Dr Keegan, what are some patient-specific characteristics that you consider when you’re choosing an agent or a regimen for atopic dermatitis?

One of the first criteria one would want to think about is what’s the age of the patient? How severe is their condition? What have they tried before, etc.? Things like that are all important criteria, and they can range from it’s the first time a patient’s ever come in and they just need some education about what things can be helpful, and what things they should be staying away from to here are topical medicines to try, if this is just going to be intermittent, and let me know how things go to I’ve already failed this and I failed that before to the I come with a grocery bag full of tubes and creams that have a variety of prescriptions that are inside of them and a whole litany of over-the-counter medicines. Then putting the bottles in my face, “Is this one OK? Is this one OK?” Me just trying to be able to move through the conversation with them in order to get down to the nuts and bolts of what’s going on. There’s definitely a range of patients and a range of patient ages.

Then you just mentioned, we were just discussing the concept of killing 2 birds with 1 stone. So what other concurrent medical conditions do they have that they might potentially benefit from? They make a decision, back again, Dupixent [dupilumab], and someone who has asthma and atopic dermatitis, can they benefit from 1 medicine that will treat both things? Both from the simplicity for the patient, cost for the insurance company, and the mitigation of risk from the perspective of prescribing the medicines vs maybe 2 medicines where we don’t always know what the risk is when we’re combining those 2 medicines together. We just have theoretical concepts of how it might work, so that may be criteria. And then, as I mentioned before, sometimes one of the biggest challenges that patients have is they say they want something, but they really want to get better, and they may sidestep us and say that they want something else or, “I’d like just this type of a medicine because my friend told me this cream is really great.” You look at it and you’re like, “But you’ve got 3 tubes of it already in that grocery bag there that you’ve given me, and that’s really not going to make a lot of progress for you.” So sometimes what buy-in can you get from patients?

I don’t want to say that I always let them make the decision about what they’re going to give, but I’ve had plenty of patients that come in and say, “My sister takes this and she’s doing great. My aunt is on this medicine and doing great,” and if I have 3 or 4 medicines in my mind that are potentials, and they lock in on 1 of them and have a positive experience before they’ve even come in the door to me, that might be enough to try, for me to help them get over the hump of getting started on a medicine, whether it’s topic or systemic. Whatever it can take to help them get onto that next step and get better would be something that I would latch on to and use to my advantage as well too. So those are a couple of them. I’m sure Dr Cameron has a few more strategies or thoughts.

I thought that was really well said. I think that clearly a patient’s perception before they come in the office is huge. There’s a reason why…

What commercial did you see on TV last night?

There’s a reason why direct-to-consumer advertising plays such an important role still. And so clearly, if there are a couple of good options, patient satisfaction is always a priority for me as well as building trust. If they come in and they want to try therapy, if I let them try that therapy, if it doesn’t work, they trust me even more, and so it’s all about just building that physician-patient relationship. In terms of your thinking about which treatments, I completely agree. I think that a lot of times we have several good options now, which is great.

Jumping back on that direct-to-consumer advertising, I think one of the things that we should all recognize is that all these medicines that we’ve talked about today are made-up words. Opzelura [ruxolitinib], Dupixent, dupilumab, these are all made-up words, and we in healthcare are really used to using those made-up words and they make up our own language. We use a lot of made-up words all day long, and patients, when they hear those made-up words in the commercials, they can’t always differentiate them, so they may come to me sometimes with concern. 

“I want to put you on Dupixent,” and they’ll say, “I don’t want to go on that. I heard that I’m going to have a heart attack and get cancer.” And I love it when they tell me what they’re thinking because then I’m thinking, “Oh my gosh, that’s not actually anywhere in the package insert and nothing that we have to be concerned about.” But when they voice their concerns for maybe another commercial that they’ve heard and aren’t really sure of what that medicine is, we can help them to navigate that foreign language that is medicine.

Drs Keegan and Cameron discuss patient-specific considerations for selecting optimal atopic dermatitis treatment strategies.

