Objective: Aimed at sharing knowledge and expertise about pulmonary hypertension (pH), with a focus on the updated treatment paradigms based on the 2022 European Society of Cardiology and European Respiratory Society guidelines.
Key Content
Prevalence and Misconceptions of PH:
It’s emphasized that pH, contrary to common belief, is not rare, affecting approximately 1% of the adult population worldwide.
The prevalence is primarily driven by common forms of pH, such as left heart disease and lung disease.
Diagnostic Approach:=
Highlighting the challenges in detecting PH and differentiating between its types.
The diagnostic algorithm focuses on unexplained dyspnea, starting from general practitioners to echocardiography.
Risk Assessment in PH:
Risk classification (low, intermediate, high) is based on the estimated mortality risk within one year.
A complex set of variables is used for risk assessment, including noninvasive markers like the WHO functional class, six-minute walk distance, and BNP levels.
Treatment Strategies for Pulmonary Arterial Hypertension (PAH):
General Measures: Includes exercise training, psychosocial support, diuretics, oxygen therapy, and iron status correction.
Calcium Antagonists: For patients showing positive vasoreactivity.
Combination Therapies:
Low or Intermediate Risk: Initial combination therapy with a PD5 inhibitor and an endothelin receptor antagonist.
High Risk: Triple combination therapy including intravenous or subcutaneous prostacyclin.
Follow-up Management: Regular risk reassessments to modify treatment.
New Developments – Sotatercept:
Sotatercept, an activin receptor ligand trap, shows promise in clinical trials.
Demonstrated benefits in hemodynamics, exercise capacity, and reduction in clinical worsening events.
Side effects include epistaxis, increased hemoglobin, and telangiectasia.
Discussion and Q&A Highlights
Clinical Implementation: Discusses how healthcare professionals are adopting the new guidelines, with emphasis on pH specialists driving treatment decisions.
Future of PH Treatments:
Speculation on the potential reduction in the need for lung transplantation and intravenous therapies with new treatments.
The future role of sotatercept in treatment algorithms.
Concluding Remarks
The webinar effectively provides a comprehensive overview of the current and future landscape of pH management. It underscores the importance of early detection, risk assessment, and the integration of new treatments like sotatercept in improving patient outcomes. The Q&A session further enriches the understanding of these concepts, offering insights into practical aspects of pH management and future directions in treatment strategies.
Today’s live event it’s titled introducing the Innovations in the 2022 pH treatment algorithm I’m Rob platika I’m working with ADM Medicom uh and we’ve been supporting the alliance for pulmonary hypertension for the past two years this is the fourth online event in our Series this year uh hosted
And organized by the alliance for pH whose mission is the sharing of knowledge uh and expertise about pH you can find all the previous event recordings and slides on the pH knowledge sharing platform and this uh event will be no different uh in a few days time you’ll find the recording and
Slides there today we have a really excellent opportunity to delve into the updated treatment paradigms for pH Guided by two Global authorities uh in this field our distinguished panelists are Professor Marius Hopper and professor Olivier sitbon uh both of whom are co-authors of the 2022 European Society of Cardiology and
European respiratory Society clinical guidelines on pulmonary hypertension uh and they will be explaining the changes to the treatment algorithm with the objective to enhance all of our Collective understanding on the management of pH uh your engagement and participation in today’s discussion is a stride towards better patient Centric approaches and improved outcomes
In the field of phare so thank you for taking part um questions can be submitted in the chat box I’m going to collect them and we’ll have some time at the end to have a little Q&A uh just a quick reminder our next webinar the fifth uh webinar is
Scheduled for the 21st of November and it is about uh CF um with two uh experts there uh professor uh Marian deacro and Javier ja uh but yeah without any further Ado I would like to pass the floor to Professor Hopper thank you thank you as well and hello for me
My name is marer I’m from Haner medical school in Haner Germany and I will start with the very quick clinical approach and overview a bit on a diagnostic and pulmonary hypertension also very briefly on risk R assessment and then I will hand over to Professor Olivier sbor from
Paris who will have the main part today focusing and describing the treatment strategies for pulmonary arterial hypertension and after that I will take over again with a brief outlook on on a drug um that will be coming very soon so but starting with the clinical approach to pulmonary
Hypertension um I took some slides from the most recent guidelines of the European Society of Cardiology and the European respirator Society I think most of you will know that they were released a bit more than a year ago and they were replacing the 2015 guidelines and in these guidelines
We also added like a summary approach to pulmonary hypertension in general and the first thing we highlighted is that um in contrast to Common belief pulmonal hypertension is not a rare condition in fact it’s estimated that it does affect about 1% of the adult global population
But this is of course not driven by the rare forms of pH which are pulmonary arterial hypertension or group one pH and chronic trauma body pulmonary hypertension group four but mainly driven by the much more common causes of pulmonary hypertension which are left hard disease and lung disease and this
