Abigail Brooks is an assistant editor for 

She joined MJH Life Sciences in August 2023 shortly after graduating from Monmouth University where she earned her BA in Communication with a concentration in Public Relations/Journalism and later an MA in Interactive Digital Media. She enjoys traveling, running, and reading books. She can be reached at abrooks@mjhlifesciences.com.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may be more effective than metformin for reducing the risk of 

, according to findings from a recent study.

Leveraging a decade of data from the TriNetX database for adults with type 2 diabetes who initiated either GLP-1 RAs or metformin as first-line therapy, the study found GLP-1 RAs significantly reduced the risk of overall dementia—particularly Alzheimer’s disease and non-vascular dementias—compared with metformin. Notably, GLP-1 RAs also provided substantial reductions in all-cause mortality, further supporting the early use of GLP-1 RAs in patients with type 2 diabetes at risk of cognitive decline.

Previous research has indicated a heightened risk of developing dementia among individuals with type 2 diabetes, with dementia risk increasing the longer a person has diabetes and the more severe it is.2 While both GLP-1 RAs and metformin have both demonstrated potential neuroprotective effects in type 2 diabetes, no head-to-head real-world comparisons have evaluated their relative efficacy in preventing dementia.

“Given the significant clinical and societal burden of T2DM-related dementia, determining which therapy— GLP-1 RAs or metformin—provides superior protection against cognitive decline is crucial,” senior author Jiaqiang Zhang, of the department of anesthesiology and perioperative medicine at Zhengzhou University, and colleagues wrote.

 “Clarifying this therapeutic distinction will offer crucial guidance for clinicians, policymakers, and researchers, potentially reshaping dementia prevention strategies in T2DM management.”

To assess the comparative effectiveness of GLP-1 RAs and metformin in reducing dementia risk, investigators conducted a retrospective cohort study using data from TriNetX for adults with type 2 diabetes who initiated either GLP-1 RAs or metformin as first-line therapy between November 2004 and November 2024. The index date was defined as the earliest prescription date post-diagnosis, with ≥ 24 months of follow-up required. Investigators employed 1:1 propensity score matching to balance baseline characteristics between patients on GLP-1 RAs and patients on metformin.

The primary outcome was the incidence of overall dementia, defined as the first occurrence of a diagnosis of vascular dementia, Alzheimer’s disease, unspecified dementia, or dementia associated with other diseases. Secondary outcomes included the incidence of specific dementia subtypes and all-cause mortality.

To address potential biases from pre-existing or undiagnosed dementia and to allow sufficient time for the therapeutic effects of the medications to manifest, investigators applied a 6-month washout period. Follow-up began on day 181 after the index date and continued until the first occurrence of an outcome, loss to follow-up, or the conclusion of the study period.

Among 87,229 matched patients per cohort, GLP-1 RA use was associated with a significantly reduced risk of overall dementia (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.85-0.95), Alzheimer’s disease (aHR, 0.88; 95% CI, 0.83-0.94), and non-vascular dementias (aHR, 0.75; 95% CI, 0.70-0.81) compared with metformin. However, no significant difference was observed for vascular dementia. Further analysis revealed the all-cause mortality rate was notably reduced in the GLP-1 RA group (aHR, 0.89; 95% CI, 0.81-0.95).

Subgroup analyses showed consistent benefit across age and sex. Investigators noted the benefits were most pronounced in patients aged ≥60 years, with significant reductions noted in those 60–79 years of age (aHR, 0.85; 95% CI, 0.80-0.90) and ≥ 80 years of age (aHR, 0.80; 95% CI, 0.74-0.88). Additionally, while both sexes benefitted, investigators pointed out females had a slightly lower aHR (0.83; 95% CI, 0.79-0.89) compared with males (0.90; 95% CI, 0.84-0.97).

