Good morning and good afternoon and welcome to the Novartis Cardiovascular Update. Please note that during the A recording of the conference call, including the Q and A session, will be available on our website shortly after the call ends. Press should anyone need assistance during the conference call, they may signal the operator by pressing star and 0. With that, I would like to hand over to Samu Shah, Head of Investor Relations. Please go ahead, sir.
Thank you very much, and good morning and good afternoon to everybody. A big, big thank you for joining us this afternoon at European Time for the Novartis Cardiovascular Update. We think today we have quite a lot of speakers, but hopefully we'll presentation, we have Dave Surgel, who is the Global Head of Cardiovascular presentation, Rod Wooten, who is the Global Head of Marketing, Novartis Pharmaceuticals Victor Borton, Head of Novartis Pharmaceuticals U. S. And our external speaker is Matthew Whitty.
He's the CEO of Accelerated Access Collaborative NHS Group and he'll be talking about the population health press release, we are expecting to start this year. And with myself, Samir Shah, Global Head of Investor Relations. Presentation. Before we start, I just wanted to read you the safe harbor statement. The information presented today contains forward looking statements that involve known and unknown risks, uncertainties and other factors.
These may press release, the results could be materially different from any future results, performance or achievements expressed or implied by such statements. Presentation, please refer to the company's Form 20 F and its most recent quarterly results on Form 6 ks With respect to the slide sets, you can follow it on our website. We did post it earlier in the day. And with that, I think I'm going to hand across to Dave presentation,
Dave? Great. Thanks a lot, Sameer. Really appreciate it. Thank you all for joining.
It's great to be here to talk about the cardiovascular renal metabolism portfolio and talk especially about the cardiovascular medicines we have in our portfolio. We have the ambition to reach 100 of millions of people with these innovative therapies and therefore improve cardiovascular health. So Rod and I are going to start today with Entresto. So if we flip to Slide 6, As you all know, Entresto has been improving and extending the lives of heart failure patients since 2015. And recently, earlier this year, we expanded Entresto's indication to include patients with Heart failure with preserved ejection fraction with below normal ejection fraction.
And this then covers about 5 out of every 6 press release, heart failure patients in the United States are now covered by Entresto's label. So if you look at this timeline, about 18,000 patients have been enrolled in randomized controlled clinical trials with Entresto across the spectrum of heart failure In rigorously designed active controlled studies versus the standard of care. And this really, I think, underpins presentation, our ambition to transform the care of heart failure. Slide 7, We're going to talk about, Paradise MI now, which was a landmark study in post acute myocardial infarction patients, And talk to you a little bit about how Paradise MI fits within the clinical trial evidence basis In heart failure. So, Paradise MRI, the aim of this trial was to show Whether or not Entresto could prevent the onset of heart failure in high risk patients after they have had a heart attack.
So as many of you are probably aware, in the post myocardial infarction setting, RAS inhibition running angiotensin system inhibition press release, we have a very high bar, again, With the ambition to transform the care of these patients to show that Entresto was superior to this standard of care approach. About 5,600 patients were enrolled in this trial. And let me reinforce, these are patients who are within a few days of having a heart attack. So these are patients who are fragile, who are sick and have had a life changing event. And we have had therefore had an opportunity to evaluate Entresto's efficacy as well as tolerability in these fragile patients.
The primary composite in Paradise Semi was cardiovascular death, heart failure hospitalization or outpatient heart failure visit, the first occurrence of any of one of those three events. Slide 8 shows you that the The results of the primary endpoint from Paradise Semi, again cardiovascular death, heart failure hospitalization or outpatient visit for heart failure. And as you can see, despite a trend favoring Entresto in this trial, unfortunately, we did not hit statistical significance For superiority versus ramipril in this study. Slide 9 shows you a bit of context For why the PARADISE MI trial was setting a high bar for Entresto to transform care. And this shows you a historical view of the care of post MI patients over the last 30 years.
And what you can see if your eyes go to the top of the graphic on the left hand part of the slide, you see the 1990s, A year after having a heart attack, about 20% of patients would be expected to die. And as you can see, over the last 30 years, Care of these patients has improved substantially, so that now that 1 year mortality rate is more in the 5% range. And this has happened for a variety of reasons. Renin angiotensin system blockades is part of it, early percutaneous coronary intervention is another part of it, high intensity statin use post demise and other and just quality metrics with respect to how these patients are cared for, I think have really changed the outcomes In a positive way for these patients after heart attack. So these numerical trends we see in PARADISE are on the basis of already substantial improvements over the last 30 years.
Slide 10 shows you other endpoints from Paradise MI, again consistent with the primary endpoint Where we saw the trend towards an improvement in cardiovascular death, heart failure hospitalization and outpatient heart failure visits, We see the secondary endpoints similarly show a trend towards the benefit for Entresto in a variety of measures. Next slide, on Slide 11, we're calling out 2 additional pre specified analyses that I think provide Additional color on the importance of Paradise MI in the context of the treatment of heart failure patients. So if you look at the left hand graphic first, this shows you the total first and recurrent adjudicated primary events in the trial. What this shows you is that, the relative risk reduction of 0.79 is Better than what we saw on the primary endpoint, which was 0.90. And what this probably reflects is that patients who have a first event of heart failure Are starting to perhaps receive some benefit from receiving Entresto as they continue on in the trial.
So what you see is future hospitalizations after that first hospitalization are then prevented compared to the placebo group Compared to the Ramipro Group, I'm sorry. The next graphic on the right hand part of the slide shows you that when you look at investigator reported press release, so when instead of looking at the CEC adjudicated events where stringent documentation is required press release, we will now be conducting a heart failure hospitalization or outpatient visit and instead you rely on the wisdom of the investigator, who in most cases is cardiologist, You see that there are more events and therefore, a nominally statistically significant result with hazard ratio of 0.85. So this gives you confidence that that trend that we see in the primary analysis may actually be a true incremental effect of Entresto in this population. Slide 12 shows you the adverse event profile. Again, in this very fragile Population of individuals who had just had a heart attack, we see that Entresto was well tolerated.
And this Actually, it was also despite the fact that there was no run-in, in this trial. So patients were just started on therapy once they were randomized in the trial. And as you can see, there were no new safety findings in this study. As we expect, we see more hypotension events in the Entresto group and more cost Actually fewer patients discontinued due to adverse events in the Entresto arm. So again, this gives you confidence that Entresto can be used in these fragile patients Slide 14 shows you just That there's a substantial amount of evidence now underpinning the utility of Entresto in the treatment of heart failure.
Over 50,000 patients have been enrolled in clinical trials and over 320,000 patients experiences in real world evidence trials have been tracked now. So this really gives us, I think, a strong basis of support, for continued use of Entresto in heart failure. And in addition, probably also reflects the fact that guidelines now support Entresto as standard of care in heart failure with reduced ejection fraction. Slide 15, so what's next? Well, Entresto also Could meet a major unmet medical need in Asia in the treatment of hypertension.
Very early on in its development path, Entresto was considered for development in hypertension. And what we saw was in Asia where there's And especially high proportion of individuals who are elderly and have a higher sodium intake, they might be particularly amenable to Entresto's mechanism. And indeed, in clinical trials, we showed that Entresto was superior to the then commonly used olmesartan China and Japan. So now I'm going to pass it to Rod to give an update on the commercial status.
