting Chief Financial Officer and Treasurer, Rocco Venezia; and our acting Chief Medical Officer, Dr. Gail Cawkwell. We'll then open the call up to take your questions, and Linda Richardson, Chief Commercial Officer, will join us for Q-and-A. [Operator Instructions]

Let me now turn the call over to our Chief Executive Officer, Jerry Durso. Jerry?

Jerome Durso -- President, Chief Executive Officer and Director

Thanks, Lisa, and good morning, everyone. Thank you for joining us on our first quarter 2021 earnings conference call. We've been focused on our priorities in the first quarter of this year and have made progress across all key fronts, including, first, finalizing our Ocaliva label update in the U.S., which is now nearly complete. We anticipate announcing our updated label in the coming days. Second, advancing our NASH development program where we've had multiple interactions with FDA, and we're in the process of generating a significant amount of additional data in support of our dialogue with the agency. And third, continuing to make progress on our pipeline.

I'm going to begin today by discussing our PBC business, including our solid performance in the first quarter. I'll then turn it over to Gail to provide an update on our labeling discussion with FDA, our NASH development program and our other pipeline activities. Rocco will conclude with an overview of our financial performance and update to our guidance before we take your questions.

Let's start with our PBC business, where we had another quarter of double-digit growth. Worldwide Ocaliva net sales in the first quarter of 2021 were $81.7 million, representing about 12% growth over the prior year quarter. We had solid performance in the U.S. with sales of $57.3 million, representing 13% growth over the prior year quarter. Nearly half of our new prescriptions were generated by new prescribers, demonstrating the success of our efforts to reach community-based gastroenterologists. Importantly, we continue to educate healthcare provider audiences through our Rethink PBC disease education campaign which highlights important data from the global PBC study group, supporting more ambitious treatment goals for lowering ALP. We believe broader awareness of these data will impact the way healthcare professionals manage PBC and encourage earlier consideration of second-line therapy within the large group of eligible patients who are not achieving ALP goals with ERSA alone. In our international markets, we recorded $24.4 million which was 11% growth over the same quarter last year. We saw a continued strengthening of new patient starts versus the previous quarter driven by our digital education activities.

I would now like to turn the call over to Dr. Gail Cawkwell to provide an update on our regulatory progress and our pipeline. Gail?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Thank you, Jerry, and good morning, everybody. I'll begin by discussing our Ocaliva label update. The process is nearly complete, and we plan to communicate the final label shortly. We expect the final label will restrict to use in patients with decompensated cirrhosis as well as in those patients with compensated cirrhosis who have evidence of portal hypertension.

As you know from our previous discussions, the Ocaliva label update process began as a result of a NISS, or newly identified safety signal of liver disorder. This was identified during routine post-marketing safety monitoring from FDA in 2020. We shared findings from a comprehensive safety assessment with FDA earlier this year and have been working with the agency to translate the implications of the NISS into updates to the Ocaliva label. These label updates focus on patients who reach the most advanced stages of PBC and not on the broader PBC population. Patients with PBC and cirrhosis demonstrate a wide spectrum of disease severity from clinically stable compensated cirrhosis to end-stage decompensated disease. The development of portal hypertension in these patients is a key pathophysiologic event along with natural disease progression and is often associated with serious consequences of advanced liver disease. From a patient identification perspective, we believe this approach is clear and will enable prescribers to delineate those who are eligible for Ocaliva, the only approved second-line medicine for patients with PBC. Regarding our post-approval studies, COBALT and 401, we continue to discuss potential modifications to these studies with FDA and EMA.

The final Ocaliva label update will play a role in the discussions about our post-marketing study requirements, but we expect that the process of defining a path forward for the studies will continue beyond the label update given the need to align with both FDA and EMA. Now let's turn to our NASH development program. As we've previously stated, alignment with FDA on the right data and the subsequent interpretation of that data are key dependencies prior to a potential resubmission. We are working toward that alignment in a step-by-step process, including multiple recent and upcoming formal interactions with the agency, each of which require significant preparation.

As a reminder, we believe there are three key items that we need to align with FDA on prior to a potential resubmission of our NDA through the accelerated approval pathway: first, a shared understanding of OCA's safety profile in the NASH fibrosis population, which will be supported by a comprehensive safety update to refresh and increase the amount of safety data to discuss with FDA; second, biopsy reading methodology, an important topic for the field as regulators, thought leaders and industry work to establish new approaches to reduce variability and improve accuracy; and lastly and importantly, what, if any, additional efficacy data will be beneficial to better support the benefit-risk profile of OCA in NASH fibrosis.

Let me provide an update on where we are with each of these three items. We've had recent FDA interactions primarily focused on safety. While these have provided deeper insight on key focus areas for the agency including liver safety and other elements of the OCA safety profile, there is additional work under way. We're also advancing our preparations for a safety update that will double the safety exposure from our first submission. Regarding biopsy methodology, FDA's public statements on biopsy methodology and our own learnings from REGENERATE have led us to a proposed approach that we believe is both scientifically rigorous and grounded in the latest thinking in the field. We're looking forward to furthering the discussions with FDA on biopsy methodology in the coming months and subsequently applying that approach to new data.

