Stada omsætning af Kingpeyo
DTP (direct to pharmacy) tallene.
Oktober 2022 € 125k (DTP og grossist tall)
November 2022 € 330k (DTP og grossist tall)
December 2022 € 407k (DTP og grossist tall)
Januar 2023 € 570k (DTP og grossist tall)
Februar 2023 € 560k (Kun grossist tall, DTP sidste måned var € 130k)
Basert på uttalelser fra Calliditas burde vel top line data for 3 b komme i løpet av neste uke.
Vil top line data som bekrefter någjeldene label bli mottatt med et gjesp av markedet?
Hvis top line data skulle tilsi at en bredere label kan gis, vil aksjen likevel bli på nåværende nivå i påvente av salgsutvikling i q1 og fremover samt mer data fra Travere og Novartis?
Calliditas har levert over flere år. Likevel virker det som om investorer ikke har tillit.
" Markets can stay irrational longer than you can stay solvent" er min følelse for denne aksjen.
Uansett ser man bort fra de ca 5,9 millioner aksjene Calliditas har trykket opp, men ikke
distribuert så er antallet aksjer ca 54 milloner og børsverdien på dagens kurs ca 5,1 milliarder SEK. Jeg skjønner ikke prisingen. Confirmation bias?
Markedet hater usikkerhet. Jeg tror endelig bekreftelse på dagens label vil dra nye investorer og fond til aksjen.
2023-03-12 18:30
Calliditas Therapeutics AB (Nasdaq: CALT, Nasdaq Stockholm: CALTX) (“Calliditas”) today announced positive topline results from the global, randomized, double-blind, placebo-controlled Phase 3 clinical trial NefIgArd, which investigated the effect of Nefecon (TARPEYO[®]/Kinpeygo[®] (budesonide) delayed release capsules) versus placebo in patients with primary IgA nephropathy (IgAN).
Denne er viktig! Øker markedspotensialet betydelig.
Fantastisk bra! Grattis til meg sjæl og alle andre som er inne!
Jadda!!! 2 år med ventetid og neglbiting er endelig i mål
Gratulerer enda en gang til de som tanket opp i oktober. N-uhde-lig jobba.
Hvor høyt skal vi imorgen mon tro?
Det er vel en ganske stor short på denne enda?
Her er shorten:
2,18% tilsvarer minimum 1 298 845 aksjer (pga oppløsningen på shortrapportering).
På kurs 100 betyr det at de må handle aksjer for vel 130mSEK - på kurs 130 må de handle for i underkant av 170mSEK…
PAS:
On Sunday evening, Calliditas announced a statistically significant and clinically meaningful topline Part B readout from the Phase 3 NefIgArd trial. The company is the first and only in the world to report such positive, disease-course changing data in the progressive and deadly kidney disease IgA Nephropathy. The data will enable full approval in the US and Europe while further boosting already accelerating sales this year. Meanwhile, it will make it tougher for the competitor Travere Therapeutics (TVTX), which has only biomarker data (no data on the kidneys) and instead lots of safety related concerns, as we previously highlighted (& in older releases). With these positive developments and despite the initial underinvestment in its sales force, we deem the stock as one of the best biotech picks for 2023 due to (i) no remaining clinical risk, (ii) fast-increasing sales and (iii) trading at x3.3/x1.1 of 2023/24 sales with an EBIT margin of 60-70%. We reiterate our Buy rating on CALTX with a 12-month target price of SEK 260. Calliditas will hold a webcast tomorrow (Monday) at 13:00 CET.
Sustainable effect on kidney filtration rate was observed at 24-month (after 9 months of dosing)
The key kidney filtration data (eGFR) over 2 years, was on average 5.05 mL/min/1.73 m2 higher with Nefecon compared to placebo (p<0.0001). This further validates the sustainable disease-halting effects of Nefecon as the eGFR difference versus placebo has broadened from the Part A readout at 9-month (3.87 mL/min/1.73 m2). The company also reported durable proteinuria (UPCR) reductions and consistent safety profile. We believe such good data will allow Tarpeyo to eventually obtain full approval from the US FDA. Simultaneously, we can see that eGFR decline is halted while on treatment (9 months) and then the effect slowly wanes off after months without Nefecon. As a result, patients will have to get back on the drug after a pause and thus will likely need chronic treatment (as expected for an autoimmune disease).
eGFR stabilisation data between 9-month (Part A) and 24-month (Part B)
(for 12 months, only the difference was reported not actual values)
Chart source: Graph prepared by Pareto based on Calliditas’ press released data
China
The Chinese regulatory authority requires Part B data from an additional 29 Chinese patients, which are expected to complete in Q3 this year. We expect the Chinese approval can potentially happen in Q4 2023 (Calliditas partnered with Everest Medicine for the 5-million patients’ large Chinese market)
En liten time igjen til webcast:
The Company will host a live webcast for investors on Monday 13 March, 2023 at 8 A.M. ET (13:00 CET).