Patient-Specific Characteristics Driving AD Treatment Regimen

Amy Brennan

Carolyn Goh, MD is a clinical associate professor of Dermatology at the UCLA David Geffen School of Medicine.

During a presentation on alopecia management, which was held at the 

American Academy of Dermatology (AAD) Annual Meeting

, Carolyn Goh, MD, spoke in a section of the talk titled ‘Approaching the hair loss patient. ’

Goh, who serves as clinical associate professor of Dermatology at the UCLA David Geffen School of Medicine, spoke in an interview with HCPLive regarding takeaways from her talk on addressing patients with alopecia as well as common misconceptions with 

Addressing Misconceptions in Hair Loss Disorders, with Carolyn Goh, MD

“I think one of the biggest things is that sometimes the hair loss patient is a big challenge for us as clinicians because there's so many questions,” Goh explained. “There are so many myths out there about hair, and it's a very personal issue for people. When their hair is falling out or they're losing it, they feel a loss of control. The whole takeaway is really to try to hone in on that part of it by giving them some component of the shared decision-making process that really puts control back into their hands.”

Goh highlighted examples such as putting in effort to establish rapport with patients suffering from alopecia, as well as defining goals of treatment more clearly with them. Goh also highlighted the importance of the exam and focusing on observations, as well as providing resources for patients.

“The there's some patient advocacy groups specifically for hair loss,” Goh said. “The 2 main ones are the National Alopecia Areata Foundation and the Scarring Alopecia Foundation. Those both have really strong patient education pieces. The National Alopecia Areata Foundation does a lot of fundraising as well and supports research, which has been pivotal in getting the drugs approved that we have now for alopecia areata.”

Goh was also asked about misconceptions she has observed in the field regarding alopecia, both in terms of patients and providers. She touched on the fact that many patients do not realize that alopecia refers to any kind of hair loss, though alopecia areata does not.

“That word, by itself, really does mean just hair loss of any kind,” Goh said. “So yes, when a patient shows up and then they say that they have hair loss, then they say and they're like ‘Do I have alopecia?’ Well, yes, you have a form of alopecia. But [also] a lot of people have taken that term alopecia to mean alopecia areata.”

For additional information on this topic, view the above video interview. To find out more from interviews at AAD, view our 

The quotes in this summary of Goh’s interview were edited for clarity. Goh has reported personal fees from Pfizer and author fees from BMJ BestPractices.

Carolyn Goh, MD, spoke in this AAD 2025 interview about her talk on guidance in addressing patients with hair disorders.

Carolyn Goh, MD

Christian T. Ruff, MD, MPH is the Director of General Cardiology in the Cardiovascular Division at Brigham and Women's Hospital.

Abelacimab Cuts AF Bleeding Risk Across Ages with Christian Ruff, MD, MPH

Abelacimab, a novel factor XI inhibitor, significantly lowered the relative risk of bleeding, compared with rivaroxaban, across a spectrum of ages, with the ability for greater absolute reduction among individuals with 

This analysis of the AZALEA-TIMI 71 trial, presented at the 

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

, showed the absolute risk reduction (ARR) for patients ≥75 was 6.2% compared with 4.2% for those less than 75 years.

In an interview with HCPLive, Christian T Ruff, MD, MPH, TIMI Group senior investigator and director of general cardiology at Brigham and Women’s Hospital, pointed to the available data on undertreatment in patients with AF, particularly age as the ultimate indicator of frailty, medical comorbidities, and concern about bleeding.

“We’re talking about huge differences in bleeding and if you had a drug that was effective, that you could use without worry in patients who were 75–85, that would be a tremendous advance for clinicians and their patients,” Ruff told HCPLive. “If you ask why an elderly patient is not given an anticoagulant, it is often because they are old, frail, and clinicians are worried about bleeding. These results will be very encouraging to healthcare providers.”