Is really driving the the the observation that pulmonary hypotension is much more common than what was initially thought the um classification the differentiation here distinction is quite important as treatment is very diffic different we have treatment established treatments for pulon Aral hypertension and chronic trauma embolic pulmonary hypertension we have now a
Very few treatments for the much more common forms of pulmonary hypertension in left heart disease and lung disease and whenever we deal on the diagnostic part with pulmonary hypertension we have three challenges first of all it needs to be detected and once it’s detected so
Once it’s clear that there is or may be pulmonary hypertension we need this classification which is extremely important for treatment decisions and then of course we have to find the best suitable treatment so detection is important and you all know and we all know as well that detection is a problem
There’s um this this this common Delay from the first symptoms then to seeking medical attention and then receiving a final diagnosis I think it has got gotten better than it was in the past but we still see every once in a while patients who what I believe is a very
Classical history of pulmonary hypertension and take to three two or three years and many doctors visit until it’s finally diagnosed and of course this needs to be improved and for that reason in the guidelines we develop figures figures summarizing the symptoms and the signs of pulmonary hypertension
In detail and unfortunately many of you know the symptoms and and the signs so I don’t want to go into any details here we have developed these figures um with the purpose to um to to enable teaching teaching of medical students teaching of young doctors and what pulur
Hypertension is and what the warning signs are and future will tell us whether this really helps improving the early detection of pulmonary hypertension and the same purpose um is is behind the diagnostic algorithm that you see on this slide here which is very different from previous notic algorithm
And the main difference here is that we don’t call it a diagnostic algorithm for ponary hypertension because patients don’t go to doctors and say hey I’m having pulmonary hypertension let’s use the diagnostic algorithm no they come with symptoms and mostly with unexplained disia so it’s really a workup um recommendation for unexplained
Disia and it starts at the level of the general practitioner who usually sees these Patients First and besides what is usually done in medical history and physical exam at least hopefully um we ask for very simple things that basically any doctor can do an ECG measurement of some biomarkers BNP and
Pro BMP and and if possible also some oxygen saturations just on the fingertip and nothing of this is specific for pulmonary hypertension but the thing is if pulmonary hypertension is driving the symptoms it’s very likely that the ECG is not going to be completely normal and
It’s very likely that the BNP anti Pro measurements shows show some abnormalities and then this triggers not not always of course because the Rarity of of most forms of ponal hypertension um that the patient is then referred for an evalation of pulmonary hypertension no but it was triggered is that the
Doctor says oh there may be something wrong with the heart and then sense the paper the patient not the papers sorry to a Cardiologist for an echocardiographic examination and this is what we want we just want to raise some flexs suggesting the possibility of pulmonary hypertension and then make
Sure that the patient undergoes an appropriate echocardiographic examination and from then it’s usually straightforward because if it’s pular hypertension it will be seen and then the pathways are very much straightforward and they end and at least they should end then in a pulmonary hypertension Center which still is quite important and the final
Confirmation of the diagnosis is then made by right heart calization but echocardiography is the key the key because it is the most important non-invasive tool that we have and here also speaking of figures we included in the recent guidelines a new figure where we summarize all the findings that can
Be suggestive for pulmonary hypens mention On echocardiography and Here Also we believe and hope that it has educational value and and it improves the detection of pulmonary hypertension and then finally as mentioned earlier right heart calization is what we need to confirm the diagnosis I know it’s not
A diagnostic um test that that patients like very much although it’s not very invasive and in more more senses doing do it in an OD basis and um and it usually fortunately doesn’t do much much much harm we really really needed to make the diagnosis to make differential diagnosis to assess the hemodynamic
Severity and to guide treatment strategies and this is not only to add the time of diagnosis but then sometimes occasionally or frequently then doing follow up for further treatment decisions and this um leads me to risk assessment once we have made the diagnosis of pulmonary hypertension and
Now I think we speak about pulmonary arterial hypertension let’s assume that pulmonary arterial hypertension has been diagnosed then of course we think about the treatment and for that we think about risk assessment and risk is basically the estimated mortal risk within one year um which we classify as low intermediate or high and
It is this is also very important to understand when we say we calculate the mortality risk is that we can’t say that you as a patient um will live or die within a certain period of time that’s not possible what we can Define is a likelihood nothing but a statistic
