James Ip, MD, is a professor and cardiologist at Weill Cornell Medicine.

Self-Administered Nasal Etripamil Restores Sinus Rhythm Safely, With James Ip, MD

Self-administered etripamil nasal spray has demonstrated significant and robust efficacy in restoring sinus rhythm (SR) in patients with acute 

paroxysmal supraventricular tachycardia (PSVT)

 outside of a health-care setting, according to a series of clinical trials.

American Heart Association’s Scientific Sessions 2025

 in New Orleans, Louisiana, by James Ip, MD, a professor and cardiologist at Weill Cornell Medicine, these data highlight the experimental treatment’s efficacy and tolerability across the NODE-1, NODE-301 Part 1 and 2, NODE-302, and NODE-303 phase 3 clinical studies.

“The nice thing about etripamil is that it is designed for at-home use,” Ip said in an interview with 

. When patients cannot terminate PSVT, the next step is to go into the ER for an intravenous dose of the medication. And when they get their drugs, some patients can have chest discomfort, shortness of breath, or tiredness; the feeling that their heart stops and pauses for a long period of time. The nice thing about etripamil is that it’s a bit gentler, there are no pauses.”

Etripamil, a fast-acting intranasal calcium-channel blocker, is designed for self-administration to terminate PSVT episodes. A series of previous trials have indicated its safety and efficacy after an initial medically supervised test dose during sinus rhythm.

The most recent clinical study investigating etripamil, NODE-303, was an event-driven, open-label, single-arm phase 3 study evaluating etripamil for multiple, at-home PSVT episodes without a test dose prior to first use. Investigators included patients with a diagnosis of PSVT by a healthcare professional, a history of PSVT, atrial fibrillation, or atrial flutter, and ≥1 prior episode of sustained PSVT. Patients with a history of second- or third-degree AV block, severe ventricular arrhythmia, symptoms of heart failure Class II-IV, systolic blood pressure <90 mmHg at any study visit, or symptoms of marked hypotension or syncope associated with a PSVT episode were excluded.

Of the 1116 patients enrolled in NODE-303, 503 treated ≥1 perceived PSVT episode, resulting in a total of 1054 episodes. Adverse events were mild or moderate and localised, with 30.2% of patients experiencing nasal discomfort, 13.9% experiencing nasal congestion, 13.1% experiencing rhinorrhea, and 7.4% experiencing epistaxis. Investigators ultimately concluded that etripamil was well-tolerated when self-administered in a real-world setting.

Ip and colleagues collected data from NODE-303 and previous similar trials for the current study. When examining efficacy data, the team included the proportion of patients converting from PSVT to SR within 30 minutes of treatment administration and the median times to conversion across all studies. The Kaplan-Meier estimate of etripamil found that 59.6% of patients who had administered treatment converted to SR within 30 minutes (n = 662; range, 53.6%-64.3%), with a median time to conversion of 18.5 minutes (95% CI, 15.7-21). The proportions of placebo patients between all trials converting from SVT to SR by 30 minutes ranged from 26.7% to 34.7%.

The combined analysis also showed the occurrence of primarily mild, transient treatment treatment-emergent adverse events, which included the same lineup as NODE-303. Of the overall number of included patients, 1107 took ≥1 etripamil test dose while in SR, after which no significant change in average baseline heart rate or blood pressure was observed within 45 minutes. A test dose failure only occurred in 1.4% of patients (n = 16).

Ultimately, Ip and colleagues interpreted these results as indicative of the safety and tolerability of etripamil for PSVT management. They noted that the self-administration model may also effectively reduce patient reliance on emergency care.

“Many patients who have PSVT, they get the medication, and within a few minutes they have another recording showing normal rhythm,” Ip said. “I’m very excited that this is something that’s going to empower patients to use wearables, or a smart watch, some device to confirm that they are having the episode, and then give the medication, confirm it’s gone, and then stay at home.”

Ip J, Noseworthy P, Piccini J, et al. Combined Efficacy, Safety, and Test Dose Tolerability of Etripamil for Acute Paroxysmal Supraventricular Tachycardia (PSVT) Across Multiple Clinical Trials. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

Ip JE, Coutu B, Ip JH, et al. Etripamil Nasal Spray for Recurrent Paroxysmal Supraventricular Tachycardia Conversion: Results From the NODE-303 Open-Label Study. J Cardiovasc Electrophysiol. 2025;36(11):2990-3003. 

