Joseph, do you have any final thoughts about, or takeaways from, this discussion?

Education is important for everybody. Many health care providers, including myself, always had this feeling about FMT [fecal microbiota transplant]. Is it dangerous? Will patients wind up getting sick? Where does the stool come from? Is it a mix of donors or a single donor? How much will it cost? And the whole idea of a colonoscopy with bowel prep and propofol, which I mentioned before, seems like a lot. We need to change the way we think about the natural course of 

 infection [CDI]. Hopefully, people will and explore all treatment options that are available at this point.

As far as education with the practitioners, it is about educating the patients as well. If they happen to be frequent fliers for, let’s say, as you mentioned, UTIs [urinary tract infections]. Or they go to their physician, and they say, “I have a cold,” and they’re given an antibiotic. You have to explain to patients as you’re seeing them come into your practice that it’s not important to get an antibiotic every time you go to your physician’s office. And to educate them and not to try to doctor-shop and get an antibiotic if they don’t get the right answer from their primary care physician [PCP] or whomever. It’s important not only for practitioners, but for patients or potential patients for 

 Certainly, we’re going to continue to need patient education, and I appreciate that comment. Andrew?

I am cautiously optimistic now, at this point, as to where we’re headed with CDI treatment, as we have the first FDA-approved FMT product at this point right now with seemingly more on the way. We’ve got the first one through the door, and it’s going to be a matter of seeing where things go from here. As you mentioned earlier, maybe hopefully in the next 10 years we’ll have narrowed it down to which key microorganisms are essential for restoring the microbiota. And if we see these improvements, then hopefully the treatments will continue to become more effective into the future as well.

Appreciate that. I have to say that I’ve considered myself in the past a drug pusher, if you will, in the good sense of the term. But I am excited the fact that there is now an FDA-approved fecal microbiota replacement and that’s a nice, good step forward with assurance that it’s screened and safe, for the most part. And that’s a major step for managing patients with recurrent 

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Experts provide practice pearls for educating patients on and using FMTs for the management of CDI.

Key Takeaways on FMTs in the Treatment of CDI

Joseph Reilly, BS, PharmD, BCGP

Patient Case No. 2

Patient No. 2 has stage 3 CKD and uncontrolled hypertension. They have a moderate reduction in their estimated glomerular filtration rate, confirming stage 3 CKD. Their hypertension is likely contributing to CKD progression.

Difficult-to-treat hypertension is a condition where blood pressure remains uncontrolled despite the use of three or more antihypertensive medications, including a diuretic. This condition is distinct from resistant hypertension, which is more common and involves blood pressure that is not controlled with three medications but may not include a diuretic. Difficult-to-treat hypertension is less frequent, affecting a smaller subset of patients with high blood pressure. It often requires a more comprehensive approach, including lifestyle modifications and potential secondary causes evaluation, to achieve optimal management.

Panelists discuss how chronic kidney disease (CKD) and uncontrolled hypertension create a damaging cycle, in which hypertension accelerates kidney damage while declining kidney function makes blood pressure harder to control.

Manesh R. Patel, MD

Phase 2 Results for Barzolvolimab for CSU Treatment

There has been significant excitement around anti-KIT therapies for CSU, with broad agreement that they may become the most potent treatments available. Early-phase clinical trials, including phase 1 and 2, have shown remarkable efficacy, with anti-KIT drugs like barselolizumab demonstrating a degree of symptom control that exceeds other treatments. Notably, data presented at a recent AEACI meeting revealed that many patients who stopped treatment after 48 weeks remained symptom free months later, suggesting the possibility that these therapies may be disease modifying and could accelerate remission in some individuals.

The data from barselolizumab, in particular, have generated enthusiasm due to its strong and sustained treatment effects observed in phase 2 trials. Compared with other existing and pipeline therapies, barselolizumab has shown numerically superior results in achieving symptom control and patient well-being. Although direct trial comparisons are imperfect, the consistently positive outcomes position anti-KIT therapies as a highly promising advancement in CSU treatment.

