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It’s the "New England Journal of IgA" these days, and we’re just living in it! In this special NephMadness edition of GN in Ten, hosts Dr. Kenar Jhaveri and Dr. Koyal Jain are joined by NephMadness co-creator Dr. Matt Sparks and Duke Fellow Dr. Ale Tomasi to break down the heavy hitters in the IgA Nephropathy bracket. Matt’s dog also joins us for a special, possibly biased cameo.
We’re moving past "ACE first, think later" and diving into the upstream battle: B-cell modulators (BAFF/APRIL inhibitors) versus Complement inhibitors. Whether you’re team "Hit Zero" or team "Alternative Pathway," this episode covers the latest trial data from ORIGIN, VISIONARY, and APPLAUSE to help you fill out your bracket.
The "Hit Zero" Hypothesis
While we all know the classic four-hit hypothesis of IgAN, new therapies are targeting even further upstream—what some are calling "Hit Zero."
- Pathophysiology Recap: IgAN starts with galactose-deficient IgA1 (Hit 1), leading to autoantibody production (Hit 2), immune complex formation (Hit 3), and mesangial deposition/damage (Hit 4).
- B-Cell Modulators: These drugs target BAFF (B-cell activating factor) and/or APRIL (a proliferation-inducing ligand) to reduce the production of those pesky autoantibodies right at the source.
The B-Cell Contenders: Sibeprenlimab & Atacicept
- Sibeprenlimab ("Sibi"): A monoclonal antibody directed at APRIL.
- The Data: Showed a 50% reduction in proteinuria at interim analysis and a nearly 98% reduction in APRIL levels.
- Status: Currently has conditional FDA approval.
- Atacicept: A fusion protein that dual-blocks both BAFF and APRIL.
- The Data (ORIGIN trials): Demonstrated a 45.7% proteinuria reduction at 36 weeks and, notably, stabilization of eGFR slope in long-term follow-up.
- Pronunciation Debate: Is it "Attack-a-cept" or "A-tassi-cept"? The investigators say "Attack," because it’s out for blood.
The Complement Contender: Iptacopan
- Mechanism: A factor B inhibitor that specifically targets the alternative complement pathway, which is increasingly recognized as a key driver of IgAN damage.
- The APPLAUSE Study: This oral, twice-daily pill showed a 38% reduction in proteinuria at nine months.
- Safety First: Because complement blockade increases the risk of infections from encapsulated bacteria, patients must be up to date with vaccinations for meningitis, streptococcal and pneumococcal infections.
The Verdict: Who Wins the Bracket?
- Tune in to find out what our experts think… then fill out your own bracket!
References
Atacicept
Lafayette R, Barbour SJ, Brenner RM, Campbell KN, Doan T, Eren N, Floege J, Jha V, Kim BS, Liew A, Maes B, Pal A, Pecoits-Filho R, Phoon RKS, Rizk DV, Suzuki H, Tesař V, Trimarchi H, Wei X, Zhang H, Barratt J; ORIGIN Phase 3 Trial Investigators. A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy. N Engl J Med. 2026 Feb 12;394(7):647-657. doi: 10.1056/NEJMoa2510198. Epub 2025 Nov 6. PMID: 41196369.
Lafayette R, Barbour S, Israni R, Wei X, Eren N, Floege J, Jha V, Kim SG, Maes B, Phoon RKS, Singh H, Tesař V, Lin CJF, Barratt J. A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy. Kidney Int. 2024 Jun;105(6):1306-1315. doi: 10.1016/j.kint.2024.03.012. Epub 2024 Mar 27. PMID: 38552841.
Sibeprenlimab
Perkovic V, Trimarchi H, Tesar V, Lafayette R, Wong MG, Barratt J, Suzuki Y, Liew A, Zhang H, Carroll K, Jha V, Quevedo A, Han SH, Praga M, Chacko B, Sahay M, Cheung CK, Kooienga L, Walsh M, Xia J, Fajardo C, Shah L, Hafkin J, Rizk DV; VISIONARY Trial Investigators Group. Sibeprenlimab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial. N Engl J Med. 2026 Feb 12;394(7):635-646. doi: 10.1056/NEJMoa2512133. Epub 2025 Nov 8. PMID: 41211929.
