November was a busy month for cardiology, between the US Food and Drug Administration’s (FDA) groundbreaking approval of plozasiran and the mountain of news presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana. From olezarsen’s efficacy in severe hypertriglyceridemia to self-administered etripamil’s restoration of normal sinus rhythm in paroxysmal supraventricular tachycardia (PSVT), several major names in the cardiovascular pipeline made significant progress towards New Drug Application (NDA) submission last month.

 has collected 7 of the most impactful headlines from this past month to make catching up a bit easier. Check them out below.


FDA Approves Plozasiran for Adults With Familial Chylomicronemia Syndrome


Announced on November 18, 2025, Arrowhead Pharmaceuticals’ plozasiran received FDA approval for the reduction of triglycerides in adult patients with 

. The approval was based on the PALISADE phase 3 trial, which saw statistically significant reductions in apoC-III, triglycerides, and acute pancreatitis incidence. Plozasiran is now available for sale in the US.


STORM-PE: Computer-Assisted Vacuum Thrombectomy Outperforms Anticoagulation, With Robert Lookstein, MD

Patients with intermediate to high risk of 

 saw much greater reduction in right-to-left-ventricular diameter ratio within 48 hours after receiving computer-assisted vacuum thrombectomy (CAVT), compared to those receiving anticoagulation therapy alone. The CAVT device has a significantly smaller and less rigid catheter, which is administered via a vacuum pump rather than an injection. Lookstein also discusses the comparatively short amount of time required for the operation, making it far more efficient than standard catheter devices or anticoagulation therapy in removing blood clots.


TRANQUILITY: Pacibekitug Safely Lowers hs-CRP in ASCVD, With Deepak Bhatt, MD

Pacibekitug, Tourmaline Bio’s investigational long-acting fully human monoclonal antibody against the IL-6 cytokine proved its safety and efficacy in lowering high-sensitivity C-reactive protein in patients with chronic kidney disease and 

. Deepak Bhatt, MD, director of the Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai and lead presenter for TRANQUILITY at AHA 2025, expressed his hope for a phase 3 trial to examine cardiovascular endpoints with the drug.


OCEANIC-STROKE: Asundexian Achieves Primary Efficacy Endpoint in Patients with Ischemic Stroke

Asundexian, Bayer’s investigational, once-daily oral FXIa inhibitor, met its primary endpoints in the phase 3 OCEANIC-STROKE trial, reducing 

 risk without increasing major bleeding in patients after an acute ischemic stroke or transient ischemic attack. This November 23, 2025 announcement came on the heels of Johnson & Johnson and Bristol Myers Squibb cancelling their own investigative programs, testing another FXIa inhibitor milvexian for acute coronary syndrome.


Olezarsen Proves Efficacy in Severe Hypertriglyceridemia, With Nicholas Marston, MD


Presented at AHA 2025 by Nicholas Marston, MD, cardiologist and assistant professor of medicine at Brigham and Women’s Hospital, the phase 3 CORE and CORE2 trials both highlighted the efficacy of olezarsen in lowering fasting triglyceride levels in patients with severe hypertriglyceridemia. The investigative antisense oligonucleotide also reduced apoC-III, remnant cholesterol, and non-HDL-C to a greater degree compared to placebo across both studies.


Sotatercept Improves Composite Mortality Endpoint in Patients With PAH, With Vallerie McLaughlin, MD


Presented at AHA 2025 by Vallerie McLaughlin, MD, lead study author and Kim A. Eagle MD Endowed Professor of Cardiovascular Medicine at the University of Michigan Medical School, this composite analysis of the PULSAR, STELLAR, and ZENITH trials indicated sotatercept’s efficacy in reducing mortality and major morbidity outcomes in 

. The first-in-class novel fusion protein rebalances pulmonary vascular homeostasis by inhibiting ligands in the TGF-β superfamily.


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


Nasal etripamil spray, a fast-acting intranasal calcium-channel blocker, has been designed specifically for self-administration in patients with PSVT, ideally for use both in and outside of healthcare centers. This conversation with James Ip, MD, a professor and cardiologist at Weill Cornell Medicine and the lead presenter of these data at AHA 2025, covers the NODE-1, NODE-301 part 1 and 2, NODE-302, and NODE-303 phase 3 clinical trials investigating the agent’s efficacy in restoring sinus rhythm. The FDA is expected to release its decision on etripamil’s NDA on December 13, 2025.

Articles

November saw significant advancements in cardiology, highlighted by the FDA's approval of plozasiran for familial chylomicronemia syndrome and notable findings from the American Heart Association's Scientific Sessions 2025. Key developments included the efficacy of olezarsen in severe hypertriglyceridemia, the success of self-administered nasal etripamil in restoring sinus rhythm in PSVT, and promising trial results for pacibekitug, asundexian, and sotatercept. These advancements underscore the progress in cardiovascular therapeutics, with several drugs moving closer to New Drug Application submissions.

Catch up with major FDA decisions, critical conference news, and more.

7 Cardiology Headlines You Missed in November 2025

Polygenic Risk Scores Linked to Specific SLE Manifestations, With Matthew Dapas, PhD

, Matthew Dapas, PhD, of Northwestern University, discussed recent findings on polygenic risk scores for 

American College of Rheumatology Convergence (ACR) 2025

. The study evaluated associations between genetic risk and clinical features derived from electronic health records across more than 32,000 participants in the Electronic Medical Records and Genomics Network.

One advantage of this study was the large database. The polygenic risk score was derived using summary statistics from a genome-wide association study of 6748 lupus cases and 11,516 controls of European ancestry.