In terms of quality of life, effective control of CSU symptoms can significantly alleviate the burden of this often debilitating condition. Barselolizumab’s broad efficacy means it has the potential to improve quality of life for a larger proportion of patients. Although other therapies like remibrutinib or omalizumab also improve quality of life for responders, barselolizumab’s wider impact may benefit more patients overall, offering new hope for better disease management.

A panelist discusses the promising potential of anti-KIT therapies, especially barselolizumab, in chronic spontaneous urticaria (CSU) treatment, and highlights their superior efficacy, possible disease-modifying effects, and the potential to improve quality of life for a broader range of patients compared with existing options.

Mark Scarupa, MD 

Natalia Nedelkopoulou, MD, is a consultant pediatric gastroenterologist at Sheffield Children's Hospital.

Unraveling the Complexities of Concomitant IBD and Hepatobiliary Disease, With Natalia Nedelkopoulou, MD

New research is shedding light on the complexity of managing children and young adults with concomitant 

 hepatopancreatobiliary (HPB) disease, highlighting ulcerative colitis (UC)/primary sclerosing cholangitis (PSC) as an especially high-risk subtype.

Findings from the retrospective analysis of patients diagnosed with IBD and HPB disease before 16 years of age with a follow-up period up to 30 years of age were presented at the 

2025 North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)

 Annual Meeting by Natalia Nedelkopoulou, MD, a consultant pediatric gastroenterologist at Sheffield Children's Hospital.

“The combination of inflammatory bowel disease and primary sclerosing cholangitis has been well described and established in the literature, and oftentimes these families come across very upsetting information on the internet about the natural history of primary sclerosing cholangitis,” Nedelkopoulou told 

. “They come to our clinics looking for answers about the long term outcomes, the morbidity and mortality of this condition.”

IBD and concomitant HPB disease diagnosed in childhood have been considered to have a milder IBD phenotype, but paradoxically are associated with increased risk of HPB malignancy and colorectal cancer later in life.

 To better characterize these patients and their long-term outcomes, Nedelkopoulou and colleagues retrospective analyzed data for patients ≤ 16 years of age diagnosed with concomitant IBD and HPB disease, with a follow-up period up to 30 years of age, at a linked pediatric-adult center with a structured transition program.

A total of 38 patients with IBD and concomitant HPB disease were identified, with a mean age at diagnosis of 17.2 years (range, 5-30 years). Among the cohort, 63.2% had a primary diagnosis of IBD, 26.3% presented with simultaneous IBD and HPB, and 10.5% had a primary HPB diagnosis. The mean time interval between diagnoses was 17.5 months (0-144).

Investigators noted UC was the most common IBD subtype (68.4%), whereas concomitant HPB disease included PSC (65.8%), autoimmune hepatitis (23.7%), and autoimmune sclerosing cholangitis (10.5%). Of note, UC/PSC was the most common combination, affecting 50% of patients.

Biologic treatment for IBD was required in 65.8% of patients, of whom 34.2% required a second biologic and 24% of these required further escalation. Infliximab was the most common primary biologic, with vedolizumab the most common second line agent. JAK-inhibitors were used in 18.4% of patients, and 34.2% achieved clinical remission with Azathioprine or 5-ASA alone. Investigators pointed out 5.26% of patients with UC/PSC required a subtotal colectomy, and there were no cases of colorectal cancer.

In the 19 UC/PSC subtype patients, 3 (15.8%) patients developed HPB malignancy; 2 had intrahepatic cholangiocarcinoma, and 1 had gallbladder cancer. All 3 patients underwent extensive surgical resection but developed recurrence within 3 years. Palliative systemic therapy was offered, and 1 patient died aged 29 years.

Non-malignant outcomes include stage 4 liver fibrosis in 1 patient with UC/autoimmune hepatitis and liver transplantation in another patient with IBD-U/PSC. IBD/autoimmune hepatitis/autoimmune sclerosing cholangitis subtypes were treated with prednisolone (61.5%), azathioprine (76.9%) or mycophenolate mofetil (15.4%). Among the cohort, investigators noted patients did not develop significant portal hypertension.

“Our study really highlighted how important it is to have very structured and multidisciplinary transition programs,” Nedelkopoulou said. “We feel that it's of utmost importance to have these programs in order to help young patients engage with the adult services and also improve the clinical outcomes long term.”

