Bristol-Myers Squibb Company (NYSE:BMY) Q1 2020 Earnings Conference Call May 7, 2020 8:30 AM ET
Tim Power - VP IR
Giovanni Caforio - Chairman and CEO
David Elkins - CFO
Chris Boerner - Chief Commercialization Officer
Nadim Ahmed - President Hematology
Samit Hirawat - Chief Medical Officer & Head of Global Drug Development
Conference Call Participants
Seamus Fernandez - Guggenheim
Terence Flynn - Goldman Sachs
Geoff Meacham - Bank of America
Chris Schott - JPMorgan
Andrew Baum - Citi
Tim Anderson - Wolfe Research
Matt Phipps - William Blair
Steve Scala - Cowen
Dave Risinger - Morgan Stanley
Good day, and welcome to the Bristol-Myers Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Mr. Tim Power, Vice President, Investor Relations. Please go ahead.
Thanks Chloe and good morning everyone. Thanks for joining us this morning for our first quarter financial year results. Joining me this morning with prepared remarks are Giovanni Caforio our Chairman and Chief Executive Officer; and David Elkins, our Chief Financial Officer. Also participating in today's call for the Q&A session are Chris Boerner our Chief Commercialization Officer; Nadim Ahmed, President Hematology and Samit Hirawat our Chief Medical Officer and Head of Global Drug Development.
As you'll note we've posted slides to bms.com for you to follow along with David and Giovanni's remarks. Before we get started, I will read our forward-looking statements. During this call we will make statements about the company's future plans and prospects that constitute forward looking statements.
Actual results may differ materially from those indicated by those forward-looking as a result of various important factors including those discussed in the company's SEC filings. These forward looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date.
We specifically disclaim any obligation to update forward-looking statements, even if our estimates change. We will also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of those non-GAAP financial measures to the most comparable GAAP measures are available at bms.com.
With that I will hand it over to Giovanni.
Thank you, Tim, and good morning everyone. I hope that you and your families are healthy and managing safely through these unprecedented times. The COVID-19 pandemic is profoundly impacting our lives, families and communities.
Over the past months our company has focused on how we can help in the global fight against the lives and effectively continue the supply of our medicines to patients globally while placing the highest priority on the health and safety of our workforce. I am very proud of how our teams around the world have reasoned to the challenge.
During this pandemic, it has been abundantly clear that the biopharma industry plays a critical role in the prevention and treatment of diseases like COVID-19. Governments, healthcare providers and the public have turned to us to identify and develop diagnostic tests, effective treatments and vaccines to prevent to the disease.
Deep scientific knowledge, development expertise and manufacturing capabilities are what will ultimately help us prevail. And I have been impressed by the collaboration and speed with which the industry is responding.
On Slide 4, let me start with what Bristol-Myers Squibb is doing to support the global COVID response efforts, focused in four key areas, our science, our communities, our patients and our team. On the R&D front, we have identified approximately 1000 compounds in our discovery library that we are making available to external researchers globally, to screen for potential molecules to treat COVID-19.
We are evaluating certain medicines in our portfolio that could be included in near term clinical trials with a focus on the inflammatory immune response associated with COVID-19. We are also participating in cross industry groups designed to foster collaboration. These include the Gates Foundation COVID-19 Therapeutics Accelerator, the California Institute for Biomedical Research, the National Institute of Health among others.
With our resources on how we can support our communities. The Bristol-Myer Squibb Foundation has provided over 170 grants to human service organizations and patient support groups in over 20 countries around the world in order to address gaps in the response to COVID-19.
We are providing personal protective equipments to health care providers on the front lines in China, Italy and to targeted community hospitals here in the U.S. And very importantly we have been focused on how to support our patients.
We have expanded our existing patient support program to help eligible and employed patients in the U.S. who have lost their health insurance due to the pandemic by offering access to any branded Bristol-Myers Squibb medicine for treatment. We are working with healthcare providers in new ways through effective virtual engagements to ensure they have the support they need to treat their patients while minimizing in person contact and the potential spread of COVID-19.
We adjusted our clinical trial operations where needed to ensure the safety of patients, providers and our employees and to avoid stressing the overall healthcare system. All clinical trial activities are planned to resume by the end of the year where local country restrictions have been lifted.
Although the impact on clinical trial timelines is still being evaluated, fully recruited trials are at lower risk of new virus. I am incredibly proud of our teams across the globe. First, our essential workers continue to work at our sites to ensure our medicine to reach patients will depend on them. I am proud of their dedication. Most of our people are working from home to keep essential workers safe and to minimize the potential spread of the virus. We are supporting our teams with increased flexibility to ensure they have design they needed to care for those at home.
Our employees who are licensed healthcare workers and wish to volunteer to provide medical services to patients during the pandemic are supported with food, salary and benefits. Now, turning to the quarter. We had excellent performance financially. And from a pipeline perspective let me start with the extraordinary pipeline execution in the first quarter on Slide 5. We have continued to deliver very well on all key value drivers. Starting with approvals in late March Zeposia was approved in the U.S. for relapsing forms of multiple sclerosis with a best-in-class label.
And we also received a positive CHMP opinions recommending approval for Zeposia in Europe. In April, we received FDA approval for Reblozyl in MDS. This is the second indication for this medicine. And we are very encouraged by the opportunity we have with this first and only EMA medicine to treat anemia.
Additionally, we just announced a CHMP positive opinion for Reblozyl for both beta thal and MDS in Europe. With respect to submissions and filings we received a priority review for liso-cel in third line plus large B-Cell lymphoma in the U.S. Now with the PDUFA date extended to November 16th, we completed our FDA submission for ide-cel, which is an exciting next step in bringing the first CAR T candidate to adult patients with multiple myeloma.