“The reality of the genetics of these diseases is that it's not one gene that causes a disease, but it's actually a constellation of very small effects that just are enough to tip the scales in one direction or the other,” Dapas told 

. “So, to identify those really small effects, you need really large databases. There's a number of large efforts, and [in] the United States… where we're trying to generate whole genome sequencing for millions of individuals to derive new discoveries and genetics because the more the more people you have in a database, the more accurate model you can build, more effective the implementation of that model will be in a clinical setting, and the better outcomes that leads.”

In the Northwestern cohort (n = 1061), the polygenic risk score predicted SLE with an area under the receiver operating characteristic curve of 0.724 and was significantly associated with both localized and systemic lupus (

= 1.6×10^-9) and systemic lupus erythematosus (

 = 3.0×10^-9). Additional nominal associations were observed for cardiac complications (

 = 2.8×10^-3) and impaired renal function (

 = 4.6×10^-3), with enrichment for circulatory system (

 = 9.7×10^-5) and hematopoietic traits (

Genetic risk was further associated with several individual Systemic Lupus International Collaborating Clinics criteria, including acute cutaneous lupus, thrombocytopenia, leukopenia, and low complement levels. Low complement was observed in 55% of patients in the highest polygenic risk score decile, compared with 30% in the lowest decile, suggesting that greater genetic risk may be linked to specific immunological features.

Dapas emphasized that although polygenic risk scores are not yet part of routine clinical practice, they have the potential to support risk assessment. Dapas noted that high-quality clinical data and patient evaluation, combined with expanding genomic databases, can help train risk models.

“I anticipate that's something that will become routine in the not-too-distant future,” he said. “One important thing to keep in mind, as a medical geneticist, [is that] we rely so much on that fundamental interaction between clinician and patient.”

He said this helps us train genetic risk models, which rely on accurate phenotyping and accurate classification

“Logging of data into a database that is then used for research is so essential, because without accurate workups of patients, it all kind of falls apart,” Dapas said. “In all my work, I work closely with a team of clinicians, and it really is kind of a symbiotic relationship. It's a whole network of individuals with different sets of expertise, working together to try and improve outcomes for patients with the disease. I appreciate what the clinicians do, and I hope, through this work and other geneticists, that we can collectively move the needle on some of these diseases.”

Dapas has no relevant reported disclosures.

Forrest N, Tuteja S, Pacheco J, Mitrovic V, Ramsey-Goldman R, Walunas T, Dapas M. Polygenic risk of lupus is differentially associated with individual EHR-derived classification criteria [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). 

https://acrabstracts.org/abstract/polygenic-risk-of-lupus-is-differentially-associated-with-individual-ehr-derived-classification-criteria/

Dapas M. Polygenic Risk Scores Reveal Genetic Drivers of Lupus Heterogeneity, With Matthew Dapas, PhD. HCPLive. November 24, 2025. https://www.hcplive.com/view/polygenic-risk-scores-reveal-genetic-drivers-lupus-heterogeneity-matthew-dapas-phd. Accessed December 3, 2025. 

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ACR 2025 research shows polygenic risk scores correlate with specific SLE phenotypes, highlighting potential applications for clinical risk assessment.

Jennifer Snaith, MBBS | Image Credit: Garvan Institute of Medical Research

Metformin failed to present improvements in liver, muscle, or adipose tissue insulin resistance after treatment for 26 weeks in patients with 

, based on data from the Insulin in Type 1 Diabetes Managed with Metformin (INTIMET) study.

Metformin is an inexpensive and safe oral medication used as a first-line treatment for 

. Previous studies have demonstrated metformin’s capacity to alter glucose metabolism in the muscle and liver in patients with type 2 diabetes based on hyperinsulinemic-euglycemic clamp data. Additionally, existing reviews of randomized controlled trials have demonstrated metformin’s capacity to reduce total daily insulin dose, which has been interpreted as an improvement in insulin resistance.

“However, studies in type 1 diabetes using the gold-standard clamp technique to directly measure insulin resistance have only been performed in adolescents,” Jennifer Snaith, MBBS, B. Med. Sci, an endocrinologist and research fellow at the Garvan Institute of Medical Research, and colleagues wrote. “No study has employed the clamp technique to assess the effect of metformin on insulin resistance in adults with type 1 diabetes.”

INTIMET began as a cross-sectional study in adults with and without T1D, aiming to quantify insulin resistance at muscle, liver, and adipose tissue and identify biochemical and clinical features associated with muscle and liver insulin resistance. Subsequently, Snaith and colleagues conducted a 6-month randomized controlled clinical trial to test the hypothesis that, among adults with T1D, relative to placebo, the addition of metformin to insulin would decrease hepatic insulin resistance and improve other cardiometabolic measures without increasing adverse effects.

Male and female patients with T1D for ≥10 years were eligible for the trial, so long as they were between ages 20 and 55 with fasting c-peptide <0.3 nmol/L and HbA1c <9.5% (80 mmol/mol). Patients who were taking medications or who had conditions known to impact insulin sensitivity were excluded. During the trial, the team assessed insulin resistance via the 3-stage hyperinsulinemic-euglycemic clamp technique with isotope-labelled glucose. The primary outcome was the change in endogenous glucose production (EGP) during the low-dose phase of the clamp.

A total of 40 patients were enrolled in the trial; of these, 20 had T1D and 20 did not. All patients underwent basic phenotyping assessment between November 2019 and December 2021. In the T1D cohort, the mean age was 37.4 +/- 8.8 years (mean +/- standard deviation [SD]), with a T1D duration of 22.9 +/- 8.9 years. The T1D cohort also had a mean BMI of 26.3 +/- 3.8 kg/m2, a mean total daily insulin dose of 0.6 units/kg/day, and a mean HbA1c of 7.5 +/- 0.9%. Of the 20 adults without T1D, mean age was 37 +/- 8.4 years, mean BMI was 26.2 +/- 4.3 kg/m2, and mean HbA1c 5.1 +/- 0.3%.