“Given the increasing global burden of diabetes-related cognitive decline and the lack of head-to-head comparisons between GLP-1 RAs and metformin, our findings provide actionable insights for clinical decision-making and may inform future guidelines. Additionally, the study underscores the importance of tailoring therapeutic strategies to optimize both metabolic and neuroprotective outcomes in high-risk T2DM populations,” investigators concluded.

 “Further randomized controlled trials are warranted to confirm these findings and evaluate the long-term cognitive benefits of GLP-1 RAs.”

Sun M, Wang X, Lu Z, et al. Evaluating GLP-1 receptor agonists versus metformin as first-line therapy for reducing dementia risk in type 2 diabetes. BMJ Open Diab Res Care 2025;13:e004902. doi:10.1136/ bmjdrc-2025-004902

Alzheimer’s Society. Diabetes and the risk of dementia. August 2024. Accessed July 22, 2025. 

https://www.alzheimers.org.uk/about-dementia/managing-the-risk-of-dementia/reduce-your-risk-of-dementia/diabetes

A recent study suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may be more effective than metformin in reducing dementia risk in type 2 diabetes patients. Utilizing data from the TriNetX database, the study found GLP-1 RAs significantly lowered the risk of overall dementia, particularly Alzheimer's and non-vascular dementias, and reduced all-cause mortality. The study emphasizes the importance of selecting appropriate therapies to optimize metabolic and neuroprotective outcomes in high-risk type 2 diabetes populations, advocating for further randomized controlled trials to confirm these findings.

Findings showed GLP-1 RAs reduced the risk of overall dementia, particularly Alzheimer’s disease and non-vascular dementias, compared with metformin.

GLP-1 RAs More Effective Than Metformin for Reducing Dementia Risk in T2DM

Abigail Brooks, MA

 saw the addition of 2 new second-line treatment options for 

 with the FDA accelerated approvals of elafibranor (Iqirvo) and seladelpar (Livdelzi).

A chronic and progressive autoimmune liver disease affecting intrahepatic bile ducts, PBC treatment has historically relied on ursodeoxycholic acid. While this continues to be the only first-line therapy, many patients do not respond to or are unable to tolerate it, underscoring the need for more treatment options to prevent progression to cirrhosis and eventual liver failure as well as to improve symptoms most negatively impacting patients, including pruritus and fatigue.

For additional insight into the clinical impact of having elafibranor and seladelpar as treatment options for PBC and what’s next in PBC research, the editorial team of 

 spoke with Aparna Goel, MD, an associate professor of medicine at Stanford University and a transplant hepatologist in the division of gastroenterology and hepatology at Stanford University Medical Center.

 Clinically, what has been the impact of now having these new second-line therapies as options to offer patients?

: It's great to have options for our patients. When we have 3 different approved second-line therapies that we can offer our patients who are not responding to Ursodial as well as we want them to, it's all about going through the historical data and looking at what long-term data we have for these drugs, what the efficacy rates are, what the side effect profile is, and understanding what other medications they are on that might impact that which drug you try to use, if they have concomitant itch or not, if they have significant fatigue or not.

It's very nuanced in terms of which medicine you might recommend, but I think it's important for us to review all these medications with our patients. Our patients are excited, I think many patients love seeing their alkaline phosphatase levels reach normal values. For the first time in decades, some of them are getting to normal values with the addition of second-line therapy that they can tolerate.

Beyond the biochemical response that patients are seeing with these drugs, I think both of them have also shown potential benefits in terms of improvements in pruritus and improvements in fatigue. It's really nice to be able to see that impact for our patients in terms of their quality of life as well.

 Are there any drugs or trials in PBC that you're most looking forward to seeing more of in 2025?

: PBC has definitely been saturated with new second-line therapies. There’s actually another PPAR currently being studied in PBC, saroglitazar, which is a dual PPAR-alpha/gamma agonist, so we'll have to see the results of that.

In terms of PBC, I think what is exciting to see on the horizon is what the long-term benefits of these medications are going to be. It's not just about improving alkaline phosphatase levels, but are we confident that the improvement in the alkaline phosphatase levels is the equivalent of an improvement in liver-related health? Are we preventing transplantations? Are we improving rates of hepatic decompensation? Only with time will we truly be able to determine that.