And we very recently announced that we received a priority review for CC-486 in first line AML maintenance. And with respect to lung cancer we received a priority review in the U.S. and CHMP validation in the EU for CheckMate 9LA for Opdivo plus Yervoy plus limited chemo in first-line lung cancer.
And we're looking forward to the PDUFA for CheckMate 227 next week. Lastly, from a clinical research perspective, we recently reported positive top-line results from two positive pivotal Phase 3 studies in our IO pipeline, CheckMate 9ER evaluating Opdivo combination with Cabometyx in first-line RCC and CheckMate-743 where Opdivo plus Yervoy demonstrators survival benefit in first-line mesothelioma.
We look forward to working with global health authorities to bring these new combination regiments to patients, who are waiting for new treatment options. This has been a truly remarkable quarter. All of these exciting accomplishments would not have been possible without the focus and dedication of our global teams.
Moving to Slide 6, we've had a very good quarter financially. Despite the emergence of the pandemic. Our business is strong. In the first quarter, we deliver $10.8 billion in sales. Excluding COVID related buying patterns. This represents a pro forma underlying growth of 8% versus last year.
Our performance was strong across brands and geographies as a result of excellent commercial execution across the board. David will provide more details in his remarks, including the shifts we're seeing in buying patterns for some of our medicines.
Let me now provide more details on how we are managing the business in the current environment. Our supply chain remains intact. We are continuing to manufacture API without the disruption and we have safety stock of raw materials and finished product available.
The pandemic has naturally caused some logistic complications and we are navigating this successfully. Our integration work is proceeding well. We continue to build on the hard work from '19 that allowed us to hit the ground running with greater efficiencies. We've seen an acceleration in the cultural cohesion of our new company during the work from home period. As the current environment has brought us together in even greater ways. We are on track to deliver $2.5 billion in synergies by the end of '22.
Finally, as we see counter is moving to Phase 2 of the pandemic and reopening parts of their enemies, our focus has shifted to recovery. And we are accelerating planning for restart of many of our operations. We will do this gradually, as conditions evolve, while continuing to keep the safety and health of our workforce, our patients and our communities, as our highest priorities.
So looking forward, while industry wide dynamics may create volatility in our business in the short-term, and there is significant uncertainty regarding the dynamics of the evolution of the pandemic. We are executing well, we remain well positioned and I am excited about the potential of the company.
With that, I’ll hand it over to David, to walk you through our financials for this quarter and how we are thinking about our future. David?
Thank you, Giovanni. Hello everyone and thanks again for joining. I hope that you and your families are staying safe and healthy while we operate virtually.
As Giovanni mentioned, I am extremely pleased with the execution of our teams during this unprecedented time. The benefits of our medicines and the strong commercial execution resulted in exceptional performance in the first quarter.
Turning to Slide 8, we had strong top line performance in the quarter with global sales increasing double-digits growing 13% versus prior year on a pro-forma basis. We saw a significant strengthening of the dollar in the latter part of March and there this had a minimal impact in the first quarter, it will be important to keep this in mind as we think about the full year outlook.
Additionally, important to note, sales were favorably impacted due to COVID-19 related stocking by approximately $500 million excluding the COVID-19 impact underlying sales performance continue to be strong with 8% growth year-over-year.
Now let's turn to our key brand performance starting with Eliquis on Slide 9. Eliquis had another strong quarter growing 37% year-over-year with sales of $2.6 billion globally largely driven by strong underlying demand.
We also saw significant favorable impact from channel on patient level stocking due to COVID-19 approximately $350 million, which is expected to reverse over the remainder of the year. Excluding COVID-19 impact, sales growth in the quarter would have been 19%.
As the COVID situation evolves, we'll continue to monitor the impact of customers and patients, including the patient starts. Although we expect some variability quarter-to-quarter due to the pandemic, remain confident of Eliquis' growth and outlook, where there's continued momentum to grow considering TRx share of 47% and new brand share of approximately 57%. Looking forward, we continue to expect significant growth driven by Eliquis’ increasingly strong position as the number one product in expanding NOAC class.
Now turning to Opdivo on Slide 10, U.S. demand trends are in line with our expectations. As previously communicated, demand is down in the low single digits sequentially. We continue to see stabilization of the second line IO eligibility poll of about one-third as well as strengthening of our position in the first line RCC market, which sets a good foundation for the potential future launch of CheckMate-9ER.
Internationally, we saw strong execution continued with sales growth of 12% year-over-year. Opdivo was minimally impacted by COVID-19 in the first quarter with strong shares across all our indications. However, we are aware that COVID-19 has impacted patient access to oncology clinics and infusion centers which could impact the volumes of infused products in the second quarter.
We will continue to monitor these factors. Importantly, as we look forward, we believe Opdivo is well positioned for return to growth in 2021, with action dates in front line long for 227 next week and 9LA later this year as well as the upcoming opportunity for CheckMate-9ER.
Now moving on to our inline multiple myeloma portfolio on Slide 11. Revlimid and Pomalyst continue to deliver strong double digit growth of 14% and 29% respectively year-over-year. This growth was driven by increased share and treatment duration due to demand for Revlimid and Pomalyst based triplet therapies.
The U.S. impact from COVID-19 was relatively minimal in the first quarter. Outside the U.S. we estimate a favorable $50 million to $100 million COVID related stocking, mainly for Revlimid. Due to the oral administration of Revlimid and Pomalyst allowing patients to take their therapy at home and the potential for relapse in myeloma patient of treatment is stopped, we expect less of an impact to the treatment disruption related to the pandemic.