Interested participants may register for the webcast here: Calliditas Webcast - LifeSci Events
Jeg tenker det betyder at de kommer til at gå for udvidet label, og at potentielle population da 3 dobbles.
Proff. Barret sa også at dette var en game chancer for patienterne. Han har tidligere også udtrykte at han vil arbejde for fuld label.
Samtidig kunne man også forestille sig en genforhandling efter 2-5 år. Hvis dataene i åben label studien vil understøtte dette.
Syntes dette begynder å se godt ut.
Lyse utsikter for både pasienter og investorer dette!
FiloD; Hva menes med “genforhandlinger efter 2-5 år”?
Undskyld der skulle stå genbehandling, skrivelejf 
03/13/2023 | 08:00am EDT
Presentation Operator Message
Operator (Operator)
Good morning, and welcome to the Calliditas Therapeutics webcast. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the Calliditas website following the conclusion of the event. I’d now like to turn the call over to Renee Lucander, Chief Executive Officer of Calliditas Therapeutics. Please go ahead, Renee.
Presenter Speech
Renée Aguiar-Lucander (Executives)
Good day, and welcome to this conference call regarding the top line data read from our Phase III study in NefIgArd.
This is obviously great news for patients living with IgA nephropathy to be able to say that we see a persistent effect on eGFR or the underlying kidney function even after 18 months of drug, which we feel is fantastic, and we’re truly very happy to be able to share this data with you today, which also just happens to be a couple of days after the World Kidney Day is very appropriate.
With me today on the call is our CMO, Richard Philipson; and Professor Jonathan Barratt from Leicester University; Andrew Udell, President North America and our CFO, Fredrik Johansson, are also going to be available for the Q&A portion.
Before we go into the actual presentation, however, I would like to draw your attention to the disclaimer page related to forward-looking statements and refer you to the company’s reports and other filings, including those which contain risk factors and our relevant information. So in terms of some of the kind of takeaways we’re going to cover in this presentation, it is with great pleasure that I can report that the long-term follow-up portion of our Phase III study successfully met its end point of eGFR with highly statistically significant.
As you will see from Richard’s presentation shortly, in terms of additional support, also 2-year eGFR slope analysis were highly statistically significant with estimates well above those, which can be derived from relevant meta analysis to predict clinically meaningful treatment effects. The beneficial effect was observed across the entire study population irrespective of UPCR baseline, and we believe that the data set supports a regulatory filing for full approval for the study population.
UPCR was shown to be durable over the entire 15 months of follow-up without medication. And despite this very long period of drug, the treatment benefit persisted. And at 24 months, the treatment arm showed only half of the kidney function loss experienced by the placebo group.
I want to point out, however, that this is headline data. We have not had the opportunity to fully analyze the data set, and there is additional work, which is required before we’re in a position to provide details which we plan to do in further publications and at conferences. So just a brief reminder of the actual study design before I hand over to Richard, and so obviously, the entire study included just over 360 patients in total. It was an oral daily treatment for 9 months, followed by 15 months with no drug being administered.
In terms of base inclusion criteria, patients came in with a biopsy-proven IgA over 1 gram of proteinuria and an eGFR between 35 and 90 ml per minute and patients were required to have well-controlled blood pressure of 140 over 9 or less to enter into the study, to ensure that there was any confounding effects on proteinuria reduction related to higher levels of blood pressure.
No immunosuppressive drugs were committed during the study and changes to the hypertensive medications were discouraged and no other medications were encouraged during the time of the trial. So with this, I’m going to hand over to Richard, who is going to take us through some of the data.
Presenter Speech
Richard Philipson (Executives)
Thank you, Renee. So I’ll begin by presenting a brief summary of the disposition, demographics and baseline characteristics of the study population in the NefIgArd Phase III trial. In total, 395 patients were randomized into the study. This includes an additional 29 Chinese patients required for local Chinese regulatory purposes only.
The safety analysis set of 389 patients includes all randomized patients who received at least one dose of study [indiscernible]. The full analysis set, comprising 364 patients, is the data set used for all efficacy analyses performed for the global study. It’s noteworthy that only just over 10% of patients withdrew from the study at any time, indicating a good rate of retention of patients in the study and early discontinuations were broadly similar in the Nefecon and placebo treatment groups.
Moving on to demographics. Overall, the enrolled patient population is clearly representative of the intended primary IgA nephropathy population. Disease characteristics describe a clinically relevant high-risk IgAN population. Treatment groups were balanced with regards to baseline characteristics. And of note, blood pressure was well controlled at study entry. There has been an increase in the proportion of Asian patients in the study population since the release of data from Part A, reflective of the active recruitment of patients in China.
