Diana Isaacs, PharmD, is an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic.

Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives!

Diabetes Dialogue: Expanding GLP-1 Usage Into Type 1 Diabetes With Viral Shah, MD

In this episode of Diabetes Dialogue, recorded on-site at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, cohosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, welcome Viral Shah, MD, professor of endocrinology at Indiana University, for a discussion centered on the evolving role of GLP-1 receptor agonists and broader diabetes classification in type 1 diabetes care. Shah challenges the traditional distinction between type 1 and type 2 diabetes, emphasizing that type 2 diabetes lacks a definitive diagnostic test and is instead a diagnosis of exclusion based on phenotypic characteristics. He explains that patients with type 1 diabetes can also exhibit features of type 2 diabetes, making these categories non–mutually exclusive and supporting the rationale for dual diagnoses when clinically appropriate.

The group explores how this framework informs the use of GLP-1 receptor agonists in type 1 diabetes, particularly for patients with obesity, cardiovascular disease, heart failure, or chronic kidney disease. Shah notes that while obesity provides a clear indication for GLP-1 therapy, he is also comfortable using these agents in patients with lower BMI when cardiovascular or renal protection is the primary goal, with careful attention to dose adjustment and avoidance of excessive weight loss or muscle mass reduction. He adds that SGLT2 inhibitors may be preferable in some leaner patients, particularly when renal indications predominate, and highlights recent clarification that SGLT2 inhibitor use for CKD in type 1 diabetes is not considered off-label when prescribed for kidney protection rather than glycemic control.

The conversation then shifts to Shah’s broader view that type 1 and type 2 diabetes differ more in pathophysiology than in long-term disease course. He argues that both conditions share progressive beta cell dysfunction and overlapping complication risks, suggesting the field should move away from rigid separation and toward a more unified understanding of diabetes progression.

This perspective leads into a discussion of “prediabetes,” a term Shah critiques as outdated and insufficient. He reviews its historical origins as a label for intermediate hyperglycemia and argues that it has unintentionally minimized urgency by framing the condition as merely a risk factor rather than part of the disease continuum. Citing evidence of significantly elevated cardiovascular, kidney, and mortality risk in people with prediabetes, he advocates for staging type 2 diabetes similarly to type 1 diabetes, rather than maintaining an artificial threshold between “no disease” and diabetes. He notes that while therapies such as metformin, semaglutide, and tirzepatide have demonstrated benefit in delaying progression, regulatory limitations persist because prediabetes is not formally recognized as a disease state.

The episode concludes with a discussion of autoantibody screening in adults labeled with prediabetes. Shah supports broader antibody testing, particularly in younger adults, to identify individuals with early-stage type 1 diabetes who may otherwise be misclassified and present later with DKA. He emphasizes that accessible antibody testing and therapies such as teplizumab make earlier identification increasingly meaningful, while also acknowledging the importance of patient preference and individualized decision-making. Across the discussion, Shah calls for greater flexibility in diabetes classification, earlier intervention across the disease spectrum, and a more proactive approach to preventing complications rather than waiting for traditional diagnostic thresholds to be crossed.

Editors’ Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others. Shah reports disclosures with Sanofi, Novo Nordisk, Lilly, Dexcom, Insulet, Tandem Diabetes Care, and others.

Shah V. Beyond Type 2: Evaluating GLP-1 Use in Type 1 Diabetes and Obesity. Presented at the American Association of Clinical Endocrinology Annual Meeting 2026 in Las Vegas, NV. April 22-24, 2026.

Podcasts

Viral Shah, MD, joins the show to break down his AACE 2026 presentation on the benefits of using GLP-1 RAs in patients with T1D.

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Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives is a monthly podcast hosted by Diana Isaacs, PharmD, and Natalie Bellini, DNP, aimed at providing a regular roundup of the latest clinically applicable insights across diabetes and metabolic diseases, with a focus on leveraging technology to improve care.