Editors’ Note: Nedelkopoulou reports no relevant disclosures.

Bruce S, Inam F, Hubbard R, et al. LONG-TERM OUTCOMES OF COMBINED INFLAMMATORY BOWEL DISEASE AND HEPATOBILIARY DISEASE IN CHILDREN AND YOUNG ADULTS: A 10 YEAR EXPERIENCE. Presented at 2025 NASPGHAN Annual Meeting. November 5-9, 2025. Chicago, Illinois.

Fousekis FS, Theopistos VI, Katsanos KH, et al. Hepatobiliary Manifestations and Complications in Inflammatory Bowel Disease: A Review. Gastroenterology Research. 

Nedelkopoulou emphasizes the importance of structured and multidisciplinary transition programs for young patients with IBD and HPB disease.

Natalia Nedelkopoulou, MD

Niels Jongs, PhD, is a statistician at the University of Groningen.

Niels Jongs, PhD

New phase 4 studies of pegloticase support the feasibility of shorter infusions and higher-dose, less frequent infusions of the 

pegloticase + methotrexate (MTX) coadministration 

These findings are from the AGILE and FORWARD studies and were presented at June’s 

European Alliance of Associations for Rheumatology (EULAR) Congress 2025

 held in Barcelona, Spain. The studies evaluated shorter, 60-minute infusions and high-dose monthly infusions, respectively.

Overall, the studies found that the investigational infusion regimens yielded comparable safety and efficacy as pegloticase 8 mg Q2W +MTX demonstrated in the pivotal MIRROR randomized control trial which led to the combination’s expanded approval in 2022.

In each trial, achievement rates of the Month 6 sUA-lowering response primary endpoint were similar to that MIRROR trial. Furthermore, discontinuation rates, infusion reaction rates, and other adverse reaction rates were similar between the 2 trials and the MIRROR trial.

 Overall the studies support the feasibility of alternative dosing schemes that may ease patients’ treatment burden.

spoke with Orrin Troum, MD, clinical professor of medicine, Keck School of Medicine, University of Southern California, and director, clinical rheumatology research, Providence St John's Hospital, Santa Monica, California, who served as a principal investigator AGILE and FORWARD, to learn more about how these latest investigations of pegloticase add to its clinical profile for treating uncontrolled gout.

How do these latest readouts from AGILE and FORWARD on monthly and shorter infusions of pegloticase add to our knowledge of its clinical benefits on uncontrolled gout?

: Recent EULAR data from the FORWARD and AGILE trials demonstrated the safety and efficacy of new dosing regimens for Krystexxa (pegloticase) with Methotrexate(MTX) in uncontrolled gout patients, showcasing treatment efficacy and dosing frequency.

AGILE: evaluated a shorter infusion duration (60 minutes) of Krystexxa with coadministration of MTX and revealed a consistent efficacy and safety profile, as the standard 120-minute infusion protocol demonstrated in the MIRROR randomized controlled trial (RCT).

A SU-lowering response rate was achieved in 67.2% of uncontrolled gout patients at 6 months.

Between 82-88% of patients achieved target SU levels post Day 1 through Week 24.

FORWARD: demonstrated that monthly dosing of Krystexxa (16mg and 30 mg) with MTX every 4 weeks maintained a similar safety and efficacy profile to the standard 8 mg Q2W regimen found in the MIRROR RCT.

A SU-lowering response rate was achieved in 68-73% of uncontrolled gout patients at 6 months, with similar efficacy maintained at 12 months.

Median time patients sustained target SU levels was 100% from Day 1 to Week 24 or from Day 1 to Week 48 for both dosage cohorts.

 What factors would guide shared decision-making for treatment regimens for people with uncontrolled gout?

Findings from the FORWARD and AGILE trials give the clinician and patient more flexibility in making a decision for the appropriate treatment regimen in patients with uncontrolled gout without compromising efficacy or safety.

 What further research would you like to see done with pegloticase?

 As the body of evidence supporting Krystexxa's efficacy, safety profile and real-world data continues to grow, as demonstrated by the findings of these two studies, other information regarding the effect of less corticosteroid use (Q 4 Week dosing instead of Q 2 week), and potentially using IL-1 blockers may be very useful in limiting corticosteroid use and worthy of future research.