The T1D group exhibited greater liver, adipose, and muscle insulin resistance compared to control, and participants with T1D had higher endogenous glucose production than controls (EGP; 5.9 +/- 2.2 µmol/kg fat free mass [FFM]/min and 3.6 +/- 1.7 µmol/kgFFM/min respectively; 

 = .0002) and higher non-esterified fatty acids (NEFA) in the low-dose phase (0.08 +/- 0.01 mmol/L and 0.02 +/- 0.02 mmol/L respectively; 

 = .001), which indicated impaired insulin-mediated suppression of hepatic glucose release and lipolysis, respectively.

Ultimately, 37 of 40 enrolled participants completed the study. At 26 weeks, no significant difference was found in the change in EGP between the metformin and placebo groups (mean difference 0.2 µmol/kg FFM/min; 95% CI, -0.4 to 0.8; 

 = .53). There was also no increase in hypoglycemia or episodes of ketoacidosis in either group.

“These results do not support prescribing metformin to reduce insulin resistance in adults with type 1 diabetes but suggest that metformin may reduce insulin dose via mechanisms independent of insulin resistance,” Snaith and colleagues wrote. “The potential cardiovascular benefits of insulin sparing and reducing peripheral hyperinsulinemia warrant further study.”

Snaith JR, Olsen N, Evans J, et al. Effect of metformin on insulin resistance in adults with type 1 diabetes: a 26-week randomized double-blind clinical trial. Nat Commun. 2025;16(1):9884. Published 2025 Nov 24. 

Liu YS, Chen CN, Chen ZG, Peng Y, Lin XP, Xu LL. Vascular and metabolic effects of metformin added to insulin therapy in patients with type 1 diabetes: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2020;36(6):e3334. 

Metformin did not improve insulin resistance in liver, muscle, or adipose tissue in adults with type 1 diabetes (T1D) after 26 weeks, according to the INTIMET study. The study used the hyperinsulinemic-euglycemic clamp technique to measure insulin resistance, a method previously applied only in adolescents with T1D. Despite no significant changes in endogenous glucose production, metformin may reduce insulin doses through mechanisms unrelated to insulin resistance. The study suggests further investigation into metformin's potential cardiovascular benefits and its role in reducing peripheral hyperinsulinemia.

Results from the INTIMET study have shown no significant differences between metformin and placebo in liver, muscle, or adipose tissue insulin resistance.

Metformin Fails to Improve Insulin Resistance in Type 1 Diabetes

Lingdolinurad (ABP-671) had acceptable safety and tolerability and reduced serum uric acid (sUA) in people with hyperuricemia or 

Findings from a phase 2a study evaluating ligdolinurad were presented at the 

American College of Rheumatology (ACR) Convergence 2025

, held October 24–29 in Chicago, Illinois, by Ullrich Schwertschlag, MD, PhD, FACP, Atom’s Senior Vice President of Clinical Development.

The study enrolled adult participants up to the age of 55 years without clinically significant kidney abnormalities on renal ultrasound and non-symptomatic hyperuricemia or gout, as evidence by 2 separate fasting sUA results of >7 mg/dL 24 hours apart. Participants were randomized to 5 multiple ascending oral dose groups including 1, 2, 4, 6, 12 mg of ABP-671 and placebo in a 7/2 ratio. The dose escalation dosing period started from 0.2 mg to 1 mg over a 9-day or 10-day period to mitigate any renal sUA overload and was then followed by a 7-day dosing period of ABP-671 or placebo. Investigators enrolled groups separately and conducted them sequentially.

Schwertschlag and colleagues found that treatment-emergent adverse events (TEAEs) were reported in 24 participants (53.3%), including 5 (71.4%), 4 (57.1%), 6 (85.7%), 4 (57.1%), 1 (14.3%), and 4 (40%) in the 1, 2, 4, 6, and 12 mg and placebo groups, respectively. There were no serious AEs, grade >3 TEAEs, or deaths. Notably, investigators did not observe AE incidence to be dose dependent. Participants followed a structured dose-escalation regimen before reaching their assigned target doses. In Group 1, dosing increased from 0.2 mg once daily (QD) on days 1–3 to 0.5 mg QD on days 4–10 and 1 mg QD on days 11–17. Group 2 received 0.2 mg QD on days 1–3, 0.5 mg QD on days 4–6, 1 mg QD on days 7–9, and 2 mg QD on days 10–16. Groups 3, 4, and 5 escalated to target doses of 4 mg, 6 mg, and 12 mg QD, respectively, administered from days 10–16.

The investigators found that sUA levels decreased in a dose dependent manner, with the max median decreases of sUA occurring at 3.00-9.00 hours post dose. Serum uric acid (sUA) levels declined in a clear dose-dependent manner, with the greatest median reductions observed between 3 and 9 hours postdose. Among participants with gout, maximum mean sUA decreases from baseline were 17.7% with placebo, 56.4% with 1 mg, 58.1% with 2 mg, 69.4% with 4 mg, 77.0% with 6 mg, and 79.2% with 12 mg. In participants with hyperuricemia, corresponding reductions were 19.9%, 50.1%, 64.1%, 73.2%, 81.2%, and 82.1%.

At 24 hours postdose, the proportion of participants reaching sUA thresholds <6.0 mg/dL, <5.0 mg/dL, and <4.0 mg/dL increased consistently with dose. For the 1-mg group, rates were 85.7%, 57.1%, and 14.3%, respectively; for 2 mg, 100%, 85.7%, and 14.3%; for 4 mg, 100%, 85.7%, and 14.3%; for 6 mg, 100%, 100%, and 57.1%; and for 12 mg, 100%, 100%, and 100%. No placebo recipients achieved any of these sUA thresholds.