Mathur M, Barratt J, Chacko B, Chan TM, Kooienga L, Oh KH, Sahay M, Suzuki Y, Wong MG, Yarbrough J, Xia J, Pereira BJG; ENVISION Trial Investigators Group. A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. N Engl J Med. 2024 Jan 4;390(1):20-31. doi: 10.1056/NEJMoa2305635. Epub 2023 Nov 2. PMID: 37916620; PMCID: PMC7615905.
Iptacopan
Perkovic V, Barratt J, Rovin B, Kashihara N, Maes B, Zhang H, Trimarchi H, Kollins D, Papachristofi O, Jacinto-Sanders S, Merkel T, Guerard N, Renfurm R, Hach T, Rizk DV; APPLAUSE-IgAN Investigators. Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy. N Engl J Med. 2025 Feb 6;392(6):531-543. doi: 10.1056/NEJMoa2410316. Epub 2024 Oct 25. PMID: 39453772.
Zhang H, Rizk DV, Perkovic V, Maes B, Kashihara N, Rovin B, Trimarchi H, Sprangers B, Meier M, Kollins D, Papachristofi O, Milojevic J, Junge G, Nidamarthy PK, Charney A, Barratt J. Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. Kidney Int. 2024 Jan;105(1):189-199. doi: 10.1016/j.kint.2023.09.027. Epub 2023 Oct 31. PMID: 37914086.
The hosts and guests of this GN in 10 episode do not have any disclosures to make relevant to the content of this episode.
Creators and Guests
Host
Host
Guest
Dr. Ale Tomasi
Nephrology Fellow at Duke University
What is GN in Ten?
A bite-size podcast brought to you by the International Society of Glomerular Disease. Nephrologists and glomerular disease experts Dr. Kenar Jhaveri (Northwell Health/Hofstra University) and Dr. Koyal Jain (UNC Chapel Hill) take a lighthearted look at the latest research, discuss clinical practice, and interview leaders in glomerular medicine — all in a short enough time to listen on your coffee break.
Episode 12: NephMadness Special! IgAN (Again?!): New B-Cell Targets vs. Complement Inhibitors
===
[00:00:00]
Laurel Damashek: Welcome to GN in Ten, a bite sized podcast brought to you by the International Society of Glomerular Disease. Our hosts are nephrologists and glomerular disease experts Dr. Kenar Jhaveri of Northwell [00:00:15] Health and Hofstra University on Long Island, New York, and Dr. Koyal Jain from the University of North Carolina Chapel Hill.
Kenar Jhaveri: All right everybody, welcome to GN in Ten NephMadness episode, and the topic today is [00:00:30] IgA Nephropathy. It's just another IgA talk. You've probably heard so many of these, but this is gonna be a NephMadness one, so a little bit of competition here. We have Ale here, one of the fellows, and Matt Sparks joining us.
Can you guys introduce yourselves? Oh, I forgot to introduce [00:00:45] Koyal again. Yeah, Koyal
Koyal Jain: Everybody forgets about me. Don't worry. I'll end this with a bang.
Kenar Jhaveri: Okay with the complement cascade. Okay, let's go.
Ale Tomasi: Hi everyone. I'm Ale. I'm a second year nephrology fellow at Duke University. Thanks for having me today.[00:01:00]
Koyal Jain: And before we go to Matt, though, Ale was one of our medical students at UNC. And so I've known her a very long time and I'm so glad that she's here on this podcast.
Ale Tomasi: Full circle moment. I love this.
Matt Sparks: We're very friendly. And it [00:01:15] might appear that we have rivalry on the basketball court, but in nephrology
Ale Tomasi: Not in clinic.