We are continuing to monitor new patient starts as well as U.S. changes to buying patterns due to the FDA advance program relaxation from 28 days to 56 day scripts. Because these products are sold through specialty pharmacies, we do not see the same level of stocking you would see with other chronic oral medications.
Now let's turn toward the strength of the balance sheet and capital allocation on Slide 12. We ended the quarter in a strong liquidity position with approximately $19 billion in cash and marketable securities with our net debt coming down to $28 billion. We generated significant cash flow from operations in the first quarter of nearly $4 billion.
The strength of our balance sheet will allow us to execute on our capital allocation priorities which will continue to be our prioritization of deleveraging and achieving less than one and a half times debt to EBITDA ratio by the end of 2023, investing in future innovation through business development and our continued commitment for dividend.
As previously stated, at the close of the Celgene transaction, we entered into a $7 billion ASR agreement of which 80% retired quickly. The remaining 20% will be completed by the end of the second quarter.
So we have a share repurchase authorization, our priority for share purchase is off setting stock based compensation and having completed the ASR. We don't plan in near term share repurchases in the current environment.
Now turning to guidance on Slide 13, reaffirming our 2020 adjusted EPS and updating our revenue range MS&A, R&D and OI&E line items. We now expect revenue to be between $40 billion and $42 billion primarily driven by currency swings I just described.
We expect MS&A to be between $6.5 billion and $6.7 billion and R&D to be between $9.2 billion and $9.4 billion reflecting reduced activity through the COVID 19 combined with incremental operational efficiencies. In OI&E we expect to have reduced interest income driven by lower interest rates.
Now let me also provide you with some perspective on 2021. We are affirming our non GAAP 2021 EPS based on positive momentum in the business and the assumptions we've made about the impact of COVID 19. As we mentioned in February, we don't plan to provide continual updates to our 2021 guidance. However, this quarter in light of the exceptional circumstances associated with COVID 19 we believe it's important to confirm that our view of 2021 is intact. Our guidance reflects what we know today and we will need to monitor how things evolve.
With that in mind, let me provide you with some color on our guidance framework on Slide 14. Our assumption is that the peak impact of COVID 19 crisis on our business occurs in Q2, 2020, with a return to a more stable business environment in Q3 and minimal impact from Q4 2020 onwards. These factors assume that our guidance include products itself significant advanced buying at the end of Q1 or see that inventory work down during the rest of the year, mostly in Q2 and to a lesser extent in Q3 and Q4.
The reduction in new brand prescriptions and physician administered product demand during Q2 recovering Q3 and fully recovered in Q4 and planning to resume all clinical activities by year end when local and country restrictions have been listed. These assumptions are based off holding FX and interest rates continent as of mid-April, 2020.
Our guidance does not include changes to macroeconomic factors that could affect not just our business but the entire industry. Of course as we move forward, the factors that are more industry related and companies specific might have an impact on our current view and when we need to incorporate this future analysis. These include persistence with the strength of the US dollar, recovery of demand post Q2 2020 and the evolution of the macroeconomic environment.
Nevertheless, the fundamentals of the business remain very strong and we you remain disciplined with respect to our management of the P&L. Before we move on to Q&A, I want to reiterate how proud I am of our employees during the world crisis.
Our strong first quarter results and our guidance demonstrate resiliency and diversification of our portfolio and we continue to feel good about the long-term growth and financial flexibility of the business.
I'll now turn it over to Tim and Giovanni to manage the Q&A.
Thanks David. So could we go to the first question please?
Absolutely. So the first question comes from Seamus Fernandez from Guggenheim. Please go ahead.
Thanks very much for the question. So one of the products that you argued is being missed in the Celgene acquisition is CC-486. I was hoping, the team could talk a little bit about the commercial prospects for 486 and kind of the durability of this asset as you said, you think about it.
And then incremental to that just wondering if you could update us on any data that would be coming outside of ASCO. I believe the EHA abstracts are hitting, frankly on the same day as the late breakers will come out either on 28th and the 29th. So, just hoping to get an update on the rest of the pipeline coming at EHA? Thanks.
Thank you, Seamus. Thank you very much. This is Giovanni. So, we're very pleased with the priority review designation for CC-486. I'll ask Nadim to give you a perspective on the commercial opportunity there. And then Samit can follow up on your questions regarding data and ASCO and beyond. Thanks.
Great. Thanks for the question, Seamus. We remain very excited about CC-486. I think it's important to provide some context. So with AML it's a very poor prognosis disease even in the newly diagnosed setting where we look at five year survival rates of around 15% to 25%, depending on the age of patients.
And even saying that most patients do have a complete response, but 80% of those patients will relapse within 18-months. So, we're very excited about the fact that CC-486 has delivered a 10 months survival benefit in that setting.
So, I think that's really important. And as we think about the opportunity, it's about 33,000 patients overall. And then if you think about the relapse rates, you can start to think about the epi-related to the disease. But the fact that we've added 10 months survival benefit, we've doubled the relapse free survival benefit.
I think we're very excited about the commercial potential, not only in terms of impacting those patients’ outcomes, but also the opportunity now to establish a maintenance treatment paradigm in AML, which other drugs have tried and we haven't seen survival benefit before in the maintenance setting.
So, I think from our perspective now having clarity on PDUFA date, the launch team preparations are going very well indeed. And we remain very excited about the opportunity to CC-486. And in terms of durability, we feel very good about the position we have our intellectual property around CC-486. So, we're very excited about the opportunity for patients and for the business of CC-486. Maybe I'll turn it over to Samit now.
Thank you, Nadim, and thanks Seamus for the question. Let me first say, what we are looking at, and then we look at ASCO as you've seen the titles that have come out. We are certainly looking forward to the very exciting data from 9LA in non-small cell lung cancer looking at a view of placebo and limited chemotherapy, along with an update with a two year update for CheckMate-227.