Thanks, Dave. Let me just take a moment and give you some additional context on the PARADISE MI study, some market performance and treatment guidelines As we move forward, so on Slide 16, if we look at the size of the opportunity that still exists in the The significant unmet need that exists in congestive heart failure, we have 8,000,000 patients alone in the U. S. And the EU5 that could benefit from Entresto today and achieve and get the standard of care. If we put the context of the population that Dave described, we've got 1,500,000 myocardial infarctions annually Knowing that approximately a third of those patients are likely developed congestive heart failure, we see that there's a significant opportunity that those press release, patients will eventually develop heart failure and they will be among the labeled population for Entresto, an opportunity to upgrade into the standard of care.
So if you flip to Slide 17, as you see on the left hand side from the weekly NBRx data, the market performance is incredibly strong. And the trajectory that you see from January post is really driven by 3 main factors. 1 is the COVID recovery. We're seeing more access to customers again and actually patient office visits are exceeding pre COVID levels. 2nd major factor is the ACC expert consensus guidelines, which I'll talk a little bit more about in a minute, This had a powerful impact on increasing Entresto first line use ahead of ACEs and ARMs.
And the 3rd major factor is the momentum that we're seeing from the launch of the expanded label and the early positive indicators So looking ahead at future growth opportunities, we're confident that Entresto press release, we continue to maintain the strong growth trajectory globally. And on the next slide, we've mentioned a number of times the importance presentation of these ACC expert consensus guidelines and they're incredibly clear in terms of Focusing on and recommending Arne as the preferred first line use ahead of ACE and ARBs And considering the other mechanisms as add on therapies to RNA therapy or Entresto in this case. So this really puts Entresto in the poll position for 70% of the HFrEF patients who are still on previous standard of care and not yet receiving Entresto as their foundational treatment. And we know very well from experience in cardiovascular and with cardiologists the The guidelines drive prescription behavior and we're certainly seeing that with the change in clinical practice, particularly from the release of these guidelines in January of 20 So if we turn to 2019 and just summarize where we're at with Entresto overall, it is clearly our anchor brand in the cardiovascular And as Dave said, while Paradise MI didn't meet the primary endpoint, the results did show incremental benefit versus a high bar And confirm the very important safety profile in the most fragile patients.
So we expect in Tremendous momentum to continue very strong throughout the globe as we continue to reinforce and educate on those treatment guidelines, Educate our customers on the new expanded label and the opportunity for patients to achieve Entresto, the first In hypertension, we could see some acceleration of momentum in the case of positive approval and broad reimbursement. So the outlook for Entresto continues to be very strong. Dave, I'm going to hand it back to you to discuss one of our other major assets for the franchise, Great. Thanks a lot, Rod.
I appreciate it. So I'm back again to talk about Lectvio, along with Victor Alberto, Head of Novartis Pharmaceuticals and Matthew Witty, CEO of Accelerated Access Collaborative for the NHS. So Let's turn to Slide 21. And there have been variations of this slide shown many times and it doesn't change. Despite the advances over the last several decades in cardiovascular care, there is still a huge burden presentation, we have a very strong quarter of the year.
We are pleased with the progress we made in terms of morbidity and mortality and in terms of cost for health systems. So if we look on the left hand part of this slide, we see that about a third of all deaths now presentation, we are now in the process of evaluating the potential for cardiovascular disease more than any other disease and more than all cancers combined. This poses a huge cost challenge for health systems, expected to exceed $1,000,000,000,000 Per annum by 2025. And of course, the number of lives lost is huge and staggering, 18,000,000 lives lost globally to cardiovascular disease last year and about 60,000,000 patients are at risk of having Cardiovascular morbidity and mortality due to ASCVD in the U. S.
And the EU5. Slide 22. For the last 50 years, we've shown as a medical academic and scientific community presentation, we have shown that there's a strong link between LDL cholesterol and cardiovascular outcomes. And that lowering LDL presentation, we can improve cardiovascular outcomes in actually a rather reliable way. So as you see in the graphic here, About a 40 milligram per deciliter reduction in your LDL Cholesterol reduces your relative risk of having a heart attack or dying of cardiovascular disease by about 20%.
So this has been confirmed over many years with many agents in a variety of settings, over 500,000 patient lives presentation, the other important thing to derive from this particular graphic is the importance of adherence and persistence presentation of the study on outcomes. And what the colored lines represent here is a situation where you have a therapeutic that Achieved 100 percent adherence and full reduction of LDL cholesterol by 40 milligrams per deciliter And the fact that that can improve cardiovascular outcomes as you see on the y axis better than other agents that perhaps have more That have more administration or patient burden in terms of taking them. So for example, monoclonals or statin. This is an analysis that was published by Kash Ray and his colleagues in SERC recently. So this relationship is Critical, Slide 23 shows you that guidelines have, of course, adopted this recognition and have become more and more specific As you can see in the left hand part of the slide, the and ACC have for individuals at very high cardiovascular risk recommend an LDL C reduction to less than 70 milligrams per deciliter and in Europe, those same patients less than 55 milligrams per deciliter.
So remarkably, despite effective what we believe are effective therapies and effective ways of being able to reduce LDL cholesterol, About 80% of patients are not able to achieve these targets. So if we look at Slide 24, this is where We believe Lecvio fits in. Based on its Phase III profile, we see that Lecvio provides presentation, we have a sustained and powerful efficacy on LDL lowering with 2 administrations per year. So as you can see in the graphic, In 3 Phase III trials ORION 9, 10 and 11, we see up to a 52.3% reduction in LDL cholesterol in patients with ASCVD on top of statin. Next slide, Slide 25.
While we saw this powerful sustained LDL lowering efficacy, Alexia was also very well tolerated, which is an important factor when you're thinking about a chronically administered medication to sick patients. So as you can see from the adverse event table, Lectio had a very was very well tolerated and really the one finding we had was self Resolving injection site reactions that really pose no burden. So this is a game changing profile that we believe We'll really be able to improve cardiovascular health. Now I'd like to pass it over to Victor to talk about our plans in the U. S.
Well, thank you very much, Dave. If we move to Slide number 26, I wanted to focus here on the particular the presentation of the U. S. Unmet need. And you can see here that we have around 20,000,000 patients treated with statins today, ASCVD patients, And that the vast majority of them are not at goal as of today.
Also notable that we see small penetration of the nonfatin therapies as well. And We have identified 3 main factors that drive this unmet need. The first one being adherence to therapy, the second one being access to these therapies and the third one being patient affordability. And we believe that LecVIO has the potential to uniquely address them. So now as we move to Slide 27, we focus on the first one of these factors being adherence.
On the left side, you can see how adherence remains a challenge both for statins and PCSK9s. And on the right side, you can see how different adherence levels may influence the cumulative incidence of events. If we move to Slide number 28, here we focus on the potential that Lecchio has to address adherence challenges based on three factors. The first one Dave just shared with us is the clinical profile and the effective and sustained LDL C reduction presentation that we've seen the clinical trials and the second one is a twice yearly dosing in the maintenance phase And thirdly, the HCP administration. Now we move to Slide number 29.