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Strategic Alliance Partnership

David Kass, MD, is the Abraham and Virginia Weiss Professor of Cardiology at the Johns Hopkins University School of Medicine.

HFpEF Myocardial Dysfunction May Be Reversible With Weight Loss

Findings from a Johns Hopkins investigation suggest that cardiomyocyte dysfunction seen in heart failure with preserved ejection fraction (HFpEF) and severe obesity may not be permanent, with weight loss associated with measurable recovery in contractile function at the cellular level.

HCPLive spoke to senior study investigator, David Kass, MD, the Abraham and Virginia Weiss Professor of Cardiology at the Johns Hopkins University School of Medicine.

 to learn more about the findings of severe obesity linked to distinct myocardial dysfunction in HFpEF.

Weight loss linked to improved cardiomyocyte function

To determine whether obesity-associated myocardial dysfunction is fixed or modifiable, investigators examined cardiomyocyte function in a subgroup of patients with HFpEF who underwent weight loss therapy, primarily using GLP-1 receptor agonists, over a median of 1.5 years.

In 16 patients with a baseline BMI of approximately 39 kg/m², reductions in body weight were associated with improved cardiomyocyte contractile performance. Those who lost at least 10% of body weight demonstrated near-normal peak force generation in isolated myocardial cells.

Kass said the improvement was consistent at the cellular level.

“In a subgroup of patients who underwent weight loss, those changes in muscle contraction improved, suggesting that this may be reversible with weight reduction,” Kass explained.

These findings suggest that at least some of the contractile impairment observed in HFpEF with obesity is not fixed structural damage but may reflect dynamic, modifiable signaling changes within cardiomyocytes.

Mechanistic basis: phosphorylation of sarcomeric proteins

To understand the biological basis for reversibility, investigators focused on the sarcomere, the contractile unit of the cardiomyocyte responsible for generating force through coordinated actin–myosin interactions.

Rather than differences in protein abundance, the key distinction between groups appeared to involve post-translational modification—specifically phosphorylation, a process in which phosphate groups modify protein function by altering charge and protein–protein interactions.

Kass described phosphorylation as a key regulator of normal muscle function. Phosphorylation is a common modification where a phosphate group is added to a protein, altering its charge and, in turn, can affect how the protein function

In HFpEF patients with severe obesity, investigators identified increased phosphorylation of cardiac troponin I at a site not typically phosphorylated under normal conditions. Importantly, this modification increased progressively with BMI and was not present in non-failing controls or less-obese HFpEF patients.

“A molecule called troponin I—stands for inhibitory troponin—showed up, and it had a phosphorylation at a particular site that is normally not there,” Kass noted. “The higher the body mass index, the more of this phosphorylation.”

Functionally, experimental modeling showed that mimicking this phosphorylation state reduced cardiomyocyte contractility, while enzymatic removal of phosphate groups improved force generation, supporting a potentially reversible signaling mechanism.

A reversible signaling pathway rather than fixed structural damage

These findings suggest that at least part of the myocardial dysfunction in HFpEF with obesity may be driven by dynamic biochemical signaling rather than irreversible structural remodeling.

In this framework, weight loss may improve cardiomyocyte function by altering upstream metabolic and inflammatory pathways that regulate sarcomeric phosphorylation states, rather than directly modifying contractile proteins themselves.

Kass emphasized that identifying the upstream kinase responsible for troponin I phosphorylation is a key next step, noting that such enzymes are often druggable targets.

Implications for HFpEF treatment in obesity

The data raise the possibility that HFpEF associated with severe obesity may represent a partially reversible cardiomyopathy at the cellular level, with improvements in body weight translating into measurable improvements in myocardial contractile function.

While mechanistic uncertainty remains, the authors suggest that therapies targeting weight reduction—and potentially the signaling pathways regulating sarcomeric phosphorylation—may represent a future avenue for treatment in this HFpEF phenotype.

Editor’s Note: Kass reports no relevant disclosures.