This transcript has been edited for clarity.

Troum O, Botson J, Fang F, Obermeyer K, Verma S, LaMoreaux B. ABS0756 Shorter Infusion Duration of Pegloticase Coadministered With Methotrexate in Patients with Uncontrolled Gout: Secondary and Exploratory Endpoints of the Agile Trial. 

 2025;84:1587-1588. doi: 10.1016/j.ard.2025.06.974

Troum O, Botson J, Fang F, et al. POS1153 Safety and Efficacy of Monthly Dosing of Pegloticase (Every 4 Weeks) with Methotrexate Co-Administration in Patients with Uncontrolled Gout: Phase 4 Forward Open-Label Trial. 

 2025;84:1225-1226. doi: 10.1016/j.ard.2025.06.503

‌Pine L. FDA Approves Pegloticase Injection Plus Methotrexate for Patients with Uncontrolled Gout. HCPLive. July 8, 2022. https://www.hcplive.com/view/fda-approves-pegloticase-injection-plus-methotrexate-for-patients-with-uncontrolled-gout

The AGILE and FORWARD studies found comparable efficacy and safety with shorter doses and higher dose, monthly doses, compared to the pivotal MIRROR trial.

Phase 4 Studies Support Alternative Pegloticase Dosing Regimens for Uncontrolled Gout, with Orrin Troum, MD

Orrin M. Troum, MD

 What else is out there? We have hydroxyurea. We have voxelotor, crizanlizumab, Endari, transfusions. What’s next? There’s a plethora of treatment options to treat the variety of patients who have who have sickle cell disease. We’re stuck with 4 or 5 options. What else is in the pipeline to treat sickle cell disease?

 If we had this conversation 5 years ago, it wouldn’t be much of a conversation. It’s a good time to be in sickle cell, and the future is bright. Gene therapy, despite the issues, is there. There are many ways to do that. As someone had mentioned, science will prevail with time. The curative options are there, but it’s important to recognize that they’re not going to be there tomorrow, and they’re not going to be there next year for the masses.

There are a number of other therapies out there. Fetal hemoglobin is out there. Fetal hemoglobin is a good target. We know about BCL11A. There are groups trying to make fetal hemoglobin higher using a medication that is in development, and I’m sure there are many ways that’s being tried. There’s a class of medications, called PKR activators, that were designed for pyruvate kinase deficiency. It’s is a very small population, but they can be repurposed to reduce hemolysis in sickle cell disease in ways not too unsimilar to voxelotor. Crizanlizumab is medicine that targets P-selectin.

Several other medications in that class are in development or are being repurposed to see if they can address pain. Because even though we’re trying to address the root cause, when a patient comes with pain, what can you do to abort that pain? We have nothing, except for opiates, which are not the solution. It’s a tough battle, but there are efforts trying to do that with P-selectin and all selectins, and many ways with inflammation. But there are many classes. This is a bigger conversation than it could have been even a couple of years ago. It’s an exciting time, and we’ll get to a point where sickle cell disease treatment is a cocktail approach. You take a couple of things, and as long as we can work on it, if we can address things from different angles, then we’ll make our patients have better lives.

Absolutely. Well, thank you so much. This has been an amazing conversation. I want to thank Abdullah, Wally, and Pat. Before we close, tell the audience your 1 big dream, or 1 final thought, that you want everybody who sees or hears or takes care of patients with sickle cell disease to know as a takeaway message from this conversation. I’m going to start with Abdullah. Your 1 final word that you want them to know about?

As you said, this has been a really exciting conversation. Wally, you, and Pat contributed greatly. Considering this discussion, there are 2 things. It’s important, scientifically, to pursue curative options like gene therapy. I’ll repeat that science will prevail. We will have to overcome the risks, understand them better, and remedy them. That’s 1 thing. 

Coming back to Wally’s point, we need more disease-modifying agents that we can use in Africa or India. The typical approach would be—I agree with Pat—new F-inducing agents or a combination of F-inducing agents. Maybe a combination of F-induction with some downstream modifications like anti-inflammatory or antiadhesion therapies. These are going to be important, and I believe these have to be pursued in sickle cell, along with these high-tech, higher-source modalities. This includes swallowing a pill, which can easily be conveyed to Africa or low-resource countries.