Now to summarize the efficacy results. The primary endpoint of Part B of the study was a time-weighted average of eGFR observed at each time [indiscernible] over 2 years. The primary endpoint was met, and over 2 years, eGFR was, on average, 5.05 ml per minute higher with Nefecon compared to placebo, a result that was highly statistically significant. On average, over 2 years, the loss of eGFR was 2.47 ml per minute for Nefecon versus 7.52 ml per minute for placebo.
Several different support analyses of eGFR total 2-year slope were performed. These are all statistically significant with improvements in slope estimated to fall in the range of approximately 1.8 to 3 ml per minute per year. The differences in 2-year total observed between Nefecon and placebo considered clinically relevant since all of the estimates are well in excess of the difference per year required to predict clinically meaningful treatment effects on the composite endpoint of end-stage renal disease, eGFR less than 15 ml per minute or sustained doubling of serum creatinine as published by [indiscernible] in 2019.
When we look at the eGFR outcomes in placebo-treated patients at 9 months, there was a decline in eGFR of approximately 8%, corresponding to a loss of approximately 4.6 ml per minute, which increased to a decline of 21.5% or loss of 12 ml per minute by 24 months.
In contrast, in patients treated with Nefecon, eGFR was essentially stable compared to baseline at 9 months. And by 24 months, there have been a decline in eGFR of 11%, corresponding to a loss of approximately 6 ml per minute.
In summary, 9 months of dosing with Nefecon in 364 patients resulted in 50% less loss of kidney function compared to placebo at 24 months. Turning to proteinuria, we have seen a cumulative improvement in proteinuria in patients treated with Nefecon versus placebo during the 9-month treatment period, which continued to improve at 12 months. At month 24, proteinuria levels in patients who received Nefecon was still at a reduced level, similar to that observed at the 9-month time point.
So in summary, the Part B primary endpoint of eGFR AUC over a 2-year period was met, showing statistical significance of Nefecon compared to placebo. Supportive analyses of 2-year eGFR our total slope was statistically significant and clinically relevant, showing a magnitude ranging from approximately 1.8 to 3 ml per minute per year with all estimates of eGFR well in excess of the threshold required to predict clinically meaningful treatment effects.
Treatment benefit on eGFR was apparent across baseline UPCR subgroups and reductions in UPCR and UACR achieved during treatment were durable and sustained proteinuria effects and long-lasting treatment benefit even after 15 months of observation following treatment discontinuation supported these modifying effect.
Now turning briefly to safety. Overall, we saw a pattern of adverse events in the safety analysis set for Part B that was similar to the Part A analysis, and which has previously been described in our publication in Kidney International, and which is also described in product information. The most frequently occurring adverse events occurring in 5% or more Nefecon-treated patients with a frequency 2% or higher than placebo in difference with peripheral edema, hypertension, muscle spasm, acne, upper respiratory tract infection, face edema, weight increase, dyspepsia, arthralgia and white cell count increase.
So overall, Nefecon was generally well tolerated with an adverse event profile similar to that seen in Part A. The most commonly reported treatment-emergent adverse events observed with an increased frequency compared to placebo for peripheral edema hypertension muscle spasms and acne. The majority of treatment-emergent adverse events were mild or moderate in severity and adverse events led to discontinuation of study drug in fewer than 10% of Nefecon-treated patients. I’d now like to ask Professor Jonathan Barratt to now make some comments with respect to the results that have just been described.
Presenter Speech
Jonathan Barratt (Executives)
Thanks very much, Richard. I’ll just check that you can hear me.
Presenter Speech
Richard Philipson (Executives)
Yes, we can hear you.
Presenter Speech
Jonathan Barratt (Executives)
That’s great. Well, thank you for allowing me to comment. I mean I think these results are really a game changer in terms of our understanding of IgA nephropathy. What we’ve seen with the data is we can truly modify this disease with a short course of directed steroid, that leads to sustained proteinuria reduction over a full 24 months, which I think is really outstanding with only 9 months of treatment showing that for the further 15 months, we are still getting suppression of disease activity.
And most exciting, of course, is that, that is translating through to sustained protection of – and reduction in the rate of loss of kidney function in these patients. So I think, collectively, what this data is really showing is that we’re able to modify the underlying disease process here and – which results in sustained impact on rate of loss of kidney function. And with a drug that is well tolerated from the data that you’ve just presented with very few treatment discontinuations, side effects that we already have known about, but really are adverse events that we are very able to inform our patients about, but are not leading to patients not being able to take this treatment.
So I think, for me, the key thing here is a 9-month treatment has a significant long-lasting effect over the 2 years of the study. And of course, we don’t know what happens after 2 years, but the exciting thing is to think that this may well be extended beyond that, but we have 2-year data to talk about today. So that’s my first impressions of the data and I’m happy if you want me to comment on anything else to answer any questions.