The HCP administration presentation has also implications for access. LECVIO was studied as an ACP administered drug and as such, we expect that the majority of LECVIO patients On the table below, we have summarized the main differences between the pharmacy and the medical benefit reimbursement. And here you can see that leg deal will have the potential to be acquired via buy and deal and that for certain populations Like the Part B fee for service population that represents around 40% of the Yale CVD population, likely will be covered to label, Which means no step edits, no prior authorizations, and therefore, much less hassle for HCPs and their offices. Moreover, For Bio and Bio, practices will be reimbursed for their administrative efforts, which is not the case for the drugs covered under the pharmacy benefit. Now one question that we get quite often is the impact of the availability of CV outcomes evidence as a driver for access decisions at launch.
And here you can see that for the Part B fee for service population, again around 40% of the population, we expect access to mirror the FDA label. And then for the rest of the populations, our experience with payers in the U. S. Is that the focus is mostly on efficacy, safety and cost. Now moving on to Slide 30, if we move to patient affordability, as you can see on the left side, The out of pocket cost for patients has a substantial impact on the abandonment rates in this market, highlighting the importance of patient affordability.
And as you can see on the right side, the medical benefit coverage for Lecvio Creates the opportunity for a $0 co pay for up to 2 thirds of patients at launch, and we believe this will be a strong driver. Now as we have just seen, Inclisiran's clinical profile and the possibility of the medical benefit reimbursement Have the potential to address the 3 key unmet needs in the market being adherence, access and affordability. Now for this to happen, cardiologists will have to grow increasingly comfortable with the buy and build process, Which is a new process for them and which will take time and effort to establish. Now if we move to Slide 31, In order to support this process and to comprehensively manage these non clinical barriers, presentation, our U. S.
Launch focuses on partnering with health care systems. As you can see in the graph in the center, the majority of U. S. Cardiologists today are employed by health care systems. And importantly, these systems have already buy and bill infrastructures implemented for other specialties, Which should help with the process of establishing bio and billing cardiology.
Some of these health care systems also have centralized prescribing influence and centralized EHR systems that enable granular patient identification. Now importantly as well, when we talk about the top 200 healthcare systems in the U. S. Who take care of 2 thirds Of the ASCVD patients in the U. S, 45% of these systems already have ASCVD as a key strategic priority, Which makes them strong partners for this launch.
Now moving on to Slide 32. We've here shown the example of one of those systems of care, these large systems of care that we're going to prioritize for the launch. And there's 2 things that are interesting to note here. 1 is the size of these systems of care. I mean this one in particular Has 23 hospitals, one dedicated lipid center, 7 advanced cardiac hospitals.
They own 40 cardiology groups, They already have 10 outpatient infusion centers that do buy and build for other therapeutic areas. The other interesting thing is understanding the granular data available to identify the ASCVD population who is not at goal today. And the fact that many of these systems already have population health experts working within the system trying to address these challenges. Now finally, moving to Slide 33, I wanted to quickly recap this section saying that we believe presentation, we have a potential to become the leading choice for ASCVD patients. On the one hand, by providing effective and sustained LDL C reduction.
And on the other hand, we believe that MEGVIO is uniquely positioned to address the 3 key unmet needs in ASCVD, which are adherence, Now in order to prepare for the launch in the U. S, we are focused on approximately 200 prioritized healthcare systems And we're deploying a highly experienced reimbursement team to help systems and HCPs navigate the early reimbursement complexity with BioEnvio. Now with that, I would like to hand it over to Matthew Bibby.
Many thanks. And yes, really grateful for the opportunity to kind of talk through this really exciting partnership work The work of the Accelerated Access Collaborative. And so this is a convening press release, the Board that brings together an industry government, regulators, patient groups and the NHS. And the aim is to remove barriers to access And to accelerate the adoption of the most important medicines, diagnostics, devices and digital products. And you can see on the slide the range of partners that we bring together, but it's probably just worth highlighting that there isn't really anything else like this In the U.
K, where you get the Chief Exec of the NHS England meeting with the The Chief Executive of the Medicines and Healthcare Regulatory Products Agency with the Chief Executive of NICE, with representation from trade bodies And also other parts of government and research and the research infrastructure as well. So it's a really unique group. And with the really senior buy in and expertise to help us solve these biggest challenges, And it's hosted by NHS England, as I mentioned as well. So that's just a bit of background to what the accelerated access collaborative is. So it's a really, really important group for driving This work through and other work with regards to the adoption of innovative technologies.
Moving on to talk about the population health approach. And I think I won't go through all the detail on these slides. I'll just talk to you the highlights in the interest of time. I think the important things to note on this are that there's a really strong alignment with this work with the aims and the specific commitments in the NHS press release, I think when we look at sort of Why we at NHS England started to wanted to sort of undertake this partnership? It was really because there was a strong clinical case for the improved reduction in LDL cholesterol lowering That really aligned with the long term plan commitments.
We had strong support from the national clinical directors. So we had the key opinion leaders at NHS England who were supportive of the approach. And we also recognize that other therapies in this area, so specifically the PCSK9 inhibitors press release, we had lower levels of uptake than we would have liked, even though they had approval from NICE And the regulatory and the nicely HCA body. So I think the opportunity to work in an area that was TGP important. Had the clinical buy in and would enable us to and the work the timing of the work enabled us to We start planning to overcome some of these obstacles to adoption in a timely manner so that we weren't in a position with NICE approving something and then the uptake being slower than we would have liked.
And there are a couple of key areas, there are 3 key areas really that we focus on here. So one is Really positioning this treatment as a primary care intervention. So typically, a lot of the uptake New medicines would be focused in secondary care. Secondly was efficient patient identification, so working with NHS digital and GP system suppliers to make it easier to identify the patients most at risk. And thirdly, working with stakeholders and making sure that their consultation and the training program It's in place as well.
So the education for clinicians is being developed as well. And we're working really closely with delivery partners Called academic health science network. So this is a network of 15 organizations that have got really good local relationships with NHS press release, we have a national level of coordination that we work with them on a range of our implementation programs. I should say as well, all of this is contingent on or linked into the deal that was agreed with NHS England, Which is contingent on the NICE approval as well, but yes, really, really strong alignment and timing wise makes perfect sense. Moving on to the impact.
So we already know, and as I mentioned, the NHS long term plan that Heartland circulatory disease causes a quarter of all deaths in the UK and is the largest cause of premature mortality in deprived areas. And it's already been recognized as the single biggest area where the NHS can save lives over the next 10 years. So in terms of sort of the level of importance of addressing outcomes in this area, it doesn't really get more important than this. And you can see on the slide here, we've got a program work where we're looking at kind of what the impact this could have on cardiovascular And then moving on presentation planning, so we've been working really closely between ourselves and Novartis and the academic health science networks presentation, to agree the implementation plan, looking at the trajectories and the key performance indicators that we're Looking into the agreements with the academic health science networks, and we're taking a local focus to looking at what the implementation looks like press release, we are looking at targeted rollout in areas where we think this is going to have a biggest impact. I briefly mentioned patient identification already and the collaboration with NHS Digital has been key to being able to effectively identify these patients in primary care and it's something that we haven't done before for outside of COVID.