We have also made progress regarding the potential generation of additional data sets to assess efficacy of OCA for the treatment of patients with NASH fibrosis. Again, FDA meetings on this topic are planned. For example, as a result of the REGENERATE study design, following the 18-month interim analysis which included 931 patients in the intent-to-treat population, approximately 500 additional biopsies were gathered from a group of later enrolling patients once they reached the 18-month time point. We now expect to include these additional 18-month biopsies as a part of any potential resubmission. Given that REGENERATE is an ongoing study, we continue to accrue data and assess other relevant data sets for inclusion and analysis. To put this in context, by the middle of this year, the patients who are part of the 18-month interim analysis will have all reached to their 48-month time points. Importantly, the REGENERATE outcomes trial is an event-driven study, meaning that the study completes when a prespecified number of events occur. As such, the exact timing of completion is difficult to predict.

As we've previously stated, our completion date is likely some years away, and our latest estimates point to a potential completion date in 2025. We also have our second large pivotal NASH Phase III study, REVERSE, under way in patients with compensated cirrhosis due to NASH. We believe the data from REVERSE will provide important learnings in the NASH compensated cirrhosis population, a group of patients with very high unmet need. We plan to take advantage of our work with FDA to align on biopsy methodology as we prepare for a top line readout at the end of this year. We also continue to make progress on our pipeline.

Our Phase II OCA plus bezafibrate trial is still currently enrolling outside the U.S., and we now have an open IND for the combination in the U.S. Enrollment in a rare disease clinical trial does not require a high number of patients, but may take more time due to COVID-19. We will provide an estimated timeline when trial enrollment is complete. Recently published data supporting the benefit of bezafibrate in PBC are encouraging and reinforce the potential for synergistic profile in a combination approach with OCA. Finally, turning to our next-generation FXR agonist, INT-787. We plan to initiate a first-in-human study later this year. We will provide additional updates once this process is under way.

I'll now turn the call back over to Jerry for further remarks. Jerry?

Jerome Durso -- President, Chief Executive Officer and Director

Thanks, Gail. As we look to the remainder of the year, our most immediate focus is on finalizing the Ocaliva label update in the U.S. It's important to note that the significant majority of patients eligible for Ocaliva will not be impacted by the label change. In terms of the population that will potentially be impacted, we're in the process of finalizing a label that would restrict Ocaliva's use in patients with decompensated cirrhosis, those with a prior decompensation event and those with compensated cirrhosis with evidence of portal hypertension. We estimate that roughly 20% to 25% of the current Ocaliva patients would have cirrhosis. The portion of Ocaliva patients that we expect to be impacted by the final label changes would be a subset of this overall cirrhotic group.

As you would imagine, the rate of cirrhosis in PBC can vary by treatment setting. For example, the rate tends to be higher at hepatology centers and lower in the community setting. We're fully prepared to support and educate patients and providers through this upcoming label update, and that process will be implemented as soon as the label is final. Following the label update, a significant majority of PBC patients who can benefit from second-line treatment will remain eligible for Ocaliva. Our long-term focus and commitment to supporting those patients will continue to be a high priority.

Turning now to NASH. Our continued objective is to align with FDA on a resubmission package for NDA that increases the probability of success. This is a multifaceted process that will require additional work and additional interactions with the agency, and therefore, we can no longer reiterate a potential submission by the end of this year. We look forward to narrowing and refining our plans for potential resubmission in the third quarter of this year. Now turning to the EU. Since our last update, we've been formally granted a six-month clock stop in the review of OCA for the treatment of NASH fibrosis. This additional time allows us to focus on executing on the feedback we've received from both FDA and EMA and provides us with the ability to potentially include some of the new data we're generating as part of the review process in Europe.

Before we turn to our financial results, I wanted to announce that Chris Weyer, our Executive Vice President of Research and Development, has decided to leave Intercept to pursue a new opportunity. I want to thank Chris for his contributions to the company and wish him well in his future endeavors. As we've previously discussed, our work toward potential resubmission in NASH fibrosis is led by a strong dedicated team of both internal experts and external advisors. Mark Pruzanski, as part of his ongoing advisory role with Intercept, will continue to support our R-and-D team from a science and strategy perspective. This will ensure business continuity and a smooth transition until the new permanent head of R-and-D is named. I want to say a few final words about Intercept's progress navigating our regulatory dialogue in both PBC and NASH. I'm pleased that we're nearing the conclusion of our work with FDA on updates to the Ocaliva label which will provide important new guidance for healthcare providers and patients with PBC. This clarity on the label will allow us to focus on the future and continue to support the significant majority of patients who will remain eligible for treatment.

As we continue our work with the FDA and EMA on our NASH program, we remain committed to taking the necessary actions to arrive at the right informed decisions regarding our path forward. In parallel with our near-term focus on the regulatory dialogue in PBC and NASH, we've continued to advance key pipeline activities that position Intercept for future success and build on our leadership position in the liver space. We expect to communicate more on our pipeline later this year. And now that we have clarity on our label update to our foundational PBC franchise, we can increase our focus on identifying additional opportunities to leverage our strengths and our expertise.