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Ip highlights the uniform safety of patient-administered etripamil nasal spray across a series of phase 2 and 3 studies.

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Tim Smith joined the MJH Life Sciences team as an assistant editor for HCPLive in August 2022. He graduated from UC Berkeley with a degree in political science, working in multimedia journalism as a staff writer prior to joining MJH. In his spare time, he enjoys reading, watching TV, listening to podcasts, and rock climbing. You can contact him at 

Recent findings on the treatment of patients with 

 treated with upadacitinib were presented at the 

2025 Fall Clinical Dermatology Conference

The data were authored by such investigators as Jonathan Silverberg, MD, PhD, MPH, associate professor of Dermatology at The George Washington University School of Medicine and Health Sciences. The poster was titled ‘Patients With Atopic Dermatitis Reported Rapid and Optimal Real‐World Effectiveness With Upadacitinib: SCALE‐UP Study Results by Prior Treatment.’

In this real-world analysis, drawn from the SCALE-UP study, Silverberg and colleagues looked into the responses of adult patients with moderate-to-severe atopic dermatitis to upadacitinib (UPA) treatment, based specifically on whether these subjects had used advanced systemic therapies (AST) previously.

The highly impactful disease of atopic dermatitis, a chronic inflammatory skin condition marked by persistent pruritus and recurrent eczematous lesions, is uniquely harmful to quality of life among patients. While upadacitinib, a selective Janus kinase (JAK)-1 inhibitor approved for moderate-to-severe disease, has been shown to be efficacious and safe in prior controlled trials, Silverberg et al noted the lack of strong representation of patients with prior systemic biologic or small-molecule treatments.

Silverberg and coauthors’ investigation was designed to capture treatment efficacy in a real-world environment, specifically comparing outcomes between those with and without prior exposure to such drugs as dupilumab, abrocitinib, or tralokinumab. The team conducted SCALE-UP as an observational, survey-based assessment of adults in the US who had also been involved in a patient support program and had been treated with upadacitinib for at least 2 months and up to 12 months.

Categorization of study subjects took place, with those involved being placed into either the AST-naïve arm or the AST-experienced arm, based on their self-reported history of treatments. In their survey, the investigative team looked at several different patient-centered endpoints.

Examples of these endpoints included the proportion of participants attaining minimal itch, defined by Silverberg and colleagues as a Worst Pruritus Numerical Rating Scale score of 0 or 1 (WP-NRS 0/1), and the percentage with near-complete skin clearance, indicated by a body surface area disease involvement of 2% or less (BSA ≤ 2%).

Additionally, the team looked at outcomes such as effects on sleep quality based on a Patient Global Impression of Sleep Disturbance due to AD (PGI Sleep AD 0/1) and ratings of quality of life determined by a Dermatology Life Quality Index (DLQI) score of 0 or 1. Those involved in this analysis were also asked how quickly they found improvements in their itch and skin symptoms took place. In this report presented at Fall Clinical, Silverberg et al focused solely on effectiveness and not on safety signals.

There were 65 AST-naïve subjects included in this analysis, with over half of having implemented upadacitinib for more than 6 months. There were 159 AST-experienced patients, with 49.0% having taken upadacitinib for the same length of time. Across both of these cohorts, Silverberg and coauthors identified significant clinical benefits.

The investigators found reports of minimal itch were noted in 56.9% of AST-naïve individuals and 54.1% of individuals with prior treatment exposure.

 Outcomes among patients related to skin clearance were shown to be similarly strong, with 72.3% of those in the treatment-naïve arm and 65.4% of experienced subjects attaining a BSA of ≤ 2%.

In their conclusions, the team also found more than half of the AST-naïve arm (52.3%) and 42.8% of the experienced arm were able to achieve both little-to-no itch and near-clear skin simultaneously.

 In their evaluation of quality-of-life shifts, the investigators found such improvements to be common, though somewhat more pronounced in treatment-naïve cohort. Specifically, 50.8% of AST-naïve subjects were shown to not have impairments versus 37.7% of AST-experienced subjects.

Respondents to this analysis also reported rapid relief of disease symptoms in approximately two-thirds of each cohort. 66.5% of those labeled AST-naïve and 65.1% of those labeled AST-experienced reported itch reductions within the initial 24-hour period of upadacitinib implementation.