Likelihood for instance low risk means that the risk of death within one year is less than 5% so it’s low that means that it’s higher than 95% that the patient will survive nevertheless of course patients may die in that time span either from pulmonary hypotension or from whatever other cause and we
Can’t say that um this is going to be this patient or this patient this is impossible so it’s it’s really just a statistical likelihood but this is very helpful to guide treatment decision and especially when it comes to making treatment decisions that become more complex like the use of Parental
Processs or the referral for a transplant evaluation a Bas line we used this model um we very recently um included for followup risk assessment the so-call forrator model which is similar low intermediate but intermediate now divided is intermediate low intermediate High simply also to make um more granular decisions when it comes to
Treatment and then of course the highest patient population that that still exist even if this becomes increasingly um smaller with the treatment approaches that we have in our hands now the goal is obtaining and maintaining a low risk profile this is the the best risk profile that we can achieve
It’s realistic for some patient population it’s not that realistic for others Olivia will touch that and we use for the system a complex complex set of variables but no worries we don’t use them all I mean we almost never do everything that’s listed here it is just
That we have now um data and evidence behind that strategy and can use these tools to make a a fairly precise never 100% precise but fairly precise individual ass assessment and you probably know that it really came down with all major risk assessment tools to three very basic variables which are
Obtained at each visit and they are noninvasive so it’s just the wh functional class that basically tells us what the um physical capacity at home a daily life of our patients are we use as a more objective measurement the six minute walk distance which you all know very
Well and again we have our biomarkers um that give us an information about how the right ventricle feels so it’s basically this strain of the right ventricle low BNP or low anti po BNP means that in simple word the right ventricle or the heart is happy even if ponary hypertension still exists the
Heart can deal with with this this form of p hypotention with the severity with only without any signs of right heart failure and this is important and it’s has become a very important biomarker for us however simplification is good oversimplification is is not and this is
Why we wrote in the guidelines and this is very important that um we use this tool we use these basic variables but as we wrote here additional variables should be considered as needed especially white heart Imaging which is mostly echocardiography but can also be cardic magnetic resonance imaging and um
Also other factors age sex the type of the disease so whether it’s idopathic pH or other forms comorbidities kidney function or on so it’s always a bit more complex and this is important so I leave it here for the time being thank you very much hand over to Olivier and um we
Will have a disc discussion at the end of this thanks a lot thank you thank you very much uh marus for your uh very nice presentation now we will discuss oops um where is my ah it’s here we will discuss the treatment algorithm I think you can see my first
Slide and I would like to cover the current approach of the treatment of pulmonary artial hypertension which is as Mario said a really rare disease that’s that’s my disclosures so let’s just summarize the story of the treatment algorithm in in in pulmonary araral hypertension we
Start in a about 20 years ago at the at the world pH Symposium and we we we we propos at that time an algorithm based just on one very simple sign which was which was the the functional class and all the indication for for therapies were based on a just very simple
Assessment of symptoms by functional class and this was continued at the next World Symposium and then again until the world Symposium on 2013 and then uh after that the first the in the guidelines of 2015 uh we introduced the notion of risk low or intermediate or high risk as
Marius showed in his presentation and now the risk it is obvious that the risk is everywhere at Baseline when we decide the first treatment and also during followup when we want to monitor the the the treatment and we want to escalate the treatment we we based on the risk uh on risk assessment
And this is the new algorithm publish in the last European guidelines it is an algorithm dedicated for idiopathic heritable drug Associated and connective tissue disease like scleroderma Associated pH but it is we can also use it for other forms of pulmonary arterial hypertension it we rest strict to these four types of pah
Because the this represents the vast majority of patient included in the large trials so if we start with the general measures and it’s I think it’s very important uh General me measures include supervised exercise training now with a very good recommendation one a is a strongest to strongest recommendation
Possible uh psychosocial support is also very important immunization diuretics in case of f renion like Leg Edema long-term oxygen therapy is not mandatory it’s just for the patient having low uh oxygen pressure in the blood so uh I think for example in the in in my patients it’s quite rare to have patient
On on oxygen because in phah usually the patient does not have any low oxygen pressure and also correction of iron St status was also included the the the the the news for this part was the anti-coagulation issue during a long time you received anti antic coagulant
But now we with the with the compelling data we have on anti-coagulation in PH we uh observe that finally anti-coagulation was not really needed in patient with pulmonary arterial hypertension and now the recommendation is that anti-coagulation is not generally recommended but it could be considered on an individual basis