Atom also presented phase 1 safety and pharmacokinetic data on its novel colchicine analogue ABP-745 at the ACR conference in healthy volunteers that demonstrated the drug was well-tolerated and exhibited dose proportional pharmacokinetics. Atom recently also enrolled the first patient in a multicenter Phase 2 acute gout flare trial that will compare ABP-745 with placebo and colchicine.

“The positive findings in both of these studies have contributed to successfully advancing our goal of providing meaningful relief to patients worldwide suffering from the damaging effects of chronic gout and the disease’s painful acute gout flares,” William Dongfang Shi, PhD, Founder and CEO of Atom, said.

 “Both ABP-671 and ABP-745 have the potential to give gout patients more effective and safer alternatives to existing gout therapies, which have insufficient efficacy and are often associated with serious or even life-threatening adverse effects.”

Schwertschlag U, Yang Y, Li J, et al. A Phase 2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of ABP-671 in Subjects with Hyperuricemia or Gout in China. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #2012

Atom Therapeutics to Present Positive Data from Clinical Trials of Its Lead Novel Oral Drugs for Chronic Gout and Acute Gout Flares at ACR Convergence 2025. News release. Atom Therapeutics. October 21, 2025. https://aijourn.com/atom-therapeutics-to-present-positive-data-from-clinical-trials-of-its-lead-novel-oral-drugs-for-chronic-gout-and-acute-gout-flares-at-acr-convergence-2025/

Lingdolinurad (ABP-671) demonstrated acceptable safety and tolerability while effectively reducing serum uric acid (sUA) levels in individuals with hyperuricemia or gout. A phase 2a study presented at the ACR Convergence 2025 showed dose-dependent sUA reductions, with the highest decreases observed between 3 and 9 hours post-dose. The study involved multiple ascending oral dose groups, and no serious adverse events were reported. Additionally, Atom presented phase 1 data on ABP-745, a colchicine analogue, indicating good tolerability and dose-proportional pharmacokinetics, with ongoing trials for acute gout flares.

A new study reveals ligdolinurad effectively lowers uric acid levels in gout patients, showcasing promising safety and tolerability results.

Lingdolinurad Demonstrates Dose-Dependent Serum Uric Acid Reductions

Rare Disease, Rapid Progress: FDA's HAE Approvals in 2025 Signal Changing Course

A disease often associated with delayed diagnosis and treatment, 

 has drawn significant attention in 2025. The US Food & Drug Administration (FDA) approved 3 HAE treatments in just 3 months: garadacimab-gxii (Andembry) in June, sebetralstat (Ekterly) in July, and donidalorsen (Dawnzera) in August.

“It's awesome. I love them all. It's like my children; you don't have a favorite,” Daniel Soteres, MD, PhD, from the University of Colorado Health Sciences Center, told HCPLive. “Every patient has an individual set of values, an individual health literacy. Their needs change over time. What works for a 5, 10, or 12-year-old may not work for a 16- or 18-year-old, [which] may not work for a 45-year-old. Having multiple options available for these patients is important.”

HAE, a rare genetic condition that causes recurrent, unpredictable, and potentially life-threatening swelling attacks in the face, throat, abdomen, hands, genitals, and feet, is estimated to occur in 1 in 50,000 people worldwide and 6,000 people in the United States.

The disease can be difficult to diagnose since its symptoms often overlap with other forms of angiodema. A report published in May 2025 stated that up to 90% of HAE-related deaths occur in undiagnosed patients experiencing asphyxiation.

HAE has a large burden on patients’ lives. At the 2025 American College of Allergy, Asthma, & Immunology (ACAAI) Annual Scientific Meeting in Orlando, Florida, several speakers, including Soteres, highlighted new data showing that children with HAE often face delayed or inconsistent emergency care, shaping long-term negative views of their condition.

 Another study found the burden is greater than previously recognized, with missed school and activities in childhood and continued academic underachievement and absences into adolescence.

Before June, there were 9 FDA-approved treatment options for HAE on the market, including 4 preventive and 4 attack-targeting therapies.8 Preventive therapies included berotralstat (Orladeyo; 2020), lanadelumab-flyo (Takhzyro; 2018), and C1 esterase inhibitor (human) products (Haegarda in 2017 and Cinryze in 2008), whereas treatments for acute attacks comprised conestat alfa (RUCONEST; 2014), icatibant (2011), C1 esterase inhibitor (human) (Berinert; 2009), and ecallantide (Kalbitor; 2009).

 These agents primarily work by replacing C1-INH, blocking bradykinin, or inhibiting kallikrein. Administration routes vary, with options of IV, subcutaneous, and oral. 

As of 2026, 12 FDA-approved products are available to prevent or treat HAE, enabling more personalized treatment plans. The newer therapies either act earlier in the HAE pathway, offer novel routes of administration, or leverage innovative molecular mechanisms.

“It makes me really proud,” said Raffi Tachdjian, MD, MPH, from UCLA Health. “I’ll speak on behalf of my colleagues, too, who are the specialists in HAE, that in the span of just 3 months, there were 3 new treatment modalities approved in HAE, which is mind-blowing, really, but it's really a testament to all the work that's gone into [the field] in the last two decades. If we think back 16 years ago, that’s when the launch of modern-era medicine came out for hereditary angioedema and and to think of how far we’ve come in the treatment landscape just makes my other colleagues and other specialties envious of the advances that we have made.”

 the only treatment targeting factor XIIa for prophylactic use to prevent HAE attacks in adults and children aged ≥ 12 years on June 16, 2025. This approval was awarded to CSL.