In addition to that from a hematology perspective, more specifically, we're looking forward to the first presentation of data from the CARMA trials at ide-cel in multiple myeloma. In addition to the liso-cel data update that we look at and very importantly, continuing with the multiple myeloma team we're looking at presentation of the data for CC-480 with CELMoD, which is going to be very, very important and exciting.
You asked about EHA. EHA will be more of encore presentations following up from ASCO, in addition to that, we're certainly looking at the data sets in terms of the outpatient use of liso-cel as well at EHA.
So these are going to be important sets at ASCO, which we will obviously continue to talk about as we go forward and then follow up. If there is anything more, I have more to say about EHA thereafter. Thank you.
Thanks, Seamus. Can we go to the next question please?
Absolutely. The next question comes from Terence Flynn from Goldman Sachs.
Great. Thanks for taking the questions. Maybe this is for Chris, you obviously have a number of upcoming launches and just wondering how you're adapting the commercial strategy here with the possibility of the current environment persists longer than maybe we'd expect.
And are you confident that you can achieve your target sales goals for a lot of these new product launches? And then follow up questions just on liso-cel BLA submission. I was wondering if you can give any more specifics about the FDA request. Thank you.
Thank you, Terrance. Let me just start. I will ask Chris to comment on your question, and Nadim and also then Samit can follow up on liso-cel. We're taking a way clear approach with launches. And obviously, the number one priority is the health and safety of our employees of the healthcare professionals.
So we don’t want to disrupt healthcare systems, right now. And so we have taken the position to really maximize early on our remote capabilities in terms of engaging with our customers in order to respect to the challenges of the pandemic.
Having said that, while we have global principles, those principles apply differently to different parts of the world. And they also apply to different brands, because the launch of a new indication for an existing well-established brands is clearly a different strategy versus a totally new medicine.
So Chris and Nadim can give you a couple of examples of how these principles we are applying them to our launches and obviously the continued support of our portfolio.
Yes, so maybe I’ll start. Terence, thanks for the question. So as Giovanni mentioned, we made the decision a number of weeks ago to pull in-person engagement with customers. That said, we have continued both on the medical and commercial side to engage with customers remotely.
The good news is that BMS has made significant investments in remote engagement capabilities over the last few years. So the teams have a lot of experience, not just for the last couple of months, but for many years in leveraging this technology to engage with customers.
And as Giovanni mentioned, we've very much taken the point of view that every launch is going to be viewed as independently. And we'll look at how we're going to engage with customers and how we're going to think about those launches, given the specifics.
So for example, you'll recall that when Zeposia was approved in late March, we decided to postpone that launch. We did so because at the time the healthcare system was really just bracing for the impact of COVID. And within the MS community specifically, we were starting to see a pretty big impact on their ability to operate through March. For example, we saw about a 25% decrease in new to brand scripts in MS.
And we frankly didn't feel that the conditions were appropriate to introduce a new medicine, without having our commercial and medical teams be able to effectively engage with customers. That said, in recent weeks we've begun to see the MS market begin to adapt to the current environment. Importantly, physicians are beginning to actively initiate new therapies. They began switching patients on therapy and as a result we plan to launch Zeposia, on June 1st.
In terms of preparations, the teams are very well prepared. We've hired a very experienced medical and commercial team that's been fully in place frankly before launch. And we've gotten very good feedback on the Zeposia profile. So we're very excited about making that opportunity available. Obviously initially that launch will heavily index and this will be true for first line lung cancer as well it will heavily index on remote engagements.
Again, we have a lot of experience in leveraging that technology. And then as conditions warrant, we'll be able to dial-up in personal promotion. And ultimately as we always do, we'll use a mix of both in-person and remote engagement to support those launches. And we have a lot of confidence in the teams across the commercial organization in our ability to execute these launches.
Nadim, anything to add.
Sure. Thanks Chris. I mean I'll just say a couple of things. One, we're very excited about the opportunity to launch four first-in-class or best-in-class medicines in the U.S. just this year. And so the launch preparations are going very, very well with the team.
Of course we'll continue to use our deep relationships with hematology experts and hematologists and also our commercial infrastructure. So between Reblozyl, liso-cel, ide-cel CC-486 that's the potential for four launches in the U.S, this year.
And just to give you some flavor what Chris was saying, we were able to very quickly with Reblozyl pivot for the MDS launch from an in-live situation, which we filled at the beginning of the year to a virtual launch and we continue to have good success stories about the ability to access our physicians and customers in general through virtual engagement.
So, we're very excited about the launches ahead of us. And as Chris said, we've really pivoted to that digital environment. I'm finding we're gaining good access. So very excited about those launches.
And then I'll hand over to Samit, for the other part of your question.
Thank you, Nadim. And thanks Terence for the question. As it relates to liso-cel, as you know, that we had submitted the application with comprehensive data sets at the end of last year. And the FDA accepted the application for liso-cel and granted a priority review in February of this year.
Now, it is typical for the FDA to request additional information as they continue their review process and ask to the company supplied information in response to several requests that the FDA has made. FDA has decided that the information they have received constitute a major amendment. And that's why the PDUFA date has been extended by three months to the 16th of November now.
We're obviously committed to ensuring this medicine is available to patients as soon as possible and we continue to meet our severe milestones. Obviously, we're not going to comment on the specifics of our regulatory discussions.
But let me just remind that we remain very confident about the data for licensed health for these patients with large B-cell lymphoma, as it is an unmet medical need and we're truly looking forward to the approval of this therapy towards the end of the year.
Thanks Terence. Chloe could we go to the next question, please?