Presenter Speech
Renée Aguiar-Lucander (Executives)
Thank you, Jonathan. So with that, I think we’ll hand over to the moderator to take any questions.
Question and Answer Operator Message
Operator (Operator)
[Operator Instructions] So our first question comes from Maury Raycroft from Jefferies.
Question
Maurice Raycroft (Analysts)
And much congrats on the data update. I was going to start with just a question around proteinuria. You mentioned that in the context of baseline UPCR greater than a less than 1.5 gram subgroups.
You noted this was seen – you’re seeing benefit across the entire population. So what are your expectations for the label in respect to proteinuria? And maybe if the company can talk about the eGFR data and next steps with updating the label with the supplemental NDA.
Answer
Renée Aguiar-Lucander (Executives)
Sure. So I guess our expectations were, obviously, the for the actual trial and for this regulatory submission, the endpoint, obviously, is eGFR. And so my expectation would be actually that the label would reflect eGFR primarily rather than proteinuria. But in terms of, obviously, we did see kind of consistent and persistent proteinuria reduction across the entire population. And we also, obviously, saw the same thing with regards to eGFR.
So our intention really is to file for full approval based on the Phase III population. And I think our target there is, hopefully, we can file around July is our target to file with the FDA.
And then obviously, depending on what the review period is we should have a response from the FDA sometime in the first half of 2024.
Question
Maurice Raycroft (Analysts)
Got it. And as a follow-up, and Dr. Barratt also talked about disease modification. Could that present some claim around disease modification, could that go into the label as well?
Answer
Renée Aguiar-Lucander (Executives)
I think it’s very difficult to comment on what the FDA – how the FDA will look at this and what they will say. I would be – my experience with the FDA is that they probably will be quite conservative around using that kind of language, but I guess we’ll have to just wait and see until we engage with the FDA on that.
Question
Maurice Raycroft (Analysts)
Got it. And maybe just one other question, if you can contextualize the 5 ml delta on eGFR? And how should the treatment duration be in the commercial setting in light of that? I guess how does that change your view around the 9-month course versus something longer than that?
Answer
Renée Aguiar-Lucander (Executives)
I mean I think that it might be a little bit difficult to already now start thinking about what – I mean how the data will guide treatment decisions, but I guess I will hand over to Dr. Barratt to see if you may have any comments on that. You’re on mute.
Answer
Jonathan Barratt (Executives)
Sorry, can you hear me?
Answer
Renée Aguiar-Lucander (Executives)
Yes, we can now.
Answer
Jonathan Barratt (Executives)
Yes. So myself and other nephrologists from around the world are very keen to get our hands on this data, as you can imagine. And we want to use this data to understand about frequency of treatment, but it’s very early, as Renee has said, this is top line data. We haven’t got an answer for that yet, but that is clearly a question we want to look at in terms of the clear disease modifying effect this treatment has.
And can we gain more by repeated administrations. We have the open label extension study happening at the moment, which will be generating data. I think it’s too soon to say, but it is a question that we, as a nephrologists, are asking, and we’ll work with Calliditas to come up with some thoughts on how we think this should be structured going forward.
Question and Answer Operator Message
Operator (Operator)
Nochomovitz from Citi.
Question
Yigal Nochomovitz (Analysts)
Can you hear me now?
Answer
Renée Aguiar-Lucander (Executives)
Yes.
Question
Yigal Nochomovitz (Analysts)
Okay. Good. Can you just clarify something on the eGFR slope. So you said minus 6 to 24 months for Nefecon, minus 12 for placebo, okay? And then you also said delta was minus 1.8 to minus 3 per year. So I’m just a little confused on the math because I would have thought the delta would have been minus 3 per year. So is there some – there must be some kind of like very large variability with the error bars. Just can you help me understand the – how it’s minus 8 to minus 3 per year when you have a 6 delta for the 2 years?
Answer
Richard Philipson (Executives)
Yes. Well, there are a number of different methods that can be used for slope analysis. So we’ve applied several different methods. In the slope analysis, they provide an estimate that ranges between 1.8 to 3 ml per minute per year. So actually, that does then correspond to that difference we’ve seen at 2 years, where we see a 6 ml per minute difference over 2 years.
Question
Yigal Nochomovitz (Analysts)
Okay. I guess I was just thinking more on the lower end of the range. The 1.8 not connect with the delta of 6, you know what I mean? But okay, I guess some great stability.
Answer
Renée Aguiar-Lucander (Executives)
I guess it all depends on the kind of statistical approach that’s used, and that’s actually – there are a variety of different ways you can do it. And that’s kind of just for completeness and transparency, we provided all of those different ways of doing it, but these are range of looking at different kind of supportive statistical analysis.
