Associate Professor, Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California

Piatek discussed findings from a healthcare resource utilization study and a sentiment analysis study presented at ASH 2024.

Caroline Piatek, MD: High HCRU, Patient Concerns Highlight Great Unmet Need in wAIHA

New research has revealed high unmet needs in people with warm autoimmune hemolytic anemia (wAIHA), as evidenced by high healthcare resource utilization (HCRU) and prevalent concerns about adverse events (AEs) and a lack of treatment efficacy.

These findings are from 2 studies, data from which were presented at the

 66th American Society of Hematology (ASH) Annual Meeting and Exposition

, held December 7-10, 2024, in San Diego, California.

® spoke with Caroline Piatek, MD, Associate Professor, Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, who served as an investigator on both studies.

In a retrospective, HCRU study, Piatek and colleagues found that HCRU remained high in both 12-month periods preceding and following initial wAIHA diagnosis in people with both primary and secondary wAIHA.

 In a sentiment analysis study powered by artificial intelligence (AI), they found a dearth of positive sentiments about rituximab treatment or transfusion therapy, notable concerns about AEs and a lack of treatment efficacy, and a prevalence of information seeking, highlighting the importance of healthcare provider support and involvement in implementing a successful treatment strategy.

During the discussion, Piatek emphasized the high unmet need that these studies revealed and the need for better treatment strategies for people with wAIHA.

“There just isn't much [out there for wAIHA]. And so, anything is helpful, but ultimately, we need better therapeutic agents in this setting… Characterizing the disease burden is important, but we kind of have to move forward from that and do something about it,” Piatek said.

Jackson LA, Pesa J, Choudhry Z, et al. A Retrospective Database Analysis of Healthcare Resource Utilization in Patients with Warm Autoimmune Hemolytic Anemia in the United States. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 2324

Piatek C, Jackson LA, Brethenoux C, et al. Sentiment Analysis Applied to Digital Conversations Among Warm Autoimmune Hemolytic Anemia (wAIHA) Patients Receiving Rituximab and/or Blood Transfusion. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 3705

Caroline Piatek, MD

Triglyceride Management and Pancreatitis Risk, With Christie M. Ballantyne, MD

New results from two Phase 2 trials—SHASTA-2 and MUIR—show that plozasiran, an investigational siRNA therapy targeting hepatic APOC3, delivers a substantial reduction in triglyceride-rich lipoprotein particles (TRL-P) and drives a favorable shift in lipoprotein composition and size in patients with 

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

, patients with severe hypertriglyceridemia (HTG) or mixed dyslipidemia received plozasiran 10, 25, or 50 mg subcutaneously at baseline and again at week 12. At the 25 mg dose, plozasiran significantly reduced TRL-P by ~50% in both trials.

“When you see high triglycerides, sometimes the low-density lipoprotein cholesterol (LDL-C) goes up. With nuclear magnetic resonance (NMR) data, you’re changing the particle, so you have an increase in the large particles and a reduction in small, dense LDL particles,” Christie M. Ballantyne, MD, chief of cardiovascular research at Baylor College of Medicine, told 

. “Reduction in small, dense LDL particles may be particularly atherogenic, but these triglyceride particles per particle might be worse for the common person. They have more LDL particles, but people with high triglycerides have different types of particles.”

Importantly, while total LDL-P remained stable, there was a shift toward larger LDL particles, considered less atherogenic. Small LDL-P declined by 20–22%, while large LDL-P increased up to 103% in MUIR. HDL particle concentration also improved, driven by increases in large HDL-P.

Insulin resistance also improved in both studies, by 24% in SHASTA-2 and 9% in MUIR, further supporting the cardiometabolic potential of plozasiran. Ballantyne noted that high triglyceride levels, particularly over 1000 mg/dL, pose an acute pancreatitis risk and could signal conditions like familial chylomicronemia syndrome (FCS).

In a recent analysis of 1.2 million patients, Ballantyne found more than 90% experienced triglyceride reductions with standard treatment, but about 1 in 5,500 had persistent chylomicronemia. Among those individuals, 26% developed pancreatitis, underscoring the need for close monitoring and targeted therapy.

“The other alarm feature is, if they've had a history of pancreatitis, you better worry about that patient, because it's like secondary prevention,” Ballantyne told HCPLive. “To keep it simpler, when you see the 1000 mg/dL, you know you need to have some alarms going off in terms of needing special attention.”