So it's a really good test case for how we can do this. I mentioned education, so it's critical that we're educating the clinicians who are going to be the prescribers for these, Both in terms of what the intervention does, but also in terms of the model for how this can work. So recognizing that this is slightly different to how the NHS would typically adopt a new medicine, which might be a little bit more cautious in keeping things within So we really kind of see this as a primary care intervention. We've got a sort of an engagement program that is kicking off next week. And then finally, we've got adherence support as well.
So linking in with the NHS digital collaboration. So we We've got various system prompts that we can build that we built into the system as well. So including a recall for patients that have been initiated on treatment. So I think that was everything that I wanted to cover. Hopefully, that's given a good flavor of sort of why we were, from an NHS perspective interested in this collaboration, how we've gone about it from an implementation planning perspective presentation and how this is different from how things have been implemented in the NHS previously.
So I think that's all I wanted to cover really.
Thanks very much, Matthew. Appreciate it. If we flip to Slide 38, The current submissions in the U. S. And globally are supported by the trials that have been completed already, ORION 9, 10 and 11.
And then as you all know, we expect our cardiovascular outcomes to the ORION-four through press release, we have a robust evidence generation plan behind those studies as well With the aims of really better understanding how best LECVIO can be used in which patients and in which settings. And as you can see, we're in the process of planning several trials to support This evidence generation and we'll be providing more information and more detail as time In good time as we get more details on the program. So in summary, Slide 39, The burden of cardiovascular disease is indeed rising despite effective therapies. And we know that LDL cholesterol is one of the most press release, we will now begin the presentation. Mainly due to adherence access and affordability challenges as Victor talked about.
The U. S. Launch is focusing on partnering with health systems to manage Non clinical barriers in the U. K, as you just heard, the NHS and Novartis are partnering on a population health approach presentation. So we'll now turn to Philip Carson, and Rod and I will walk you through this exciting program as well.
So Slide 41 introduces you to Lipoprotein, if you haven't heard about it before is an LDL like Independent cardiovascular risk factor that's genetically determined. Currently, there are no known therapies That reduced lipoprotein and in fact diet and exercise don't improve your lipoprotein statins, etcetera. None of those therapeutic alternatives We'll improve your lipoprotein or reduce your risk. So, we have an opportunity to develop a new therapy for patients With cardiovascular risk that's currently not managed. Slide 42 shows you the evidence that links Elevated lipoprotein to cardiovascular risk.
And so you see there are a variety of sources of data. Presentation study showing you similar data whereas you have elevated as your Lp increases on the y axis, Your hazard ratio also goes up. So these there are several lines of evidence that link lipoprotein to increasing cardiovascular risk. And indeed, guidelines and are increasingly recognizing Lp as an important risk factor to Slide 43 shows you an important piece of information, which is so I said at the beginning that Lp looks a lot like LDL cholesterol, but interestingly, they're not very highly correlated. So You still should measure an Lp if they've had a heart attack or they have ASCVD, right, to appropriately assess their risk.
So what this tells you is because these two risk factors are independent, LDL and Lp level A are independent, you need to measure both of These risk factors in order to really judge a patient's risk for cardiovascular Morphisia mortality. Slide 44 shows you a potential approach presentation, we will now begin the presentation for the treatment of elevated Lp and the reduction of cardiovascular risk and that's pelicarcin. Pelicarcin is an antisense oligonucleotide, Which specifically reduces Lp and as you see from these Phase 2b data, doses of 20 milligrams a week or 80 milligrams a month reduce Lp substantially and getting about 90% presentation, we will be conducting a number of patients below the higher risk threshold of 50 milligrams per deciliter. So this is exciting data that shows us that We can target specifically target lipoprotein in the blood and reduce it in patients. And the question then is How this influences patients' cardiovascular risk.
As we also saw in this Phase 2b study, polyparsin was very well tolerated, again, important when you're Talking about treating patients chronically with the medication. On Slide 45, we have 2 studies running right now. On the left hand panel, we have Lp heritage, which is a prevalent study, which seeks to evaluate Lp levels in patients with established cardiovascular disease. It's a very large trial where we evaluate prevalence and we initiate this trial in April of 2019 and expect results later this year. The Phase 3 outcomes trial is called Horizon, which is summarized on the right hand part of the slide.
This is Cardiovascular outcome study looking at major adverse cardiovascular events in patients with Lp greater than 70 milligrams per deciliter. This study was initiated in 2019 and we expect the primary outcome in 2024.
Next slide, I'll pass to Raj. Thanks, Dave. If we flip to Slide 46 and we look ahead to the commercial opportunity that exists for pelacarson will really build on our strength in cardiovascular and leadership position that we've had in heart failure with Entresto. And we've just shared with you our plans with Lecpio so that we can address another very large significant addressable population And that's the potential to impact cardiovascular disease at scale. We see already that 1 in 5 people worldwide Have elevated Lp, that's 1,400,000,000 people, that have one of the strongest genetic cardiovascular disease risk factors.
And while that prevalence can vary globally, in the U. S. And Europe alone, over 200,000,000 people have elevated Lp. To modify Lp levels, awareness overall is very low, particularly among general practitioners. And what we see from our data, if you look at the middle table, you see that the risk is Similar as Dave shared to that of elevated LDL C, but the physicians rank its importance much lower And many of them misperceive that it could be treated with current cholesterol lowering therapies, which just isn't the case.
When you combine that low awareness and knowledge, it also translates, as you see on the far right, to incredibly low testing rate. So that's the real challenge and the opportunity because even amongst diagnosed ASCVD patients, the Because even amongst diagnosed ASCVD patients, the rate is significantly below 1%. And that will really be the focus presentation of our efforts, it's truly around education to raise awareness and level of testing, leveraging the heritage study that David just talked about earlier. And on Slide 48, one of the things that we have in our favor and we'll continue to work towards stronger education The guidelines are very clear and they're progressive on this particular topic. In the U.
S, the recommendation is to test Patients with a history of ASCVD for LP and in Europe, it's recommended to test everyone once in a lifetime. So as we prepare for launch and why it's so important that we do this early and educate through medical education Another effort is really about raising awareness of Lp and the need to test and that will be our primary focus. The other thing we will leverage on Slide 49 is clearly there are synergies that we'll leverage in the marketplace. But the one is the The head of the commercial organization, but I just referenced for me it's all about education. It's about education to the key prescribers, the The healthcare systems and systems of care that Victor alluded to earlier in the U.
S. And that Matthew acknowledged in the UK the presentation, we will continue to focus our efforts on making sure that this deadly cardiovascular risk factor is more acknowledged and testing rates dramatically increase, Which is why we're focused over the next 4 years in doing that. LECTIO will continue to be our cornerstone in ASCVD management, press release, the pelacarson has the potential to promote CV health on a completely another level.