Thank you so much, Abdullah. I’m going to follow up with Wally. Wally, what are your 1 or 2 big-picture, take-home thoughts?

 I’d like to put my public health hat on. I want our audience to know about a report that came out in November from the National Academies of Sciences, Engineering, and Medicine. Ify, you and your colleagues did wonderful preparing 512 pages about all that is wrong in sickle cell care in the United States and what needs to be done to make sickle cell care better. There were 7 pillars that you pointed out, and they had to do with education and social policy. They had to do with patient empowerment and disparities. You declared sickle cell to be a disparities disease, as Pat said earlier. They had to do with therapy as well. But it wasn’t just therapy that you focused on. You focused on social determinates of health, you focused on policy, racism, and changes in the fabric of the health care system, especially for adults with sickle cell. We don’t even have an adult sickle cell disease health care system. We have a shack instead of a home for adults with sickle cell disease. That’s the 1 thing I want to take away. None of this discussion we just had will matter is there’s nobody to care for the patients. And in many parts of the country, there’s nobody—doctor, nurse, or other—to care for these patients.

Very well said. Thank you so much, Wally. 

I’m going to add to that because it’s so important. The names of the medicines don’t matter. Whether you live in Cincinnati, or Angola, or India, if we have good therapies, they should be available. We need to leverage that equity to global treatment of sickle cell disease. Hydroxyurea was developed in the 1980s and ’90s and is only now becoming available in Africa. Not really, even. I don’t want to give a talk when I’m retiring in a few decades telling patients about all these new therapies that we’re using in the United States and how sickle cell disease is history, except in Africa, where 90% of kids are still dying before they’re adults. That can’t happen. As these therapies are developed, by Bill Gates or whomever, we’re going to need a lot of people. We need to be sure that these are truly equitable in a timely manner, or we’re doing a huge disservice to the global sickle cell community.

Thank you so much. I’m going to give my thoughts. The first thing I want the audience to recognize is that sickle cell disease is a lifetime genetic disorder. It doesn’t go away when you become a teenager or when you leave pediatrics. It doesn’t disappear when you get married. It’s there for the rest of your life. It does shorten your life span. 

The second thing is pain with sickle cell disease. It’s important, but it’s not the only important thing. Organ damage, that chronic, slow slump of devastation to the organs is a reality, and no patient will die because of pain. They will die from strokes, kidney disease, pulmonary hypertension, infection, heart problems, lung problems. It’s important to look at them as treating not just pain but the entire person. That entire person will also involve their quality of life. Ask them how they’re doing, how are they functioning. Do they get up and go to work? If not, why not? When you’re giving treatment, look at the impact of treatment. Not just on their pain, as we talked about, but on their overall quality of life. 

We talked about screening for sickle cell disease at birth, screening for complications following the guidelines, and early intervention. For example, retinopathy picked up early can prevent blindness, treating hyposthenuria early prevents ESRD [end-stage renal disease], and picking up pulmonary hypertension can prolong life by putting the right treatment in place. But there’s also supportive care. And let’s not forget the role of the primary care provider. The last time I checked, having sickle cell disease does not protect you from getting breast cancer, colon cancer, high blood pressure, diabetes, or diverticulitis, or any other thing that anybody else gets. My patients have all this, and they deserve whole care—not sickle cell care but all-around holistic medical care.

Thank you so much for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to the e-newsletter to receive upcoming Peer Exchanges and other great content right in your in-box.

Experts look into what is next for sickle cell disease and provide key thoughts on the space. 