If we move to the uh uh indication for calcium antagonist you know that during the first right C catheterization we perform a Vaso reactivity testing usually with inhalation of nitric oxide for a few minutes and we look at what happened in terms of hemodynamics and
Here we have a typical example of a good good responder this is the the the patient having a very high level of uh high level of um mean papap at Baseline and just after a few seconds of inhalation of nitric oxide we observed an almost normalization of pressure in
When we have this kind of response we can say we can treat the patient with very simple treatment with calcium channel blockers like nephine and lodipine DM very very simple and of course we reassess regularly the response to the to to the treatment then for the vast majority of
Patient that are nonvasoactive because the vasor reactive patient represent only maybe 5% of the of the patient with ph but for the others the vast majority there is now that we have quite good recommendation and the first step is to distinguish in between patient without cardio cardiopulmonary comorbidities or patient with cardiopulmonary morbidities
What are cardiopulmonary comorbidities that the patient that that are are risk to have another form of PA of pH sorry of pulmonary hypertension in particular postc capillary pulmonary hypertension it means pulmonary hypertension secondary to left heart disease and for patient having hypertension diabetes obesity or coronary heart disease there is an
Higher risk to have a less good response to the treatment and also there are some tolerability issues in those patients so let’s start with patient without comorbidity in patient without comorbidity we look at the risk as as uh Marius mentioned and we distinguish in between high risk and low
Or intermediate risk it’s very very simple and for and now we have the the lot of of of Treatment available aable targeting three uh Pathways which we we consider those pathways are the pathways of on what we called endotelial dysfunction we have the otellin receptor antagonist we have the pd5 Inhibitors
And we have the pro the pronoid and a non pronoid IP receptor Agonist you know all those medications I don’t want to go into too much details but this medication Target the three Pathways of otelia dysfunction and uh what there was one question we have to that has been
Addressed in the in in the guidelines it was should initial oral double communition therapy versus monotherapy be used in symptomatic patient with pah and the the the response was in patient with P Who present at low or intermediate risk initial combination therapy with a pd5 inhibitor s orap and an endine receptor antagonist
You know umon Banton Mason this is recommended but the quality of evidence is quite low because this uh is based only on the result of one study which was the ambition study demonstrating a difference in between D initial double combination therapy to oral drugs as compared to initial monotherapy
And that’s why the recommendation of to to to combine omon and talil as first line therapy is recommended also madap and maybe also other Endo receptor antagonist n pd5 Inhibitors but as you can see the triple combination therapy of mcant tadala and selexipag is not recommended because we have a study that study
Was it was not possible possible to demonstrate any difference in between initial triple combination therapy with these three drugs and initial classical double combination therapy with Menton and tala let’s move to the patient with the highest risk of death for in those patients we the there is a
Recommendation not to use double not two drugs but to use three drugs but not the same that the previous one we use this is the recommendation is to use double combination of oral drug plus the third drug being intravenous or subcutanous procycling either intravenous ostinol or subcutanous Tren
And with this approach we have amazing results in terms of heo clinical improvement hemodynamic improvement and also survival which is very very important so uh irrespective of the the the first uh um the first regimen uh initiated in low or intermediate risk patient or at in patient at high risk we
Have to regularly follow up follow those patient and to regularly assess the risk at followup and that’s what marus showed with the for tra uh risk assessment uh at followup now when we reassess the risk in forc rator the only objective is to achieve a low risk status when you
Achieve a low risk status you can continue with the same treatment that in the initial therapy if you are at intermediate low risk you have the choice in between adding a procycling receptor Agonist which is selex pack today or to switch from a pd5 mimet to another another drug which is
Rioa and for the other for the most severe patient at intermediate high or high risk the the option is to had an intravenous or subcutanous procycling and or to evaluate for lung transplantation for the eligible patients now there are some new development to Target th those those three well established pathological
Pathway in PH there are some uh uh there are some studies on high do matin which is an OT receptor antagonist we also have some trial on pd5 Inhibitors given by inhalation or inale soluble Granite cyclas stimulator uh given also by inel root and we also have some um new we
Will have soon some information on Rin which is kind of treatment very similar to to selexipag and also with hiled TR prostin however we know that there are many many other targets and there is no shortage of drug targets beyond the endotelial dysfunction the classical approach targeting endotelial