AZALEA-TIMI 71 randomized 1287 patients with AF to abelacimab 90 mg or 150 mg monthly or rivaroxaban 20 mg or 15 mg daily across a median follow-up of nearly 2 years. This analysis used Cox proportional hazards to examine major and clinically relevant non-major bleeding by treatment age, older or younger than 75.

Nearly half (49%) of patients were ≥75 at baseline, with these patients reporting a lower body mass index (BMI) and a lower likelihood of being on antiplatelet therapy, but more likely to report creatine clearance ≤50 mL/min than younger patients (

Both abelacimab doses reduced the risk of major and clinically relevant non-major bleeding, irrespective of age, compared with rivaroxaban. Those above the age threshold had higher ARRs (7.1% and 6.2%) than those below 75 years (4.7% and 4.2%) in the 90 and 150 mg dose cohorts, respectively.

Notably, abelacimab reduced bleeding risk in patients ≥75, irrespective of renal function, BMI, and the use of concomitant antiplatelet therapy

“I think for the development program of abelacimab, the huge initial advance will be getting data in these populations who we're not treating at all, and they're at consequence for fatal strokes or permanent neurologic disability, loss of independence,” Ruff told HCPLive. “If we could deliver effective and safe therapy to those patients, that would be a remarkable achievement.”

Disclosures: Relevant disclosures for Ruff include Anthos Therapeutics, AstraZeneca, Bayer, Janssen, Novartis, and others.

Al Said S, Patel SM, Giugliano RP et al. Bleeding with the FXI Inhibitor Abelacimab Compared with Rivaroxaban in Older Individuals with Atrial Fibrillation: Analysis of the AZALEA-TIMI 71 Trial. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

Anthos Therapeutics shares new data from the landmark Azalea-TIMI 71 study demonstrating the factor XI inhibitor Abelacimab significantly reduced bleeding in patients regardless of age or bleeding risk. Anthos Therapeutics. March 29, 2025. Accessed March 31, 2025. 

https://anthostherapeutics.com/press-release/anthos_2025-03-29_release/

Ruff discusses a new analysis of AZALEA-TIMI 71 at ACC.25, which shows that the novel Factor XI inhibitor significantly lowered bleeding in elderly patients.

Christian T. Ruff, MD, MPH

Denise Kent, PhD, APRN, is an assistant professor for the department of biobehavioral nursing science at the University of Illinois Chicago.

Enhancing Standards for Ethical Responsibilities within Clinical Research

A set of challenges have been identified in clinical research within the United States given inefficiencies in different processes, slow participant enrollment, and high costs. In an interview featured in the second issue of 

, the quarterly pulmonology research newsletter powered by the American Lung Association Research Foundation, Denise Kent, PhD, APRN, discussed her team’s research in this area.

Kent serves as an assistant professor for the department of biobehavioral nursing science at the University of Illinois at Chicago. Kent spoke in the latest issue of The Respiratory Report about the Returning Computed tomography rEsults to actIVE Lung Health Cohort participants (RECEIVE) study and its aims.

“The received study is an ancillary study embedded within the Lung Health Cohort study, also referred to as the LHC,” Kent said. “The LHC is funded by the National Heart, Lung, and Blood Institute, and is a study of 4000 healthy individuals between the ages of 25 and 35 years. It is the first ever study to focus on millennials. The overarching objective of the LHC is to establish a cohort of young adults for the purpose of defining lung health and developing targets to intercept chronic lung disease at its earliest stages.”

Kent went on to describe additional details regarding the RECEIVE study’s objectives and the implications of her team’s work.

“The overall objective of the received study is to develop a tool to support the return of chest CT results within the LHC,” Kent said. “The long term goal is to establish a process by which the return of individual research results is standardized for participants. Hopefully, our approach will inform how other studies return individual research results across a range of diseases and conditions across multiple studies.”

To learn more about Kent's research, view the interview above or read her contribution to the second issue of The Respiratory Report here:

Ethical Excellence: Returning Computed tomography rEsults to actIVE Lung Health Cohort participants (RECEIVE)

This summarizes the latest in our pulmonology research quarterly newsletter powered by the American Lung Association Research Institute.