What’s Next and Final Thoughts in SCD 

Patrick McGann, MD, MS, Cincinnati Children’s Hospital  

OX40/OX40L Target Shows Promise for Atopic Diseases I Raj Chovatiya, MD, PhD Insights at ACAAI 2025

, Raj Chovatiya, MD, PhD, from Northwestern Feinberg School of Medicine, said that the OX40/ OX40L target shows promise as a first-line treatment for conditions such as 

atopic dermatitis, asthma, and chronic urticaria 

“I think that these therapies definitely are going to be the right first-time choice for some patients, for others that might feel that they want to get a little more experience; they might be used after other systemic therapies,” Chovatiya said. “The nice thing is that we have data for both of these populations, and so I look forward to seeing some more of those sub-analyses to really help us understand what it means to be truly naive, or treatment-experienced and be treated with drugs like rocatinlimab and amlitelimab.”

Chovatiya will present the OX40/OX40 ligand target at the 

2025 American College of Allergy, Asthma, & Immunology (ACAAI) Annual Scientific Meeting 

in Orlando, Florida, on Saturday, November 8, during the session, “7 for 11: Hot Therapeutic Targets in Allergy and Immunology.”

 spoke with Chovatiya about what we know to date about the OX40/OX40 ligand pathway from clinical trials and how OX-40-targeted therapies fit into existing treatment. He talked about 2 treatments under investigation: rocatinlimab, an antibody that binds to the OX40 receptor on T cells, and amlitelimab, an antibody that binds to the OX40 ligand on activated antigen-presenting cells.

Although rocatinlimab and amlitelimab show promise in atopic diseases, Chovatiya noted one major challenge, which is the lack of real-world data.

“These are very different drugs [from the] ones we've had before,” he said. “It's not like we're seeing yet another blocker of the IL-13 pathway, so we have an idea what to expect clinically. I think there's going to be a lot of challenges and growing pains, like with any new therapeutic class when it's introduced into the real world.”

Chovatiya looks forward to hearing his colleagues’ experiences with integrating these OX40-targeting therapies into real-world practice. He said he is curious to see how it will fall into the treatment paradigm, whether it will be used as a monotherapy or combination therapy, the timing of when patients will experience improvement, and the long-term advantages of these therapies over therapies with other targets.

“I want people to get excited, because at the end of the day, excitement is what drives more innovation,” Chovatiya said. “Understanding that we need more drugs for atopic dermatitis and every drug is going to have a slightly different home and a different scenario… really allows us to have a number of distinct therapies that coexist. You really have to be into the science…and you have to try [these drugs] …and figure out the right patients. By virtue of all of us being able to stay on top of the data and clinical use, we're going to really be able to create a picture of exactly finding the right treatment for the right patient.”

Relevant disclosures for Chovatiya include AbbVie, Amgen, Apogee Therapeutics, Arcutis, Argenx, ASLAN Pharmaceuticals, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, Eli Lilly and Company, FIDE, Formation Bio, Galderma, Genentech, GSK, Incyte, LEO Pharma, L’Oréal, Nektar Therapeutics, Novartis, Opsidio, Pfizer Inc., Regeneron, RAPT, Sanofi, Sitryx, and UCB.

Chovatiya R. 7 for 11: Hot Therapeutic Targets in Allergy and Immunology (OX40/OX40L). Presented at 

Amgen And Kyowa Kirin Announce Top-Line Results from Rocatinlimab Phase 3 Ascend Long-Term Extension Study in Adults With Moderate To Severe Atopic Dermatitis. Amgen. Amgen. Published 2020. 

https://www.amgen.com/newsroom/press-releases/2025/09/amgen-and-kyowa-kirin-announce-top-line-results-from-rocatinlimab-phase-3-ascend-long-term-extension-study-in-adults-with-moderate-to-severe-atopic-dermatitis

Press Release: Sanofi’s amlitelimab met all primary and key secondary endpoints in the COAST 1 phase 3 study in adults and adolescents with atopic dermatitis. Sanofi.com. Published 2025. 

https://www.sanofi.com/en/media-room/press-releases/2025/2025-09-04-05-00-00-3144170

Ahead of ACAAI 2025, HCPLive spoke with Chovatiya on challenges in translating these promising immunologic targets into real-world clinical practice.

Next Step for OX40/OX40L: Real-World Data in Atopic Dermatitis, With Raj Chovatiya, MD, PhD

Raj Chovatiya, MD, PhD

Final Insights

Video content above is prompted by the following:

Are there any final insights you’d like to share regarding LDL-C and Lp(a) screening and management of high-risk cardiovascular patients?