Dysfunction we have a lot of of drug Target and this is summary it’s just just a summary of what we had and some novel drugs have been developed but also some repurposed drugs so we know those drugs and the indication was for different diseases but because of the of the mechanism of
Those drugs we can repurpose those those drug to treat pulmonary arterial hypertension the problem is that we have a lot of negative study I don’t want to go into too much details but we have a lot of negative St these and in red on
The top of the of the slide you can see that I I surrounded the genetic approach in particular with scept and and Marius will give you more information on that and also for me the um the pdgf receptor uh um um antagonist that are imatin and sertin and those drugs are also very
Interesting to to treat patient with ph and this is the the a cartoon representing all those drugs uh in in PH and we can have some cross talk in between these different pathway and again I don’t want to go into too much details but we in the future we we will
Be able to combine some of those drug in addition to what we have today so I would like to finish fin with this uh the the treatment the current treatment algorithm algorithm and ask the question how will future drugs fit into this new this treatment algorithm
And we can say that it is likely here for patients who who fail or to for the patient who are not sufficiently improved after initial communition therapy probably and those those patient may benefit from new drugs and marus will discuss that in his forcoming presentation but maybe we can
Also one day discuss to treat earlier with the new drugs but today we have a question mark and finally for the patients at with comorbidities because today the the patient with comorbidity the recommendation is quite weak it just initiate initiate oral monotherapy and then look at what happened maybe there
Will be a place for this new drug in this particular uh patient we will see and I would like to thank you very much and now I’m giving the floor to Marius thank you very much thanks a lot Olivier I’m going back to the screen here
And as Olivia pointed out and I will be talking briefly about new developments and I will focus entirely on soep as this drug is expected to be available next year at least in many parts of the world and act soep is the first member of a new class
Of drugs which is which is called activ in sick Inhibitors and this is basically what they do they inhibit active insing and this is something that most of us would not talk about a few years ago because you didn’t really know what active in mean and do do not be anxious here I’m
Not going to into the the details details of these very complex Cascades um what what I want to highlight is the simple fact that um over the past 20 years or so we have come to understand that ponal hypertension the changes in the small pulmonary vessels that drive
The disease and are not so much caused by vas a constriction but they are caused by an obliterative process and this this um is coming from a hyper proliferation of the cells that line the Lumen of the the the vessel the so-called endal cells and the M cells
Beneath the cells so they proliferate and with proliferation as you can see on the sketch here the Lumin of these vessels becomes narrower and narrower and sometimes these vessels are fully obliterated or occluded and this is the increase in the resistance to blood flow that that really causes the disease and
This hyperproliferation is due to a disbalance of factors that promote proliferation and these are includes the activins and factors that are anti-proliferative such as the so-called bmps or Bor morphogenetic proteins and you know that um some of these receptors are involved and have been identified in heriditary or familiar forms of
Pulmonary hypertension the important thing is the and concept behind this whole treatment strategy is that by affecting these Pathways and by bringing this into balance again um we hope that we cannot only delay disease progression but that we also can at least partly reverse this remodeling process and
Reopen the vessels bringing the vessels back closer to normal and this is possible because the cells that find the Lumen that obliterate these vessels they need these gross factors and if we take these gross factors away this hell sty we call this process apoptosis and thereby these these cells can disappear
And therefore it’s possible that we reopen the Lumen and in fact in animal models of pulmonary hypertension it has been demonstrated that this is happening of course in humans it’s very difficult to prove that this mechanism is active but we can at least demonstrate that these substances are working and the
First substance that we have is called satata set I think all of you have heard about this this drug before it is it is a very exciting new development and soep is one of these drugs that acts as a trap for activin and other growth factors so we take away the
Proliferative signal and and by that we hope to to affect fundamentally the disease and from the data that we have this really seems to be the case you know that there has been a so-called Phase 2 study so an early development developmental study and with scept in pre-treated patient with
Pulmonary arterial hypertension again we’re only talking P Aral hypertension not the other forms here this is very important and in that study it was demonstrated that satata improved the hemodynamics so the pressure in the p arteries and the resistance and it also improved the six minute walk distance as
A marker of Exercise capacity after 6 months of therapy and the study had an open label extension which demonstrated that over an extended period of time so after 18 to 24 months on therapy and these improvements were maintained so the improvements in the pulmonary vascular resistance 6 minute walk