Scientists find people with severe obesity and heart failure have weakened heart muscle contractions. Weight loss may reverse this condition. EurekAlert! Published April 23, 2026. Accessed April 24, 2026. 

https://www.eurekalert.org/news-releases/1124709

Jani VP, Rhodehamel M, Fenwick AJ, et al. Severe obesity in human HFpEF alters contractile protein function and organization. 

Kass explains recent findings from a study that suggest myocardial dysfunction in HFpEF may be reversible with weight loss. 

Cardiology

Cardiology condition center page is a comprehensive resource for clinical news and insights on cardiovascular and cardiometabolic diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for heart disease and cardiovascular events, as well as associated diabetes, renal failure, and more...

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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.

HFpEF Myocardial Dysfunction May Be Reversible With Weight Loss, With David Kass, MD

Funke Pickering, MD, senior medical director at Inovalon.

Social risk factors are playing a significant role in driving greater hospitalization rates and healthcare costs among patients with

. In a 2024 analysis, lower income, lower educational attainment, and greater comorbidity burden were strongly associated with increased hospitalizations and spending among patients with MDD.

Hospitalization rates were nearly twice as high among Medicaid patients compared with those with commercial insurance (29.6% vs 14.7%), with annual costs exceeding $21,000 vs $14,500, respectively. Additional findings showed that individuals living in areas with greater access to mental health specialists experienced higher short-term hospitalization rates, potentially reflecting improved identification and management of more severe disease.

In this Q&A, Funke Pickering, MD, senior medical director at Inovalon, discusses how social determinants of health influence hospitalization risk in MDD, where current risk adjustment and care models fall short, and what clinicians can do to better identify and address these upstream drivers of utilization and cost.

 How do social risk factors, such as income, education, and comorbidity burden, shape hospitalization risk among patients with MDD?

 The data is clear; patients with MDD who face greater socioeconomic disadvantage are not just harder to reach, but they’re getting sicker, cycling through higher-acuity care, and costing the system more. In our research using real-world data, hospitalization among patients with MDD was meaningfully higher for Medicaid than commercial populations.

 We also observed…lower income and educational attainment were associated with higher hospitalization rates and total costs, and a greater comorbidity burden was associated with increased hospitalization risk.

Clinically, this matches what many of us see. Depression care is rarely “just a prescription.” Many patients need both medication management and psychotherapy…but coverage for both is not always the same. Income can often decide whether a patient can sustain their treatment or if they’ll fall through the cracks.

Comorbidities add another layer of complexity because they make mental health easier to overlook. Physicians have limited time, and patients who are trying to balance diabetes, heart failure, autoimmune disease, or other chronic conditions need more than a quick wellness visit. Mental health conditions, unfortunately, are too often treated in siloes, making continuity of care a challenge for clinicians.

 What practical steps can clinicians take to identify social risk factors that may increase the likelihood of hospitalization in patients with depression?

 By screening more consistently, this communicates to patients that their mental health is an important part of their overall health, while also allowing providers to identify changes in a patient's circumstances that may place them at risk.

While most clinicians working with high-risk patients already have a sense of when something is off…they’re often at a loss for what to do next. Connecting patients to the right resources is a challenge, and navigating health plan benefits and community-based services requires coordination that many clinicians simply don't have the bandwidth for. There needs to be an intervention further upstream before they walk into the office that starts with their health plan identifying, documenting, and communicating any barriers with the patient’s care team.

Once they leave, clinicians lose visibility: Did they fill the prescription? Could they afford it? Will transportation or scheduling make follow-up possible? I’ve seen many cases where the treatment plan appeared appropriate, but we later learn, when the patient is readmitted or ends up in the emergency room, that it wasn’t feasible because they couldn’t keep up with the regimen.

It's important to be honest about access. Provider directories can be misleading, and there is evidence that even when a region appears to have mental health providers, actual appointment availability can be far lower. A 2023 study found that 81% of entries in physician directories across 5 large national health insurers contained inaccuracies or inconsistencies, raising concerns that patients may not have a reliable, legitimate referral pathway.