We also need to understand more about the side effect profile of these medications. There was an increased risk of fractures for both seladelpar and elafibranor in the studies, so I think really understanding what the PPARs are doing to the bones will be interesting.

We need to better understand these drugs’ impact on quality of life. These are exploratory endpoints that were studied in both of the trials, and while there were signals for improved itch and improved fatigue, I think we have to understand what the mechanism is there and how we can potentially use these medicines to help patients with these symptoms, even if their alkaline phosphatase levels might not be incredibly abnormal.

There's a big push in PBC of not just treating to mild elevations of alkaline phosphatase, but really pushing to normal values. I said 40-60% of the population of those with PBC are nonresponders, but that's if we look at an alkaline phosphatase threshold of 1.5 or 1.67 times up the limit of normal. If we look at anyone that's above normal after a year of Ursodial, that number probably goes up to closer to 70%, maybe even 75%. I think there's a big population of patients who will benefit from bringing their alkaline phosphatase levels down to normal, and it’s important to understand the clinical impact of that and what the benefit is for our patients.

Editors’ note: Goel has no relevant disclosures.

Brooks A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed March 24, 2025. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed March 24, 2025. 

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

In 2024, the FDA approved two new second-line treatments for primary biliary cholangitis (PBC): elafibranor and seladelpar. These options are crucial for patients who do not respond to or cannot tolerate ursodeoxycholic acid, the only first-line therapy. The new treatments have shown potential in improving symptoms like pruritus and fatigue, enhancing patients' quality of life. Future research will focus on long-term benefits, side effects, and the impact on liver health. Saroglitazar, another PPAR agonist, is currently under investigation for PBC.

Goel describes the clinical impact of having 2 newly approved second-line PBC therapies and looks ahead to what’s next and where more research is needed.

Understanding Elafibranor and Seladelpar for PBC, with Aparna Goel, MD

Aparna Goel, MD

SAGA Trial Results for Gildeuretinol Treating Geographic Atrophy with David Boyer, MD

At the 2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, David Boyer, MD, adjunct clinical professor of ophthalmology at the Keck School of Medicine at the University of Southern California, presented results of the SAGA trial, which evaluated gildeuretinol in treating 

SAGA, a 24-month, double-masked, randomized, placebo-controlled study, enrolled 198 participants, who were then randomized in a 2:1 ratio to receive gildeuretinol 14 mg per day (n = 135) or placebo (n = 63). The mean age of enrolled participants was 78.4 years, and 68% of patients were female.

The primary endpoint was GA lesion growth rate from baseline to 24 months on fundus autofluorescence (FAF); secondary endpoints included change at 24 months in low luminance visual acuity (LLVA) and best-corrected visual acuity (BCVA), Visual Function Questionnaire (VFQ)-25 score, and Functional Reading Independence (FRI) index score.

“It would be a hard sell for me at this point to use one of the current FDA approved complement inhibitors in a patient with intermediate AMD with 20/30, 20/40 vision,” Boyer told 

. “These patients have great vision, but they’d have to come in frequently and get intravitreal injections, and the risk-benefit ratio at that point for intermediate AMD is too high.”

Boyer and colleagues noted that mean GA lesion growth was reduced with gildeuretinol when compared to placebo (-.25 mm2/year; 95% CI, -.53 to .03; 

 = .075). This was measured through a pre-specified sensitivity analysis evaluating GA lesion growth from 6 to 24 months, which demonstrated a significant reduction in GA lesion growth rate: -.29 mm2/year (15.4%; 95% CI, .58 to 0.0; 

At 24 months, the gildeuretinol group lost fewer LLVA and BCVA letters than placebo, with differences of mean 4.402 letters (

 = .0990) less, respectively. Additionally, investigators associated gildeuretinol with a smaller reduction VFQ-25 and FRI index scores over time. Most treatment-emergent adverse events were mild or moderate, and notably, the safety profile exhibited no indication of delayed dark adaptation, chromatopsia, or vasculitis.