 Sleep-related outcomes were also shown to be positive, with 89.2% of the naïve group and 82.4% of the experienced group describing no or almost no sleep disruption due to their skin condition.

Skin improvement was also identified rapidly, with 35.6% of naïve and 31.3% of experienced subjects perceiving better skin within 3 days.

 Silverberg and colleagues also found 67.8% and 68.8%, respectively, noted such improvement within a single week's time.

Overall, those treated with upadacitinib in this real-world setting, regardless of prior systemic drug use, reported rapid and meaningful benefits across itch, skin manifestations, quality of life, and sleep measures.

For any further information on topics such as these, view the latest coverage of the 

Silverberg J, Calimlim B, Bunick C. Patients With Atopic Dermatitis Reported Rapid and Optimal Real‐World Effectiveness With Upadacitinib: SCALE‐UP Study Results by Prior Treatment. Poster presented at the 2025 Fall Clinical Dermatology Conference, Las Vegas, Nevada, Oct 23-26, 2025.

Guttman-Yassky E, Thaçi D, Silverberg JI, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020 Mar;145(3):877-884. 

Articles

Recent findings from the SCALE-UP study highlight the real-world effectiveness of upadacitinib in treating moderate-to-severe atopic dermatitis. The study compared outcomes between patients with and without prior exposure to advanced systemic therapies. Results showed significant clinical benefits, including rapid itch reduction and skin clearance, improved quality of life, and better sleep outcomes. Both AST-naïve and AST-experienced patients reported rapid symptom relief, with many experiencing improvements within 24 hours. The study underscores upadacitinib's efficacy across various patient-centered endpoints, regardless of previous treatment history.

The SCALE-UP study, assessing patients with atopic dermatitis treated with upadacitinib, points to rapid real‐world efficacy findings on this medication.

Atopic Dermatitis

Atopic Dermatitis condition center page, audiences can find a variety of coverage mediums for medical news and updates, including articles, video interviews, podcasts, and breaking news on dermatitis research, treatment, and drug development.

Dermatology

The HCPLive dermatology page is a resource for medical news and expert insights on skin disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for dermatologic conditions, and more.

SCALE-UP: Findings on Real-World Use of Upadacitinib in Atopic Dermatitis

Jonathan A. Bernstein, MD: University of Cincinnati

Phase 2 data presented as a late breaker at the 

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

 demonstrated that povorcitinib 75 mg rapidly and safely reduced itch and hives in patients with 

The phase 2 randomized, double-blind study assessed the efficacy and safety of povorcitinib, a selective kinase 1 (JAK1) inhibitor, in 136 adults with moderate to severe CSU who were ≥ 3 months refractory to second-generation H1 antihistamines. The primary endpoint was the change from baseline in weekly Urticaria Activity Score (UAS7) at week 12. Secondary endpoints included patients who achieved UAS7 ≤ 6 (disease control), patients with UAS7 = 0 (complete response), daily UAS, and safety and tolerability.

Participants were randomized 1:1:1 to placebo (n = 34) or daily povorcitinib, either 15 mg (n = 33), 45 mg (n = 34), or 75 mg (n = 35) for the 12-week placebo-controlled period. Participants on povorcitinib 75 mg had a greater least squares mean (LSM) change in UAS7 from baseline than those on placebo (-23.91 vs -17.90; 

 =.0470). Moreover, more patients on the 75 mg dose achieved disease control at week 12 (44.1%) than those on placebo (29.4%) or on the 45 mg (44.1%) or 15 mg doses (30.3%).

Compared with placebo (23.5%) and the doses 45 mg (29.4%) and 15 mg (24.2%), more participants on povorcitinib 75 mg became symptom-free at week 12 (42.9%). By day 3, povorcitinib 75 mg showed rapid improvement in daily UAS (mean change from baseline, -1.3 vs -0.7). All povorcitinib doses were well tolerated, with no safety signals.

 sat down with Jonathan A. Bernstein, MD, from the University of Cincinnati, to discuss the significance of these findings.

 Based on the phase 2 results, how would you characterize povorcitinib’s efficacy across different doses in reducing hives, angioedema, and pruritus compared with placebo?

 The data was very interesting. It showed that there was a dose-response improvement in the reduction of hives. This was sustained at different time points, both at week 4, at week 8, and at week 12. However, the placebo also tended to increase a little bit. The effect change was approximately 5.8 points, so there was a significant improvement in urticaria.