So if we go to
the last slide just to summarize the opportunity and the focus we have for pelacarsen going forward, Lp is a significant independent and genetic risk factor for ASCVD. And with no current treatment options available, we still need to drive access to LP testing and a significant increase So that the patient's other cardiovascular risk factors can be optimally managed. And while the awareness of LP is very low right now and The rate of testing is low. We know that guidelines are very strong and clear in the importance of testing for patients, which will drive our education efforts And ultimately lead us up to the potential launch where we know palacarsen significantly reduces and modifies LP delay in cardiovascular disease patients. And with our strong capabilities that we've built in cardiovascular disease with Entresto and heart failure, the footprint that we've had with Lekvio Around the globe, we anticipate a significant opportunity for pelicarsen and a leadership in ASCVD long into the future.
So now let me hand it back over to Samir for the Q and A.
Thank you very much team. And perhaps
And your first question comes from the line of Laura Sutcliffe at UBS. Please ask your question. Your line is now open.
Hello, thank you. I've got two questions on TQJ, please. Firstly, for the Horizon trial and the AT mg dose, Are you expecting the same sort of efficacy that you've got for the 20 mg once weekly just with fewer discontinuations? Or is that not the right way to think about it? And then secondly, if you just think about what the outcomes are for these trials is sort of getting below a threshold, as you've named here on your graph, The most important thing or is it more about an absolute reduction in LPD LIFO A for these patients?
I think there's some literature that suggests that
Thank you very much, Laura. And perhaps I can I'll ask Dave to address both the questions. So the first one with respect to the dosing and the second one with respect to Threshold an absolute threshold or not, please?
Yes, great. Thanks for the question. Yes, so If I understood your first question, you're asking if 20 milligramsq week is equivalent to 80 milligramsq month and the answer is yes. We saw in the Phase 2b study that it was actually a very nicely designed trial looking at different doses and intervals, which gave us Very strong ability to be able to predict what's going to happen with the 8 milligram dose. And And your second question is a great one.
And being 1st in class is a great opportunity, But it comes with some scientific questions that we have to answer, and I think that's your question is exactly along those lines. The good news is that pellet carcin is incredibly effective on Both angles, so both in terms of percent change and in terms of absolute reduction. So when you see, For example, an Lp of 100, we expect to get that patient down below 30 with pelicarsen. It's a very strongly effective agent. And so we think no matter how you look at it, whether it's a threshold or a percent decline that we'll be able to achieve that.
Thank you, Jerry. Thank you, Laura. Operator, next question please.
Thank you. And your next
Thank you. And thank you, team Novartis, for hosting this deep dive. I really appreciate it. Two separate questions, please. First one on Lekweo.
Am I right in interpreting the tone of the launch as being different to your previous press release, we have a lot of commentary today seem to be very bullish about near term estimates. And perhaps you might want to address that in the context of kind of 2025 consensus of 1,500,000,000 call. Excited about it than the Medicines company was, do you think consensus is getting it wrong? Kind of any color there would be helpful. And then secondly, as we look at the outcome study for LP, can you help us think about kind of the potential for interim analysis And what kind of when potentially that might happen?
Thank you.
Great. Thank you very much, Keos. So if I could put the first question to Rod and the second question will then go to Dave. Thank you.
Yes. Thank you for the question. I think if we think about the Lectio launch and particularly what you saw today from Victor and how we've established it, We know it will take time to establish the infrastructure for buy and bill and how we're working with healthcare systems. And so We know that will take a few years in order to be able to develop those relationships and the Comfort in working within the flow of their system to identify the patients and treat them. And so that will be a main driver in some of the early launch.
We've also acknowledged the The fact that as we look at ex U. S. Markets, it will take outcomes data before we get to the build. So I think the most important Our position for us is to establish those foundational partnerships that we would have with healthcare systems in the U. S.
And major healthcare systems like Matthew talked to in the UK to ultimately maximize the assets in the long term. So that's how we're continuing to think about it. Press release, we will now begin to see the new way addressing the non clinical barriers with these partnerships, access, affordability as well as adherence I think we continue to be confident in the consensus that we have and the expectations that we have with the outlook for 2025. Thank you, Sameer.
Great. Thank you. And coming back today for the second question on potential interim analysis.
Yes, I love the question because I'm going to assume it's because of the person's confidence in this trial. So presentation As in most cardiovascular outcome study, there is indeed an interim analysis built in it. This is an event driven trial and the interim analysis is dependent on a certain number of events accruing. So I can't say exactly when that's going to happen yet. The bar is high For an early stopping for cardiovascular outcome study, especially for a 1st in class therapy, where you really want to accumulate long term efficacy and safety data in the population.
So our expectation is that it will run to the end of the trial, but there is an IA built in.
Thank you, Keyur, and thank you, Dave and Rod. Operator, next question please.
Thank you. And your next question comes from the line of Emmanuel Papadakis at Deutsche Bank. Please ask your question. Your line is now open.
Thank you for taking the question. A couple if I may. Just a bit nearer term, Lekki, the refinery you've reiterated Q2, Q3. It does however see an FDA inspection is likely to be warranted whether you file on 3rd party and or your internal tech transfer facilities, but the FDA does have quite
a backlog. So could you just talk
to your degree of confidence around Timing approval in the first half of next year and how that regulatory process is proceeding. Second question on the thank you. It's very helpful on the NHS collaboration. To my knowledge, you haven't actually given us any commercial Details in terms of the terms around the arrangement. So is there anything you can say to pricing or value associated with that contract?
And indeed, By extrapolation, is there anything you could say in terms of pricing benchmarks we should think relevant to the U. S. Market will be CSK-nine antibodies, For example, a relevant factor to consider. Thank you.
Okay. Thanks, Emmanuel. So on the first question with respect to the timing of, A, the re filing and B, when we like to get FDA to review things. That would be for Dave. And the second question with respect to NHS and how to help Emmanuel model from a pricing, etcetera, and benchmark presentation that I'll give to Rod.
So the first question please on timing for refiling, Dave?
Yes, got it. Thanks, Sameer. Yes, thanks for the question. So yes, we remain confident in the refile Q2, Q3, as As we've said, it's up to the FDA as to whether or not to conduct an inspection. So what we can say is that typically these re reviews take 6 months and that our expectation is to make the refile as we've said.
Thanks. And Rod?
Yes. Thanks for the question, Emmanuel. With our agreements with the NHS at this point, What I can say is we've signed memorandums of understanding. The contract we expect to be signed in July Prior to our launch in Q3 and it's still subject to NICE outcome. So I can't share any details in terms of the benchmark or pricing at this And so we've established that contract and the NICE outcomes, which is why at this point with Matthew and his colleagues, we're focusing on Once those are established, how do we start to identify those patients, work within their primary care networks and make sure that we're giving the prescribers the confidence and the education they need with patients, but more details to come later following the NICE outcome.
Great. Thank you. And thank you, Emmanuel, for the questions. Next question please, operator.
Thank you. And your next question comes from the line of Andrew Baum at Citi. Mr. Baum, your line is open. Please ask your question.
Yes,
sorry about that. A couple of questions to John and Victor. Firstly, in relation to the PARADISE MI data set. With paradigm, it was clear that the FDA was I'm keen for you to file despite the 0.06p value for the primary endpoint. In relation to the Paradise MI data set, How much push is there compared to pull in relation to the dynamic between Novartis and the FDA given the interactions you've had to date?