Denise Kent, PhD, APRN

The panel concludes the discussion with key takeaways on the evolving treatment landscape for COPD.

Key Takeaways on the Evolving COPD Treatment Landscape

Video content above is prompted by the following question:

What are your key takeaways on the evolving COPD treatment landscape?

Fernando J. Martinez, MD, MS

 In the little time that we have left, I want to go around and get some final thoughts from each one of you. I would like you to address the whole issue of using naloxone. How do you address this with patients? How do you address this with clinicians, and what is your view about going forward? How is this going to change the landscape of opioid use in the United States? Why don’t we start with Jeremy, and we will keep going from there? Take 30 seconds, and we will just keep going.

 I think we have covered a lot of ground today. We know, and have known for a long time, that opioids have certain risks. They pose risks to patients, and they pose risks in the community when they are taken unsupervised or misused. From a safety measure perspective, there are things we can do. We can do a better job identifying the patients at risk or when identifying those patients who should or should not receive opioids. At the same time, I think we need more community awareness, and we can do this by using the naloxone program or some of the other programs discussed today. Rhode Island sounds amazing, and I am interested to learn more about what is happening out there. The tools we have today can enhance the safety of what we are doing on the medical side and help out there in the community with the substance misuse and illicit side. That is outside of the reach for some of us who do not work in settings where one can reach out to the community, but I think that these types of tools are underutilized. If these tools are utilized on a more frequent basis, and in a more normalized way, we have the potential to reverse what we have seen here with opioids and the subsequent harm caused by them.

 While acknowledging that opioids are still commonly used as part of a multidisciplinary approach to pain management and that opiates are still being misused illicitly, we need to have strategies that emphasize the availability of naloxone so that people can be as safe as possible. As Dr Adler said, this must be normalized, and we need to realize, when we think about this, it is going to take more years than we would like before it will become normalized, but we need to step it up and work toward that.

 I cannot agree more with my colleagues. I think that, when it comes to normalizing naloxone, we need to take the lessons we have learned from what successfully normalizes this method of treatment. Whether it is enacting policy interventions, having naloxone everywhere, putting up billboards, or getting that access. What we are doing is studying people, saying what makes you dispense naloxone, to pharmacists? Saying what makes you dispense it, to primary care physicians? What makes you want to give it, to a caregiver? What are those barriers? How do we break them down? I look forward to the day of over-the-counter naloxone that is still covered by insurance so we do not have financial barriers. There is a lot that we know, areas where we have been successful, and I think that yes, it is going to be around a long time. We have seen how COVID-19 has created these divisions. I think, by solving those divisions during COVID-19, we will solve some of the divisions in access to care for people with opioid use disorder or people who use opioids.

I see naloxone as one part of the puzzle here, one part of the comprehensive approach that we try to take in the emergency department [ED], and that is decreasing the barriers that patients need to overcome to get naloxone. This is improving their access to naloxone not only in the ED but also in other areas of life where they have access to health care, and in their daily lives. Having it available works, whether it is having a naloxone box sitting next to an AED [automated external defibrillator] box somewhere or offering it to patients proactively and not requiring them to have to ask for it.

Additionally, I think that, as science for medication-assisted treatment continues to be redefined every day—how effective that is for treatment—it is our responsibility to not only make sure that our patients are safe as they go out and use this, or that their community is safer because naloxone is out there. But we also need to provide multiple opportunities for patients to get linked to treatment, to be linked to peers, and to have access to medication-assisted treatment. I think this is equally important and should be offered as routinely as possible.

Theresa, some people hate to be the last one to speak when all the good stuff is taken.

Theresa Mallick-Searle, MS, RN-BC, ANP-BC:

heresa Mallick-Searle, MS, RN-BC, ANP-BC: 

As the token nurse on the platform here, I am really big into listening to my patients. It is not that my colleagues are not, but I want to hear what is important to the patient. I want to be able to have them partner with me in their health care. I want to be able to encourage my peers to look at the bigger community and be in it for the long term, to decrease the amount of fear out there. As a health care provider, for anything that we do, we are trying to do the best we can to take care of our patients.