Distance also in this biomarker anti BNP that were made ained and those patients who happen to have been assigned to Placebo for the first six months into the study also had the same Improvement than patients who were originally assigned to the treatment and from that study and this is why I’m showing this
Here we also got for the first time a clearer picture on the side effect profile of soat which is unique and this is important just focus here on the very right column and here you see after 18 to 24 months so about two years of exposure to
Scept um the typical side effects which were epistaxis occurring in about 20% of these patients we also know this from other drugs like like sanil tadil but it’s more common with sat it’s usually might rarely needing intervention but episis is one of the typical side effects another one is the increase in
Hemoglobin which is not unexpected because the drug was originally developed as a drug to treat anemia in certain forms of um of your bom neoplasias and so T set can also cause trombocytopenia so fall in the blood PL account which is usually very mild and usually not relevant from a clinician’s
Perspective and then we have the so-called T anasia which a small dilations of vessels in the skin we see it mostly on the face and on the chest so the cleavage but it can affect the entire body you see that here in that study 10% of the patients were affected
It’s usually fairly mind but some patients um have it quite extensively and sometimes it even requires dose reduction but usually it’s m but nevertheless so but it demonstrates that we don’t have a specific mechanism of action on the pulmonary vessels so we also have effects on systemic vessels
And you see here the observation time has been up to two years it has now been 2 to 3 years in some patients up to 5 years but we don’t really have long-term experience and this is important when it comes to the side effects we need to understand what’s going to happen with
Long-term Administration but this was the data that we had when we went into the so-called phase three which is the prival part of a drug development because this is the study part which leads them to approval or non-approval of of drugs for the use in patients outside of pical Trials and this study
Was similar to the phase two study it also enrolled patients um with pulmonary arterial hypertension um idiopathic hereditary forms drug Associated connected tissue disease so what we usually have in clinical trial programs a bit more than 300 patients were enrolled in this study one half received placeo the other half s said relatively
Young patients average a 40 years 48 years um almost 80% female mostly the idopathic hereditary forms patients in functional class two or three despite background therapy patients had a long history of pulmonary hypotension you see the average time from the initial diagnosis J Roman his study was nine years and um
Almost all patients were on double therapy or triple therapy 60% on Triple and 40% on Triple including and parental which is intervenous or subcutaneous procy and in these heavily Tre Tre patients the study met the primary endpoint which was Chang in six minute walk distance from Baseline to week 24
The average Improvement was about 40 meter which is quite meaningful and the study met several secondary endpoints including improvements in the pulmonary hemodynamics again improvements in risk and also improvements in quality of life and it delayed the time to clinical worsening so this is a typical curve that shows shows you um clinical
Worsening events so which can be pH hospitalizations or aeration in Exercise capacity or even death and the risk of having such a worsening event was much higher in those patients who were assigned to placeo than in those patients who were assigned to satp there was a substantial risk reduction here
With satp but which was one of the very positive and promising findings here and coming back to the side effect profile it was very similar to what we saw in the open level extension of the phase two study so again we had the bleeding events mostly episis also some gum beds
Mostly minor and we believe it’s basically the same thing then with theil anasia that we saw again now here in 14% of the patients and it’s probably also dilated vessel on the mucos or membranes in the nose and in the fings as I mentioned earlier for most patients it’s
It’s what I would call a little Annoying nothing major but it it it can be relevant to some patients of course and once again we don’t know what’s going to happen with real long-term admin Administration overall the safety profile of of the drug is quite good and
We had and have up today very few patient patients were discontinued from study medication or from the studies at all due to side effects it’s it’s quite rare in fact is RAR with any of the other drugs that we currently have in our field but we need to better
Understand um the long-term effects of this this compound and we also looked and I just like to make this brief I just very much like to like this disc graph here we look very carefully um about what happened in this study to the heart especially the right heart of
Course in patients who had been exposed to soat placeo and what we found is was a substantial reduction in the mean pulmonary artery pressure in fact much more substantial than with any other treatment approach that we currently use in in our field um some patients but few patients um really normalize the
Pressures um most patients um have residual pulmonary hypertension but much improved and improved to such an extent that the function of the right ventricle improves substantially so we basically unload the right ventricle it doesn’t have to work as heavily anymore so it works better it’s easier for the right