And then second, I'm sure that you have done a very comprehensive cardiology survey in terms of the desire press release, inclisiran in the absence of outcome data, perhaps you could share with us the differences In the U. S. In particular, how much reluctance is there? And how much do you believe you could overcome once you're out in the market, Given it's going to be a while before the outcome data comes through. Many thanks.
Thank you very much, Andrew. So on the first one about presentation, Dave, would you like to take that one, please?
Yes, sure, Sameer. Thanks for the question, Andrew. So the data from Paradis are still relatively fresh. We're still doing analyses. The first presentation was just at ACC this past weekend, as you know.
So we continue to do analyses and we will update you on any future discussions with FDA As warranted, at this point, we do plan to share the ACC presentation with FDA, and we will see their feedback.
Great. And then with the second question, I think we've split it into 2 parts. And first, I'll go to Victor. The importance of outcome data press release, we will now begin to take outcomes data for Europe. So the importance for uptake,
Victor of Atkins data. Yes. Thank you very much, Andrew, for the question. So we don't believe this will be a challenge at launch, having discussed presentation on the one hand there is a strong body of evidence linking LDL C and outcomes and when talking to cardiologists the linkage between LDL The outcomes is really clear. On the other hand, inclisiran works within a pathway of LDL C lowering that has already been shown To improve outcomes.
Now on the access front, because we will be routed to the medical benefit mostly For 40% of that population, the coverage is to label, and therefore, we don't expect an impact on the CV outcomes evidence. And for Medicare Advantage and commercial populations, the focus is mostly on efficacy, safety and cost.
Thank you, Victor. And then Rod, importance of outcomes in Europe, please?
Yes. Thanks, Andrew. I think We can acknowledge that the importance of outcomes and for reimbursement and broader access overall Outcomes are important. We have launched in Germany and Austria already, but that's to a limited population of patients with very ICV risk and while the feedback has been physicians are impressed with the immediate drop that they see in LDL C that Dave spoke to and the sustained efficacy Our strategy, including Europe, is for Lecchio to benefit a much broader number of patients And overcome those non clinical barriers. So while we will pursue the outcome study and know those markets Look at it as an important piece, we are actively exploring commercial partnerships like we talked about today with Matthew in a number of countries Around the world and making sure that LDL C and targeting a larger population that ultimately could be benefit It's a cornerstone of our cardiovascular disease health promotion strategy.
So the first of which obviously will be the U. K. When we would expect that launch
Thank you, Rod. Operator, we're ready for the next question, please.
Thank you. And your next question comes from the line of Graham Perry at Bank of America. Please ask your question. Your line is now open.
Great. Thanks for taking my question. So Firstly, going back to Entresto, just to be clear, what's the base case for Novartis or the range of possibilities you see On Paradise Semi label inclusion, so do you see there's a possibility you could get a label inclusion of the data or possibly even an indication? Or do you just see this as a sort of not negative positive trends that helps the overall perception of Entresto and its safety, particularly in fragile patients? Secondly, a question for Matthew Whitby.
There are obviously approved and reimbursed antibody based PCSK9 inhibitors available in the market already. So why wasn't a collaboration like this possible with one of those products and their manufacturers? Was this just proactivity from Novartis that led to collaboration or is it just the less frequent dosing? Could you just help us understand the reason why this product is treated could be treated differently? And then lastly on pelacarson, you flagged LP as being a causal risk factor for MI, stroke and PAD.
Can you just remind us how causality is being established given today? I think we're just looking at some observational epidemiological data. And so what are the risks that modulating levels doesn't have the impact on outcomes as we've seen with some other CV biomarkers and you just end up with this being a coincident finding?
Thank you very much, Graeme. So perhaps we can start with the first question for Matthew. And I think the key point from Graham was why are you working now with incloserum with Novartis
Matthew?
Thanks very much. And it's a great question. I think there's a couple of things to note, Billy. So firstly, As part of the voluntary scheme, so the pricing scheme that was put in place, there was an agreed element about NHS England to produce something called the commercial medicines framework that was published Publishing in January, but we actually started using it about a year or so ago. So timing wise, it fitted really well with sort of a newer and more innovative approach to commercial models press release that NHS England was looking for.
So that was a big part of why we were able to sort of use that greater commercial Innovative there's more innovative commercial approaches for this drug where which wasn't in place at the time for the PCSK9 inhibitors. But also, I think there was a sort of a proactive approach as well in that the other companies, when they approached us, went down a different route Looking at how they would use their commercial freedoms in a more traditional approach, if you like. So it was sort of Partly timing in terms of the new flexibilities afforded to us under the commercial medicines framework and partly a Novartis having a more approach to pricing then the competitors.
Thank you, Matthew. And Dave, I think the other two questions are for you. So the first one relates to The range of possibilities which you could get visavis the label, I think Graham was also trying to work out what you think is most likely. So be careful with that one. And the second part of his question, apart from the interest of your potential label, With respect to petrochem, so you said, yes, a number of potential markers Which suggests increased disease activity.
But how confident are you that reducing LPD We'll be established as a therapeutic agent.
Okay, great.
Yes, I
got it.
So I guess first, Graeme, on Entresto and Paradise MI, I mean, clearly, we saw Numerical trends favoring Entresto on the primary endpoint, but we didn't reach the pre specified superiority Statistical threshold. So we did not succeed in the trial and the P value as you saw on the slide was 0.17. So I think we have to acknowledge that. There are clearly supportive analyses through the secondary endpoint hierarchy that support the numerical trend, but at the end of the day, the trial was neutral. So I think what we see from this study is that patients post to my have much better care than they did 30 years ago and Entresto may have an incremental benefit on top of that, But this trial did not prove that finding.
What we did see is that in these patients who again are very sick patients A few days after having a heart attack, Entresto was well tolerated. So the data from PARADISE in terms of safety and tolerability complement trials like PIONEER and TRANSITION in heart failure patients who'd been hospitalized, to give practitioners' confidence that this drug can be used in fragile patients. Turning then to TQJ230 and palacarson. You raised a great point. And again, coming back to a comment I made earlier is when you're 1st in class, presentation, you weigh the scientific evidence supporting your target and the likelihood of success.
And so why do we believe in this case that we have a greater success and previous efforts. Well, first of all, it's the weight of the evidence. So I showed you two lines of evidence, Epidemiologic data, Mendelian randomization data, there's also data from statin trials, the meta analysis from statin trials, Again, all showing us that elevated Lp confers higher cardiovascular risk. And then the question is, if you reduce that pharmacologically with palacarcin, the scientific question is and medical question is, When you reduce Lp pharmacologically, do you achieve an outcomes benefit? And what we see from colcharcin is that the The degree in Lp lowering and some of the other salutary effects that they saw on other lipids in Phase 2b gives us more confidence We're going to have beneficial effects in this population.
But at the end of the day, that's why we run the trial.
Okay. Presentation Great. Thank you, Dave. Thank you, Graham, sorry. Operator, we're ready for the next question, please.
Thank you. And the next question comes from the line of Jo Walton at Credit Suisse. Please ask your question. Your line is now open.
Thank you. I've got three questions, please. Firstly, on Entresto. We know that patients with heart failure They tend to be old. They tend to be on lots of medicines, fair rattling around.