There were no unexpected safety signals identified in this population. If you looked at the most common side effects, there may have been some worsening acne, some other minor problems [such as] headache [and] nasopharyngitis.

[We didn’t see] any difference between subgroups, but this was a small study.

 How do these findings compare with the efficacy profiles of existing standard-of-care CSU treatments, including antihistamines and omalizumab?

 We see a similar response in other therapies. The magnitude of response is comparable. It might be a little lower than what you see with some of the other therapies in terms of UAS7, where people had complete control. It probably wasn't as great a magnitude as other therapies [with reduction in hives], but it was considered statistically significant.

 What aspects of the povorcitinib data might warrant caution or closer monitoring?

 You would expect that you'd see more separation from placebo at the end of the 12 weeks, and the placebo had a 17.9-point reduction, whereas the active drug 75 mg was [a] 23.9-point [reduction]. That was a little disappointing. It was statistically significant, but not of great magnitude, as you'd expect with others that we've seen with other drugs. Especially in a phase 2 study, you'd expect to see a greater magnitude of an effect.

 Is there anything else you would like to highlight about these findings?

 JAK inhibitors are an interesting target. There are certainly more downstream in the IgG pathway, and there seems to be an effect. The safety was good, which is encouraging, so I think it is feasible that there could be a role for JAK inhibitors in the management of chronic spontaneous urticaria.

Relevant disclosures for Bernstein include SANOFI-AVENTIS U.S. LLC, Pharming Healthcare, Inc., Novartis Pharmaceuticals Corporation, BioCryst Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc., Regeneron Healthcare Solutions, Inc., CSL Behring, Blueprint Medicines Corporation, Dermavant Sciences, Inc., Incyte Corporation, Eli Lilly and Company, and GENZYME CORPORATION.

Metz M, Bernstein J, Pinter A, et al. EFFICACY AND SAFETY OF POVORCITINIB IN ADULTS WITH CHRONIC SPONTANEOUS URTICARIA: PHASE 2 RESULTS. 

. 2025;135(5):S3. doi:https://doi.org/10.1016/j.anai.2025.10.020

Phase 2 data from the ACAAI 2025 meeting revealed that povorcitinib 75 mg effectively reduced itch and hives in chronic spontaneous urticaria (CSU) patients. The study involved 136 adults with moderate to severe CSU, refractory to second-generation H1 antihistamines. The primary endpoint was the change in Urticaria Activity Score (UAS7) at week 12. Povorcitinib 75 mg showed significant improvement compared to placebo, with rapid symptom relief by day 3. All doses were well tolerated, with no unexpected safety signals, suggesting a potential role for JAK inhibitors in CSU management.

New phase 2 data reveals povorcitinib effectively reduces itch and hives in chronic spontaneous urticaria, showing promise as a treatment option.

Povorcitinib 75 mg Rapidly Reduces Itch and Hives in CSU, With Jonathan Bernstein, MD

A session providing clinical pearls to clinicians in the pediatric dermatology care space, titled ‘Pediatric Dermatology – Who Has Better Pearls?’ was presented at the 

 by Lawrence F. Eichenfield, MD, and Lisa A. Swanson, MD.

Eichenfield is known for his work as chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego and professor of dermatology and pediatrics at UC San Diego’s School of Medicine. Swanson is known for her role as a dual-board-certified dermatologist and pediatric dermatologist at Ada West Dermatology.

“Doing a cutthroat competition between two pediatric dermatology doctors is kind of like watching pandas fight,” Swanson joked.

Eichenfield highlighted his and Swanson’s aim, which was to provide procedural pearls on treating children with various dermatologic conditions. He began their session by discussing the treatment of various bumps and cysts identified on children in dermatology practices. He presented an image to the audience depicting what he described as ‘typical keratosis pilaris’ on a child, and a concerning bump highlighted by the child’s family

“So the question is what this is,” Eichenfield said. “Is it sebaceous cysts, pilomatricoma? One pearl is that an otoscope can help you make the diagnosis of a pilomatricoma, because this is a pilomatricoma, otherwise known as calcifying epitheliomas, and calcium does not transmit light. This is unlike a sebaceous cyst. So if you take an otoscope and put it to the skin, you’ll commonly see this bluish discoloration, and it doesn't illuminate through. Then you can make the diagnosis of pilomatricoma and reassure the family.”