Garadacimab-gxii is the first HAE treatment to provide once-monthly dosing from day 1. Administered through a citrate-free, subcutaneous autoinjector in 15 seconds or less, it targets the top of the HAE cascade to prevent attacks. The therapy already holds approvals for treating HAE attacks in Australia, the United Kingdom, the European Union, Japan, Switzerland, and the United Arab Emirates.

The FDA’s decision relied on pivotal data from the placebo-controlled phase 3 VANGUARD trial, which evaluated garadacimab-gxii for prophylactic HAE treatment. In the study, participants received monthly subcutaneous injections of garadacimab-gxii or placebo for 6 months after an initial loading dose. Garadacimab-gxii led to 62% of treated patients remaining attack-free and produced ≥ 99% reductions in overall HAE attacks, attacks requiring on-demand therapy, and moderate or severe attacks compared with placebo. 

On July 7, 2025, KalVista Pharmaceuticals announced that the 

, the first oral, on-demand therapy for the treatment of acute attacks of HAE in adult and pediatric patients aged ≥ 12 years.

Sebetralstat, a novel plasma kallikrein inhibitor, was studied in the phase 3 KONFIDENT and KONFIDENT-S open-label extension trials, where investigators reported a median time from attack onset to treatment of 4 minutes among 19 adolescents patients, with symptom relief beginning at a median of 1.79 hours, severity decreasing by 3.53 hours, and complete resolution occurring by 15.09 hours. These results build on the topline 2024 KONFIDENT data showing a median 1.3-hour time to symptom relief across 136 patients experiencing laryngeal, abdominal, or breakthrough attacks while on prophylaxis.

The third HAE approval of 2025, Ionis Pharmaceuticals’ donidalorsen, was announced on August 21, 2025. The 

, an RNA-targeted medicine, to prevent HAE attacks in adults and children aged ≥ 12 years.

The decision followed a 2023 Orphan Drug Designation and drew on pivotal data from the phase 3 OASIS-HAE and OASISplus trials and the ongoing phase 2 OLE study, which together showed that donidalorsen, targeting prekallikrein, produced sustained reductions in HAE attacks, including a 96% mean reduction over 3 years in the OLE trial.

In OASIS-HAE, donidalorsen 80 mg every 4 or 8 weeks significantly lowered monthly attack rates by 81% and 55%, with 91% of patients on 4-week dosing achieving good disease control. OASISplus further demonstrated continued improvement after switching from other prophylactic therapies, with more than 90% attack-rate reductions and strong patient preference for donidalorsen.

ADARx Pharmaceuticals’ ADX-324: A short-interfering RNA therapy in development to reduce the production of prekallikrein

Pharvaris’ deucrictibant: An oral bradykinin B2 receptor antagonist in development for both on-demand and prophylactic use

Astria’s navenibart: A plasma kallikrein inhibitor delivered subcutaneously)

Intellia’s lonvoguran ziclumeran: A single-dose gene-editing therapy using CRISPR/Cas9 technology, designed to inactivate the kallikrein B1 gene that controls kallikrein production

Beyond these drugs, several experts addressed the same critical need for HAE: treatments indicated for children under 12 years old.

“The burden of these attacks on children has previously been considered more of [an issue beginning at] the onset of puberty—you know, 11, 12, 14, 15 years old,” Soteres said. “It turns out [that] when you talk with healthcare providers, the caregivers, and the adolescents who are helping control and manage this disease and understand this disease, the attacks actually start a lot younger, as early as 5 years old, and some reports even as young as 2…As a pediatric-trained hereditary angioedema specialist, I see a lot of adults, but I do worry about the younger ones.”

In an interview with HCPLive, Michael Manning, MD, an allergy, asthma, & immunology specialist located in Arizona, also pointed to the limited treatment options for children under 12 with HAE as a key unmet need.

“HAE is really a disease of childhood,” Manning said. “Eighty-five percent of patients develop symptoms before the age of 20.”

Experts also highlighted additional research needs, including improving treatment portability and addressing gaps for rural patients, individuals who dislike or require frequent injections, and those who prefer not to take a daily pill.

But for now, the approvals of garadacimab-gxii, sebetralstat, and donidalorsen reflect a field gaining unprecedented momentum.

“We joke a little bit that there's going to be more HAE drugs than patients out there,” Manning said. “You know that's way off, but it's nice because the more we know, and the better we get at treating this, the better we get [at] finding a medication that is going to reach that goal of total control, and things like donidalorsen really get us really close with a potentially a 6 time a year injection to control this, versus something you’re doing every 2 to 3 or 4 days initially. So [we are] making great strides, and I’m happy about it. I like the research and development and finding ways to find something that everybody is going to potentially do well with.”

Derman C. FDA Approves Factor XIIa-Targeting Garadacimab-gxii (ANDEMBRY) for HAE Attacks. Hcplive.com. Published June 17, 2025. Accessed November 26, 2025. 

https://www.hcplive.com/view/fda-approves-factor-xiia-targeting-garadacimab-gxii-andembry-for-hae-attacks

Johnson V. Sebetralstat FDA-Approved as First Oral, On-Demand for Hereditary Angioedema. Hcplive.com. Published July 7, 2025. Accessed November 26, 2025. 

https://www.hcplive.com/view/sebetralstat-fda-approved-as-first-oral-on-demand-for-hereditary-angioedema

Derman C. FDA Approves Donidalorsen to Prevent Hereditary Angioedema Attacks. HCPLive.com. Published August 21, 2025. Accessed November 26, 2025. 

https://www.hcplive.com/view/fda-approves-donidalorsen-to-prevent-hereditary-angioedema-attacks

Learn About Hereditary Angioedema. DiscoverHAE. 