It shouldn’t be up to physicians alone to do the screening. Health systems, payers, government agencies, and community organizations must work together.

 How should clinicians incorporate screening for social determinants of health into routine care for patients with MDD?

 Mental health and social risk screening should be as routine as taking vital signs and medication reconciliation during a care visit.

While screenings are more common than they used to be, they’re often not embedded in a comprehensive, standardized process. Patients may be asked a few high-level questions, but the assessment rarely captures critical factors such as food security, housing stability, financial strain, or language barriers, which can change within weeks and quickly derail an otherwise sound treatment plan. That’s why screening should be integrated into the overall health assessment and diagnosis, not treated as a one-time check-the-box step.

I also wouldn’t limit screenings to wellness visits, since many patients skip routine appointments and only seek care when something is wrong. Screenings should be conducted regularly throughout the year.

 How do current risk adjustment and care models fall short when social risk factors are not adequately accounted for?

 A big limitation is that most risk adjustment models are still built around diagnosis coding. They rely on ICD-10 clinical conditions and do not meaningfully incorporate social drivers of health, even when those drivers are documented. Utilizing ICD-10 Z codes that document the context around a patient’s health, including social and environmental risk factors, is one way to track conditions over time. Though historically, the use of ICD-10 Z codes has not been incentivized or reimbursed when treating vulnerable patients.

For example, you can screen a patient and identify food or housing insecurity, but those findings often aren’t captured in a way that “counts," and reimbursement still largely follows disease-based coding.

The practical issue is that 2 patients can have the same MDD diagnosis and look similar in a model, while their real-world utilization can vary based on their life circumstances. That is exactly what our research showed. Social and economic conditions were linked with hospitalization and spending, and models that ignore those factors underestimate expected resource use.

This dynamic is most evident in value-based care settings. When caring for high social risk populations, visitation patterns can be unpredictable as there’s a higher likelihood that they won’t come in unless they’re already sick of experiencing a crisis episode. Even if clinical staff have access to social risk data, it’s often not linked to claim outputs.

 What role can data analytics and population health tools play in helping clinicians identify patients with depression who are at higher risk due to social factors?

 Population health tools help clinical staff across the care continuum identify patients with MDD who also have high comorbidity burden, repeated no-show visits, complex medication regimens, and known barriers like transportation or language needs. This visibility allows teams to route them to proper care management earlier and get ahead of crises. When implemented correctly, predictive analytics can support proactive follow-up.

When treating depression, this matters because the condition often hides in plain sight. People may be struggling to sleep enough or eat well, losing interest in activities they once enjoyed, yet still pushing through. Stigma is still real, and some people suffer in silence, meaning the data we have on MDD could actually be worse than what we see.

 What strategies should clinicians and health systems prioritize to address the social drivers of depression-related hospitalizations?

 I see 2 recurring failures that drive hospitalization. First, we too often fail to screen for and diagnose depression early enough. Without routine screening, we miss early-stage MDD and fail to identify patients at risk of admission. Second, we are not consistently screening for and documenting social drivers of health, including the barriers patients face and how those barriers impact outcomes.

Managing these barriers should be a part of the patient’s treatment plan, not an afterthought. We shouldn't have to wait until a patient arrives at the hospital during a mental health crisis when the system already knew they hadn't filled their last 3 prescriptions.

Teigland C, Mohammadi I, Agatep BC, Boskovic DH, Velligan D. Relationship between social determinants of health and hospitalizations and costs in patients with major depressive disorder. 

Butala NM, Jiwani K, Bucholz EM. Consistency of Physician Data Across Health Insurer Directories. 

Articles

Socioeconomic disadvantage materially increases hospitalization risk and total cost of care in major depressive disorder, with Medicaid populations demonstrating substantially higher admission rates and annual spending than commercially insured peers. Lower income, lower educational attainment, and higher comorbidity burden correlate with greater utilization, reflecting gaps in sustained access to combined pharmacotherapy and psychotherapy and the complexity of competing chronic disease demands. Routine, longitudinal screening for both depression and social needs is positioned as foundational, alongside payer–provider–community coordination, improved documentation (including Z codes), and analytics-enabled population health workflows to anticipate crises.