The procedure can also be potentially planned differently, Eichenfield said, as pilomatricomas can be popped out of the skin. Next, Eichenfield discussed localized alopecia areata, highlighting a male patient with a quarter-sized alopecia spot on his scalp, but then developed rapid loss of a single eyebrow.

“We have these incredible new therapies,” Eichenfield said. We have oral ritlecitinib for patients who are twelve years of age or older. We have oral and topical minoxidil, but they’re not really relevant for localized alopecia…I treated him with topical clobetasol. A super potent topical corticosteroid, but not for a long period of time. Seven days, and then I did only a few days after that.”

Eichenfield also highlighted pediatric procedures, noting the difficulties commonly encountered in treating or examining certain younger children in pediatric dermatology practices. He pointed to using an iPhone to distract a child during such events as a simple yet helpful practice.

“I put forward ‘IPH’ as something you should adopt,” Eichenfield explained. “What is IPH? IPH is iPhone hypnosis. It’s really helpful in pediatric practice. Screentime might be an issue over a child’s lifetime of development, but it’s fine during a dermatology visit.”

Eichenfield also highlighted the use of a sheet wrap, or what he nicknamed a ‘burrito wrap’ for a young patient, as a way to immobilize a child’s joints for procedures. Eichenfield went on to discuss systemic treatment plans with caregivers of patients with atopic dermatitis.

“I ask, ‘When was the skin last totally clear?’” Eichenfield said. “...Of course I ask about sleep. I always ask about going to sleep and staying asleep. Two different aspects, allowing a little bit more conversation about that. I like to know the infection history because if you have an infectious history, you can explain that the consequences can be more serious. Sometimes family history is important. It's not just a document. Family history means they may have preconceived notions about therapy. They may have preconceived concerns about topical steroids.”

Swanson later discussed some of her biggest clinical pearls for pediatric practices, adding to the discussion of aversion to topical steroids. Swanson highlighted a variety of alternatives for patients’ requests.

“All of these are approved down to the age of two years now, which is really special,” Swanson said. “Tapinarof is great for hands and feet, and it doesn't get orally absorbed. So if a two-year-old puts their hands in their mouth, it's no big deal. I have found in clinical practice that tapinarof either works super, super awesome or not as well. There's kind of nothing in between. For roflumilast, we now have two strengths approved down to the age of two. It's a whole new phosphodiesterase-4 in a very special vehicle. People like the way it feels.”

Swanson highlighted roflumilast as a bit slower, though she also noted its consistency and its helpfulness to patients with atopic dermatitis. She added its use twice a week for maintenance.

“Fifty-seven percent of patients didn't have to go back to daily use for a year by using it twice a week,” Swanson explained. “Topical ruxolitinib is also approved down to two years of age. Super fast. Super effective. Great for patients with tactile sensitivity. It does have the boxed warning, but I tell people that this is in a family of medicines called the JAK inhibitor family. The family has the warning.”

Swanson added that she feels topical ruxolitinib is the one topical option that can take a patient who may be ready for dupilumab and keep them in the topical category.

 She added her view on topical ruxolitinib, potentially taking patients on dupilumab and putting such patients back into the topical realm.

“Pearl number two, compounds to the rescue,” Swanson said. “My two favorite compounds. The first is the Aron Regimen. This stuff is super dilute. It's an eight-ninths moisturizer, but it works like magic. At the pharmacy I use in Idaho called Portico, it costs forty-five dollars for a half-pound tub. They charge eight dollars to ship. So if your local compounding pharmacy wants to charge more than fifty-three dollars for it, get it from Portico. I have a vested interest in them. It can be applied up to five times a day for bad flares, and it can safely be used every night at bedtime for prevention and maintenance. And it's safe anywhere on the body.”

For any additional information on topics such as these, view the latest coverage of the Fall Clinical Dermatology Conference.

The quotes contained in this session summary were edited for clarity.

Swanson L, Eichenfield L. Pediatric Dermatology – Who Has Better Pearls? Session presentation at the 2025 Fall Clinical Dermatology Conference, Las Vegas, Nevada, Oct 23-26, 2025.