Ventricle to to pump the blood through the lungs the right ventricle gets smaller the degree of tritation here in the valve between the right ventricle and right adum declines and these these are all very favor favorable results and as as Olivia have mentioned when you finish this talk and I’m also finishing
My short presentation with this one here is we don’t really know where we will place SAS in the future will depend on many things what we know for sure at least for the time being it’s not going to be a true first line treatment it has
Not not been studied as a first bline treatment and first bline treatment will remain the combination of an end recept antagonist and the phosphos 5 inhibitor plus minus a proster cycling but then of course we do our typical reassessment usually 3 to six months after treatment initiation which and I believe this is
Going to be quite important in the future which will often include right hardcut reparation and then we make a decision not after seven eight or nine years into the disease but early on whether or not to add suata at that time point we have studies ongoing which urr
Be assessing whether satas have similar or even better effects in patients who haven’t had such a long disease history and there will be studies but this these yet have to start on the initial use but for the time being the data that we have is as an adjunct or addon treatment so I
Leave it here I expect a couple of questions related to tsep soep which is quite normal as this is an extremely exciting new development and I’m looking forward to the discussion that we are having now thanks a lot thank you very much Professor Hopper uh Olivier do you have any uh first
Questions or reactions to uh what Mario said today thank you for no I think um I think so scept is really a new step in the in the management of patient with with P because we didn’t have a lot of progress for long time we we we had a
Lot of of medication We Know Better how to use them how to combine them not to wait too much as marus said uh and now we have the opportunity to improve more uh the the the patient states the clinical status the hemodynamics and maybe the outcomes but
We now it’s maybe too early to know what will be the impact on the long-term outcome but I’m pretty sure that so intercept will have an effect but this has been should be should be proven before um to conclude for an effect on that so I think it’s very very important step
Um and now will see what what uh uh um other drugs may have in addition to what the soep already achieve so I think uh it would the now the the the the step would be much much higher oh great thanks yeah let’s get to a question from Melanie and hopefully
You guys can see it on screen here too uh do you know how many countries are allowing combination therapies and how many have treatments at all who wants I I I can I canop topic thanks thank you Melanie for for this question uh I think in in in the EU
In the EU the majority o of countries they can use they have almost all the drugs available or at least one drug targeting a specific specific pathway and regarding combination therapy it is it is widely accepted and and reimbursed in vast majority of uh of countries um in the UK it’s a bit
Different because in the UK it is not really um um allowed to start initial combination but they use mono and after one week they add another drugs which is almost the same but uh I think in Europe it’s quite uh it is widely used
And uh it is it is re the problem is that the population has changed and now the population we have much older population with more comorbidities and initial monotherapy is the most widely used approach because the it is due to the population treated because we have much more patient with comorbid disas
Mayus want to comment on that no you summarized it very nicely I I I think we should proceed I I expect there will be many other questions yeah sure another one from Melanie I’ve heard that there might be uh Tre Pro denil uh which would be less painful do you have
Any info on this um honestly I don’t have any information on that this is the the pain related to the infusion of of subcutaneous infusion of trosin is really an issue really an issue and many many patient they stop the drug due to the to the pain induced
By by the drug and and for example in France I can I can give the example in France that 40 40 to 50% of patient stop subut prenal and then they prefer to have an IV line because it is there is no pain with IV L there is there are
Other problems of course but there are no pain so I don’t know Marius if you have information on on that no no no I I wouldn’t know of that but it would be a major advancement that’s for surey we are in the fortunate situation that we have these fully
Implantable pumps so um it’s it’s the the pump is implanted subcutaneously but the drug is administered interven s which is quite convenient and um not associated with pain but still quite invasive um it it’s going to remain an important treatment but U with the new developments I believe that in the
Future there will be fewer patients in need of Parental prosty epoprostenol or TR prenal than presently uh so our next question which some of these might be very difficult to answer here you know uh on a live stream and not in a doctor’s office knowing uh all the background information and also
Not having a crystal ball to tell the future as this isn’t uh approved treatment yet as you’ve been saying it’s in clinical trials but can we start triple combination with so tartrap in high-risk younger age groups yeah it I mean the official answer is it has not been studied and we
Don’t know yet what the label is going to be is Olia mentioned for so some countries it may be that that it the labor will say it has to be add on to to other therapies but as I mentioned it then would be an early add on and i’ i’