Thank you all very much. I want to thank you at home as well for watching this HCPLive® Peer Exchange. If you enjoyed this content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

I am Dr Peter Salgo, and I will see you again next time.

The multidisciplinary panel of experts share final thoughts on strategies to normalize naloxone and decrease barriers to its obtainment and utilization. 

Final Thoughts on the Opioid Crisis and Normalizing Naloxone

Jeremy Adler, DMSc, PA-C, DFAAPA, Pacific Pain Medicine Consultants 

panel discussion on a head-to-head sequence study of rizankizumab vs ustekinumab in the treatment of CD, as well as approaches to choosing first-line treatment.

Sequence Study of Risankizumab vs Ustekinumab in CD

This is a video synopsis/summary of a panel discussion involving Marla Dubinsky, MD; David Rubin, MD; Miguel Regueiro, MD; Remo Panaccione, MD, FRCPC; and Sara Horst, MD, MPH.

The transcript discusses the findings of the sequence study, focusing on the comparison between two drugs, P41 (referred to as risankizumab) and P19 (referred to as IL (interleukin)-23 therapy). The study aimed to evaluate the efficacy of risankizumab in patients with Crohn's disease who had been exposed to TNF.

The results indicate that risankizumab-exposed patients were more likely to achieve clinical response, clinical remission, and endoscopic improvement compared to those on P40 (risankizumab with IL-12 and IL-23). The transcript emphasizes that the head-to-head comparison provides valuable insights, guiding clinicians in choosing the most effective therapy.

It highlights that risankizumab, along with its biosimilar, is an approved and effective option for Crohn's disease. The discussion touches upon the significance of the sequence study's second primary endpoint, endoscopic remission, and how it could be a pivotal moment in the field.

The conversation also touches on the evolution of clinical trials in Crohn's disease, emphasizing the importance of endoscopic outcomes and the progression from subjective measures to objective proof of efficacy. The participants express optimism about the potential impact of risankizumab, especially when used as a first-line therapy.

Furthermore, the transcript discusses the importance of early intervention in Crohn's disease, suggesting that initiating treatment early is more likely to result in a positive response and prevent further damage. The participants encourage setting higher expectations for patients and discuss the advantages of using risankizumab in biologic treatment-naive patients.

In conclusion, the discussion underscores the positive findings from the sequence study, positioning risankizumab as a promising option for Crohn's disease, particularly in terms of achieving endoscopic remission and improving patient outcomes. The participants stress the need for effective communication with patients about treatment options and the potential long-term benefits of early intervention.

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

David Rubin, MD, leads the panel discussion on a head-to-head sequence study of rizankizumab vs ustekinumab in the treatment of CD, as well as approaches to choosing first-line treatment.

Miguel Regueiro, MD

Nada Elbuluk, MD, MSc, is a dermatologist in California. 

A group of 9 experts reflect on what they are looking forward to most in 2025 following the AAD annual meeting. 

Expert Perspectives: Dermatology's Top Story to Watch in 2025

Although nearly all medical professionals can point to a “flagship” meeting or annual conference for their specialty, few serve the same role as or measure up to what the 

American Academy of Dermatology annual meeting

A testament to the draw and magnitude of the AAD’s annual showcase, the 2025 annual meeting, which was held in Orlando, Florida, from March 07-11, 2025, had more than 20,000 registered attendees. In addition to being the field’s largest meeting, one of the unique aspects of the AAD annual meeting is its placement on the calendar. While many organizations opt for end of year or mid-year meetings, the AAD annual meeting typically occurs in Q1 and, for many, sets the tone for the remainder of the year.

With this in mind, the editorial team of HCPLive Dermatology included a simple question on the end of our interviews from the meeting with 9 leading subject matter experts in dermatology: “What is going to be the most important storyline to watch for dermatology for the rest of 2025?”