Relevant disclosures for Ballantyne include Arrowhead, AstraZeneca, Eli Lilly and Company, Abbott Diagnostics, NewAmsterdam, and others.

Ballantyne CM, Gaudet D, Rosenson RS, et al. Effect Of Plozasiran Targeting APOC3 On Lipoprotein Particle Number And Size Measured By NMR In Patients With Hypertriglyceridemia (Htg). Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

Christie M. Ballantyne, MD, discusses the role of plozasiran in managing elevated triglycerides and reducing pancreatitis risk.

Christie Ballantyne, MD

This interview in the latest issue of The Respiratory Report features Divay Chandra, MD, MSc, discussing lithium's potential enhancement of alveolar repair after injury.

Exploring Lithium: A Potential Disease-Modifying Therapy for Emphysema

While chronic obstructive pulmonary disease (COPD) remains a leading cause of death worldwide, there is still no treatment that reverses or halts its progression.  Recent research is exploring the potential of lithium, a drug commonly used for bipolar disorder, as a candidate to repair lung damage by targeting a key regenerative signaling pathway in the lung.

This study is being led by Divay Chandra, MD, MSc, an associate professor in the Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, at University of Pittsburgh in Pennsylvania. Chandra spoke in the third issue of 

 that is powered by the American Lung Association Research Institute, on his team’s current research in this area.

Chandra and his team analyzed data from large population cohorts to assess whether individuals taking lithium for other conditions had less lung disease and then measured environmental lithium exposure in people not on the drug. They found that both therapeutic and naturally occurring lithium levels were associated with reduced COPD severity, supporting its potential as a disease-modifying agent. The next step in Chandra's research is scaling up their studies to look at longitudinal progression and is enabled by an American Lung Association grant.

"Despite decades of research and multiple clinical trials, as yet, we have not been able to identify a disease modifying agent in COPD. And that is really the frustrating part. We have drugs that can treat symptoms. You know, we have drugs which can treat eosinophilia, which can reduce exacerbations, but we have no drug that can get at the fundamental disease process that drives this lung disease. That is exactly where lithium could play a role," Chandra said.

To learn more about Chandra's research, view the interview above or read his contribution to the third issue of The Respiratory Report here:

Exploring Lithium as a Potential Disease-Modifying Therapy for Emphysema

This interview in the latest issue of The Respiratory Report features Divay Chandra, MD, MSc, discussing lithium's potential enhancement of alveolar repair after injury.



Divay Chandra, MD, MSc

Chalmers discussed how brensocatib’s potential approval may transform the currently empty treatment landscape for bronchiectasis.

Investigating Brensocatib, Potential First Treatment for Bronchiectasis, with James Chalmers, MBChB, PhD

The FDA has accepted and granted priority review to Insmed’s New Drug Application (NDA) for brensocatib, a potential first treatment for patients with non-cystic fibrosis bronchiectasis. The therapy has a Prescription Drug User Fee Act (PDUFA) of August 12, 2025.

The NDA submission was based on data from the landmark Phase 3 ASPEN study, which met its primary endpoint of clinically and statistically significantly reducing the annualized rate of pulmonary exacerbations compared with placebo over 52 weeks in both its 10 and 25 mg dosages. The study assessed brensocatib 10 mg, brensocatib 25 mg, or placebo once daily for 52 weeks, followed by 4 weeks off treatment, in adults and adolescents.

® spoke with James Chalmers, MBChB, PhD, Professor, Asthma and Lung UK Chair of Respiratory Research, MBChB, PhD, FRCPE, FERS, Clinical Professor (Teaching and Research) of Respiratory Research, Respiratory Medicine and Gastroenterology, University of Dundee, United Kingdom, who served as a primary investigator on the ASPEN study, to learn more about bronchiectasis and its unmet needs in the field. He discussed brensocatib and how it may benefit patients with bronchiectasis as the potential first treatment to be approved for the condition.

“[Bronchiectasis has] been neglected, a bit of a Cinderella condition. In 2011 the European Respiratory Society… described bronchiectasis as the most neglected disease in respiratory medicine, because there's so many patients, but nobody was really doing research into it, and nobody, nobody was doing any clinical trials. And so, it's really exciting that that's now changing, because our patients really need it to change. And this [potential] first licensed therapy is a step towards addressing that major burden,” Chalmers told 

Chalmers shared his excitement for the potential FDA approval of brensocatib and also discussed some priorities in bronchiectasis research and care that will follow after getting a first treatment.