And now I'll turn the call over to Rocco Venezia for financial updates. Rocco?

Rocco Venezia -- Chief Accounting Officer, Acting Chief Financial Officer and Treasurer

Thank you, Jerry, and good morning, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the first quarter ended March 31, 2021. In the first quarter, we recognized $81.7 million in the worldwide Ocaliva net sales. This was an increase of $9 million versus prior year quarter. Our worldwide Ocaliva net sales were comprised of U.S. net sales of $57.3 million and ex U.S. net sales of $24.4 million. This represents growth of approximately 13% and 11%, respectively, versus the prior year quarter. As Jerry mentioned earlier, our solid first quarter results in the U.S. were driven primarily by continued demand growth. Although as anticipated, we have seen slower growth in new patient starts as a result of COVID-19.

During the first quarter, half of all scripts were generated by new prescribers. We also experienced the typical seasonality in Q1 as patients were impacted by the resetting of insurance plans and Medicare coverage cap. This led to a higher gross to net percentage for the quarter. Our GAAP operating expenses and non-GAAP adjusted operating expenses for the quarter were $111.0 million and $101.7 million, respectively. This was a decrease of $45.1 million and $41.2 million versus the prior year quarter. As a reminder, our non-GAAP adjusted operating expenses exclude stock-based compensation and depreciation. Non-GAAP adjusted operating expenses is a non-GAAP financial measure under SEC regulations. Please refer to our press release issued earlier this morning for a full explanation and reconciliation of this measure.

Our cost of sales was $0.8 million in the first quarter as compared to $0.9 million in the prior year quarter. Selling, general and administrative expenses for the quarter were $59.3 million. This was a decrease of $39.3 million over the prior year quarter and was driven by our efforts to lower operating expenses in order to provide a strong financial foundation for the company going forward. Research and development expenses for the quarter were $50.8 million. This was a decrease of $5.9 million over prior year quarter and was primarily driven by lower NASH and Ocaliva API development costs. As of March 31, 2021, we were well positioned with cash, cash equivalents, restricted cash and investment debt securities available for sale of approximately $418.6 million.

And now turning to our financial guidance for the year. As a reminder, last quarter, we issued full year 2021 worldwide Ocaliva net sales guidance between $325 million and $355 million. As a result of the latest dialogue with the FDA which we expect to result in a label update restricting the use of Ocaliva in patients with decompensated sclerosis and then a subset of patients with compensated cirrhosis, we are narrowing our Ocaliva net sales guidance range. We now expect full year 2021 worldwide Ocaliva net sales to be between $325 million and $340 million. Once the label is finalized as we monitor post-label update market dynamics, we will plan to refine this range throughout the year as necessary. We are reiterating our full year 2021 non-GAAP adjusted operating expenses to be between $380 million to $410 million.

In summary, I am pleased with the strong commercial performance and our ability to manage expenses in the first quarter. We remain well positioned to continue investing in the growth of our Ocaliva franchise, supporting our NASH regulatory processes with FDA and EMA and furthering our pipeline by building on our strong foundation.

With that, I'd now like to turn it over to the operator for any questions. Operator?

Questions and Answers:

Operator

Thank you. [Operator Instructions] -- [Technical Issues] And our first call is from -- please excuse if I mispronounced your name, I'm sorry -- Ritu Baral from Cowen. Go ahead please.

Ritu Baral -- Cowen -- Analyst

Hi, guys. Thanks for taking the question this morning. So Jerry, I wanted to just drill down further on the percentage of patients, PBC patients with compensated portal hypertension that we could be expecting. I know we have the revised guidance, but can you -- could you let us know if like the definition of portal hypertension, whether it's like the ranges of millimeters of mercury or the -- any point within the workup for portal hypertension is different for PBC patients than, I guess, the standard portal hypertension? Yes, standard portal hypertension workup, like should we be thinking about that 15 millimeters of mercury or more?

Jerome Durso -- President, Chief Executive Officer and Director

Okay. Thanks for the question. I think what would be good, I'll have Gail give you an overview on what we're expecting from the label. Again, we're at the end of the process we would anticipate based on the interactions that we have had to date that the process will end shortly, but perhaps Gail can give you an overview of what we're expecting to see, what we anticipate and then I can comment a little bit on the front end of your question in terms of some of the ranges. Gail?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Thanks, Jerry. So to give a little clarity, let me take one step back for just a second and just again define what we said is where the label will change will apply to different patients. First, patients with decompensated cirrhosis, the most severe group of patients, will be excluded from the label. This is a population that can be quite sick, and studying a medicine in that setting can be very, very challenging, particularly one for chronic use. The -- your question focused on this population with portal hypertension, so just to clarify again for a second before we step right to your question, cirrhosis on a compensated side can be divided into two subsets. There's those who are early on in the spectrum of cirrhosis and who are really somewhat indistinguishable from patients without cirrhosis until they develop portal hypertension.