While SAGA did not achieve its primary endpoint of FAF change, Boyer and colleagues still consider the trial a success, as it exhibited fewer vision losses and better low luminance vision versus sham. Additionally, it has the capacity to seriously alleviate treatment burden, as an orally administered drug requires far fewer clinical visits and injections.

Currently, plans for a Phase 3 trial testing gildeuretinol for GA have not been announced; instead, parent company Alkeus Pharmaceuticals is moving forward with testing the medication for the treatment of Stargardt disease. However, Boyer is anticipating an eventual GA Phase 3 trial, as the medication may prove a turning point in the study of GA lesions.

“This would be, to me, a fairly easy trial to enroll,” Boyer said. “I think that with having a safe oral medication that may be able to be entertained earlier in the course of AMD, possibly slowing down the process, is extremely important. So, I look forward to when they do their phase 3 trial, to participating, and to hopefully help prevent our patients from progressing further.”

Editors' note: Boyer reports the following disclosures: Alexion, Biogen, Novartis, Ophthea, 4DMT, and others

Boyer D, Saad L, Washington I, et al. Oral Gildeuretinol Treatment in Geographic Atrophy Secondary to AMD in the SAGA Trial: Safety, Efficacy and Patient-Reported Outcomes. Abstract presented at Association for Research in Vision and Ophthalmology in Salt Lake City, UT, from May 3-May 8, 2025.

The recent trial indicates that the oral treatment gildeuretinol reduces GA lesion growth rates, as well as achieving better BCVA scores.

David Boyer, MD

Referring Patients with Alzheimer Disease to Neurologists and Improving Patient Communication

Frontline clinicians often have a low threshold for referring patients to neurologists or memory specialists, especially when early signs or strong family histories raise suspicion. They prioritize early intervention, recognizing that prompt referral can lead to more effective management and better outcomes. Typically, they consider subtle changes such as minor memory lapses, reduced executive function, or behavioral shifts. When available, they utilize genetic testing like for 

, along with neurocognitive assessments, to identify at-risk individuals. Even if the findings are minor, they prefer to err on the side of caution, understanding that early diagnosis allows for lifestyle modifications, clinical trials, or emerging therapies that can slow disease progression.

Effective communication about referral decisions involves building trust and using a thoughtful approach. Providers often use humor or light conversation to lessen patients’ anxiety and to encourage openness about cognitive concerns. They emphasize that early detection is not a death sentence but a chance to access new treatments and supportive resources. Explaining that many cognitive changes are normal with aging, but that some signs warrant further evaluation, helps patients feel supported rather than alarmed. Providing reassurance and highlighting the benefits of early diagnosis—such as establishing baselines for future comparison—facilitates acceptance of referral to specialists.

Barriers to timely referrals include logistical issues like cost, insurance coverage, and appointment availability. Many patients face challenges scheduling appointments with specialists due to busy calendars or transportation issues. To improve the process, clinicians can provide clear information about insurance coverage, including Medicare, and advocate for their patients’ access to care. Additionally, primary care providers can frame questions to encourage patients to open up, using humor or empathetic language to reduce stigma. Establishing a trusting relationship and normalizing concerns about cognition help patients feel more comfortable discussing their worries, making them more receptive to evaluation and treatment options. Creating seamless pathways for referral and education about the importance of early detection remain vital for optimizing patient care.

Panelists discuss how frontline clinicians tend to refer patients promptly to specialists when early cognitive signs or family history suggest risk, emphasizing the importance of early intervention, clear communication, and addressing logistical barriers to ensure timely diagnosis and access to emerging treatments that can slow disease progression.