Would be certainly inclined to use it very early in in in some high-risk patients and as we have some seen some very impressive results in the in the clinical trials trial programs thanks another question from Melanie who uh needs to be our next co-host uh because she just does a great
Job of uh asking very poignant questions I think do you as Physicians have the feeling that the new treatments make patients that need prosta cycling class to delay this it it it may be a problem it may be a problem so first of all when you say
Prying class I I I’d be very careful so it’s press cying intravenously or subcutaneously so trotin epoprostenol these are very effective drugs the other pryes that we have like like oral drugs like cipac like inhal iloprost trinal they are not as efficacious and they are not rescue therapies absolutely not if
Somebody is is so is is really in a bad condition and needs something effective it has to be subur intervenous because the oral and hate approach do not work sufficiently so this this this has to be very clear and it’s very important so and if today a patient is in such a
Highrisk condition or a risk condition that the physician says it’s really necessary to go on intervenous subcutaneous drug it should be done and it shouldn’t be delayed by um the perspective of of drug like soat said being on the market in in basically in Europe still almost a year from now so I
Mean it’s it’s much better than now to stabilize a patient with these drugs and see if if they can be withdrawn once s has be introduced we see this now in many of our study patients that they come off the prostoy which some of them had for years so it’s it’s a possibility
And of course this can never be promised but possibility but delaying such a treatment these days for something that that may come soon but we don’t know it for sure and um is is is a risky approach Olivia anything to add there I would I would say that you right Mario
That as an initial commun therapy today we don’t have any information but it is it is really appealing to start with with with scept in the next future but I think if we if we start with quite early scept maybe this approach will postpone the potential need for intravenous or subq
Procycling maybe yeah postpone or even prevent yeah I think will prevent postpone or prevent postpone or prevent and the other approach is very interesting is the deescalation U after adding after adding sat and we have both experience of um uh per cycling withdrawal in in some patients is amazing results so let me
Ask you the next guideline should be uh in 2027 uh if my math is correct more or less around that do you expect big changes um especially in terms of first line treatments for pH um today I think today is it’s too early to to to to to address this
Question and to to to to um because we don’t have enough data on initial therapy initial therapy we have the data of ambition is double oral is better than mono oral and also for triple also for triple IV or triple subq we don’t have the information the information comes from registry data and
Uh we we published that in France and in other in other countries and uh but that that just it’s very very difficult to to to have a a proper study comparing initial triple with IV or subq and compared to double I think that’s a that’s a plan for us to test this
Approach with scept triple with scept as compared to double that’s that’s a plan but um we will see uh I’m not sure we will see if if the the companies would like to launch this kind of study uh we will discuss we already discussed with Mario about that point and we we we
Would like to and to to to do it we would like to do it it’s for sure but um I would see great um so in your experiences are uh hcps updated and effectively implementing these new uh treatment guidelines uh or is it still where you have to spread the word and uh
Give a bit more effort so that you know different Specialists are are following uh this hard work that the whole group has put together I I think I mean pH doctors who should be the one who drivve the treatment in in patient with pomal hypertension they’re very well aware of
Of the data of the newest data and and and consider all the options that they have at their hands I would be worried about that sure great um so one last question from uh Melanie uh who even had more but uh we we won’t get to them all maybe
We’ll continue that conversation by email do you think we will need less and less transplantations I would I would say I would say I would say it’s like it’s like procycling if we if we delay if we postpone procycling probably we will do the same for for for lung transplant and
We can expect we can expect that we will have less transplants in in with the availability of of new drug but only the future will answer this question Marius yeah but but still yeah I mean we already have um much fewer transplantations for pulmonary AAL hypertension than we had like 20 years
Ago when I started working in the field all we had was was was lung transplantation there was no other option and at that time um pomal hypertension was one of the main indications for lung or heart lung transplantation and and and now it’s only 3% of the patients who undergo lung
Transplantation were transplanted because of of them having pulmonary Abal hypertension so we already have made progress and I I think um we will see another big step now in the very near future uh Melanie thanks you for your answers to all of her great questions uh I also
Thank you for uh taking part in today’s webinar um and supporting the alliance for pH and its mission to help uh spread awareness and you know further details about these treatment guidelines uh so uh if you have any other uh last comments please uh feel free but uh no
Thank you both very very much for a interesting fascinating uh very scientific discussion today thank you okay see you next time everyone bye bye thanks