Pediatric lipid screening is crucial for early detection and management of dyslipidemia, which can prevent cardiovascular diseases later in life. Current guidelines recommend universal lipid screening for children between ages 9-11 and 17-21, with selective screening for those with risk factors. However, implementation remains inconsistent due to barriers such as lack of awareness and time constraints in clinical practice. To improve uptake, strategies include integrating screening into routine pediatric visits, utilizing electronic health records for reminders, and educating healthcare providers and families about the importance and benefits of early lipid screening.

Panelists discuss how effective cardiovascular risk management requires comprehensive screening for both LDL-C and Lp(a), along with aggressive treatment strategies for high-risk patients.

Seth Baum, MD

Stuart Gordon, MD, is a professor of medicine at Wayne State University School of Medicine and director of the division of hepatology at Henry Ford Hospital.

Exploring Seladelpar as Monotherapy for PBC, with Stuart Gordon, MD

New research is shedding light on the safety and efficacy of seladelpar (Livdelzi) as monotherapy in patients with 

 and an intolerance to ursodeoxycholic acid (UDCA).

The data were presented at Digestive Disease Week (DDW) 2025 by Stuart Gordon, MD, a professor of medicine at Wayne State University School of Medicine and director of the division of hepatology at Henry Ford Hospital, and suggest use of the selective PPARδ agonist as monotherapy yields similar safety and efficacy results as those observed for seladelpar combined with UDCA.

“The treatment landscape for PBC has evolved remarkably over the past year,” Gordon told 

, citing the US Food and Drug Administration approvals of 2 new second-line agents.

In August 2024, the US Food and Drug Administration approved seladelpar for the treatment of PBC in combination with UDCA in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.

 In a pair of phase 3 placebo-controlled studies, ENHANCE and RESPONSE, treatment with seladelpar led to a significantly greater rate of composite biochemical response and alkaline phosphatase (ALP) normalization compared to placebo.

Gordon and colleagues conducted a post hoc analysis of pooled efficacy and safety data for seladelpar 10 mg monotherapy versus placebo from ENHANCE and RESPONSE through month 3 to assess the effects of treatment with seladelpar alone. In these studies, patients intolerant to UDCA were eligible if their last dose was >3 months before study entry.

In total, 369 patients were randomly assigned to seladelpar 10 mg or placebo across both studies, 16 of whom received seladelpar monotherapy and 6 of whom received placebo without UDCA. Investigators noted mean baseline ALP was similar between monotherapy patients receiving seladelpar vs placebo.

At month 3, 62% of patients receiving seladelpar monotherapy demonstrated a composite biochemical response compared with 17% receiving placebo, and 23% of patients on seladelpar achieved normalized ALP versus no patients on placebo. Additionally, the mean percent change from baseline in ALP at month 3 was −46% with seladelpar versus −2% with placebo.

At month 3, 56% of patients on seladelpar monotherapy experienced an adverse event (AE) compared with 83% on placebo, but no serious AEs and no discontinuations due to AEs occurred through month 3 with seladelpar monotherapy.

However, Gordon notes there is still much work to be done when it comes to PBC treatment research and education.

“There's so many unmet needs. We have very good therapy, and now we have even better therapy, but we need to see how that therapy plays out in terms of improvement of outcomes… we're anxious to look at real-world evidence outcomes,” he explained, additionally calling attention to the importance of educating both patients and physicians on PBC.

Editors’ note: Gordon has relevant disclosures with AbbVie, Arbutus, CymaBay, DURECT, Genfit, Gilead, GSK, Hightide, Intercept, Mirum, Pliant, and Merck.

Gordon SC, Neff G, Rodriguez M, et al EFFICACY AND SAFETY OF SELADELPAR AS MONOTHERAPY IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INTOLERANCE TO URSODEOXYCHOLIC ACID. Abstract presented at Digestive Disease Week 2025 in San Diego, CA, from May 3 - May 6, 2025.

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. 

. August 14, 2024. Accessed May 5, 2025. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

Findings from a posthoc analysis of 2 phase 3 trials suggest seladelpar monotherapy has similar safety and efficacy to seladelpar combined with UDCA.

Authors