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

Grumach AS, Riedl MA, Cheng L, Jain S, Nova Estepan D, Zanichelli A. Hereditary angioedema diagnosis: Reflecting on the past, envisioning the future. World Allergy Organ J. 2025 May 14;18(6):101060. 

doi: 10.1016/j.waojou.2025.101060. PMID: 40487881; PMCID: PMC12142509.

Stewart P. Emergency Care Still Falling Short for Children With HAE, With Patricia Stewart, MD. Hcplive.com. Published November 18, 2025. 

https://www.hcplive.com/view/emergency-care-falling-short-children-hae-patricia-stewart-md

Tachdjian R. Importance of Addressing the Psychosocial Burden of HAE Among Children, With Raffi Tachdjian, MD. Hcplive.com. Published November 18, 2025. 

https://www.hcplive.com/view/importance-addressing-psychosocial-burden-hae-among-children-with-raffi-tachdjian-md

US Hereditary Angioedema Association. Haea.org. Published 2020. 

Hereditary angioedema (HAE) has seen significant advancements in treatment options, with the FDA approving three new therapies in 2025: garadacimab-gxii, sebetralstat, and donidalorsen. These approvals expand the arsenal of HAE treatments, offering more personalized and effective management strategies. HAE, a rare genetic disorder causing unpredictable swelling, poses diagnostic challenges and significantly impacts patients' lives, especially children. The new treatments target different mechanisms and offer varied administration routes, enhancing patient care. Ongoing research aims to address unmet needs, particularly for children under 12 and rural patients.

Recent advancements in HAE treatments offer hope, but experts stress the need for more pediatric options and diverse therapies.

November delivered a wave of advances across asthma, COPD, and related inflammatory airway diseases, reflecting the accelerating shift toward precision medicine in respiratory care. New data showed pulmonary rehabilitation’s unexpected anti-inflammatory impact in asthma—particularly a 40% FeNO reduction among patients who began PR with high levels—while an open-label extension of tezepelumab demonstrated substantial steroid-sparing benefits, with nearly all OCS-dependent patients tapering to 5 mg or less and half discontinuing steroids entirely. The month also brought promising phase 2b results for rezpegaldesleukin, an IL-2 receptor pathway agonist that improved both atopic dermatitis and asthma control, underscoring its potential as a dual-benefit therapy for patients with overlapping disease.

Alongside these trial updates, expert discussions at CHEST 2025 and a recent 

 clinical forum highlighted the practical realities of implementing targeted therapies for asthma and COPD. Nicola Hanania, MD, MS, emphasized the growing importance of biomarkers such as blood eosinophils and FeNO in navigating an increasingly crowded biologic landscape, while Meilan Han, MD, and colleagues examined how real-world factors—including payer barriers, clinician familiarity, and multidisciplinary coordination—are shaping biologic adoption in COPD.

Check out this November 2025 pulmonology month in review for a recap of HCPLive’s coverage of the top news and research from the past few weeks:

1. Pulmonary Rehabilitation Reduces Type 2 Inflammation in High Inflammation Asthma

Pulmonary rehabilitation (PR) was shown to meaningfully reduce airway inflammation in people with asthma who began treatment with elevated FeNO, with the high-FeNO group experiencing a 40% drop in levels during the 3-week program. Improvements in asthma control and exercise capacity occurred across all baseline FeNO categories, but the anti-inflammatory effect was exclusive to those with high initial FeNO.

2. Tezepelumab Drastically Reduces OCS Use for Asthma in Open-Label Trial

Nearly all patients with severe, OCS-dependent asthma in the WAYFINDER trial were able to lower their daily steroid dose to 5 mg or less after 52 weeks of open-label tezepelumab, and half fully discontinued OCS while maintaining asthma control. These improvements were consistent across inflammatory subgroups, though the absence of a control arm makes the magnitude of benefit harder to interpret.

3. Rezpegaldesleukin Shows Strong Phase 2b Results for Atopic Dermatitis, Asthma

Rezpegaldesleukin, an IL-2 receptor pathway agonist, improved both atopic dermatitis severity and asthma control in the phase 2b REZOLVE-AD trial, with the highest dose (24 μg/kg every 2 weeks) delivering the strongest skin responses. Patients with comorbid asthma also saw meaningful improvements, including clinically significant ACQ-5 reductions in 75% of those with uncontrolled asthma at baseline.

4. The Asthma and COPD Precision Medicine Era, with Nicola A. Hanania, MD, MS

Nicola A. Hanania, MD, MS, professor of medicine and director of the Asthma Clinical Research Center at Baylor College of Medicine, discussed some of the sessions and data presentations from CHEST 2025 that speak to these latest innovations in asthma and COPD. He highlighted the expanding role of targeted therapies, the difficulties clinicians face in selecting among six asthma biologics, and the growing importance of biomarkers such as blood eosinophils and FeNO in guiding therapy.

5. Personalized COPD Treatment: Lessons from Biologic Trials and Clinical Practice

 clinical forum led by Meilan Han, MD, clinicians reviewed new biologic data alongside the evolving framework for identifying the right biologic candidates through biomarkers such as blood eosinophil counts. Faculty also discussed real-world considerations shaping the adoption of biologics, noting differing comfort levels among clinicians, the need for payer navigation, and the importance of multidisciplinary collaboration to integrate these therapies into routine COPD care.

November saw significant advancements in asthma, COPD, and related inflammatory airway diseases, emphasizing the shift toward precision medicine. Pulmonary rehabilitation showed a notable anti-inflammatory effect in asthma patients with high FeNO levels. Tezepelumab demonstrated substantial steroid-sparing benefits, allowing many patients to reduce or discontinue OCS use. Rezpegaldesleukin showed promise in improving both atopic dermatitis and asthma control. Expert discussions highlighted the importance of biomarkers and real-world factors in adopting targeted therapies for asthma and COPD, underscoring the complexities of integrating biologics into clinical practice.