Question
Yigal Nochomovitz (Analysts)
Have you guys actually seen the slopes yet? Or you just have seen the numbers? And when would we see the actual graph in the slope?
Answer
Renée Aguiar-Lucander (Executives)
I think that what we’ll do, obviously, is we are going to have to kind of look at the data more in detail and do more analysis. And I think that it will probably most likely be part of kind of our plans in terms of releasing additional information at conferences and in publications. So I can’t give you an exact time, but it will be part of that type of kind of disclosure or information.
Question
Yigal Nochomovitz (Analysts)
Okay. And I had a question for Dr. Barratt. I would be curious on your thoughts, Dr. Barratt, as to how you would compare and contrast what we’ve seen now for Nefecon with this 2-year data with what was seen in the testing trial for methylprednisolone as I’m sure you’re familiar with, how would you compare these two studies?
Answer
Jonathan Barratt (Executives)
So I think we need to think very carefully about these studies. What I think is really exciting for me is the pattern of proteinuria change that we see with this drug is completely different to the pattern of proteinuria change, we see with this high dose systemic steroids, telling me that we are doing something fundamentally different in terms of the disease pathogenesis and to see that the proteinuria is still at 30% lower at 2 years despite only having a 9-month treatment, suggests to me that we are doing something fundamental to the production of the abnormal IgA.
I think the testing study, you give a very high dose. You have multiple tolerability issues. We know this is associated with significant toxicity for patients, which we just haven’t seen in terms of the data that Richard has presented to you.
So I think there is an efficacy issue that is telling us this is doing something fundamentally different, in my view, to the underlying disease compared to a large systemic anti-inflammatory dose of steroids and we also have the safety efficacy aspect in terms of tolerability, remembering that the dose of steroids used in testing equate to between 30 to 14 milligrams of overall prednisone, which we know from many, many studies, patients find very difficult to tolerate.
So I think as more data comes out, as Renee has said, we will be looking very closely at the differences we see. We’re already seeing very significant differences in terms of patterns of response with this therapeutic approach compared to large [indiscernible]. So I think there’s more to be come from this. But I think from the data that I’ve seen, and again, it’s early days, we’re seeing fundamental differences in the pattern of response.
Question and Answer Operator Message
Operator (Operator)
Our next question comes from Dan Akschuti from Pareto Securities.
Question
Dan Akschuti (Analysts)
Can you hear me now?
Question and Answer Operator Message
Operator (Operator)
Yes.
Question
Dan Akschuti (Analysts)
Congrats to the whole Calliditas team on this major milestone. So most of the questions were already answered, but maybe one question to Professor Barratt, which was partially taken up already, but how would you see currently the treatment course for a patient over 3 years, let’s say? And where do you see the potential of that second drug that has now been conditionally or accelerated approved based on biomarker data? And where do you – how do you look at those currently to available drugs with quite different profiles and data?
Answer
Jonathan Barratt (Executives)
So I guess the retreatment discussion we’ve already had, I think we are going to be looking very closely at how we use this drug over the longer term, remembering our patients are diagnosed in their 30s and have a lifetime ahead of them where we need to control this disease. And we’ve always thought that a large number of patients are going to need a second or third course. We need to look at the data to better understand what those criteria might be for retreatment and where we look at where we gain extra benefit and the open-label extension study that is currently ongoing is going to give us some really useful information about that.
So I’m not – I can’t give you an answer because I just haven’t seen the data to give you a sensible answer on that, but I know we will be looking at that in close detail. In terms of where this therapy fits in, in the context of other therapies, I think that we have got a really clear indication here of a safe and effective therapy, but we can always think about where we might gain advantage with other therapies. So I think combination therapies of things nephrologists are going to look very carefully at. We clearly need to ensure that we gain on efficacy while not increasing safety signals and so mode of action is going to be critical to make sure that we don’t compound any effects in terms of certainly immunomodulation or infection risk.
And the good news is we saw real infectious signal here with the NefIgArd trial, unlike the testing study where there were significant infections leading to death. So I think we – this is an open book. We are at the very beginning of a journey, and we are going to be asking those questions in terms of combination therapies, the right combinations for the right patients.
We’ve never had that opportunity before in managing IgA nephropathy, quite frankly, have had no drugs. So I think we will be looking at all opportunities, and I’m sure Calliditas and every other company, will be looking at as many opportunities as possible to improve the lives of patients with kidney disease and to prevent kidney failure in the lifetime of patients with IgA nephropathy. And so that must be our focus. And we now have a drug with 2-year eGFR data, the first data we’ve ever had, showing a really beneficial effective treatment that potentially is disease-modifying. And so we need to work on that.