Pickering discusses data linking social risk factors to hospitalization and costs in MDD and implications for screening and care models.


Psychiatry

Psychiatry condition center page is a comprehensive resource for clinical news and insights on mental illnesses. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for depression, schizophrenia, bipolar disorder, anxiety, and more.

Major Depressive Disorder

Major Depressive Disorder condition center page, resources on the topics of medical news and expert insight into depression can be found. Content includes articles, interviews, videos, podcasts, and breaking news on MDD research, treatment, and drug development.

Social Risk Factors Drive MDD Hospitalization, With Funke Pickering, MD

Ryan Livingston joined the MJH Life Sciences team in March of 2025, shortly after graduating from TCNJ with a bachelor’s degree in English. He enjoys creative writing, reading, and scuba diving. He can be reached at rlivingston@mjhlifesciences.com.

Image Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has cleared Tandem Diabetes Care’s Control-IQ+ automated insulin delivery technology for use during pregnancy complicated by type 1 diabetes, expanding the label for the company’s t:slim X2 and Tandem Mobi systems. 

According to the company, this makes Control-IQ+ the first commercially available automated insulin delivery system in the US with a pregnancy indication.

“Glycemic goals are tighter during pregnancy,” said Jordan Pinsker, MD, chief medical officer at Tandem Diabetes Care. “The higher time in the pregnancy-specific glucose range seen with Control-IQ can help improve pregnancy outcomes.”

The clearance was based on the CIRCUIT randomized clinical trial, published in 

 in 2025. In the multicenter study, pregnant individuals with type 1 diabetes were assigned either to a t:slim X2 pump using Control-IQ technology or to standard therapy consisting of multiple daily injections or insulin pump therapy with continuous glucose monitoring. 

From 16 weeks’ gestation to the end of pregnancy, participants using Control-IQ spent 12.6% more time in the prespecified pregnancy glucose target range of 63 to 140 mg/dL, about 3 additional hours per day, than those receiving standard care, according to the press release and trial publication.

Type 1 diabetes in pregnancy remains a high-risk clinical setting. Current guidelines recommend stringent glucose targets during gestation because hyperglycemia is associated with congenital anomalies, preeclampsia, large-for-gestational-age birthweight, neonatal hypoglycemia, and other complications.^2 Continuous glucose monitoring has improved management in this population and is recommended by major professional societies, but achieving targets remains difficult for many patients despite intensive insulin therapy.^2,3

Automated insulin delivery has been increasingly adopted outside pregnancy, supported by randomized trials showing improved time in range and lower mean glucose levels compared with sensor-augmented pump therapy or standard care in children and adults with type 1 diabetes.^4 

However, pregnancy has posed a specific regulatory and clinical gap because algorithms developed for nonpregnant users may not reflect gestational insulin resistance, tighter glucose thresholds, and fetal safety considerations. The new clearance helps to address this gap, although its use remains contingent on pairing the pump with a continuous glucose monitoring system suitable for pregnancy, according to the updated indication in the company announcement.

Control-IQ+ is an advanced hybrid closed-loop system that adjusts basal insulin based on continuous glucose monitor readings and predicted glucose values and can deliver correction boluses when glucose is expected to exceed a set threshold. Before this pregnancy expansion, the technology was already indicated for management of type 1 diabetes in patients aged 2 years or older and type 2 diabetes in adults, according to the release.

Important questions remain. The company said maternal and neonatal outcomes were similar overall between groups, although they favored Control-IQ; detailed outcome data and absolute event rates are best interpreted from the published trial rather than the press release alone.

Donovan LE, Lemieux P, Dunlop AD, et al. Closed-loop insulin delivery in type 1 diabetes in pregnancy: the CIRCUIT randomized clinical trial. 