Matt Sparks: Yeah. In nephrology we are banded together to take care of patients with kidney disease. So I'm Matt Sparks. I'm the program director at Duke, and I'm also one of the co-creators [00:01:30] of Neph Madness and on the executive team. I'm proud that we're in our 14th year and just as Kenar mentioned, we've covered IGA frequently, I think just two years ago, and it's just so many things happening. We felt like we had to go back again.
Ale Tomasi: We'll probably be back [00:01:45] in two years as well.
Koyal Jain: Can I tell you, I feel so validated with this writeup when I saw the two topics, which was BAFF-APRIL versus B-cell modulators versus complement inhibitors. I feel so good because the last time when we were voting on this, [00:02:00] I said that it would be one of the immunosuppressive agents, but everybody voted for the DEARA and the, the non immunosuppressive.
And so now I feel so good that we're back.
Kenar Jhaveri: I mean, I think it's about time nephrology goes to ACE [00:02:15] last and not ACE first because I think we're not treating the disease. Just the downstream fibrosis all the time, and that's where you go first for that rather than second. So I'm glad you are putting immunosuppressants up in the map right now rather than these ARB, [00:02:30] SGLT 2, those are fine, but they should be the last thing you put on the patient, not the first thing.
I think the immunosuppression or chemo should be first for targeted therapies. So with that IgA, just another talk. We have I don't know, 19 drugs approved for IgA somewhere [00:02:45] around the world.
Matt Sparks: Another one today. Actually, not Just kidding, it's not
Kenar Jhaveri: It's like the New England Journal of IgA these days.
Matt Sparks: New England journal of IgA, I like that.
Kenar Jhaveri: We have these chronic drugs that are for more CKD like the SGLT twos, the [00:03:00] ARBs, the, endothelin antagonists and maybe MRAs will come there soon and GLP-1s, I'm sure. Despite that we have the immune mechanism that triggers IgA, the four-hit hypothesis, and even some people even call the zero hit.
But [00:03:15] the four drugs there are really your steroids, your budesonide. And then you have the two new kids, which you guys are gonna talk about, is the complement inhibitors and the April- BAFF inhibitors. Let's maybe start with the four-hit hypothesis and maybe you [00:03:30] can just remind people about that and then go into the two kids on the block.
Ale Tomasi: So pathophysiology of IgA four-hit hypothesis. One, you have your production of galactose deficient IgA, then you have production of IgG and IgA [00:03:45] antibodies against this galactose deficient IgA. And then these all form immune complexes containing IgA, IgG, galactose deficient IgA and ultimately, hit four is that these deposit in the mesangium of your glomerulus causing kidney damage and disease.
Koyal Jain: One of [00:04:00] the things that has come up is how does complement play a role with IgA nd all these new agents that we're talking about, the two groups that we'll actually talk about: the B-cell modulators, which is like BAFF-April agents, and then complement inhibitors.
How are they playing a [00:04:15] role?
Matt Sparks: I think as Kenar alluded to, I think we're really starting to get more upstream targets. And as a four hit hypothesis, this sort of goes after the first hit, which is the production of IgA autoantibodies and the galactose [00:04:30] deficient IgA in the hinge region. So BAFF and April are really interesting and we're learning more and more about these.
So the drug that we're going to talk about here is called sibeprenlimab, which is now conditionally FDA, approved, and there's a second [00:04:45] drug in the pipeline likely to be approved sometime this year called atacicept. And what they do is they target proteins called BAFF and April. April and BAFF work on B cells to one, have [00:05:00] plasma cell survival, and two, allow the B cell to have class switching so that they make IgA.
And so when we look at the clinical trials, we're going to see that the patients get very low levels of IgA, IgG and other [00:05:15] subtypes. And so that really limits the ability of all the autoantibody generation and then deposition into the kidney. Really takes a proximal approach.
And as Kenar mentioned, the traditional therapies that we've had prior to this, [00:05:30] not including steroids and also a complement, which we'll talk about later. This really hits a proximal portion. So I'm very excited about these drugs as possible therapeutic options for our patients. And now we actually have the ability to give them.