Incytye. Incyte Announces Additional FDA Approval of Opzelura® (Ruxolitinib) Cream in Children Ages 2-11 with Atopic Dermatitis. September 18, 2025. Accessed November 19, 2025. 

https://investor.incyte.com/news-releases/news-release-details/incyte-announces-additional-fda-approval-opzelurar-ruxolitinib

Pediatric dermatology experts Lawrence F. Eichenfield and Lisa A. Swanson shared clinical insights at the 2025 Fall Clinical Dermatology Conference. They discussed diagnostic techniques, treatment strategies, and procedural tips for pediatric dermatologic conditions. Eichenfield emphasized using an otoscope for pilomatricoma diagnosis and highlighted new therapies for alopecia areata. He also recommended using iPhones and sheet wraps to manage young patients during procedures. Swanson discussed alternatives to topical steroids, including tapinarof, roflumilast, and ruxolitinib, and shared her preference for the Aron Regimen for atopic dermatitis management.

At the Fall Clinical Dermatology Conference, this session provided clinical pearls to clinicians in the pediatric dermatology space.

Clinical Pearls in Pediatric Dermatology Highlighted in 2025 Fall Clinical Conference

Mazen Noureddin, MD, MHSc, is a professor of medicine and a transplant hepatologist at Houston Methodist and director of the Houston Research Institute.

The therapeutic landscape for metabolic dysfunction-associated steatohepatitis (MASH) continues to evolve rapidly, with multiple trials exploring new mechanisms to address the complex metabolic and inflammatory pathways driving disease progression. Among the emerging agents drawing attention is HU6, a novel, oral, first-in-class controlled metabolic accelerator in development for the treatment of obesity and associated cardiometabolic diseases, including MASH.

American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025

, Mazen Noureddin, MD, MHSc, a professor of medicine at Houston Methodist Hospital and co-chairman of Summit Clinical Research’s Board of Directors, presented phase 2 data highlighting the efficacy of HU6 in reducing liver fat and improving metabolic parameters in adults with MASH.

In the study, 273 patients with MASH with a VCTE score of 7.0–15.0 kPa and an MRI-proton density fat fraction (PDFF) ≥8% were randomly assigned to receive placebo or HU6 at 150, 300, or 450 mg/d for 26 weeks in a ratio of 2:1:2:2. The primary endpoint was percent change from baseline in liver fat content by MRI-PDFF. Secondary endpoints included categorical liver fat reduction, changes in body weight, body composition, and exploratory markers of metabolic health.

At week 26, the primary endpoint was met where HU6 reduced liver fat in patients across all doses (least-squares mean difference: −29.4%, −31.2%, −27.0% for HU6 doses of 150, 300, 450 mg, respectively, vs –6.7% for placebo; 

<.005 vs placebo for each). Additionally, a ≥30% liver fat reduction occurred in the majority of patients, 57%, 58%, and 50% for HU6 doses of 150, 300, 450 mg, respectively, versus 22% with placebo (

Investigators noted HU6 doses of 300 and 450 mg reduced body weight versus placebo (

<.05). Body fat mass was reduced with ~2:1 selectivity for visceral over subcutaneous fat at the 450-mg dose, with no change in lean or skeletal muscle mass. HU6 was generally safe and well tolerated, consistent with results of 2 prior phase 2 trials.

For additional insight into the data and HU6’s potential in MASH, the editorial team of 

 spoke with Noureddin in the following Q&A:

: Can you explain a bit about HU6 and its potential utility in MASH?

: HU6 is a novel, oral controlled metabolic accelerator, and it works on the mitochondria. What you have in the mitochondria, usually in the interspace in the mitochondria, is an abundance of protons, which create what's called hyperpolarization, which leads to oxidative stress and inefficient oxidation of fat and sugar. With HU6, it opens the channels, improves this protein gradient and leads to decrease in this hyperpolarization immediately to decrease oxidative stress and improve the oxidation of blood and sugar. So it works in a selective, precise way in decreasing fat, particularly in the liver in this patient population.

How do the phase 2 data presented at AASLD add to our understanding of HU6 for MASH? What were some of the key findings?

: There was a previous trial that was done on a milder patient population, MASLD, and there also was another trial in an obese HFPEF population. They were both positive, so we extended this trial into the MASH and F2 F3 population that had transient elastography stiffness between 7 and 15. They had to have enough fat on MRIPDFF, and then we randomized them into either placebo, 150 mg, 300 mg, or 450 mg. We saw a nice drop in the MRIPDFF, the 30% drop reduction was achieved between 50 and 58% of the patient population, all statistically significant, which was really nice to see. There was also weight loss in this patient population, about 2.6 kilograms, and most of it came from the fat after we measured it. In addition, there was a differential loss of fat in the adipose tissue, visceral adipose tissue compared to subcutaneous ratio, 2 to 1, and this is usually the opposite. So we preserve the muscle and got rid of the fat from the bad places that it is not supposed to be. It's also very well tolerated in comparison to the GLP-1s.