FDA Grants Priority Review to Insmed's Brensocatib for Treatment of Bronchiectasis with PDUFA Target Action Date Set for August 12, 2025. News release. Insmed. February 6, 2025. https://www.prnewswire.com/news-releases/fda-grants-priority-review-to-insmeds-brensocatib-for-treatment-of-bronchiectasis-with-pdufa-target-action-date-set-for-august-12-2025-302369466.html

James Chalmers, MBChB, PhD

Matthew J. Budoff, MD: Examining the Interplay of Coronary Artery Calcium and Osteoporosis

22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC)

, Matthew Budoff, MD, a professor of medicine at the David Geffen School of Medicine at UCLA and an investigator at The Lundquist Institute, discussed the intersection of 

 and osteoporosis, emphasizing how these conditions share overlapping pathophysiology as diseases of aging.

Budoff highlighted findings from studies, including the Multi-Ethnic Study of Atherosclerosis, showing that elevated CAC scores not only predicted cardiovascular events but also correlated with lower bone density and increased fracture risk. Importantly, this relationship is bidirectional—osteoporosis independently increases the risk of atherosclerosis, myocardial infarction, stroke, and cardiovascular mortality. Leveraging advanced imaging techniques, clinicians have developed algorithms to measure bone density from coronary calcium scans or routine CT imaging, allowing simultaneous diagnosis of atherosclerosis and osteoporosis. Budoff indicated this approach could bridge the diagnostic gap, as only 8% of Medicare beneficiaries currently receive bone density testing despite the high osteoporosis prevalence.

The conversation also addressed high-risk populations, including older adults, smokers, Caucasians, and those undergoing significant weight loss due to obesity medications, which exacerbate osteoporosis risk. Budoff urged clinicians to prioritize bone density screening for postmenopausal women and men over 65, using existing CT imaging when DEXA scans are unavailable. By recognizing the dual risk of cardiovascular disease and osteoporosis, Budoff suggested healthcare providers can implement earlier interventions to improve patient outcomes.

Relevant disclosures for Budoff include AstraZeneca, Amarin, Merck, Novo Nordisk, Regeneron, and others.

Budoff MJ. CAC in ASCVD Relation to Bone Density & Osteoporosis. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Matthew J. Budoff, MD describes bridging the gap between atherosclerosis and osteoporosis through advanced Imaging techniques.

Matthew J. Budoff, MD: Examining the Interplay of Coronary Calcium and Osteoporosis

Matthew J. Budoff, 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  

Skin of Color Savvy: The Art and Science of Treating Patients of Color

Skin of Color Savvy: News Update—SOCS Awards, My Best Winter Skin, & TORPEDO Program, with Robert Brodell, MD

Skin of Color Savvy: News Update—SOCS Awards, My Best Winter Skin, & TORPEDO Program

In the inaugural Skin of Color Savvy: News Update, host Robert Brodell, MD, introduces the 

 and its mission to promote excellence in skin of color dermatology. Founded in 2004 by Susan C. Taylor, MD, SOCS is a global leader with members in over 30 countries. Through its pillars of research, education, mentorship, and advocacy, SOCS is committed to advancing dermatologic care, increasing diversity in the field, and addressing the unique needs of patients with skin of color.

SOCS initiatives designed to support innovation and diversity in dermatology

. These include the Sanofi and Regeneron Diversity, Equity, and Inclusion Mid-Career Award, the Institutional Research Fellowship Grant for underrepresented minority physicians, and the Early Career Innovations Award, which fosters creative solutions in the field. SOCS also supports cutting-edge research through its annual Scientific Symposium, where experts present the latest findings in skin of color dermatology.

The episode also introduces SOCS’s “My Best Winter Skin” campaign, launched to promote optimal winter skincare practices and raise awareness about skin health. This initiative includes an international awareness day, volunteer events, educational materials, and product donations sponsored by Clinique. Brodell encourages dermatologists to participate in outreach efforts within their communities to promote skin health and support SOCS’s broader mission.

In the final update, Brodell shares details about TORPEDO (Training Opportunities and Residency Programs to Enhance Diversity and Outcomes), an initiative at the University of Mississippi to foster diversity in dermatology. Through mentoring, away rotations, and research opportunities, TORPEDO supports students from historically Black colleges and universities, addressing gaps in mentorship and training.

The January 15, 2025 SOCS News Update highlights research ongoing/upcoming initiatives and awards, the My Best Winter Skin Campaign, and the TORPEDO program.