Now, the way portal hypertension is described here is clinical evidence of portal hypertension or evidence of portal hypertension. So we're not looking for an invasive procedure or something else to assess portal hypertension, but rather the clinical evidence that doctors use in their practice really every day since they recognize that once patients with cirrhosis progress to having portal hypertension, their risk for adverse liver outcomes really increases. Again, once you have cirrhosis and progress to portal hypertension, we then will have a contraindication at that point.

Jerome Durso -- President, Chief Executive Officer and Director

So if we think then in the context of the overall cirrhotic group, so we do estimate based on a variety of sources both from the U.S. and ex U.S., the proportion of Ocaliva patients overall that have evidence of cirrhosis, is in that range of 20% to 25%. Again, the decompensated group, as Gail mentioned, will -- we anticipate will be restricted by the new label that's in the mid-single digits, and then you have the compensated group. We're somewhere in the range of about half of the compensated group might fall into this evidence of portal hypertension. So that's how we think about the picture at this point. Of course, as the label is finalized, we'll monitor the dynamics in the market and continue to update.

Ritu Baral -- Cowen -- Analyst

Got it. And then a very quick follow-up on the NASH side. You noted like the three topics of discussion with FDA, safety biopsy methodology and risk-benefit analysis. On the safety side, you guys highlighted liver toxicity. Is it fair to assume that the conversations on that safety topic focus more on liver safety at this point than any lipid changes? Or are lipid changes still a topic of discussion?

Jerome Durso -- President, Chief Executive Officer and Director

Gail?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Sure. So it's important to recognize that FDA has really been interested in the full spectrum of the Ocaliva -- or the OCA, excuse me, safety profile. And I note that there's really a lot of published material in the public domain about the safety profile, and we're continuing to generate more as the REGENERATE study continues.

Ritu Baral -- Cowen -- Analyst

Great. Thanks for taking the question.

Jerome Durso -- President, Chief Executive Officer and Director

Thank you.

Operator

Okay. And our next question comes from Brian Abrahams from RBC. Brian, go ahead.

David Cithu -- RBC -- Analyst

Hi. Thanks so much for taking my question. This is actually David Cithu on for Brian. I guess just thinking about the NASH study and building off of Ritu's question maybe, could you just help us understand maybe what exactly changed in sort of your understanding of the cadence of interactions maybe or what needed to be aligned when we think about the three buckets that led to maybe less clarity on a potential timeline to refiling here?

Jerome Durso -- President, Chief Executive Officer and Director

Thank you for the question, David. As we mentioned in the prepared remarks, we have had multiple interactions. We have more planned. I think we continue to work overall on the question of risk benefit, as you could imagine, and then in that context, the three areas that we've outlined, the comprehensive safety update, the biopsy approach and ultimately, the potential for additional efficacy. So I think we've gotten, as we've indicated, some better clarity on some of the specifics around the data we need to generate as we prepare for the comprehensive safety update, which we anticipate that, that data will be a significant increase in the level of exposure which we think could be important. We've been encouraged by the level of engagement from the agency. We have had interactions. We have more planned coming. I think our focus continues to be on getting clarity. Sometimes that clarity creates some better insight on the work we have to do as well as a better idea of the sequencing of the interactions to come. And so as we work on this thing holistically on the overall picture, it's all of those elements that, in the context of the step-by-step approach and us wanting to avoid unknowns later on, that we continue to work on the plan moving forward. And do anticipate we'll come back in quarter three with refinement on that.

David Cithu -- RBC -- Analyst

Got it. Helpful. And a quick follow-up on the PBC side, if I may. Just thinking more about the, I guess, the ex U.S. side, it was a strong quarter, and I think you noted, driven by both new patient outcomes and not digital education activities. I guess could you just help us better understand the dynamics on the EU side? I know quarter-over-quarter is a little bit more maybe volatile on that side. But sort of how are you thinking about the rest of the year as you maybe continue the digital education activities? And I guess I want to try to understand how much of a run rate here we might see and how much it contributes maybe to guidance.

Jerome Durso -- President, Chief Executive Officer and Director

So I can start on that and perhaps Rocco would want to add on. We do continue to execute our Ocaliva plan in the markets in different situations depending on where COVID is. So in the ex U.S. context, obviously, we have different progress occurring in terms of the activities in the market. So when we think about quarter one and the previous quarters, there has been a specific, I think, opportunity to enhance the digital approach, which is we signaled that in the prepared remarks and the impact that, that has had. Ex U.S., obviously, again, the different countries are in different situations now in context of the guidance. Rocco, perhaps you want to give a little more color around how we're seeing the guidance with the label change and looking at the regions?

Rocco Venezia -- Chief Accounting Officer, Acting Chief Financial Officer and Treasurer

Yes, sure. Thank you for the question. As we had mentioned earlier in our prepared remarks, we've narrowed our sales guidance. With respect to our ex U.S., despite all of the challenges, as many of us know and the repeated closures in many of those markets, we've continued to do well. So that is all factored in, in our latest guidance. And with respect to the approach that we're taking, I could turn it over to Linda to perhaps add additional color on that.