So I can’t give any complete [indiscernible] of course, we need the full 2-year data for any other drug to make sure we understand both its efficacy and its safety so that we know how we combine these drugs going forward, if that’s what we choose to do.
Question
Dan Akschuti (Analysts)
Okay. And a follow-up to that. So you just mentioned, yes, there is no – currently, there is no such data from any other drugs, so you would kind of hold off on other drugs as until they have such data as Nefecon has?
Answer
Jonathan Barratt (Executives)
Well, so I can’t – so if I – so I could only speak that we only have one approved drug in the U.K. and in Europe at the moment. As new drugs become available, we will be starting to think about how we might combine them in the right type of patient. But that is something – [indiscernible] was only approved 2 weeks ago. It’s very early. So we really are just starting to think how we might start combining therapies.
But what we need to know is we need to have the confidence around safety and efficacy, and that’s where the 2-year data come in. And so we have the most confidence around safety and efficacy with Nefecon at the moment. And therefore, that’s the drug that really has set the benchmark in my view for where we go next.
Question
Dan Akschuti (Analysts)
Okay. One last question to the company. Do you have any indication or data on patients that are going back on drug after 9 months already, like after a certain [indiscernible]. Do you have anything related to that?
Answer
Renée Aguiar-Lucander (Executives)
So obviously, in terms of – kind of in terms of our commercial drug in the U.S., it’s a little bit early probably at this point in time to know kind of whether people are going back on drug. But I mean what we have seen, obviously, is that for some patients, the physicians’ choices to keep them on drug after the 9 months. But I think it’s probably a little bit early for us to have any of that data in terms of retreatment at this point in time. We haven’t been in the market long enough to actually have any of that data.
Question and Answer Operator Message
Operator (Operator)
Our next question comes from Annabel Samimy from Stifel.
Question
Annabel Samimy (Analysts)
Can you hear me?
Answer
Renée Aguiar-Lucander (Executives)
Yes we can hear you.
Question
Annabel Samimy (Analysts)
Great. So just a question for Dr. Barratt. You just mentioned that this is a different protein area change than systemic steroid, would you say that the proteinuria change that you’re seeing here might also be different than the new ERA class, such as sparsentan. And obviously, we know what the mechanism is here. You’re addressing the source of the disease here. So do you have any thoughts on how the – how predictive proteinuria is for other drugs in this space?
Answer
Jonathan Barratt (Executives)
So a good question. We haven’t seen any data for sparsentan. There’s been a press release. There have been no scientific presentations, no publications.
And therefore, it’s really impossible to comment on the pattern of proteinuria change we see with an endothelin receptor antagonist because the data is just not in a public domain at the moment. So it’s really difficult to comment. I think the fundamental mechanisms are very different in terms of sparsentan having a predominantly hemodynamic effect, whereas Nefecon is impacting on the fundamentals of the disease and ultimately reducing immune complex deposition within the kidneys is our theory.
So I would love to have the patents approaching [ ERA ] up next to one another to try and understand how these are potentially working in different ways and what the patterns might mean clinically. But of course, proteinuria is a [indiscernible] what we’re ultimately interested in is eGFR protection. And that’s what we need to see in terms of any drug to ensure that the proteinuria reduction we’re seeing is acting as a true surrogate of future kidney function protection.
So I think we’ve got that now with Nefecon and we need to wait to see that with other drugs and other mechanisms of action. So I think the challenge really is because of the way the approval process accelerated to improve the process is working, data is at a premium in terms of what is in the public domain, and we need to wait for that to come out before we can give any sensible comments.
Question
Annabel Samimy (Analysts)
Okay. Great. And maybe other questions for the company. So I know that this is top line. Will you be breaking out eGFR benefit based on severity similar to what you recently showed us on the fourth quarter call where patients with greater than 1.5 UPCR had significantly better eGFR. So I guess how – is there any sense of how you’re going to break up the data to sort of illustrate who gets the most benefit here?
Answer
Renée Aguiar-Lucander (Executives)
So I guess that is part of what we’re going to have to do kind of going forward and additional analysis will certainly be conducted. I think that, obviously, what we have seen is actually that the treatment benefit is very consistent across the study population. So I’m not sure what we will find or if we will find any kind of particular benefit in different subgroups, but that is certainly something that is a little bit further down the line when we’ve had a chance to look more properly at the data set.
Question
Annabel Samimy (Analysts)
Okay. Great. And if I could just ask a couple of other questions related to financials. So when you laid out your guidance for 2023, did your guidance already assume this positive outcome? And then just a follow-up to that, do you have any sense how this might facilitate reimbursement, have payers been also waiting for this data to, let’s just say, facilitate the process? I know your coverage is strong, but just to facilitate the process for the nephrologists?