So sibeprenlimab affects April, [00:05:45] and atacicept affects both April and BAFF.
Kenar Jhaveri: All right. Some people might even call it hit zero because it's even way before hit one. And that's, some people are actually calling this now the five hit hypothesis, so starting at [00:06:00] zero.
Maybe Ale can tell us a little bit about the two trials in the BAFF April world and then we'll go into the compliment part.
Ale Tomasi: So I'll start with atacicept. The two main trials to hit on there, no pun intended, are the ORIGIN 2 and 3. So as [00:06:15] Dr. Sparks mentioned, atacicept is a BAFF and April inhibitor. It's a fusion protein and it's provided as a once weekly injection. So the first trial that came out, the phase two trial ORIGIN-2, enrolled 113 participants and each of these patients [00:06:30] received varying doses of atacicept: 25 milligrams, 75 milligrams, or 150 milligrams, or they received placebo. And what they found was at 24 weeks in the combined atacicept group, patients had a 25% reduction in proteinuria compared to placebo.
And this was [00:06:45] sustained at 36 weeks. They also showed that patients had a 60% decrease in galactose deficient IgA circulating antibody levels as well. And so following this phase two was an open-label extension study, and patients were able to receive [00:07:00] 150 milligrams of atacicept for an additional 60 weeks, so 96 weeks total.
And again, patients showed a sustained reduction in proteinuria. This time, 52%. There's also reduction in hematuria, circulating galactose deficient IgA-1 levels, all at [00:07:15] 96 weeks. And I think a key finding here as well was the slope EGFR data. The average was 0.6 in the treatment group. So patients overall had stabilization of their kidney function while receiving atacicept.
And so of course this phase two trial lent itself to [00:07:30] the phase three ORIGIN-3. This is ongoing. It has 203 patients enrolled, but we do have an interim analysis published for this. The inclusion criteria were adult patients with IgA nephropathy, biopsy proven, at least one gram of [00:07:45] proteinuria, an EGFR of at least 30.
And then well-controlled blood pressure less than 150 over 90, and on maximally tolerated and stable dosing of ACE inhibitor or ARB. And what this study is showing is that patients on atacicept had a [00:08:00] 45.7% reduction in proteinuria compared to 6.8% in the placebo group. And additionally, more than 80% of patients had reductions or resolution in hematuria compared to 20% in the placebo.
Now we don't yet have slope EGFR data for this. As I mentioned, we just have the [00:08:15] interim analysis, but I anticipate that it'll be coming out fairly soon, and I'm very excited to see what that shows.
Koyal Jain: Okay. A fun question. Do we all accept that it is "attack-a-cept" or is it "a-tassi-cept"? What do we decide?
Ale Tomasi: I had this internal [00:08:30] debate 'cause TACI is technically the receptor, right? And so I went and said a-tassi-cept, and then I went to a SN and everyone was saying attack-a-cept. So I retrained my brain. I'm happy to retrain it back.
Koyal Jain: I don't know, actually. I'm just asking.
Matt Sparks: I did [00:08:45] a podcast with some of the investigators and they corrected me. They like to call it attack-a-cept. It does sound like it's attacking, so I don't know if that's why they decided that instead of a-tassi-cept, which is not as forceful.
Kenar Jhaveri: Just call it Attack [00:09:00] and Sibi.
Ale Tomasi: Sibi. I like Sibi.
Kenar Jhaveri: Sibi is good.
Matt Sparks: Now I'll go with sibi all the way.
Ale Tomasi: Do you wanna talk about sibi? Yeah, let's talk about sibi.
Matt Sparks: Okay. Sibeprenlimab is a monoclonal antibody that's directed towards April. [00:09:15] And this was a phase three clinical trial that's now published and this now has conditional FDA approval, unlike atacicept, which likely will have approval soon. This was a very similar inclusion criteria, about 150 patients in the [00:09:30] sibi group and about 168 in the placebo group.