. 2025;334(24):2176-2185. doi:10.1001/jama.2025.19578  

American Diabetes Association Professional Practice Committee. 15. Management of diabetes in pregnancy: Standards of Care in Diabetes. 

Feig DS, Donovan LE, Corcoy R, et al. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. 

. 2017;390(10110):2347-2359. doi:10.1016/S0140-6736(17)32400-5  

Brown SA, Kovatchev BP, Raghinaru D, et al. Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes. 

. 2019;381(18):1707-1717. doi:10.1056/NEJMoa1907863

FDA clearance expands Tandem Diabetes Care’s Control-IQ+ automated insulin delivery label to include pregnancy complicated by type 1 diabetes on t:slim X2 and Tandem Mobi, positioning it as the first US commercial AID system with a pregnancy indication. The decision is supported by the CIRCUIT randomized trial showing a 12.6% absolute increase in time-in-range for 63–140 mg/dL (≈3 additional hours/day) from 16 weeks’ gestation through delivery versus standard therapy. Benefits appeared within one week and were consistent across baseline HbA1c and prior therapy.

FDA cleared Control-IQ+ for pregnancy in type 1 diabetes, expanding automated insulin delivery options during gestation.

FDA News

FDA Clears Control-IQ+ for Use in Pregnancy With Type 1 Diabetes

Chelsie Derman is an associate editor for 

who covers allergy and  psychiatry. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

A single dose of lonvoguran ziclumeran (lonvo-z) reduced 

attack rates by 87% compared with placebo in the phase 3 HAELO trial, according to topline 6-month efficacy data released by Intellia Therapeutics.¹

“The results we are seeing from lonvo-z demonstrate its potential to eliminate the need for chronic medication and related challenges,” said HAELO lead investigator Aleena Banerji, MD, professor at Harvard Medical School and director of clinical care at the Center for Drug and Vaccine Allergy at Massachusetts General Hospital, in a statement.1 “If approved as a one-time treatment, I would expect lonvo-z to be an appealing option for many patients.”

HAELO was a randomized, double-blind, placebo-controlled trial evaluating a single 50 mg intravenous dose of lonvo-z, an in vivo CRISPR-based gene editing therapy formerly known as NTLA-2002, in 80 patients aged ≥16 years with type I or II HAE.¹ A total of 52 patients received lonvo-z and 28 received placebo; 71% were receiving long-term prophylaxis (LTP) at baseline and discontinued these therapies before dosing.¹ The primary endpoint assessed the mean monthly attack rate during weeks 5 through 28.

During the 6-month efficacy period, the mean monthly attack rate was 0.26 in the lonvo-z arm compared with 2.10 in the placebo arm (

 <.0001), meeting the primary endpoint.¹ All key secondary endpoints were also met, including a 62% rate of patients who were both attack-free and LTP-free, compared with 11% in the placebo group (

 <.0001).¹ At data cutoff, all patients treated with lonvo-z, including those who crossed over after week 28, remained off prophylactic therapy.¹

Safety findings were consistent with earlier-stage data. The most common treatment-emergent adverse events, all reported as mild or moderate, included infusion-related reactions, headache, and fatigue. No serious adverse events were observed in the treatment arm during the primary observation period.¹

HAE, a condition characterized by recurrent, potentially life-threatening angioedema attacks driven by dysregulated bradykinin production, remains a rare genetic disorder affecting approximately 1 in 50,000 individuals.² Despite the availability of targeted therapies, including plasma kallikrein inhibitors such as lanadelumab and berotralstat, management often requires chronic administration and does not fully eliminate breakthrough attacks.³

⁴ The need for frequent injections or daily oral therapy contributes to treatment burden and adherence challenges.

Lonvo-z is designed to address this unmet need through in vivo gene editing. Using CRISPR/Cas9 technology, the therapy targets and inactivates the KLKB1 gene in hepatocytes, reducing kallikrein production and downstream bradykinin generation.¹ This mechanism builds on established clinical validation of kallikrein inhibition in HAE but introduces the possibility of sustained effect after a single administration.