Linda Richardson -- Chief Commercial Officer

Sure. I'm happy to take that. I think there's been a real focus on non-personal promotion, right? We need to get into those centers. And many in the -- unlike the U.S., in Europe, many of the practitioners are in institutions, healthcare settings that were closed to sales representatives and pharma in general because of the need to take care of provocation. There's been a serious restriction on that. Our team quickly pivoted to many innovative programs, using telecalls, reaching out, using Internet programs, etc., to keep awareness up, and that went very well for us. And we followed those same tactics in the U.S.

David Cithu -- RBC -- Analyst

Got it. Thanks.

Jerome Durso -- President, Chief Executive Officer and Director

Thanks, David.

Operator

Okay. And our next question comes from Michael with Jefferies. Go ahead, Michael.

Aryeh Gold -- Jefferies -- Analyst

Hi. Thanks. This is Aryeh Gold on for Michael Yee. Yes, just a couple of quick questions. Can you talk a little bit more about the recent dialogue with the FDA? And then when you give that update in the third quarter, are you just going to come out and sort of say that you have alignment now? Are you going to give more color around that? And then secondly, can you just sort of set expectations for the Phase III data that we should be getting around the year -- end of the year? Thank you.

Jerome Durso -- President, Chief Executive Officer and Director

Thanks, Aryeh. I'll start. So I think the -- as we've outlined on NASH, the interactions, we have had multiple formal interactions and I think, importantly, a good view forward for some steps to come. I think that in the context of the quarter three update, we anticipate to have feedback from some of these key discussions on some of the key topics, again, coming back to progress on clarity on what the safety update should look like. Some of the details that we'll have to work through yet with the agency, for example, on the analysis plan on safety biopsy, We will anticipate making some progress. So the update that I referred to in quarter three, we should think about that, both update on our work and our planning as well as an update on some of the key elements coming from the regulatory dialogue.

I think your second question was about REVERSE. So we are continuing to view REVERSE as an important data set in an important population. As a reminder, this is a group of NASH patients with compensated cirrhosis. It's our second major Phase III that we're working toward the top line readout by the end of the year where we're going to learn more about the role of OCA in a different incremental patient population. So we're working toward that.

Aryeh Gold -- Jefferies -- Analyst

Thank you.

Jerome Durso -- President, Chief Executive Officer and Director

Thanks, Aryeh.

Operator

Okay. And the next question is from Alethia from Cantor Fitzgerald. Alethia, go ahead.

Emily -- Cantor Fitzgerald -- Analyst

Hi. This is Emily [Phonetic] on for Alethia. Just a quick question, do you still expect the REGENERATE trial results to be enough to refile and efficacy for NASH? It kind of sounded like you may need additional data besides the study, so I'm just wondering what the base case is still and if there's been any updates on that. Thank you.

Jerome Durso -- President, Chief Executive Officer and Director

Thanks, Emily. Our approach has been focused on defining a path forward and alignment on a potential resubmission package that would support accelerated review. We did reference in the prepared remarks that there is this additional group of patients that were not part of the interim cohort that we do have an opportunity on the 18-month biopsies to include that efficacy element in any potential resubmission. And as I indicated, we're also interested in what, if any, additional efficacy items might be relevant to the agency's thinking and that topic will be one of the topics discussed in the future interactions that I described.

Emily -- Cantor Fitzgerald -- Analyst

All right. Thank you.

Jerome Durso -- President, Chief Executive Officer and Director

Thanks, Emily.

Operator

Okay. And next question is from Steve with Raymond James.

Ryan Deschner -- Raymond James -- Analyst

Good morning. This is Ryan Deschner on for Steve Seedhouse. Can you elaborate a little more on the difference between the additional data sets to assess efficacy and the actual 48-month efficacy on the interim patient population coming in mid-2021?

Jerome Durso -- President, Chief Executive Officer and Director

So I'll start, and then I'll ask Gail to comment. So what I did indicate is that we're open to the discussion on potential additional efficacy beyond the interim data that we've already generated. And we did reference the additional 500 biopsies as another data item that we would anticipate could be part. Gail, maybe you want to give some additional color on the efficacy side?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Sure, I'm happy to do so. So look, by the middle of the year, the study is ongoing. That means that we're just progressing through the protocol. And by the middle of the year, the original patients who are part of the interim analysis will have all reached the 48-month time point. It's a point also where there's an additional -- biopsy, but it also means our exposure is really greatly increased. So both on the safety and the efficacy side, we really have a large and robust database that just continues to get bigger. And we are looking to those FDA interactions to define exactly how we can provide the most compelling data.