The individuals had a proteinuria of about 1.3 grams on 24 hour urine, and they received this drug. And then this is the interim analysis. [00:09:45] Again, we do not know the slope EGFR data, because how these drugs are approved now, they can get conditional approval once they meet the proteinuria outcome, and then they can receive full approval once the EGFR slope data [00:10:00] is seen after two years and they have a favorable safety profile. And so this drug sibi resulted in a 50% reduction in proteinuria at the interim analysis.
And this was sustained throughout that entire period. As we [00:10:15] mentioned, this is I guess we're calling it hit zero now. And you have really profound diminished galactose deficient IgA, almost a 60% reduction after about 12 weeks or so that sustained throughout the entire period, and [00:10:30] also importantly, almost a 98% reduction in April levels.
So this really, it's doing its job. The adverse event profile looked really good at this time point. There were concerns that with these drugs that you [00:10:45] might not have a good response to vaccinations. From my discussions with the individuals that are involved in these trials and also some experience using these in the oncology literature, you can have a good response to immunizations, but that really [00:11:00] hasn't been completely explored.
So I think that this is another great example of really having a targeted therapy hitting really proximally for this disease. And I think it's really exciting and very excited to [00:11:15] see where this heads.
Koyal Jain: This is so cool.
Kenar Jhaveri: Both of them are sub-q injections. One is once a week, the other is once a month. Sibi is once a month.
Matt Sparks: Once a month is also very convenient. So I, I agree that these are really changing the [00:11:30] way we deliver care.
Kenar Jhaveri: I don't know which one's gonna be better. I don't know if Koyal has any thoughts, but, blocking both April and BAFF would be better? Or just blocking April, I don't know which one will be better in IgA down the road.
Koyal Jain: I have a sense that both maybe, [00:11:45] because if you think about just April, April doesn't attack the BAFF receptor. There's-- oh, this is a great segue for our listeners. There are three receptors. There's a TACI receptor, there's a BAFF receptor and there's a BCMA, I believe receptor [00:12:00] and the BCMA and TACI are blocked by April and BAFF both, but the BAFF receptor is only blocked by BAFF essentially. And I wonder... you're blocking more so dual block, it might be better, but I don't really know. Like none of us [00:12:15] have a head-to-head analysis of any of these drugs to really know what's gonna happen.
Matt Sparks: One of the things I was really intrigued about is with the long term atacicept data on EGFR stabilization. And that's gonna be really impressive to see that [00:12:30] it almost makes their EGFR slope to normal. And that is going to be a game changer if that really holds true when we see the data coming forth, right.
But I agree, it's unclear which is better. It makes sense that two is better than one. [00:12:45] But we don't know.
Kenar Jhaveri: Should we move on to the complement?
Koyal Jain: We must move on to the complement cascade. Oh no, I'm up. And you will understand when you listen to the C3G podcast.
Kenar Jhaveri: Yeah. One day, April might compliment you.
Matt Sparks: My dog is named April, so I just wanna make sure [00:13:00] that that's something else to to note here.
Koyal Jain: I will also say this is completely random, but I can see Matt and every time he speaks, his
dog just leaves the room. And so this has happened every time I've seen him talk. But anyways...
Matt Sparks: he is like, I've heard this...
Kenar Jhaveri: The dog's probably like, "IgA [00:13:15] again?!"
Koyal Jain: "I'm leaving." So cute. So let's talk about the complement cascade. I'm not gonna go into details. Typically when we think about antigen antibody binding and we think about that as a trigger mechanism, we think about classical pathway. However, that's not [00:13:30] quite so true for IgA. There's some controversy that in IgA, nephropathy, you have more of an alternative complement pathway and/or lectin pathway that are affected.
And that is why we're thinking that some of these complement blockade agents that we'll talk about next might [00:13:45] actually be beneficial. And so briefly, we all have the C3 takeover mechanism where we have our alternative complement pathway partly active, and if there's a bigger trigger, it'll get ramped up.