No. It had very low GI side effects. People ask about this class of drug and if there was any flushing. There was transient and gradient, no issues and no one discontinued from it. People also ask about fevers. There was no fever in this patient population, and there was no increase in heart rate or no tachycardia.

Is there anything else you would like to add or highlight?

The drug is moving forward. I think it's a very promising oral drug as a standalone for the MASH population, especially with controlled weight loss and a low discontinuation rate. It also can be added on to many other oral medications.

Editors’ note: Noureddin reports relevant disclosures with Gilead, GlaxoSmithKline, Madrigal, Novo Nordisk, Takeda, 89BIO, Altimmune, Boehringer Ingelheim, and others.

Noureddin M, Khan S, Schott R, et al. HU6 Oral Investigational Therapy Reduces Liver Fat and Improves Adiposity Markers in Adults with MASH: Topline Results from a Phase 2 Randomized Placebo-Controlled Trial (M-ACCEL). Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

Rivus Pharmaceuticals; Rivus Pharmaceuticals Announces New Data from Phase 2 M-ACCEL Trial of HU6 in MASH in Late-Breaker Oral Presentation at AASLD The Liver Meeting® 2025. November 7, 2025. Accessed November 19, 2025. 

https://www.rivuspharma.com/news/press-releases/110725/

HU6, a novel oral metabolic accelerator, shows promise in treating metabolic dysfunction-associated steatohepatitis (MASH) by reducing liver fat and improving metabolic parameters. Phase 2 trial results presented at the AASLD 2025 meeting demonstrated significant liver fat reduction and weight loss in patients treated with HU6 compared to placebo. The study highlighted HU6's selective reduction of visceral fat over subcutaneous fat, with no adverse effects on muscle mass. HU6 was well tolerated, with minimal gastrointestinal side effects and no significant safety concerns, making it a potential standalone or adjunct therapy for MASH.

Noureddin explains HU6’s mechanism of action and phase 2 data presented at AASLD The Liver Meeting supporting its use in MASH.

Hepatology

MASH / MASLD

The HCPLive MASH & MASLD page is a comprehensive resource for clinical news and insights on metabolic dysfunction-associated steatotic liver disease and steatohepatitis. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for fatty liver disease, steatohepatitis, and more.

Understanding HU6 and Its Emerging Role in MASH, With Mazen Noureddin, MD, MHSc

Gulati discusses how cardiologists should change their standard care practices to include and educate patients, which will reduce treatment burden and improve adherence.

Heart Failure

The HCPLive heart failure page is a resource for medical news and expert insights on HF. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for heart disease, reduced and preserved ejection fraction, and more.

Broaching the Issue of Patient Education in Heart Failure Care, With Martha Gulati, MD

Jason A. Trubiano, PhD: Melbourne Medical School

At ACAAI 2025, Trubiano discusses repurposed immunomodulators, T-cell–targeted approaches, and genetic screening for delayed hypersensitivity management.

Allergy

Allergy condition center page is a comprehensive resource for clinical news and insights on allergic and inflammatory diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for food and seasonal allergies, as well as allergic asthma and related conditions.

Emerging Strategies for Delayed Hypersensitivity Reactions, With Jason Trubiano, PhD

The panel focuses on recognizing extra-cardiac manifestations that often precede cardiac symptoms in ATTR-CM. Orthopedic signs—such as bilateral carpal tunnel syndrome, cervical or lumbar spinal stenosis, biceps tendon rupture, trigger finger, and recurrent joint replacements—may occur five to ten years before cardiac involvement. Neurologic and autonomic features, including peripheral neuropathy, orthostatic hypotension, constipation, diarrhea, urinary retention, and erectile dysfunction, also serve as early clues, though frequently attributed to aging or unrelated conditions. The discussion emphasizes the importance of educating clinicians across specialties to identify these signals and consider amyloidosis when patterns cluster.
The panel notes that orthopedic surgeons, neurologists, primary care physicians, and geriatricians play key roles in spotting early presentations. Advanced practice providers can also help bridge communication and referral pathways. Rather than screening every patient with common conditions, the group recommends viewing these findings as risk indicators and prompting coordinated evaluation to facilitate earlier diagnosis and treatment.