The program has received multiple regulatory designations, including Orphan Drug and Regenerative Medicine Advanced Therapy (RMAT) designations from the US Food and Drug Administration, as well as PRIME designation in the European Union.¹ Intellia has initiated a rolling biologics license application (BLA) submission, with completion anticipated in the second half of 2026 and potential US launch in 2027 if approved.

Although the magnitude of effect observed in HAELO is notable, interpretation remains constrained by the limited follow-up duration of 6 months for the primary endpoint. Longer-term durability, potential delayed adverse effects, and real-world generalizability remain key unanswered questions, particularly given the permanent genomic modification underlying the therapy. In addition, the trial required discontinuation of baseline prophylaxis before dosing, which may not fully reflect clinical practice patterns.

If confirmed and approved, lonvo-z would represent a new therapeutic paradigm in HAE, shifting from chronic suppression of disease pathways to potentially durable modification of the underlying biology.1 However, clinicians will likely weigh efficacy against uncertainties related to long-term safety, reversibility, and patient selection in considering integration into practice.

“As the first phase 3 data reported for an in vivo gene editing therapy, today’s HAELO results represent a profound milestone for Intellia, the broader CRISPR and precision medicine fields, and most importantly, the HAE community,” said Intellia President and Chief Executive Officer John Leonard, MD, in the press release.

“These data affirm lonvo-z’s potential, with one dose, to offer prolonged freedom from both attacks and the need for ongoing therapy.”

Intellia Therapeutics. Intellia Therapeutics reports positive phase 3 results in hereditary angioedema, marking a global first for in vivo gene editing. April 27, 2026. 

https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-reports-positive-phase-3-results

Learn About Hereditary Angioedema. DiscoverHAE. 

https://www.discoverhae.com/what-is-hereditary-angioedema

Lanadelumab Cuts Monthly HAE Attack Rates in Real-World 3-Year Study. HCPLive. Published on July 22, 2025. Accessed April 27, 2026. 

https://www.hcplive.com/view/lanadelumab-cuts-monthly-hae-attack-rates-in-real-world-3-year-study

Derman C. FDA Approves Oral Berotralstat for Children Aged 2 – 11 Years with HAE. HCPLive. Published on December 12, 2026. Accessed April 27, 2026. 

https://www.hcplive.com/view/fda-approves-oral-berotralstat-children-aged-2-11-years-hae

Intellia Therapeutics Initiates Rolling Submission of Biologics License Application to FDA for Lonvoguran Ziclumeran (lonvo-z) as a One-Time Treatment for Hereditary Angioedema - Intellia Therapeutics. Intellia Therapeutics. Published on April 27, 2026. Accessed April 27, 2026. 

https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-initiates-rolling-submission-biologics

Phase 3 HAELO topline data show a single 50 mg IV dose of lonvoguran ziclumeran achieved an 87% reduction in mean monthly hereditary angioedema attack rates versus placebo through weeks 5–28 (0.26 vs 2.10; P<.0001). Most participants discontinued baseline long-term prophylaxis pre-dose, and 62% became both attack-free and prophylaxis-free versus 11% with placebo. Safety was consistent with prior studies, with mainly mild-to-moderate infusion reactions, headache, and fatigue, and no treatment-arm serious adverse events in the primary period.

Phase 3 HAELO data show significant reductions in attack rates and treatment burden with a single-dose in vivo CRISPR therapy; BLA submission underway with FDA.

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.

Single-Dose Lonvoguran Ziclumeran Cuts HAE Attacks by 87% in Phase 3 Trial

Michelle Bichchau Nguyen, MD, MBA, MPH, is an associate professor of dermatology at Tufts University School of Medicine and the director of Mohs Micrographic Surgery.


In this interview, Nguyen discusses improving patient experiences during surgical procedures in dermatology practices, such as Mohs surgery.

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.