Answer
Renée Aguiar-Lucander (Executives)
I guess in terms of the payers, I’ll give a quick – and maybe Andy wants to comment on that. My view is really kind of that – I mean this can only improve any kind of situation with payers, but I wouldn’t say that payers have been waiting for this data. But certainly, we’re going to be in conversation with them. But Andy, maybe you want to cover this?
Answer
Andrew Udell (Executives)
Yes. I mean as you pointed out, Annabel, I mean, we have currently over 90% of U.S. lives covered for TARPEYO. However, we continue to have dialogue with payers.
And obviously, this data further supports the value of TARPEYO. It’s health and economic benefits and it’s going to be shared with payers at the appropriate time in order to support the appropriate management of our products. So we’re very excited, but it could only improve, I would say, from this data.
Question
Annabel Samimy (Analysts)
And just on the guidance?
Answer
Renée Aguiar-Lucander (Executives)
Did you have a follow-up question, for Andy?
Question
Annabel Samimy (Analysts)
Yes. Well, just on the guidance that you provided for 2023, did your guidance already assume this positive outcome?
Answer
Renée Aguiar-Lucander (Executives)
So I think, obviously, in terms of the guidance, we were certainly assuming that we would get, I would call it, kind of reasonable data out of this – out of the trial. I think we have very, very good data. So I guess we’re positively surprised in terms of where we’ve ended up. I mean, at this point in time, we’re not – we’re certainly not going to reguide or change our guidance.
I think realistically, this type of data obviously cannot be used in promotion and that’s highly regulated, as you know. So I think it’s still be – it will be a while before this information and data gets kind of into conferences and publications and where nephrologists really can take kind of partake of it properly.
So my assumption is that the full effect will kind of be more medium term than near term. But obviously, there will be, in my assumption, kind of clearly some positive impact near term from the fact that nephrologists are going to be aware of the fact that there is this long-term effect.
Question and Answer Operator Message
Operator (Operator)
Our next question comes from Ingird Gafanhão from Bryan Garnier.
Question
Ingird Gafanhão (Analysts)
Congrats on data. I have two questions if I may. Let me start – so over the call, you mentioned a couple of times the open-label study. So I was wondering if you can provide us with some update on what is the status of the open-label study? And when do you think or when you are planning to share some more data on that?
Answer
Richard Philipson (Executives)
Yes, sure. So I mean the study is ongoing. We continue to enroll patients into the study. But the number of patients who are now eligible to get into that study. That’s clearly low as most patients now have completed the pivotal study. There’s only a few patients coming out of that, who can get into the open-label extension. We expect, therefore, that study to complete in terms of the last patient completing study in the first half of 2024.
Question
Ingird Gafanhão (Analysts)
Great. And as a reminder, all of the patients that are being enrolled, they are getting a new course of therapy, right?
Answer
Richard Philipson (Executives)
Yes, that’s right. So all patients who go into the open-label extension will receive treatment with Nefecon.
Question
Ingird Gafanhão (Analysts)
Okay, clear. If I may have a second question for Dr. Barratt. I was hoping, can you maybe contextualize eGFR data for us a little bit more on how you look at it. So Calliditas presented like the data on the total slope. We also have some point data for what happens eGFR 12 months. But in your practice in your life, how do you look at eGFR yourself? And what does it mean in terms of clinical benefit for patients?
Answer
Jonathan Barratt (Executives)
Yes, thanks. So clearly, the thing that matters to patients, and therefore, matters to me is the risk of kidney failure, ending up leading on transplant or needing dialysis. And that is determined by how quickly your kidney function deteriorates. And that’s what we’re looking at here in terms of the data that Richard presented that over the 2-year period, the placebo patients lost 12 ml of GFR.
So if you think about someone starting off with a GFR of 60 ml, it’s going to take 5 years, and they will have 0 ml. And before then, they will need to have dialysis. If you slow that rate of progression, you are delaying the time to which the average patient is going to need to start dialysis and every year is precious to these 30- to 40-year olds, who are living with kidney disease.
And we’ve worked out using real-world data, and we presented this data on multiple occasions, and we will rework the data and now we actually have this data in front of us that if you’re able to reduce proteinuria by 30% that you can delay the time to dialysis for the average IgA patient by a decade. Now what we can do now is look at the assumptions we made in those calculations related to the data we have from the Phase III, which I don’t think are far off, in fact, may even be better the assumptions we made in the original calculation.
So what we’re talking about here is a really meaningful impact on the risk of kidney failure and the time to dialysis or transplantation for most patients with IgA nephropathy. And that is what patients are asking us for. That’s what we as nephrologists want to achieve. So this – you cannot underestimate how important these data are for patients in terms of what it means for their quality of life, for how they live their life in terms of their ability to work, their ability to enjoy time with their family.
And it is exactly what patients have been asking for the last 30, 40 years. So really is groundbreaking data here in terms of what this means for patients.