Absolutely. The next question comes from Geoff Meacham from Bank of America.
Thanks for the question. I just had a couple, as a follow up for David if the environment normalizes this year, maybe still be a lower run rate for some of your new launches. Since if this affects how you think about 2021 in terms of revenue or cash flow, and other opportunities for synergies to be realized on an accelerated basis.
And then Giovanni, big picture on the BD front. You talked about deals still being focused on as well integrate cells. And so just curious whether the COVID-19 environment offers this view either their priorities or perhaps the size and scope? Thank you.
Thank you, Geoff. Let me ask David to start and give you a perspective on 2020 and '21. It's really what has been reflected in our guidance. And I'll get to your second question immediately after.
So, thank you for the question. Particularly on guidance, as we're thinking about it, as we said is, right now we think the inventory build-up that came through is going to really sell mainly in Q2 and for the remainder of the year.
As far as what we're watching closely for new patients starts in anticipation that that recovers in Q3 and we're back to normal in Q4. And as well as the infusion centers in the volumes returning to normal. And that would continue into 2021 on.
What I would say is that the underlying performance of the business is very strong in the first quarter. And as you heard about what the product launches are confidence in those four product launches are coming this year, as well as the product launches next year.
That gives us the confidence in reiterating our guidance for both this year and next year, but we're going to keep a very close eye on the macroeconomic factors that could wind up impacting entire industry as I talked about in my remarks.
As far as the synergies, we continually review those synergies both internally as well as with our board. We are really pleased with the progress we've been making on the synergy front. And the progress with the third party vendors has done very, very well.
And as far as getting the organization in place, the vast majority of our placements of the organization are done. And as far as site selection is concerned bringing our sites together that's moving along as planned as well. So we remain confident in delivering kind of essential targets that we have.
Thank you, David. So just going back to your question, Geoff. So let me just say first of all, we are very, very happy with the progress we've made with the integration of the company, and at the same time, the strength of execution in the company.
So on one side, our business continues to perform really well. As you've seen, we've made great progress with the pipeline against all key value drivers. We're executing well. We've made progress.
I would say we are progressing really well with synergies as well. And we have tremendous flexibility from a P&L perspective and from a financial perspective. So going forward, we will continue to be very disciplined in terms of how we think about resource allocation and expenses given evolutions related to the COVID pandemic.
Now, given our strong position, as David mentioned earlier, we've not really changed our capital allocation strategy. Business development remains the central pillar of our strategy. We are very focused on continuing to bring the new assets and innovation into the company.
I expect that to continue to be the case and it's very possible in fact that there are more opportunities available to us going forward. And going to we are definitely focused on business development as we've always been. So, thank you.
Great. Thanks, Giovanni. Are we ready for the next one?
Absolutely. The next question comes from Chris Schott from JPMorgan.
Great. Thanks so much for the questions. Just two for me. The first one, in light of the 9ER study, can you talk about the RCC market and the opportunity you see for Opdivo Yervoy versus IO TKI combinations over time? And how you see Bristol positioning these two different frontline offerings they're going to have as you think about how you're going to position them relative to one another?
My second question was on COVID and drug pricing. I think you mentioned some of these kind of macroeconomic factors, but when you think about high unemployment as well as growing budget deficits from government payers.
How do you see that flowing through as you think about net pricing, looking out later this year and into 2021? Core of the question do you think it's likely that we're going to see some sort of incremental impact to pricing from what's occurring with COVID right now? Thank you so much.
Thank you, Chris. Let me start. I'll give you my perspective on pricing. And then I'll ask Chris to comment on, 9ER and RCC. It's exciting there.
So first of all, I think a lot of, first of all, I would say Chris, the issue of drug pricing is one, where we've been in dialogue now for a period of time. And we, as an industry and as a company continue to think that there is a real need to be strategic. And think about reforming some of the elements of the pricing system in the U.S. that are creating affordability issues for patients.
As you know, we believe there is a real opportunity through rebate reform and other measures that are market based to address the issue of drug pricing in terms of patient affordability, which is the real issue.
Now, with respect to your question, first it is early days and it is early to say, and it is difficult to speculate on the future. Of course the focus of many and I think that was at the center of your question is, what happens in an environment where unemployment is higher and a significant impact to the commercial markets.
So one way to think about, if you look at our business, where 60% of our business approximately in the U.S. So of that 60%, about 25% of our business is in the commercial space. And when you look at the dynamics that may play out in the commercial space. I think a lot depends on what happens to patients that may be unemployed and potentially lose coverage.
So some of those patients will move to a spouse's insurance plan. Some of those patients may take up COBRA. And obviously any strategy or policy that makes that more affordable would be - even more affordable would be beneficial for patients. Some of those patients will be eligible for Medicare if they're over 65.
There may be some shifts to government programs like the exchanges or Medicaid and hopefully no patient or very few patients is covered. So these are all of the dynamics that we're going to be working through.
And of course a lot depends on the shape of the recovery and how long unemployment lasts. But I think these are sort of the macro factors that we'll be looking at together. So with that, I'll ask Chris to give you his perspective about the RCC market and the excitement with 9ER.
Yeah, thanks for the question Chris. We're very excited about the data that we saw with 9ER. Maybe in answering your question, I'll start with just kind of an update on where we are with Opdivo plus Yervoy today in first line renal.
If you go back a year, one of the things that we said when we first started to see the IO TKI data was that we anticipated that Opdivo plus Yervoy would remain a standard-of-care in first line. And that's precisely what's happened.
And we think that's been driven primarily by the impressive long-term benefits that you have seen with Opdivo plus Yervoy. We just saw the 42 month OS update at ASCO GU, that OS was about 56% in the ITT population. And that's sort of been continued strong performance of Opdivo plus Yervoy in first line.