Gayatri Devi, MD, MS, FACP, FAAN

Video content above is prompted by the following:

Overview of Spesolimab for Management of GPP

Spesolimab, an IL-36R inhibitor, is now FDA-approved to treat GPP. Can you give a brief overview of spesolimab and the efficacy and safety evidence we have seen to date.
a.	EFFISAYIL-1—IV formulation (Bachelez, 2021)
b.	EFFISAYIL-2—SQ formulation (Morita, 2023)


Panelists provide an overview of spesolimab, an IL-36R inhibitor now FDA-approved for treating GPP, discussing the efficacy and safety data from the EFFISAYIL-1 trial (intravenous [IV] formulation) and the EFFISAYIL-2 trial (subcutaneous
[SQ] formulation).


Harrison Nguyen, MD, MBA, MPH, FAAD 

mavacamten as the first approved cardiac myosin inhibitor for oHCM, balancing the increased risk of heart failure with the medication, REMS program.

Role of Mavacamten in Treating oHCM

This is a video synopsis of a discussion involving James L. Januzzi, MD, detailing the use of mavacamten (cardiac myosin inhibitor) in obstructive hypertrophic cardiomyopathy (HCM) and the associated Risk Evaluation and Mitigation Strategy (REMS) program. Mavacamten is the first approved drug for adults with symptomatic NYHA class 2-3 obstructive HCM, aiming to improve functional capacity and symptoms. Despite favorable efficacy and safety data from clinical trials, the FDA mandated inclusion in the REMS program due to philosophical concerns regarding the potential for an excessive drop in ejection fraction.

The REMS program requires prescribers and patients to follow specific steps to ensure safe administration and monitoring of mavacamten. Prescribers must enroll in the program and educate patients about its requirements, emphasizing that it's not a one-and-done therapy. Patients undergo baseline echocardiograms before initiating treatment and at four-week intervals until reaching a maximally tolerated dose. Regular echocardiograms continue every 12 weeks or with any changes in drug regimen or use of cytochrome P450 inhibitors.

Close therapeutic alliance with patients is crucial, necessitating their active engagement in the REMS program. Patient selection prioritizes those with obstructive HCM, and shared decision-making sessions underscore the program's ongoing nature. Involving a pharmacist in discussions helps mitigate risks and enhance education for patients and clinicians alike.

Monitoring for drug-drug interactions, especially with cytochrome P450 inhibitors, is essential to manage potential complications. The REMS program emphasizes collaborative decision-making and close follow-up to optimize patient outcomes while minimizing risks associated with mavacamten therapy in obstructive HCM.

Video synopsis is AI-generated and reviewed by HCPLive® editorial staff.

James L. Januzzi, MD, comments on mavacamten as the first approved cardiac myosin inhibitor for oHCM, balancing the increased risk of heart failure with the medication, and the role of the REMS program.

James Januzzi, MD

 is an assistant professor of medicine at Harvard Medical School and director of the Massachusetts General Hospital Alcohol Liver Center.

Discussion between 3 subject matter experts on the impact of stigmatization on delays in diagnosis of alcohol-related liver disease.

HCPLive Alcohol Stigma Discussion Part 1

Recent years have seen a drastic increase in alcohol use in the United States. Alongside this growing prevalence has come an influx of severe morbidity and mortality linked to 

, with the National Institute on Alcohol Abuse and Alcoholism citing alcohol’s involvement in nearly half of all liver disease deaths among people 12 years of age and older in 2022 and labeling alcohol as one of the leading causes of preventable death.

Many cases of ALD are rooted in underlying 

, a medical condition involving frequent or heavy alcohol consumption that often requires an individualized treatment approach with a combination of medication, behavioral interventions, and mutual support groups. According to the 2022 National Survey on Drug Use and Health, 29.5 million people ages 12 and older had AUD in the past year. Of this group, 2.2 million received alcohol use treatment.

Although it is a mental health disorder, AUD’s role in the development and progression of ALD underscores the importance of its treatment alongside medical intervention for the liver and other potential negative physical impacts of alcohol use. However, it tends to fall by the wayside due to a number of patient, clinician, and system barriers, many of which are linked to the stigma surrounding AUD and its negative impact on patients’ willingness to seek care as well as clinicians’ ability to provide adequate care.