Question and Answer Operator Message
Operator (Operator)
Our next question comes from Rami Katkhuda from LifeSci Capital.
Question
Rami Katkhuda (Analysts)
I wanted to pass my congratulations on the update as well. Two quick ones for me. First, can you provide any more context about how the eGFR slopes kind of changed after the 12-month period? Do you expect eGFR for the Nefecon arm to kind of start to fall at a similar rate to placebo? Or is there a potential for it to be slightly more accelerated?
Answer
Renée Aguiar-Lucander (Executives)
I think at this point in time, we really haven’t kind of had the opportunity to really kind of review the data set completely. And so that type of information we will share as kind of we get to conferences and publications, et cetera.
Question
Rami Katkhuda (Analysts)
But, I guess, is there any proof from prior studies? Or is this kind of too novel, and we have to wait for the data?
Answer
Renée Aguiar-Lucander (Executives)
I think we do have to wait for the data. I don’t think that there are any other studies really that we can rely on. I think if you’re going to do that, I think you need lots and lots of different studies and then kind of try to draw some kind of general conclusions, but I don’t think we’re in that situation. So I think it is very much waiting for the data here.
Question
Rami Katkhuda (Analysts)
Makes sense. And then can you remind us when the Kinpeygo guidelines are updated and whether this data can be included or whether you need to wait for full approval?
Answer
Renée Aguiar-Lucander (Executives)
I actually – my understanding – and maybe Dr. Barratt has better information on this, but actually, my understanding is that there is plan-- there are plans at least to update the Kinpeygo guidelines for this year before the end of this year. But I don’t know if Dr. Barratt has better information on that.
Answer
Jonathan Barratt (Executives)
Yes. So I’ll be leading that revision. And you may or may not have seen, but the lupus KD guidelines are now out for public consultation. It was always agreed that lupus and vasculitis would go first. And clearly, there’s a limited capacity within KD go to do this. So we are next, but we haven’t got a definitive time line, but I think we will have revised guidelines out for public consultation at some point in 2023, but we haven’t started the process yet. So there is every opportunity that this data could be included in those. But as I say, we haven’t got a start date yet.
Question and Answer Operator Message
Operator (Operator)
And then [indiscernible] from [indiscernible].
Question
Unknown Analyst (Analysts)
Congrats on the data. I just have a follow-up regarding your guidance for the coming year. Very helpful the color that you already gave on what assumptions on the data we’re underlying in there. But I’m wondering if you can elaborate on what factors we should think about regarding potential upside or downside to reaching that guidance what could be sources of potential positive surprises? And where do you see potential risk for reaching your sales numbers?
Answer
Renée Aguiar-Lucander (Executives)
I guess I’ll hand over to Andy, but I guess my core kind of view really is that this is very much driven by physicians having experience with the drug, right? So you have positive success stories from patients, your peer to peer recommendations. Physicians are clear about how the drug works, et cetera. And we’re just about getting to that point, obviously, because we’ve not been in the market for a sufficient period of time. But I don’t know, Andy, if you have any comments on that.
Answer
Andrew Udell (Executives)
I’d echo that. I mean, I think there’s a lot of things that we continue to focus on and add promotionally with our expanded field force. But I think, as Renee alluded to, we’re getting to the point now that physicians are getting more and more experienced with the product and just further these kind of things, this data further gives us confidence and the consistency in the product and how it’s performed and new data, certainly, this data, we only could see as a huge positive as Dr. Barratt said, things like game changer and groundbreaking data and what it means for patients. Hopefully, that’s echoed and that is going to be well received.
Question
Unknown Analyst (Analysts)
Got it. And can you elaborate on what you see currently as the key barriers to further adoption?
Answer
Andrew Udell (Executives)
So currently, I don’t think – I think – we’re not seeing a lot of barriers to adoption. We’re seeing physicians that are trying to find the right patients in their practice that meet criteria that they feel are appropriate for this. And it just takes time. There’s habits, there’s a lot of things. This is the first – we were the first real specialty product that a lot of these nephrologists have been exposed to. So there’s some adoption period that takes and this is normal. So I don’t think that there’s been a lot of barriers per se.
Question and Answer Operator Message
Operator (Operator)
This concludes our question-and-answer session today. I’ll now turn it back over to Renee for closing remarks.
Answer
Renée Aguiar-Lucander (Executives)
So thank you very much. First of all, I want to thank Professor Barratt for taking time to actually be part of this call. It’s greatly appreciated. It’s always insightful to have a practicing nephrologist with a completely kind of different view, obviously, on this than many of the people on the call. So thank you very, very much for taking the time to comment on this. I think it’s very insightful and very helpful. And thank you for all of you who listened to this, and we look forward to sharing additional data as we continue to work through the data set. So thank you again.