Market share right now is between 30% and 35% overall. It's on the upper end of that range, when you look at the labeled indication that we have in intermediate core. We do get some non-promoted use in the favorable population, which is off label for us of about 15% Opdivo plus Yervoy use there.
And we've also seen, that the majority of the use that existing IO plus TKI therapies have gotten in first line renal has largely been at the expense of TKI monotherapy. So Opdivo plus Yervoy has held up really well and in fact we've seen a bit of an uptick in Opdivo plus Yervoy over the last number of months.
9ER very exciting data, we're very happy to see both the OS and the PFS data that we saw there, also very encouraged by the safety profile for 9ER. In terms of how we're thinking about positioning it, still very early days and we're working through the data, but we think these data compete very well against the existing IO TKI therapies.
As a result, we think there's an opportunity to drive share from existing IO TKI therapies. We also think that there's an opportunity to drive share from TKI monotherapy in spite of advances in first line renal TKI monotherapy is still about 20% to 25% of share, mostly in the favorable population.
And with respect to favorable, we think there's an opportunity there for us as well since 9ER crossroads status and included that favorable population patient and now once approved, we'll have access to that population promotionally.
Importantly, the last thing I would say is that once approved 9ER really does give us the opportunity to offer patients multiple IO modalities. We'll be the only company, frankly, to have dual IO, but also what we believe would be a best in class IO TKI offering.
So very excited about the opportunity that 9ER offers us to help patients and provide another modality to those patients. And I think that there's a nice opportunity.
Thanks, Chris. Chloe can we go to the next question please?
Certainly. The next question comes from Andrew Baum from Citi.
Thank you. So questions for Samit please. In terms of attending 9LA data at ASCO, what is the follow up of that data for both OSN for PFS? My question is all physicians going to come after that presentation and rethink that strategy for first line non-small cell lung on the back of that data, is there enough follow-up there?
Second, in terms of the 9ER trial, could you talk to cover that too? I remember that when you ran the Phase 2, there was a question about toxicity and making sure and be use the low dose. So given it's a much more promiscuous TTI, should we assume a favorable or comparable tops profile? Anything you could share that would be interesting.
And then finally on TIGIT, Roche's pushing forward very aggressively with that TIGIT antagonist. Merck clearly is interested and active with as your program seems not to been very much. Is that a function of resource allocation or is it a function of what you're seeing with this particular molecule? Thank you.
Thank you, Andrew. So Samit I believe all three elements of the questions are for you.
Thank you, Andrew, as always very thoughtful questions. And certainly a thought provoking from our 9LA perspective certainly we're looking forward to the first presentation of the data. At ASCO, virtually, but certainly going to be very meaningful.
As you recall we had finished enrollment towards the beginning of last year. So at the first readout of the data, the interim analysis, the follow-up is short. What we will be able to share is follow on data from that perspective. It's very important I think to realize from 9LA perspective a few things that are questions that we will be looking towards the data to answer.
One is as we continue to follow on and as you continue the follow up, what happens to that OS curve? Does it start to flatten out? Number one. Number two, what happens to that beginning part of the curve that we saw in CheckMate227 where we have the early progresses and how a limited amount of chemotherapy can impact that?
I think those are the very important answers that we be looking for as you look towards the presentation of the 9LA data. We remain excited. I think both of them have to be considered together with 227 data and the 9LA data in overall management of a patient as you look towards non-small cell lung cancer management as we go forward.
So I think that dual IO inhibition becomes very important along with that shortened duration of chemotherapy for some patients required. I will obviously ask towards the end of when I finished that to Chris also to comment from commercial perspective was that really need.
On the 9ER side, as you mentioned, a couple of medics will use a dose of 40 milligrams and certainly that is going to be important in terms of management of the safety profile. As we've already said, that overall what we have seen is generally quite manageable safety profile.
Chris also spoke about, that this provides an opportunity for further use of Opdivo in all the risk categories in combination with this potential. So certainly very exciting news there the trial has met all three endpoints, the major endpoints if you look at from an overall survival benefit, as well as looking at DFS and response rate, in addition to a very well managed safety profile.
And I'll finish off on the TIGIT and then I'll pass it on to Chris to comment further on both9LA as well as 9ER. On the TIGIT perspective, we are looking forward to see the data that Roche will be presenting, certainly a very complex mechanism, as you very well know.
We have our molecule which is in Phase 1. We continue to evaluate the Phase 2. And the overall dose profile for that agent and certainly there's no data to be shared yet, but we will certainly learn from what Roche is going to present and then we'll see if we can manage differently. Chris, do you want to add things?
Sure. I think that Samit stood on most of the points around 9LA. What I would say from a commercial standpoint is obviously we've had a lot of discussions with physicians over the last few months about 227 and 9LA. And it's important what Samit said that physicians and we really do think that 227 and 9LA really need to be thought about together.
227, you'll recall that what we showed was about 50% of responders were still responding at two years, and we saw this nice flattening of the OS curve. You'll see how that data matures at ASCO into few weeks. But then the way physicians are thinking about 9LA is very much as complimentary to 227.
In that they offer the benefit of Opdivo plus Yervoy to patients who don't need chemotherapy, that's 227. And for those patients who potentially do need chemotherapy and that's where 9LA comes into play. And I think Samit hit on some of the key things that you want to pay attention to when that data are presented at ASCO in a few weeks.
Two other things that I would just keep in mind with respect to Opdivo plus Yervoy in lung. First about half of the lung cancer treaters have used Opdivo plus Yervoy either in melanoma or renal. So, they're familiar with the benefit that we see with that regimen there and those physicians account for about two thirds of total lung cancer patients.