In the above video, we highlight the perspectives of these experts. Below, you can find a brief summary of the backgrounds and expertise of each individual included in this feature video.

, is a professor and vice chair for Diversity, Equity, and Inclusion at the Perelman School of Medicine. She also serves as president of the American Academy of Dermatology.

, is chairman at Innovaderm Research. He is also the principal investigator of the ICONIC-LEAD trial, which was presented at AAD 2025.

, is a dermatologist and internal medicine specialist with Riverchase Dermatology.

, is an associate professor of Dermatology for the USC Keck School of Medicine. She is the founding director of the USC Skin of Color and Pigmentary Disorders Program and also the president of the Skin of Color Society.

, is the owner of Medical Dermatology Specialists, chief of inpatient dermatology at BannerHealth, and the founder of US Dermatology Partners.

, is a dermatologist and the medical director at the SKiN Centre for Dermatology.

, is an associate professor in dermatology at the Yale School of Medicine.

, is the director of the Advanced Acne Therapeutics Clinic at the Brigham and Women’s Hospital and the co-chair of the American Academy of Dermatology Acne Guidelines Work Group.

, is vice chair of research in dermatology at the Icahn School of Medicine at Mount Sinai and director of the Mark Lebwohl Center for Neuroinflammation and Sensation.

Nada Elbuluk, MD, MSc

Experts discuss this class of agents for treatment of insomnia and discuss other therapeutic advancements in the field.

Dual-Orexin Receptor Antagonists for Treatment of Insomnia

This is a video synopsis of a discussion involving Dr Paul Doghramji, a distinguished family physician practicing at Collegeville Family Practice and serving as the Medical Director of Health Services at Ursinus College, both located in Collegeville, Pennsylvania. Dr Doghramji introduces an upcoming Peer Exchange program titled "Dual Orexin Receptor Antagonists for Treatment of Insomnia."

In this program, Dr Doghramji will moderate a conversation with esteemed colleagues regarding the use of dual orexin receptor antagonists and other therapeutic advancements in treating insomnia. The discussion covers several key topics, starting with the standard of care for insomnia and the associated challenges.

Dr Doghramji emphasizes that cognitive behavioral therapy is considered the best treatment for chronic insomnia. However, challenges arise as many patients struggle to find therapists or commit to the recommended duration of therapy. Consequently, medication becomes a prominent option, and Dr Doghramji outlines various FDA-approved categories, including benzodiazepines, selective benzodiazepine receptor agonists, melatonin receptor agonists, and others.

The discussion introduces the newest entrants in insomnia treatment—dual orexin receptor antagonists. Dr Doghramji explains that these medications block the effects of orexin, a neurotransmitter promoting wakefulness. The three approved medications in this category, suvorexant, lemborexant, and daridorexant, have shown efficacy in helping patients both initiate and maintain sleep.

Dr Doghramji provides a comprehensive comparison of traditional treatments and dual orexin receptor antagonists, emphasizing the latter's advantages, including no tolerance, no rebound effects, and no withdrawal symptoms. Additionally, he highlights unique features of daridorexant, such as improved efficacy over time and a positive impact on next day sleepiness at higher doses.

In conclusion, Dr Doghramji introduces these dual orexin receptor antagonists as a promising category of medications with potential benefits for patients experiencing insomnia, addressing some of the challenges associated with traditional treatments.

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

In an upcoming Peer Exchange program entitled “Dual-Orexin Receptor Antagonists for Treatment of Insomnia” Dr Paul Doghramji will moderate a conversation with physicians about this class of agents for treatment of insomnia and discuss other therapeutic advancements in the field.

Paul Doghramji, MD, FAAFP

Virginia Clark, MD, is a professor of medicine and program director of the gastroenterology fellowship in the division of gastroenterology, hepatology, and nutrition at the University of Florida.