In this HCPLive special report, our moderator, Hersh Shroff, MD, MPA, is joined by Jay Luther, MD, and Chris Kahler, PhD, to discuss the stigmatization of AUD. The first segment of their conversation focuses on defining stigma, both at the public and structural level, and outlining its role in delaying and hindering care for these patients.

Shroff introduces the topic and poses a question to Kahler about the different forms and definitions of stigma and how public perception of AUD may contribute to delays in seeking care. Kahler responds by describing stigma as a “complex construct,” explaining its manifestation at both social structural levels and individual levels as well as how the stigma surrounding AUD may lead patients to underreport their alcohol consumption, avoid discussing concerns with their clinician, and hesitate to seek care from a specialist.

Shroff expresses agreement with Kahler’s response and poses a similar question to Luther, this time inquiring about how structural stigma in the health care system perpetuates disparities for patients with ALD. Similar to Shroff, Luther notes he agrees with Kahler’s response and mentions how certain aspects of this individualized stigma are also present at a greater structural level.

He goes on to describe how the disease has been labeled, pointing to inherent problems with the terms alcoholic liver disease and alcoholic hepatitis and how the term “alcoholic” contributes to the ongoing stigma in ways clinicians may not even realize. Structurally, Luther notes that there has been little to no overlap between the treatment of liver disease and the treatment of alcohol addiction, forcing patients to see different specialists and potentially making them feel as though they are being judged or blamed for their alcohol use.

However, Luther goes on to explain how some institutions, including his own, are taking strides to combat this structural stigma by incorporating what he calls a “team approach” with combined efforts from a hepatologist, an addiction specialist, and a social worker whose shared goal is to “get you feeling better to get you healthier.”

Check out the second half of the discussion:

Addressing Stigma to Improve Outcomes in Alcohol-Related Liver Disease

 a transplant hepatologist and an assistant professor of medicine at the University of North Carolina School of Medicine

 an assistant professor of medicine at Harvard Medical School and director of the Massachusetts General Hospital Alcohol Liver Center

 a professor of behavioral and social sciences, a professor of psychiatry and human behavior, and the director of the Center for Alcohol and Addiction Studies at Brown University

Shroff, Luther, and Kahler have no relevant disclosures.

National Institute on Alcohol Abuse and Alcoholism. Alcohol Use in the United States: Age Groups and Demographic Characteristics. Alcohol’s Effects on Health. 2023. Accessed April 30, 2024. 

https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-use-united-states-age-groups-and-demographic-characteristics

National Institute on Alcohol Abuse and Alcoholism. Alcohol and the Human Body. Alcohol’s Effects on Health. 2024. Accessed April 30, 2024. 

https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-and-human-body

Cleveland Clinic. Alcohol Use Disorder. Diseases & Conditions. June 2, 2021. Accessed April 30, 2024. 

https://my.clevelandclinic.org/health/diseases/3909-alcoholism

National Institute on Alcohol Abuse and Alcoholism. Alcohol Use Disorder (AUD) in the United States: Age Groups and Demographic Characteristics. Alcohol’s Effects on Health. 2023. Accessed April 30, 2024. 

https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-use-disorder-aud-united-states-age-groups-and-demographic-characteristics

In the first segment of this HCPLive special report, experts discuss the stigma surrounding alcohol use disorder and alcohol-associated liver disease.

Recognizing Stigma's Impact on Care for Alcohol-Related Liver Disease

Jay Luther, MD

Berotralstat was well-tolerated and seemed to durably reduce hereditary angioedema (HAE) attacks, in findings from the APeX-P open-label study. 

Data from the study were presented at the 

2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress

, February 28-March 3, in San Diego, California, by Jolanta Bernatoniene, PhD, pediatric infectious disease department of Bristol Royal Hospital for Children.

spoke with Bernatoniene while at the congress to learn more about APex-P, berotralstat, and how the therapy could potentially benefit the HAE population.