Robert Brodell, MD

 Looking forward, how do you envision implementing therapies in a more aggressive fashion? I’m going to go to each of you to share some clinical pearls about how you envision the heart failure world getting its arms around the need to take a chemotherapy-like approach to our patients in getting them on therapy. Since you were the last to speak Muthiah, I’ll ask you to be the next to speak.

I’m going to jump forward, I’m going to look to the future. I think we are looking at an environment in which these drugs are going to be accessible, affordable, easy to administer, and I think we should start to engage our patients and have patients have a more active role in the initiation and titration of these drugs. We can envision a system much like insulin titration, in which at least some patients who are engaged in their care could modulate dosing, could initiate new drug therapy, in their home environments with relatively limited monitoring structures.

We’ve got a cancer analogy, now we have an endocrinology analogy, that’s great. Rob, what do you think? What does the future hold in structuring rapid titration and getting patients to target?

I’m really hopeful on a couple of fronts. One is that we strike this term “consider.”“We’ll consider starting ARNI [angiotensin receptor-neprilysin inhibitor] at follow up.” We’ve got to eliminate that from our vernacular, that can’t be in a discharge summary. We need to start these therapies in the hospital, and I think it’s all as others have highlighted, this multidisciplinary team. We’ve learned about the tremendous success of having a pharmacist who can help a case manager if there’s paperwork and other financial limitations. So the future is multidisciplinary teams, it’s rapid sequence. We’ve got to do better for our patients.

Javed, what do you think? At Baylor Scott and White [Health], how are you thinking about this?

No, I don’t have much to add on top of what Muthiah and Rob said. Let me just take a moment and make a plea to all our listeners. Symptoms should be targets of therapy in heart failure, not a guide for therapy. Things like high blood pressure, diabetes, lipids, these diseases by definition are asymptomatic. We have many cancers that are diagnosed on screening, and that comes as a surprise to patients, they are asymptomatic. We would never leave these patients alone because their symptoms are OK. You treat the biology of the disease. Heart failure is the same thing. Whether you have a lot of symptoms or you have few symptoms, we need to target the underlying biology and treat them aggressively with appropriate indicated therapies. Just because somebody says they’re doing OK is not a reason to not treat them appropriately.

Absolutely, an important take-home message from Dr Javed Butler. At our institution at [Massachusetts General Hospital], we recognize the need for infrastructure for rapid sequence initiation and titration, even before STRONG-HF trial data came out. We have a clinic called the GDMT [guideline-directed medical therapy] clinic, and it is in existence for one job, which is education, initiation, and titration of GDMT. We’ll either start outpatients or we will take patients who have just been discharged in continuity to get them to target. It’s a 12-week process or shorter. We utilize many of the tools Dr Vaduganathan mentioned, not only education, but home-based titration, including virtual care, virtual laboratory testing as well, in order to get patients to target, because by and large that’s really the most important monitoring piece in this process. Blood pressure matters to be sure, but provided patients are not symptomatically hypotensive, we will continue titrating. We get patients in the office periodically, however, we have a nurse practitioner-based approach but we also have a pharmacist, as Dr Mentz mentioned. In our patients in our GDMT clinic, we are achieving quadruple therapy in over 90% of our patients, with nearly 90% on sacubitril/valsartan, and over 60% on target doses of all 4 drugs.

We’ll close with the point, Rob, in the CHAMP-HF Registry, how many patients were at target dose?

 This is striking, you can count it on a couple of hands.

It was single digits. The point is that it can be done. GDMT works for our patients, it reduces morbidity and mortality. We should not wait for initiating and titrating, getting patients feeling better and living longer. Four drugs, 5 pathways, 6 years of extra survival.

Thanks to all of you for this rich and informative discussion, and thank you for watching this peer exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming peer exchanges and other great content right in your inbox. I’m Jim Januzzi, thanks for watching.

Drs James Januzzi, Javed Butler, Robert Mentz, and Muthiah Vaduganathan share practice pearls for treating patients with heart failure, focusing on the future of treatment.

Clinical Pearls for the Treatment of Heart Failure

Robert J. Mentz, 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.

Stuart Gordon, MD

Future Directions in the Management Atopic Dermatitis in Adult Patients

Video content above in prompted by the following:

Please provide your final thoughts on the future of atopic dermatitis treatments.

Panelists discuss how the future of atopic dermatitis treatments is evolving with novel biologics, Janus kinase inhibitors, and precision medicine targeting immune pathways. Advances in gene therapy, microbiome modulation, and personalized treatments offer promising long-term management options.

Authors