Ryan Deschner -- Raymond James -- Analyst

Okay. Thank you. And then also the additional data sets to assess the efficacy, will that entail a reread of biopsies in a pooled manner as in, a read of all post-treatment biopsy sort of scrambled together?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Yes. So I think that we're looking at the way of rereading the biopsies and discussing this with FDA really -- right now and in the short term. It's important to recognize that FDA has publicly said that they believe a consensus approach to reading biopsies is an important next step, and that's something that we will be discussing with FDA to assure that we have an approach that will have the objective of really decreasing variability and improving accuracy so we get the best readings. FDA has not asked us at present to go back and reread earlier biopsies, but we're looking forward to having those discussions and aligning on an approach in the near future.

Ryan Deschner -- Raymond James -- Analyst

Okay. Thank you very much.

Operator

All right. Our next question comes from Yasmeen with Piper Sandler.

Jesse -- Piper Sandler -- Analyst

Hi, guys This is Jesse [Phonetic] on for Yas. I was wondering, was there a reason why that an IND was not filed for the OCA intensify rate in the U.S. when the study began?

Jerome Durso -- President, Chief Executive Officer and Director

I'm sorry, Jesse, can you repeat the question? It was a little low on this end.

Jesse -- Piper Sandler -- Analyst

Yes. No problem. I was wondering why an IND was not filed for OCA and bezafibrate in the U.S. when the study began as opposed to why the IND is being filed right now?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Great. It's Gail. So we do have an open IND right now. It's not just filed, but it's open and ready to start a study later this year. We took advantage of the approval of bezafibrate in Europe to get things going earlier ex U.S. And our Phase II OCA-bezafibrate rial is currently enrolling and progressing outside of the U.S. We believe this provided a way to move our development program along expeditiously.

Jesse -- Piper Sandler -- Analyst

Great. Thank you. And then one more. Maybe I missed it, but is the NISS for OCA, is that cleared? Or when should we expect a decision on it?

Jerome Durso -- President, Chief Executive Officer and Director

I'm sorry, Jesse, it was difficult. Can you just repeat?

Jesse -- Piper Sandler -- Analyst

Yes, sorry. Is N-I-S-S, the NISS, for OCA, is that cleared? I might have missed it earlier in the discussion. And if it's not cleared, when can we expect a decision?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Yes. I can take that one. So the NISS process, as we've said, it's a relatively new process, so there's very few drugs that have gone through the totality of the process. But based on the communications we've had with FDA, the new label change is really the output and the actions that FDA has taken based on their assessment in the NISS process. So I think you can look at that as the totality of the process.

Jerome Durso -- President, Chief Executive Officer and Director

And again, from our end, based on the most recent interactions, we do anticipate that we're nearing the very end of the process, and we would anticipate that the new label happens shortly.

Jesse -- Piper Sandler -- Analyst

All right. Thank you.

Jerome Durso -- President, Chief Executive Officer and Director

Thank you.

Operator

All right. And our next question is from Brian from RW Baird.

Luke -- RW Baird -- Analyst

Hello. This is Luke [Phonetic] on for Brian. For PBC, could you provide some color with where your dialogue is on Subpart H post-approval studies and requirements to maintain labeling? So in the midst of labeling updates taking place, do you see a path to converting to full approval at this point?

Jerome Durso -- President, Chief Executive Officer and Director

Hello. Yes. Important topic. Gail, can you give the update on the post-marketing conversations with both agencies?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Sure. So As we mentioned in the prepared remarks, we are continuing to discuss potential modifications to our post-approval requirements, the COBALT study and the 401 study, with both FDA and EMA since they are commitments in both parts of the world. The final Ocaliva label update that we anticipate, as Jerry said, just in the next short period of time, will play an important role in the discussions about our post-marketing study commitments. But we do expect that the process in defining a path forward for the studies will continue beyond the label update given the need for that alignment.

Luke -- RW Baird -- Analyst

Great. Thank you.

Operator

Okay. Next question -- excuse me -- is Ed RC. Please go ahead.

Thomas Smith -- SVB -- Analyst

All right. Good morning, everyone. This is Thomas Smith asking a couple of questions for Ed. So first question perhaps on the financial side, you guys mentioned about 20% to 25% of PBC patients have cirrhosis. Can you tell us the financial impact of this proposed updated PBC label? Has passed that been fully baked into the $15 million revised sales guidance for full year 2021?

Jerome Durso -- President, Chief Executive Officer and Director

Yes. Maybe I'll start and then Rocco can comment just to clarify. So the estimate of the 20% to 25% is where we're estimating the overall rate of cirrhosis. The impact of the label is with a subset of that population. We've tried to factor that dynamic into the sales guidance as we look at the rest of this year. Rocco, some additional color might be helpful for Thomas' question.

Rocco Venezia -- Chief Accounting Officer, Acting Chief Financial Officer and Treasurer

Yes, sure. Absolutely. As we had indicated, we have narrowed our sales guidance for the year to $325 million to $340 million. Obviously, this contemplates the various scenarios that we've discussed, and we will continue to refine the sales forecast as we work through that process and implement the new label.

Thomas Smith -- SVB -- Analyst

Got it. Thanks. Thanks for the clarification. Perhaps one more question regarding NASH. With the six-month clock stop with the EMA, is it safe to assume that any dialogue in that market will come after your concurrence with the FDA perhaps sometime later this year, third quarter or fourth quarter this year?