Virginia Clark, MD: Understanding Fazirsiran’s Potential in AATD Liver Disease

New data from the open-label extension of the phase 2b SEQUOIA study of fazirsiran support the investigational small interfering RNA therapy’s long-term safety and efficacy in patients with 

The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD)

 in San Diego, California, by Virginia Clark, MD, a professor of medicine and program director of the gastroenterology fellowship in the division of gastroenterology, hepatology, and nutrition at the University of Florida.

, Clark described AATD as being frequently overlooked and underdiagnosed, explaining the importance of establishing the presence of fibrosis and cirrhosis to determine the next steps in disease management.

In the absence of an approved therapeutic option for the treatment of AATD-associated liver disease, transplantation is the only choice for patients who develop more severe complications. For patients with stage 2 or 3 fibrosis who fall in the “gray zone” and are at high risk of progression, Clark pointed to the promise of investigational agents in clinical trials.

“These new therapeutic agents may have the potential to reduce the toxic burden of the alpha-1 within the liver, and that may change the trajectory of what their disease does over time,” she explained.

A hepatocyte-targeted investigational RNA interference therapeutic, fazirsiran is designed to degrade alpha-1 antitrypsin and mutant misfolded Z alpha-1 antitrypsin (Z-AAT) messenger RNA in hepatocytes, subsequently reducing protein synthesis and inhibiting further accumulation of Z-AAT polymers to allow normal cellular mechanisms to dispose of mutant proteins.

The SEQUOIA trial enrolled 40 adults with Pi*ZZ AATD who were randomly assigned to receive fazirsiran at doses of 25 mg, 100 mg, or 200 mg, or placebo for ≤ 148 weeks. One-year findings showed treatment with fazisiran resulted in sustained, dose-dependent reductions in Z-AAT concentration and improved histological findings, including periodic acid-Schiff staining with diastase digestion (PAS+D) globule burden, a hallmark of AATD-associated liver disease.

Patients with fibrosis at screening and a post-dose liver biopsy at week 48, 72, and 96 entered the open-label extension and received fazirsiran 200 mg every 12 weeks for a total treatment period of ≤ 197 weeks. In total, 23 patients received ≥1 dose of fazirsiran during the open-label extension, 14 of whom received fazirsiran (FAZ–FAZ cohort) and 9 of whom received placebo (PBO–FAZ cohort) during the double-blind study phase.

“No real pulmonary complications were seen over placebo and the pulmonary function tests were stable, so that is very encouraging in the short-term,” Clark explained.

In addition to stable mean percent predicted pulmonary function in both cohorts and improved mean laboratory measures in the PBO–FAZ cohort, results showed serum Z-AAT levels reduced by a mean of 36.3% (Standard deviation [SD], 34.1) for the FAZ–FAZ cohort and 85.5% (SD, 13.1) for the PBO–FAZ cohort. Among the 20 patients who reported a treatment-emergent adverse event in the open-label extension, most were mild or moderate and 1 led to study withdrawal.

“The findings were very consistent with what we'd already seen in the first 2 studies, which was decreased liver tests and stain reduction in how much alpha-1 could be measured within the serum,” Clark said. “Overall, the results were very promising, quite consistent, and really support further development of this drug for treatment of alpha-1.”

Editors’ note: Clark has relevant disclosures with Vertex, Takeda, and Novo Nordisk.

Clark V, Strange C, Strnad P, et al. Long-term safety and efficacy of fazirsiran in patients with alpha-1 antitrypsin deficiency-associated liver disease enrolled in the phase 2 placebo-controlled SEQUOIA trial. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.

Brooks, A. SEQUOIA: Fazirsiran Reduces Serum, Liver Z-AAT Concentrations, Improves Hepatic Globule Burden. HCPLive. July 10, 2024. Accessed December 17, 2024. 

https://www.hcplive.com/view/sequoia-fazirsiran-reduces-serum-liver-z-aat-concentrations-improves-hepatic-globule-burden

Clark reviews open-label extension data from the phase 2b SEQUOIA study of fazirsiran for AATD liver disease.

Authors