November 2025 saw new data on asthma therapies and new insights from experts on continuing trends in the field.

5 Pulmonology Headlines You Missed in November 2025

New research has identified an association between 

 and reduced vessel length density in the deep capillary plexus (DCP) ischemia with increased instances of macular microaneurysms (MA), introducing MA count as a possible marker for systemic microvascular disease in patients with referable diabetic retinopathy (refDR).

“A heavier MA burden would signal deep capillary plexus (DCP) ischemia and track with extraocular vascular comorbidity in high-risk patients with refDR,” wrote study investigator Amani Fawzi, MD, a professor of ophthalmology at Northwestern University’s Feinberg School of Medicine, and colleagues.

 “Demonstrating such relationships could elevate MA counting from a purely ophthalmic marker of DR activity to a readily accessible proxy for an individual's broader microvascular health, enabling earlier interventions and closer collaboration between ophthalmologists and primary care providers.”

A noninvasive, depth-resolved approach to microvessel imaging, optical coherence tomography angiography (OCTA) provides particular quantitative perfusion metrics within the deep capillary plexus (DCP), the network tied to visual decline and DR complications. There has been limited exploration of these OCTA-derived macular perfusion metrics with MA counts, ultra-widefield fluorescein angiography ischemia, and CKD.

To evaluate the utility of MA count as a screening tool for systemic vascular comorbidities, Fawzi and colleagues conducted a cross-sectional study of patients who underwent multiple fovea-centered 3 × 3-mm OCTA scans (304 × 304 pixels). They calculated vessel density, vessel length density, and geometric perfusion deficits on the averaged images for the superficial capillary plexus (SCP) and DCP slabs. In the DCP, large superficial vessels were subtracted before GPD calculation to avoid projection artifacts.

OCTA imaging was captured in 83 eyes for 65 patients with refDR without diabetic macular edema (DME), and with CKD, defined as an eGFR persistently below 60 mL/min/1.73 m² for at least 3 months. While DME commonly occurs in refDR, this study excluded eyes with this condition.

Univariate linear mixed models were fitted for macular MA count with fixed effects for DR severity (moderate nonproliferative DR [NPDR], severe NPDR, or proliferative DR [PDR]), axial length, lens status (phakia or pseudophakia), diabetes type and duration, HbA1c, as well as the presence of hypertension, ischemic heart disease, CKD, cerebrovascular disease, or dyslipidemia.

Additionally, among the DCP and SCP slabs, investigators analyzed vessel density (VD-DCP/VD-SCP), vessel length density (VLD-DCP/ VLD), geometric perfusion deficits (GPD-SCP/ GPD-DCP), and nonperfusion index (NPI).1 In univariate analyses, with MA count as the dependent variable and each parameter entered as a single fixed effect, increased MA count was significantly associated with CKD, NPI, VLD-DCP, GPD-SCP, and GPD-DCP.

To further understand these associations as independent of potential confounders, Fawzi and colleagues fitted 3 multivariable large multimodal models, including VLD-DCP, GPD-SCP, or GPD-DCP.1 Upon multivariable analysis, CKD remained a significant independent predictor of higher macular MA count across all models (β ≈ 9.6–10.6; 

 ≤ 0.013). Among the OCTA metrics, only VLD-DCP remained significant (β = −2.46; 

 = 0.089) were not. Age showed a modest inverse association with MA count in the VLD-DCP model (

 = 0.049).1 In a sensitivity analysis including BMI as an additional covariate, CKD and VLD-DCP remained independently associated with MA count, whereas BMI was not significant.

In a receiver operating characteristic analysis, investigators used MA count as the predictor and CKD status as the binary outcome, demonstrating that macular MA burden had a fair discriminative ability for identifying CKD, with an area under the curve (AUC) of 0.755. The Youden index was maximized by a threshold of 14 macular MAs, yielding a sensitivity of 58.8% and a specificity of 86.4% for detecting CKD.

“Taken together, our findings highlight macular MA burden as a cross-disciplinary biomarker that encapsulates both localized deep capillary plexus ischemia and systemic microvascular injury reflected by CKD,” investigators concluded. “By combining high-resolution OCTA with UWF-FA, we demonstrate that macular MAs can stratify systemic risk within a relatively high-risk cohort."

Busza A, Fawzi AA. Macular Microaneurysms Are Associated With Chronic Kidney Disease and Deep Capillary Plexus Ischemia in Referable Diabetic Retinopathy. 

Investigative Ophthalmology & Visual Science

Ong JX, Konopek N, Fukuyama H, Fawzi AA. Deep Capillary Nonperfusion on OCT Angiography Predicts Complications in Eyes with Referable Nonproliferative Diabetic Retinopathy. 

https://doi.org/10.1016/j.oret.2022.06.018

Research has established a link between chronic kidney disease (CKD) and reduced vessel length density in the deep capillary plexus (DCP) ischemia, with increased macular microaneurysms (MA) in patients with referable diabetic retinopathy (refDR). This suggests MA count as a potential marker for systemic microvascular disease. Optical coherence tomography angiography (OCTA) was used to assess vessel density and perfusion metrics. CKD was a significant predictor of higher MA count, and MA burden showed fair discriminative ability for identifying CKD, highlighting its potential as a cross-disciplinary biomarker.

In a cross-sectional OCTA analysis of patients with referable diabetic retinopathy, CKD emerges as an independent predictor of higher MA burden. 