Jerome Durso -- President, Chief Executive Officer and Director

Yes. So as we did announce, we received the six-month clock stoppage. It allows us to execute and work in parallel on the work with the FDA and EMA and potentially include some of the additional data on the responses in the process in Europe later this year.

Thomas Smith -- SVB -- Analyst

Okay. Got it. Thank you so much for taking my questions and we look forward to the update this year.

Jerome Durso -- President, Chief Executive Officer and Director

Thank you, Thomas.

Operator

Okay. Next question comes from Navin Jacob with UBS.

Jon Lim -- UBS -- Analyst

Hi, everyone. It's Jon Lim on for Navin Jacob this morning. I'll keep it to one question, and I'll keep it broad. But if possible, could you give us an overview of the status of your conversations with EMA for Ocaliva across PBC and NASH? Understand that the last call, we were talking about day 120 responses, any updates from there?

Jerome Durso -- President, Chief Executive Officer and Director

Yes. So maybe Gail can start on the PBC view with Europe, and then we can come back to NASH.

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Sure. So on the PBC side, our focus of our discussions has been on the post-marketing commitment studies, COBALT and 401, and assuring we find a path forward to meet commitments, particularly those around our conditional approval. We're also given a label update in the U.S. We'll plan to file a type two variation. And I would say that EMA has had a somewhat different approach to thinking about things as they are want to do, for example, after our periodic benefit risk annual update this past year, PRAC the EMA regulatory authority that looks at safety did note that the benefit risk was unchanged given the current label. Nonetheless, we will be doing a type two variation on the PBC side.

Jerome Durso -- President, Chief Executive Officer and Director

And to reiterate on the NASH side, so we did talk last quarter about submitting our responses to the day 120 questions. And then after the response from the agency, we did receive the six-month clock stoppage, and so that's where the process is currently. Again, it gives us an opportunity to work in parallel to potentially use some of the additional data as we work on the approach with Europe importantly working toward definition of responses that highlight the risk benefit in the right population in that context. So more to come later this year.

Jon Lim -- UBS -- Analyst

That's very helpful. Thank you very much.

Jerome Durso -- President, Chief Executive Officer and Director

Thanks.

Operator

Okay. Next question is from Matthew with BMO.

Jean -- BMO -- Analyst

This is Jean [Phonetic] on for Matthew. Yes, two for me. So you guys read through guidance for the resubmission timing. Where is the gating step for the refiling? Are you guys just waiting for the 48-month data to mature? Or is there anything else that you guys are waiting on? And I have a follow-up after that.

Jerome Durso -- President, Chief Executive Officer and Director

Yes. Thanks for the question. As we work on the overall risk-benefit dialogue with the agency, I think we're, again, we're looking at this combination of the feedback that we will continue to get as we get clarity on some of these items, the operational impact of some of those requirements. And it's really that full picture that we have in mind as we come back and clarify that, at this point, we're unable to reiterate the guidance of a potential resubmission by the end of this year. So it's a holistic view on the dialogue. I think importantly, we have upcoming planned interactions with them where we'll continue to advance the conversation on some of these key topics, get further clarity and be in a position at each step to define what's the right path ahead. And as I said before, I look forward to coming back in quarter three as we've continued our work, as we've continued the dialogue and provide refinements to the plan.

Jean -- BMO -- Analyst

Got it. And then -- and it looks like the new guidance doesn't reflect the label update. Is it fair to assume the addressable patients for PBC may come down to say, like 80% of the initial market? And what are your potential -- like what are your expectations for the potential outcomes of the FDA discussion on the COBALT post-marketing trial?

Jerome Durso -- President, Chief Executive Officer and Director

So maybe we'll start with COBALT, which, as Gail indicated, is an ongoing discussion, which will be -- where we'll be able to -- which will be impacted by the finalization of the label. Gail, maybe you want to start on that, and then we can come back to the first question?

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Sure. So on the COBALT side, it's important to recognize, this is a commitment. We have a Subpart H approval. We will find a path ahead. It's a question of working through the process with both FDA and EMA and the time it takes to align on that path forward.

Jerome Durso -- President, Chief Executive Officer and Director

And then, Rocco, maybe on the second one?

Rocco Venezia -- Chief Accounting Officer, Acting Chief Financial Officer and Treasurer

Yes, sure. Just to clarify, the narrowing of our guidance does include all of the scenarios which we've contemplated with the label update. So I just wanted to make sure that, that was clear because I think your question was if it did or did it not.

Jean -- BMO -- Analyst

Okay. Yes. That's helpful.

Operator

Okay. Next question is from Jerry of Oppenheimer.

Jay Olson -- Oppenheimer -- Analyst

Hi. It's Jay Olson from Oppenheimer. Thanks for taking the question.

Jerome Durso -- President, Chief Executive Officer and Director

Hi, Jay.