And if you [00:14:00] had a mutation genetically, which is a little bit less common than a functional problem, where you have some nephritic factors or something that is now causing increased activity of this alternative complement pathway, you can imagine that you have this whole cascade that's almost always [00:14:15] active, and that can affect from C3 to C5 to the terminal complex that is formed, like the soluble MAC complex. So really, let's talk about the complement drugs that have come in the world of IgA nephropathy, and where do we go from there?
Ale Tomasi: The main drug [00:14:30] that we covered in NephMadness that we can talk about today is iptacopan. And this is a complement factor B inhibitor, so it specifically is gonna target that alternative pathway. The data we have for iptacopan is the APPLAUSE study, so I can go into that a little bit right [00:14:45] now.
This enrolled 443 patients, again with biopsy proven IgA nephropathy, and at least one gram of proteinuria over 24 hours despite optimized supportive care, and again, a GFR greater than 30. Although the study does mention that there will be data for patients [00:15:00] with reduced GFR as well in the future. Of these 440 patients, 222 received iptacopan and two hundred twenty-one received placebo, and this is dosed at 200 milligrams twice daily. It's an oral pill. And what the APPLAUSE study showed was that at [00:15:15] nine months, proteinuria levels were lower in those receiving the complement inhibitor by 38%. So, clinically and statistically significant.
And importantly is to know that there was really no significant difference in adverse events between the two groups. When we think about complement inhibition, we do worry about [00:15:30] infection risk, particularly encapsulated bacteria. And it's important to know that there are ways to mitigate this risk clinically when prescribing the drug, and that ultimately we can be reassured about the safety profile of this medication.
Koyal Jain: Thank you so much, Ale. Really appreciate it. You [00:15:45] mentioned a little bit about the vaccination requirements and the risk with encapsulated bacteria. Matt, do you wanna talk a little bit more about that for our listeners?
Matt Sparks: Yeah. This is a lot of complement discussion today and if you listen to our other podcast on C3G, it's very similar [00:16:00] 'cause it's the same drug. Encapsulated bacteria really require the complement cascade to get rid of it so that when you don't have that system and you block it with this drug, you're going to be at risk for a meningitis, [00:16:15] streptococcal infections and Haemophilus influenzae. So getting those vaccinations is very important. They recommend that you get these vaccinations at least two weeks before starting the drug. And at least for IGA nephropathy, you might be able to time that, with the patient. And so you [00:16:30] need to get serotype A, C, W, Y and B. Those are the meningitis vaccines. And there's a little bit of difference in how, you know, when you actually give them. And you need to get boosters as well. You need to get the pneumococcal vaccine. And the good thing is we have the new conjugate [00:16:45] vaccines, which are really great.
Make sure they have their Haemophilus influenzae vaccination as well. Now, if you can't time it and get these vaccinations before you start the drug you should still do the immunizations, but you can also [00:17:00] give antibiotic prophylaxis. The preferred is [penicillin] V or if you can't take that, then you can take ciprofloxacin.
And so that's another really important piece here. The last thing is that you need to really monitor them for [00:17:15] signs and symptoms of infection while they're on this drug and let them contact you and if they have anything, they need to have some prophylactic antibiotics as well. So yeah, this is a really important topic and I think as a nephrologist we start to dive more into the complement [00:17:30] cascade.
We're going to see more and more diseases that we're going to be treating with complement cascade blockers. And as we already mentioned, they've already got two new diseases and then we're gonna keep adding and adding down the road.
Kenar Jhaveri: [00:17:45] Just one more thing, 'cause people I'm sure have used iptacopan now for IgA or C3. It's important to monitor lipids as a lot of people who have hyperlipidemia at baseline or you develop nephrotic syndrome with the setting of IgA, they will get hyperlipidemic, and [00:18:00] with iptacopan you might want to add a statin along with that if there are rising lipids at the same time. So just something to monitor as well, as we have seen that in practice.