And Entresto is one of the branded products, which is more expensive for them. So do you have any real world adherence data showing how many patient or what proportion of patients are still taking the drug 1 year on, given that particularly in the U. S, they are still having to pay a reasonable amount of co pay. Secondly, on inclisiran, I wonder just so as I understand this, do you not have press release, you talk about patients being able to get this drug essentially free from the point of launch. But wouldn't they have to go through some form of deductible to get that beforehand before it became free?
My third question, I don't know if you can still hear me.
We can hear you. We can hear you, Joe. Yes.
Perfect. Good. My third question is on the U. K. Side of things.
So just so I can understand this, Has the system worked so that if a doctor puts the patient on this in the UK, This is budget neutral for the local trust because I'm assuming that this is a little bit more expensive than some of the other treatments that they might choose to use. And is there something built in whereby the doctors get some reimbursement so that there's an actual pull from the economics from the U. K. Doctors press release, I think you said that What happens when you get the final outcome data? So it's not a price that will be set and then when we get the The outcomes data and hopefully you find this linear relationship and a fantastic reduction in cholesterol Gives a great reduction in cardiovascular death.
At that point, does the pricing change? Or is the price set now? I'm assuming that Novartis gets the benefit of using this data. Is there any way that this could bring forward The global knowledge about cardiovascular risk, it could U. K.
Data, real world data press release, many thanks.
Hey, Joe. Thank you very much. And I decided press release, so what I'm going to do is, first of all, I'm going to ask Rod to talk about the pricing issue with respect to The U. K. Partnership.
Then I'll ask Matthew to specifically talk about the trust versus the doctor practices And how the economics works there. And the other two questions which you had both with respect to Entresto In terms of adherence in the U. S. At 1 year as well as the deductible will go to Victor. So the first question, Rod, simple one.
Can you talk anything more about what happens from a pricing perspective Post outcomes, pre outcomes.
Yes, Joe. Thanks for the question. And as it relates to the U. K, and we have We throughout this process, whether it was The Medicines Company or now through Novartis, NICE has been were still an important part of the evaluation that will occur prior to the final agreements and contract signing. Now to your specific question, another expectation has been as we would get the availability of the data of the outcomes trial, We would relook at and that's been part of the agreement the pricing and the cost effectiveness analysis in the populations that we've studied.
And so that is an expectation that we would revisit at the presentation that we would revisit at the appropriate time. I think the important thing that Matthew acknowledged and what we're excited about is with This program, particularly addressing some of those non clinical barriers, we'll be able to generate strong evidence, real world evidence As we lead up to those outcomes data with our colleagues in the UK and NHS England and see the real impact that we're making on the disease as we address both the clinical and non clinical barriers. So it's an exciting opportunity.
Thank you, Rod. And Matthew, if you could perhaps address the issue of the The local trust versus the doctor practice and the economics and how that would work, please.
Yes, thanks. I think one thing to note really is that the typical launch for a new product, as I mentioned earlier really, would be sort of focused around specialists In secondary care initiating and then that practice and the prescribing sort of slowly diffusing into primary care, We really saw this as a primary care intervention. So a lot of the incentives and the payment flows that we've been looking at Sort of how we can support that money flowing through to primary care. So that's in a number of ways. So we're looking at the presentation, whether there's a more efficient way to identify the patients, as I mentioned, through the NHS digital work in primary care, we're looking at the payment flows to GPs.
So we're looking at Exploring whether or not we can actually have a direct payment to prescribes as part of the way that we Get the drug out to patients. And we're also looking at some other areas, particularly around other incentives for primary care clinicians. So we've got The quality outcomes framework. So this is whereby a payment mechanism for GPs presentation, we're looking at a particular clinical outcomes, they get additional points, which add up to additional payments. And we're also looking to see whether we can include a cholesterol target within that as well.
So sort of a range of measures we're looking to get those incentives right. Press release, it's primary care focused, not secondary care focused.
Great. Thank you. And Victor, the first of your questions was related to Adherence data in the real world in the U. S. For Entresto.
And the second question relates to the issues about deductibles
Great. So thank you very much for the question. So if I start with Entresto, We have worked really hard over the past years to make access and trust of both affordable and easy for patients and HCPs and that has been one of the Key pillars of our growth of what we've seen. And as of today, more than half of the Entresto patients pay no more than $10 per month. And most of them have preferred access, 99% in the Part D space and 80% in the commercial patients.
This is translating in around 70% of the patients remaining on therapy at 12 months and reinforces our strong position Yes, in heart failure to continue to grow. And just highlighting, for example, that in the breast population, we just penetrated around 30%. So we see Tremendous space there to continue to grow with Entresto. On the inclisiran side, in terms of out of pocket for patients, It depends on the population. So we would have for the Medicare Part D population, which represents 39% of the ASCVD patients, 80% of those patients will pay as little as $0 per month because they have supplemental insurance.
For the commercial population, which is around 34%, they would be eligible to pay as little as $0 because of our support. And then finally, the Medicaid and federal population will pay less than $10 The only population that would be left with a little bit of a higher Co pay would be the Medicare Advantage population where it varies depending on the plan of the coinsurance. But all in all, 2 thirds of the patients at launch We'd be having a $0 co pay, which we believe is a very important factor in the uptake of drugs in this space.
Thank you. Operator, next question please.
Thank you. And your next question comes from the line of Kerry Holford
I have 3, please. On Lexioni associated costs that you see in the U. S, I'm looking at Slide 33, Where you mentioned developing test injections and networks, are you aiming to do that within each of your target 200 healthcare systems at launch. And if so, who's funding that? Is that something that you are funding or is it in conjunction With these healthcare systems, and from a promotional perspective, what's the overlap with the Entresto prescribing physician pace?
And have you already recruited Additional sales or medical reps in order to launch Lexio, is that required? Thank you, Jay. I wonder if it's possible to talk about potentially extending the dosing frequency even further Once monthly, is once every 6 months dosing, I. E. Similar to LECIO, realistic opportunity?
And is there actually any value in Combination with Lecio, I think perhaps the answer is no given that correlation you talked about, but we'll be interested to hear your thoughts on that. And then finally a question for Matthew Witty. You mentioned how CBD was already a sort of daily target area within your team's Long term objectives here and that led to your proposition with a nice overlay there. I would be interested to hear whether there are any other chronic diseases that are on your target list, perhaps obesity, where presentation you might be interested in or indeed actually working on similar partnerships with our veteran manufacturers. Thank you.
Thank you. So if we just take each of those questions in turn, I think you asked some operational related questions with respect to Lexio, Which I'd hand across to the U. S. I think it is about who actually did the injection and setting up of the clinics As well as the potential overlap with the interest of field force. So that will be for Victor.
And with respect to the TQJ question, I'll let Dave answer that. And of course, Matthew with other areas other than Lexia presentation, so Victor first please.
Well, thank you very much Gary for the question. So as we've stated, one of the key challenges at launch will be to establish the buy and bill processes within cardiology's offices, Because today it's not a reimbursement pathway they use often. And for that, we will be working on the one hand with these Systems of care because they already have established processes to buy and build other products in other therapeutic areas. So our efforts are mostly connecting the dots within those systems that cardiologists can utilize those efforts. And on the other hand, we've mentioned that we're developing an alternative injection center network To provide this acquisition and administration flexibility for those cardiologists who cannot or do not want to Established by and within the center or in their office.