Can you give some background on berotralstat and the APeX-P trial?

Berotralstat is an oral, once-daily plasma kallikrein inhibitor for prophylaxis to prevent HAE attacks in adults and pediatric patients 12 years and older. HAE is a rare, inherited disease characterized by repeated painful and unpredictable attacks of severe submucosal and/or subcutaneous swelling in various parts of the body.

APeX-P is an open-label trial evaluating berotralstat in patients two to <12 years of age with HAE. The study was designed to collect pharmacokinetic data to inform appropriate weight ranges and doses for children to match the exposure of berotralstat seen in adult patients. Secondary objectives were to assess the safety and tolerability and describe the effectiveness of berotralstat in these patients.

Of note, APeX-P is the largest trial to evaluate a prophylactic therapy for HAE in patients two to <12 years of age, and enrollment was completed ahead of schedule and included more than the initial target number of participants.

The results from APeX-P show berotralstat was well tolerated in pediatric patients enrolled in the study, with early and sustained reductions in monthly attack rates, and no new safety signals identified beyond those previously described in prior adult and adolescent trials.

Specifically, the median (range) and mean (±SEM) monthly attack rates in the standard-of-care period were 0.96 (0–5.0) and 1.5 (±0.2) attacks/month, respectively. After one month of taking berotralstat, median and mean monthly attack rates dropped to 0 (0-4.0) and 0.5 (±0.2), and the median monthly attack rate remained at 0 through month 12 (month 12 range: 0-1.7); the mean monthly attack rate at month 12 was 0.3 (±0.1).

In APeX-P, we observed that children with HAE are experiencing severe swelling attacks at a very young age, with a median age of HAE symptom onset at two years. These ﬁndings support an earlier age of symptom onset and need for HAE prophylaxis than has generally been understood.

How do you think berotralstat could benefit the HAE population?

There are currently limited therapeutic options for pediatric patients with HAE under the age of 12, which are on-demand or long-term prophylaxis therapies administered either through subcutaneous injection or intravenous infusion. These routes of administration can be challenging, burdensome, and time consuming for patients and their caregivers.

Treatment through these routes of administration may cause caregivers and pediatric patients with HAE to feel nervous, overwhelmed, and stressed, which can become problematic because these emotions are known to trigger HAE attacks. This can also cause some physicians to hesitate to prescribe long-term prophylaxis to their young patients.

The oral granule formulation of berotralstat being evaluated in APeX-P could help reduce the treatment burden on children with HAE that is associated with currently available long-term prophylaxis therapies administered either intravenously or through subcutaneous injection or infusion. The oral granule formulation is designed to be less invasive for children to take and caregivers to administer. The granules, housed in a packet, are sprinkle-like in appearance and size and can be poured directly into the mouth and swallowed immediately with water or milk, or sprinkled over a spoonful of soft, non-acidic food, for more convenient treatment.

I am encouraged by the response to the results that were presented at the 2025 AAAAI/WAO Joint Congress, and I believe this new formulation of berotralstat has the potential to significantly reduce the treatment burden for children and families impacted by HAE. Also, I have personally experienced significant positive impact of berotralstat on the lives of children with HAE and their families, including significant improvement in their quality of life. The children were able to participate in their school and after school activities with no significant interruption.

Jolanta Bernatoniene, PhD, discussed positive results from the APeX-P study of oral berotralstat in children with hereditary angioedema.

Oral Berotralstat May Reduce Symptom Burden in Pediatric HAE

Jolanta Bernatoniene, PhD

Exploring Oral Systemic Therapies for Plaque Psoriasis: Efficacy, Safety, and Clinical Considerations

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Lauren Miller, MPAS, PA-C; Jayme M. Heim, MSN FNP-BC, and Kirk Gautier, PA-C, discuss recent advancements in plaque psoriasis treatment, focusing on novel oral systemic therapies like the TYK-2 inhibitor deucravacitinib and its clinical trial data, to inform therapeutic decisions for this systemic disease.

Authors