Koyal Jain: So the question in everybody's mind is, which group wins? And the [00:18:15] reason I'm bringing this up is because I wanna go last and I do not wanna give Matt the chance of going last for this question. So we are going to start with Dr. Sparks.
because he went last, the previous one.
Matt Sparks: Okay. To me the winner is the [00:18:30] BAFF-april inhibitors, the new B-cell modulators, and going after hit zero. Sounds like that's where we need to go. So I'll stop with that. I'll say I'm all the way team BAFF and April and my dog's named April, so I have to do [00:18:45] that.
Koyal Jain: Okay, Dr. Tomasi, you're next.
Ale Tomasi: I am Team BAFF April too. I promise I'm not just saying that. We talked about the four hit hypothesis. We're gonna hit hit zero, hit negative one, hit negative two. Pathophysiologically, this makes the most sense. And really the data [00:19:00] from ORIGIN and from VISIONARY are really compelling.
My vote goes for the B-cell modulators as well.
Koyal Jain: Okay, Dr. Jhaveri.
Kenar Jhaveri: I think for me it's pretty slam dunk that it's gonna be BAFF-April inhibitors. I think they're gonna be like the hydrochloroquine [00:19:15] of IgA. They'll be for most patients. And iptacopan, steroids and budesonide can be used as like when you have flareups, but these April BAFF inhibitors are gonna be your drugs to stay for chronic management of [00:19:30] IgA to decrease the whole flare up process.
Koyal Jain: Oh my goodness. It's my turn. And the reason I went last is because I can't decide this, I've actually been like torn between the two of them.
Matt Sparks: I thought you had some insider information.
Koyal Jain: I do not have any inside [00:19:45] information. My inside information is you actually. So my,
Matt Sparks: Maybe you can go against the grain here.
Koyal Jain: I would, yeah.
Ale Tomasi: We can go four for four. Four hits for five.
Kenar Jhaveri: Yeah.
Koyal Jain: No, I genuinely am, the reason I'm conflicted is because one, BAFF, for all of the reasons that you've talked about the B-cell modulators, [00:20:00] but the thing about the complement inhibitors is that they can be used for so many of the diseases right now, right?
Like they, I know we're talking about IgA, but in reality, they help so many patients. It's not just IgA. They help so many patients.
Matt Sparks: Poor complement system doesn't [00:20:15] even need to be on anymore.
Kenar Jhaveri: I don't think any of these will win the whole thing in NephMadness. So just Koyal,
Matt Sparks: Oh, come on!
Koyal Jain: So I can decide whichever one, and it's good.
Matt Sparks: Oh, that's interesting because we have, actually, the complement could be against each other in the finals.
Koyal Jain: Ooh, that'll be, So that'd fun.
Kenar Jhaveri: That would be [00:20:30] interesting.
Koyal Jain: I'll watch that.
Yep.
Matt Sparks: you've gotta make a decision. This is really important.
Koyal Jain: I'm gonna go against the grain then.
Let's not do four for four. Let's do complement inhibitors.
Ale Tomasi: I respect that.
Koyal Jain: And I will say only because somebody has a flare up, I don't wanna give them [00:20:45] steroids.
Matt Sparks: Love it. I like that. That's legit.
Ale Tomasi: Yeah.
Koyal Jain: Okay. With that, thank you everybody for listening to us on this amazing Neph Madness episode on IgA nephropathy. I would like to thank Dr. Sparks and Dr. Tomasi for joining us. And [00:21:00] Kenar and I are going to sign off. Thank you again and have a wonderful day.
Ale Tomasi: Thank you so much.
Koyal Jain: Thank you.
Laurel Damashek: This has been GN in 10 from the International Society of Glomerular Disease. You can listen and subscribe wherever podcasts are [00:21:15] found and tweet at us at ISGDtweets. Thank you for joining us.
Matt Sparks: This one will be a lot easier.
Koyal Jain: Oh, wait, what? Who was next?
Kenar Jhaveri: It sounds like a drink.