And basically those are independently owned injection center networks. The only thing we're doing is Helping connect the dots and helping cardiologists understand that they would be able to send their patients to these systems. Now in terms of your question on the overlap, there's a very substantial overlap, of course, from a healthcare professional, Both on the cardiology front and those primary care physicians that do take care of those patients, Also around 60% of the key Entresto targets are affiliated with these prioritized health care systems for Legview. Answering your question on whether we've recruited more reps, the answer is no. We believe that the current footprint that we have with our interest of field team What we are doing and we have done already is hire Develop a strong field reimbursement team that will work with these offices and the healthcare systems.
As I said, on the one hand, to connect the presentation, the dots within the system and to, if needed, establish relationships with 3rd party injection sites.
Thank you. And on the TQJ question, Dave, with respect to perhaps more prolonged dosing As well as the possibility of a combination.
Yes.
Thanks for your enthusiasm on that, Sameer. I really appreciate As of today, we don't see a way to easily increase the durability of Lecpio, I'm sorry, of T2J and increase its duration of action to match the Q6 month administration of Lecpio. But we're continuing to turn this one around and see if there is a way to make that happen. As of today, we don't have a way of Designing a way to achieve that.
I was only kidding, Dave, anyway. So Matthew, the last part of the question was
presentation, I'm afraid I can't talk about Active deals that we're either pursuing or considering at the moment, but I would say that the NHS long term plan gives a really good Indicated about the areas that we're prioritizing, one of those other areas being earlier diagnosis of cancer. So we've got a specific target in the long term plan to diagnose more cancers at stage 1 or stage 2. So currently, the NHS Is it about 56%, 57% of cancers being diagnosed as Stage 1 or Stage 2? And there's a commitment to increase that to 75% of cancers. And we published information on a deal that we did with a company called Grail on a new cancer diagnostic Back in the deal was done back at the end of November 2020.
So yes, it's a long term plan to have a really good idea about Kind of the areas we're interested in and how that's driving particular focus for future deals as well.
Great. Thank you, Matthew. We've only got about 5 minutes left and there are still 3 people in the queue for questions. Could I just ask that each So operator, the next question please.
Thank you. And your next question comes from the line of Laurent Cespedes at Societe Generale. Please ask your question. Your line is now open.
Good afternoon. Thank you for taking my question. So I will ask one on pellacarson. What is the level of efficacy you're targeting with the Horizon trial on the primary endpoint? What is the level Of relative risk reduction and the design of the trial, is it 20% relative risk reduction or more that you are targeting,
Thank you, Florent. Dave? Yes.
Thanks, Florent, for the question. We're actually in the process of Preparing the study design paper now, which will give you a lot more information. But what we've already talked about is we have 2 tiers of Lp level that we're evaluating as primary endpoints, 70 milligrams per deciliter, which would be the total population at 90 milligrams per deciliter. So We have two ways of being able to achieve success. We haven't publicly stated what level of MACE reduction we're looking at Within the population at this point, but I think if you again, if you look at the evidence that indicates Lp's role in cardiovascular risk and the degree to which colicarcin reduces Lp, You can infer that there will be a clinically important benefit at the end of the trial.
Thank you very much.
Thank you, Dave. Thank you, Flora. Operator, next question please.
Thank you. And your next question comes from the line of Charles Pittman at Redburn. Please ask your question. Your line is now open.
Thank you very much for taking my question. Just on inclisiran, I was wondering how will the rollout be communicated? And will this be done by the NHS All by Novartis, primarily. And just in terms of the pandemic, how this affected the plan, Given that on one hand, cardiovascular disease is a risk factor for severe COVID and the other has created significant disruption and backlogs within primary care.
Okay. So one question becomes 2, I think. So in terms of communications, Rod could address that. And in terms of impact of pandemic and COVID, perhaps Matthew could talk to that. So the first question is for Rod.
Yes, thanks for the question. I think that's the important element and Matthew can speak to it too From the beginning of the working relationship and the unique nature of the agreement is our teams are really working very closely together, Co creating what that education plan and implementation will look like within the primary care network. So it truly will be a joint effort in How we work together within the NHS system and importantly identify the right patients, the right education process and the right A follow-up, so that patients can ultimately get the outcome and benefit. Matthew can speak to it as well, but it's been one of the unique relationships To tackle this together.
Thank you. And Matthew?
Yes, agreed. I mean, it's been one of the sort of the key It's been a backbone of the agreement really that it's been a sort of a collaborative effort and it will continue to do so in terms of the communications. In terms of the second part of the question, in terms of COVID, clearly, it's we've seen that patients with Having worse outcomes from COVID, so it's really only heightened the importance of this work. I should also flag that my boss has led the rollout of the vaccine program as well. So as part of this work, we had the we also had the minister who was overseeing that and sort of feed into our work program, so we could understand some of the lessons, Which we've sort of fed in and that's around sort of easier identification of patients.
It's around primary the importance of primary care leadership As well, so we're feeding in those lessons. So yes, it's impacted it in terms of the sort of the The ability of GPs to engage early on in the process, I would say. But we've also learned the lessons from the vaccine rollout program. We've fed those into the Into our work plans, and it's only really heightened the importance of us delivering.
Great. Thank you, Matthew. And operator, we have time for presentation.
Thank you. And your final question comes from the line of Richard Parks at Exane PNB. Please ask your question. Your line is now open.
Hi. Thanks for taking my question. I've got 2, but I'll just ask the 1, and if there's time for the second, then you can squeeze in. It's just one for Matthew. I just wondered if you could give us a sense of what kind of levels of uptake you're Planning for within the 300,000 patient target population.
I don't know whether you're Making any input into the NICE budget kind of impact assessment. So maybe you could talk about that and what you feel is the biggest barrier to Achieving that. Thank you. So Matthew, over to you in terms of the question. Yes, it's
probably best To pass to Novartis colleagues really on specific uptake targets only to say that we've got kind of a shared press release, I think, in getting this out to as many patients as possible from both a clinical perspective but also a commercial perspective.
Okay. So Rod, do you want to give a final word on that?
Yes. I think the ambition is high from both presentation Obviously to try and identify these patients. We know there will be learnings along the way and that's why the important aspect of presentation, the relationship is really focusing on the non clinical barriers, the identification of the right patients, initiating on therapy and the follow through and follow-up It's a regular appointment. So while we're very enthusiastic about the partnership and encouraging how we're approaching it, the The uptake, we'll have to see as we go, but we both created ambitious targets for ourselves through the 1st 3 years, through the implementation science that we'll also be doing So that we can identify there are other factors that limit uptake and how would we address those, of course, through the course of the relationship and the agreement. So It's really meant to be implement together, learn and continue to work for new ways that we can make sure we get the right treatment, like the open hands of the right patient.
Great. So thank you very much, and this brings us to a close for our conference call. I'd like to particularly thank all the participants and those who press release, I'd also especially like to thank our external guest, Matthew, for helping us to press release, what population health is and also to our Novartis colleagues, Rod, Dave and Victor.