Q&A: Tips to Improve Dermatologic Surgery Experience, With Michelle Bichchau Nguyen, MD, MBA, MPH

Tim Smith joined the MJH Life Sciences team in 2022 and is currently an associate editor for HCPLive. He is also the executive producer of two podcasts: Skin of Color Savvy and The Medical Sisterhood. Previously, he was the producer of the Lungcast podcast. He graduated from UC Berkeley and worked in multimedia journalism as a staff writer prior to joining MJH. You can contact him at tsmith@mjhlifesciences.com.

This supplemental New Drug Application for roflumilast cream (Zoryve) to the FDA was supported by the INTEGUMENT-INFANT open-label study.

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.

Roflumilast Cream 0.05% sNDA Submitted to FDA for Infants Down to 3 Months with Atopic Dermatitis

Abigail Brooks is an assistant managing 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.

The FDA approved anifrolumab via a once-weekly subcutaneous autoinjector for moderate to severe SLE based on phase 3 TULIP-SC trial results.

Nephrology

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

Anifrolumab (Saphnelo) Wins FDA Approval for Subcutaneous Self-Administration in SLE

Patrick Campbell is the editorial director of HCPLive. Patrick has spent years spearheading coverage surrounding cardiometabolic health and rheumatic disease for MJH Life Sciences. Before joining MJH Life Sciences in 2019, he spent time as a beat reporter and/or multimedia specialist with the Pocono Record, Star News Group, and NJ Advance Media. He is the executive producer for multiple HCPLive podcasts, including Diabetes Dialogue, Don't Miss a Beat, Kidney Compass, Medical Ethics Unpacked, The Medical Sisterhood, and Skin of Color Savvy. 


Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

The FDA approved a lumateperone sNDA adding relapse prevention data in schizophrenia based on a 63% reduction in relapse risk versus placebo.

Schizophrenia

The HCPLive schizophrenia page is a resource for medical news and expert insights on the mental disorder. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for schizophrenia, and more.

Lumateperone sNDA Approved with Relapse Prevention Data in Schizophrenia

AbbVie submitted an FDA application for risankizumab subcutaneous induction in Crohn's disease based on phase 3 AFFIRM data.

Gastroenterology

Gastroenterology condition center page is a comprehensive resource for clinical news and insights on digestive and GI conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for 

, IBS and IBD, Crohn's disease, and more.

Inflammatory Bowel Disease

On the HCPLive inflammatory bowel disease page, resources on the topics of medical news and expert insight into IBD can be found. Content includes articles, interviews, videos, podcasts, and breaking news on IBD and more.

Risankizumab (Skyrizi) SC Induction Application Submitted to FDA for Crohn's disease

Andrea Cipriani, MD, PhD, from the University of Oxford.

In a randomized trial, PETRUSHKA improved antidepressant continuation and 24-week symptom outcomes by integrating clinical data with patient preferences.

PETRUSHKA Tool Improves Antidepressant Continuation, With Andrea Cipriani, MD, PhD

Armstrong spoke in an interview regarding several different sessions presented at the 2026 AAD meeting.

Plaque Psoriasis

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

Q&A: IL-23, Oral Therapies, and Inflammatory Disease Management, With April W. Armstrong, MD, MPH

Eingun James Song, MD, is the director of clinical research for Frontier Dermatology. 

OX40 for Atopic Dermatitis: A Target at a Crossroads

Kass explains 2 distinct biological subgroups discovered in HFpEF and how they relate to a paradigm shift. 

Latest News

Diabetes Dialogue: Expanding GLP-1 Usage Into Type 1 Diabetes With Viral Shah, MD

HFpEF Myocardial Dysfunction May Be Reversible With Weight Loss, With David Kass, MD

Social Risk Factors Drive MDD Hospitalization, With Funke Pickering, MD

FDA Clears Control-IQ+ for Use in Pregnancy With Type 1 Diabetes

Single-Dose Lonvoguran Ziclumeran Cuts HAE Attacks by 87% in Phase 3 Trial