Video Series

Extra-Cardiac Clues and Care Team Integration for Earlier ATTR-CM Detection

This program brings together leading experts to discuss evolving strategies for reducing recurrent cardiovascular risk in patients with ASCVD, emphasizing the importance of cumulative LDL-C exposure and the need for earlier, more intensive lipid lowering. The panel explores current guidelines, emerging data from recent trials, and practical approaches to integrating PCSK9-targeting therapies to improve long-term adherence, access, and outcomes in secondary prevention

Lipid Management in ASCVD: Current Guidelines and Key Clinical Updates

Exploration of combination and sequencing strategies for patients with refractory or advanced disease to achieve comprehensive disease control.

Application of S1P Receptor Agonists for Treating IBD

In this discussion, the panelists explore the identification of risk factors and the broader impact of psoriatic disease. The experts explain that certain clinical features—such as scalp and nail involvement, higher body surface area, and disease severity—are associated with an increased likelihood of developing psoriatic arthritis (PsA). They also note that modifiable factors like obesity, smoking, and metabolic syndrome further contribute to this risk. While genetics play a role, the experts emphasize the importance of addressing lifestyle factors and systemic inflammation early. The conversation highlights that psoriasis should be recognized as a systemic disease rather than one limited to the skin. By identifying high-risk patients and initiating systemic therapy sooner, clinicians can better manage inflammation, improve quality of life, and potentially reduce PsA progression. The panel underscores the importance of patient education and multidisciplinary care to optimize outcomes.

Identifying Risk and Recognizing Impact in Psoriatic Disease

Panelists discuss how the treatment landscape for psoriasis continues to evolve, with oral agents expected to play an expanding role alongside biologics. Ongoing innovation in TYK2 inhibition and PDE4 modulation may yield even more effective and tolerable options, reshaping patient expectations for convenience and control.

Panelists discuss how integration of real-world data and head-to-head comparisons will clarify positioning of oral therapies across disease severities. Future directions include exploring combination strategies and earlier oral intervention to delay or reduce biologic use.

Panelists discuss how continued advancement in oral therapy represents a broader shift toward personalized, accessible psoriasis care that empowers patients and supports sustained disease control.


Looking to the Future of Oral Therapies in Psoriasis Care

Cumulative LDL-C Exposure and the Persistent Challenge of Recurrent ASCVD

In this opening segment, the experts introduce this series focused on rethinking treatment goals in psoriasis. The discussion begins with an overview of the strong pathophysiologic link between psoriasis and psoriatic arthritis (PsA). The panelists explain that both conditions share an IL-23/Th17 inflammatory pathway, where activation of Th17 cells leads to cytokine release—such as IL-17A, IL-17F, and IL-22—driving inflammation in both skin and joints. This common mechanism helps explain why approximately one-third of patients with psoriasis eventually develop PsA. The experts emphasize that recognizing this overlap supports the need for therapeutic strategies that target shared cytokines early in the disease course. By addressing systemic inflammation before joint damage occurs, clinicians may be able to modify disease progression and improve long-term outcomes for patients with psoriatic disease.

Understanding of the Pathophysiologic Connection Between Psoriasis and Psoriatic Arthritis (PsA)

The panel opens by outlining the significant clinical burden of ATTR-CM. Patients often initially present with atrial arrhythmias or conduction abnormalities before developing heart failure, which commonly manifests first as exercise intolerance. Without treatment, the disease follows a progressive course that impacts both patients and caregivers, many of whom are unfamiliar with amyloidosis at diagnosis. The discussion highlights notable delays in identifying hereditary ATTR-CM, particularly among Black and Caribbean patients with the V142I variant, emphasizing the need for improved community and provider awareness.
The conversation then shifts to trends in diagnosis. While recognition of ATTR-CM has increased and patients are being diagnosed earlier—with outcomes improving when therapy is initiated sooner—significant barriers remain. A major challenge is persistent misperception of ATTR-CM as rare. The panel stresses reframing heart failure with preserved ejection fraction as a syndrome requiring etiologic evaluation and encourages clinicians to consider ATTR-CM in older patients with increased ventricular wall thickness, prompting timely, appropriate diagnostic workup.


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