And then the second thing not a trivial thing is that we have a very experienced team with a track record of being able to establish Opdivo plus Yervoy at a standard of care in both of the tumors in which we've been approved with that regimen.
And then they're incredibly excited and prepared to launch Opdivo plus Yervoy in first line lung cancer and we're really looking forward to the PDUFA date for 227 next week.
Thank you, Chris.
Thanks, Chris. Chloe, could we get to the next one, please?
Certainly. The next question comes from Tim Anderson from Wolfe Research. Please go ahead.
Thank you. Couple of questions, please. Quite a few number of Bristol narrowed its footprint in emerging markets intentionally to focus on I think what it felt was geographies where it had more scale and presence.
But with Celgene folded in you're a much bigger organization. And it kind of makes me wonder what the plan is with emerging markets going forward. I don't even see emerging markets or China, mentioned in the press release or in the slide deck. But as we've seen across industry, geographies, like China are very important, especially in their oncology.
So it makes me wonder if there's kind of an untapped revenue stream here. And what's the solution, if you think there is indeed a problem that you don't have a big enough footprint now given the size of the company?
The second question is on LAG3. If I understand it you have pivotal LAG3 plus Opdivo in combination data coming up around year-end, in first line melanoma as a program that doesn't seem to be get talked about very much investor expectations are low. My question is, should those expectations be low do you view this as a high risk program?
Thank you, Tim. Let me just answer your first question. And then I'll ask Samit to give you his perspective on the ongoing LAG3 program. I think you're point is really important. It is a very good question. You are right that given our focus on oncology and all of the work that we have done over the last few years, we have been focused primarily on, I would say the developed world.
I must say we have a meaningful presence in developing countries. And when we've seen when we look at the development of our oncology business in particular, we have had significant success actually outside of the US and Europe and major markets, including Central and Eastern Europe and some of the key markets in Latin America. And as you know recently with the approval of Opdivo in China.
So it is also accurate that now we have a broader portfolio and more opportunities to establish a larger presence outside of the tier one top markets. And I'm actually really confident we have the right capabilities there. And we have a strong base to continue to invest internationally.
There is a real opportunity, but there is also already a presence of the BMS portfolio that has been successful there. So, we'll continue to invest, across different geographies and there is an opportunity with a broader portfolio to have an even broader approach with respect to the footprint. Samit?
Thank you, Giovanni. I'll take on the last three questions, so, I think, first of all, a lot has happened in terms of drug development part in patients with melanoma and certainly BMS player. BMS has played a big role in getting the FDA together both Opdivo and Yervoy.
Lastly as a new mechanism that we are excited about from the early Phase 1 data we have seen, and also from the biomarker data perspective looking at the T-cell exhaustion and how to get the immune system going again.
From that perspective, this is going to be a very important study. The trial is currently enrolling and this is certainly seeing from the investigators perspective. They remain excited and they continue to enroll patients in the trial.
It is on track. From an enrollment perspective, we continue to collect data we look into where's the readout towards the end of the year. And in parallel, we continue to plan lifecycle management studies in terms of looking at visual indications that you will hear about as we roll them out towards the end of the year, early next year as well.
Thanks Samit. Can we go to the next one please Chloe?
Certainly. The next question comes from Matt Phipps from William Blair.
Thanks for taking the question. First given the current environment and potential trouble accessing infusion clinics, is there any reason to accelerate the development of our subcutaneous nivolumab and other trials going on there since 2018 looking at that?
And secondly, for the TYK2 a small molecule just want to confirm that psoriasis trials are on track to complete or midyear this summer. And all the physician assessments can be completed. And then there's been a lot of formulation work ongoing according to clinical trials.gov. And just wondering if any of our impact potential filings in new clinical trials are successful?
Thank you, Matt. So Samit, I think there's two questions on subcu nivo and then the status of the TYK2 program.
Absolutely, thank you. So, the only thing I can say about the subcu nivo that we are currently evaluating that. It is ongoing. I think acceleration will depend on the outcomes of the first Phase 1 studies as we look towards the dosing and the tolerability and safety, which should be available sometime soon.
And then based on that, we'll continue to progress further, looking into the further development and bringing it to the patients. We recall the Phase 2 data we are certainly very, very promising Phase 3 trials, both over 046, 047 completed enrollment.
So at this time we are looking at follow-up of these patients, collection of the data and cleaning activities so that we can push the database lock. There's no reason to believe that there will be any delays. We're looking towards the end of the year for readout of the first study of 046 and first quarter of next year for 047 for the psoriasis program.
So, those two are the updates for TYK2 and subcu nivo. Back to you Tim.
Thanks so much. I know we're starting to run close to the end of our normal time. I think it's maybe time to squeeze in two more questions Chloe. Could we go to the next one?
Absolutely. The next question comes from Steve Scala from Cowen. Please go ahead.
Thank you. Your comments on the liso-cel PDUFA extension reflected no real concern whatsoever. And it's one of the four new launches you called out for this year. It seems you are completely comfortable with the FDA meeting the regulatory timeline.
I just want to make sure that that's the impression you wish to convey to us? And then secondly, it was stated that the COVID-19 could lead to inventory destock and a drop in patient visits to infusion centers in the second quarter as well as beyond that. I'm just curious, what was the decline in these metrics during the month of April? Thank you.
Sure. Thank you, Steve. So I think we've already made comments on liso-cel, but I'll ask Samit, if there's anything he wants to add, and then David can give you a perspective about different market dynamics and how we see that impacting the business for the rest of the year.
Thank you, Giovanni. And thanks Steve for the question. For liso-cel what we have said that we remain confident in the data. We remain confident in the data that is submitted to the FDA. It is very normal for the FDA as they review the file to ask questions. Certainly we are looking towards the approval date now in November.