Jay Olson -- Oppenheimer -- Analyst

Hi. I was curious, can you talk about what percent of your operating expenses are dedicated to NASH versus PBC? And what would the financial profile of the company look like if Intercept chose to become a PBC-only company. And have you contemplated that scenario internally? And when -- if so, when might the company be willing to make a decision like that? Thank you.

Rocco Venezia -- Chief Accounting Officer, Acting Chief Financial Officer and Treasurer

Sure. So thank you for the question. With respect to our R-and-D costs, as a reminder, we have two large Phase III trials that are ongoing. So specifically, 2/3 of, I would say, our R-and-D costs are NASH specific. And I guess I'll turn it over to Jerry perhaps to answer your question on some of the strategy.

Jerome Durso -- President, Chief Executive Officer and Director

Yes. So as Rocco indicated, the cost structure around NASH, at the same time, if you can -- we're intensely engaged on the process that we've outlined on NASH and ensuring that we're working toward alignment and making sure at each step along the way, we're advancing and making the right decision on the path ahead. I think the -- that work will continue to get more insight from some of the important interactions, which are common, which are planned. We have talked about in the past, if you viewed the stand-alone PBC franchise, it would be a profitable franchise which plays on some of our core capabilities and our strengths. And I think as we move forward now and implement the label change, that's an important short-term focus that also gives us a better ability to be able to work on some of the future opportunities that still exists in the PBC market.

Jay Olson -- Oppenheimer -- Analyst

Great. Thanks for taking the question.

Jerome Durso -- President, Chief Executive Officer and Director

Thanks, Jay.

Operator

Okay. Our next question is from Jeff with Bank of America. Jeff, go ahead.

Aspen -- Bank of America -- Analyst

Hi, guys. It's Aspen [Phonetic] o n for Jeff. Thanks for taking the questions. Just two kind of quick ones. First off, maybe you can walk us through how you're thinking about the NISS update and your expectations for the label as it specifically pertains to your development pathway for OCA-bezafibrate combo? I guess, are there any specific learnings to apply there in terms of the development or the design of some of these studies? And then secondly, maybe you can talk through what the contingency plans are, if any, for REVERSE, trying to incorporate the feedback from the FDA workshop a few weeks or I guess a month or so ago? Thank you.

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

So with regard to the OCA-bezafibrate program, look, we -- you always learn over the course of the development program, one of the objectives of a Phase II study is, of course, define the right dose. And in a combination product, it's that extra step of finding the right synergistic dose ideally between two different medicines. Our hope is that, that can be a relatively low dose for both so that we can really look for opportunities to have the sort of an optimized benefit risk profile. That said, there's always a component of looking at a new medicine, learning as you go, but we have been very encouraged by the data that exists, a really wide array of data that exists on bezafibrate and PBC, OCA and PBC or Ocaliva and PBC and even some data that independently exists and has been published where both medicines are on the market on the two together.

Jerome Durso -- President, Chief Executive Officer and Director

And I guess just on the question on REVERSE. So the importance of the REVERSE data is something that we continue to stress. Again, it's an incremental data set in an incremental population. We have had historical conversations with the FDA on the potential path forward based on a successful REVERSE readout. However, in the context of our overall approach and really stressing alignment at each stage, I think we would look forward to regrouping with the agency with a positive data set in hand if we're in that scenario and discussing the path ahead.

Aspen -- Bank of America -- Analyst

Got it. Thanks, guys.

Jerome Durso -- President, Chief Executive Officer and Director

Thank you.

Operator

Okay. And that concludes our Q-and-A session. Now let me turn the call over to Jerry Durso for closing remarks.

Jerome Durso -- President, Chief Executive Officer and Director

So thanks, everyone, for joining us today. We were able to bring forth another quarter of double-digit revenue growth while working to finalize our updated Ocaliva prescribing information with FDA and advance our NASH regulatory process and our pipeline. We remain as committed as ever to serving patients with progressive non-viral liver disease as well as the healthcare providers who care for them. And we definitely look forward to updating you on our progress on the future calls. Thanks for the time today.

Operator

[Operator Closing Remarks]

Duration: 59 minutes

Call participants:

Lisa DeFrancesco -- Senior Vice President of Investor Relations and Corporate Affairs

Jerome Durso -- President, Chief Executive Officer and Director

Gail Cawkwell -- Acting Chief Medical Officer and Senior Vice President of Medical Affairs, Safety and Pharmacovigila

Rocco Venezia -- Chief Accounting Officer, Acting Chief Financial Officer and Treasurer

Linda Richardson -- Chief Commercial Officer

Ritu Baral -- Cowen -- Analyst

David Cithu -- RBC -- Analyst

Aryeh Gold -- Jefferies -- Analyst

Emily -- Cantor Fitzgerald -- Analyst

Ryan Deschner -- Raymond James -- Analyst

Jesse -- Piper Sandler -- Analyst

Luke -- RW Baird -- Analyst

Thomas Smith -- SVB -- Analyst

Jon Lim -- UBS -- Analyst

Jean -- BMO -- Analyst

Jay Olson -- Oppenheimer -- Analyst

Aspen -- Bank of America -- Analyst

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