Deep Capillary Plexus Microaneurysms A Sign of CKD in Diabetic Retinopathy

November brought a mix of regulatory milestones, late-phase clinical insights, and evolving digital health trends across 

. From the US Food & Drug Administration’s (FDA) first clearance of Deep Transcranial Magnetic Stimulation (Deep TMS) for adolescents with

to a New Drug Application (NDA) filing that could introduce a novel ADHD mechanism of action, the month highlighted both therapeutic innovation and shifting treatment paradigms.

Clinicians also saw new phase 4 data on adjunctive perospirone for treatment-resistant depression and fresh evidence revealing the engagement challenges of mental health apps. Here are 4 psychiatry headlines you may have missed.

FDA Clears BrainsWay’s TMS Device for Adolescents with MDD Aged 15 to 21 Years

The FDA has cleared BrainsWay’s Deep TMS system for adolescents aged 15 - 21 years with major depressive disorder (MDD), expanding its previous approval for adults aged 22–86. This decision marks the first clearance of Deep TMS for a younger population that often has limited effective treatment options.

The expanded indication was supported by one of the largest real-world adolescent neuromodulation datasets submitted to the FDA, demonstrating substantial reductions in depressive and anxiety symptoms. In the supporting study, participants completed 36 sessions of either high-frequency Deep TMS or intermittent theta-burst stimulation, achieving a mean 12.1-point improvement on the PHQ-9 and a 66.1% response rate. Treatment consists of noninvasive magnetic stimulation delivered through a cushioned helmet in 20-minute daily sessions over 4–6 weeks. Adverse events were mild and consistent with adult data, most commonly headaches and localized discomfort.

Deep TMS is also FDA-cleared for OCD, anxious depression, and smoking cessation.

Otsuka Pharmaceuticals Submits NDA for Centanafadine to Treat ADHD in Children

Otsuka Pharmaceuticals has submitted an NDA to the FDA for centanafadine, a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) for treating ADHD in patients aged 4 – 55 years. The NDA is supported by 4 pivotal phase 3 trials evaluating once-daily, extended-release centanafadine across children, adolescents, and adults. In these studies, centanafadine produced statistically significant and clinically meaningful reductions in ADHD symptoms compared with placebo, measured by ADHD-RS-5 in younger patients and AISRS in adults.

High-dose treatment consistently showed the strongest effects, including significant improvements in children aged 4 - 12 years and adolescents aged 13 – 17 years, while both 200 mg and 400 mg doses were effective in adults. The medication was generally well tolerated; common adverse events included decreased appetite, nausea, rash, fatigue, and abdominal pain. The study observed somnolence in younger patients and decreased appetite and headache in adults.

Adjunctive Perospirone Safe, Well-Tolerated for MDD in Phase 4 Trial

Phase 4 trial results show perospirone is safe and well-tolerated as adjunctive therapy for MDD over 8 weeks, with potential, but inconclusive, efficacy benefits. The study enrolled 210 patients with inadequate response to SSRIs or SNRIs, randomized to perospirone or placebo added after 4 weeks of antidepressant treatment. While remission rates were greater with perospirone (55.2% vs 38.9%), response rates were similar between groups. Investigators noted a high placebo response, and expectancy effects may have reduced the observed drug-placebo difference. Overall, early adjunctive perospirone may offer benefit, but efficacy findings remain preliminary and require further study.

Mental Health Apps Gain High Uptake but Struggle With Adherence, Retention

A meta-analysis of 79 RCTs found that mental health apps achieve high uptake (92%) but only moderate adherence, with many users failing to complete follow-up assessments. Engagement improved with reminders and human support, while gamification did not boost retention. Across trials, 62% of users continued using apps, though real-world uptake is likely far lower.

Attrition rates ranged from 19% during treatment to 28% at follow-up, similar to dropout levels in psychotherapy and pharmacotherapy. Investigators noted that accountability features reduce attrition, and clinicians can use these insights to guide app recommendations and set realistic expectations for patients.

November saw significant developments in psychiatry, including FDA clearance of Deep TMS for adolescents with MDD and an NDA submission for a novel ADHD treatment. Phase 4 data on adjunctive perospirone for treatment-resistant depression showed safety and potential efficacy, though results were inconclusive. Mental health apps demonstrated high uptake but faced challenges with adherence and retention, highlighting the need for improved engagement strategies. These advancements underscore the ongoing evolution of therapeutic options and digital health trends in psychiatry, offering new insights and opportunities for clinicians and patients alike.

This month in review highlights November’s biggest psychiatry stories, including FDA moves, phase 4 findings, and new data on digital mental health tools.

4 Psychiatry Headlines You Missed in November 2025

Mavacamten Monotherapy Improves Cardiac Function in oHCM, With Ozlem Bilen, MD

Mavacamten monotherapy has proven its efficacy in improving cardiac function and symptoms in patients with 

obstructive hypertrophic cardiomyopathy (HCM)

, according to data from the COLLIGO-HCM trial.

Mavacamten has long been known to improve cardiac function and symptoms in patients with HCM; several clinical studies have indicated its efficacy and favorable safety profile. However, little literature exists regarding monotherapy in real-world studies.

 met with Ozlem Bilen, MD, associate professor of medicine in the cardiology division and chief of cardiology at Emory University Hospital, to discuss the implications of these data, highlighting the potential of mavacamten monotherapy in patients with HCM.

“When we looked into the improvements in NYHA class, about 60% of patients in mavacamten monotherapy and 61% of patients in background medical therapy had improved their NYHA class by ≥1 class,” Bilen told 

. “And when we looked into the changes in LVOT gradients, we saw significant improvement in both groups as well. About 94% in monotherapy and 87% in the background therapy group have reached resting LVOT gradients of <30, which is the threshold used to define obstructive HCM.”

Bilen discusses the COLLIGO-HCM trial, investigating the real-world efficacy of mavacamten monotherapy for patients with obstructive HCM.

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