During the review process, there may be many more questions that come to us. But that's a very normal process. So I think that's the way to look at it. I obviously cannot comment specifically on types of questions or one that relates to from a regulatory point of view. We remain confident and we are looking forward to bringing this treatment to patients as soon as possible towards the end of this year.
And just on the question around the stocking that we saw. So as we entered the pandemic situation in February and March, what we saw was across the board, we saw safety stocks increasing so we saw wholesalers, making sure they had increased inventory. We also saw that pharmacies had extra safety stock. And then we installed with patients getting longer scripts, as we talked about it.
Revlimid was an example doubling the number of days that they could get. We are starting to see some of that destocking come out. And we anticipate, as I said earlier that the majority of that will come out in Q2. So of the $500 million that we talked about, majority of that come out in Q2, and then we'll see it coming out to in Q3 remainder is what we're anticipating.
As far as what we're seeing on the new patient started early days. What we're seeing there, but we did see some of those new Rxs declining 10% to 20%, depending upon them. And we'll be watching that very closely in the second quarter, and we'll update you on that.
And then on the infusion center, similar, that we're seeing in that 10% to 20% range as well, fewer patients. So again, that's something that we're going to keep an eye on in the second quarter as well. Chris, I don't know, if there's anything that you wanted to add to that.
I think you've managed to hit on the key points. The only other thing I would say is that the drop that we've seen in patient volume and particularly in new patient starts has varied really across therapeutic areas. So in the CV space, it's been sort of on the order of 20% to 25% across the NOAC class.
A lesser extent in oncology and the tumors that we are in, it's been on the order of 5% to 20%. And as David mentioned, that has led to some choppiness, for example, in Opdivo sales in April, which we think is attributable to the new patients, to the drop in new patient starts.
That said, we would expect that as David had mentioned, that would the biggest impact for that would be in the second quarter that would begin to normalize and be back to more normal levels by the third quarter - by the fourth quarter, and that's what we'll be continuing to monitor.
Thanks, Chris. Maybe we can go to our last one Chloe.
Absolutely. The next question comes from Dave Risinger from Morgan Stanley.
Thanks very much. So congrats on the results in the prospects. I have two questions. First, could you just comment on the ozanimod opportunity and all sort of colitis and the expected timing of Phase 3 top-line results?
And then I missed part of call earlier, so I don't know if you discussed it. But could you also comment on Opdivo adjuvant trial readouts to watch? And maybe you could focus on the biggest incremental commercial opportunities with respect to those adjuvant trials? Thank you.
Thank you, David. So Samit and Chris can address both of your questions.
Samit, do you want to start with the data on IBD and then I'll pick up on the commercial opportunity to talk about attributes.
Sure, absolutely. And then certainly for the data that we're looking forward to for ozanimod in ulcerative colitis. We are still on track as the trial had already completed enrollment and we're looking towards the third quarter of this year for the top line readout.
Let me give back to you for adjuvant timelines and the impact. Chris?
So just on the commercial opportunity in IBD, what I would say to build on what Samit started with around the data is that with both ulcerative colitis and Crohn's disease, as you may know, these are chronic conditions, they require multiple treatments to manage. And in both of those disease areas, there really is a need for more efficacious drugs with a manageable safety profile.
In terms of how we seek, we could play in that space with ozanimod. In the pre-biologic space, I think there's a need for safe convenient options with efficacy that's on the order of what you see with biologics. That's especially true in Crohn's disease, which lacks any sort of a well-established first line treatment.
And then in a post-biologic space, there's really a need for safe options with a different MOA for patients as they develop immunogenicity to biologics. And as Samit alluded to, the data are still relatively young and ultimately the opportunity that we're going to have is going to be data dependent there.
With respect to the adjuvant opportunity as we've talked about routinely, we're excited about the adjuvant opportunity. It's a space where IO should work given you have an intact immune system. The data that we've seen so far, both in adjuvant melanoma with Opdivo and Yervoy and some of the early data that we've seen with Opdivo in the neoadjuvant setting where we saw about a 45% pathological response rate looked very encouraging. And we think it's the opportunity to have the biggest impact on patients.
In terms of those commercial opportunities, we watching out for. Remember the way to think about it commercially is not only the patients who are treated today but much like what we saw with the introduction of IO in adjuvant melanoma, you really have an opportunity to improve the treatment rates.
So you need to look at both, patients who are treated today, but also what's the treatment rate. So the ones to keep an eye on would be lung. Lung is an area where in the U.S. are about 10,000 patients treated today. But the treatment rate in adjuvant lung is only about 40%.
Similarly, we're excited about the opportunities in renal cell and esophageal. Those are also potentially large opportunities. Renal in particular, the treatment rate in adjuvant is only about 15%. And then obviously we have ongoing programs in adjuvant melanoma as well.
Other programs that are of interest would be gastric bladder. And the nice thing about the portfolio of adjuvant programs we have is that we've got multiple approaches and we're also looking at traditional adjuvant as well as neoadjuvant and peri-adjuvant. So really excited about the opportunity.
Thank you. Thanks Chris. So thanks everyone for participating in the call. This was a very strong quarter. I'm very proud of our execution and the resilience of our organization. I look forward to what we work on to achieve together.
In closing, it is clear that the pandemic is impacting our lives. It's also shining a light on the potential we have as an industry and as a company to transform the lives of patients to the science. We're focus on doing our part and continuing to deliver medicines that our patients are depending on.
Thanks everyone and our team will continue to be available to answer the rest of your questions. Have a good day. Thank you.
This concludes today’s call. Thank you for your participation. You may now disconnect.