Linda Stein Gold, MD, is a dermatologist at Henry Ford Health. 

Zasocitinib achieved PASI 100 in 36.5% of patients versus 13.9% with deucravacitinib at Week 16.

Stein Gold attributed the gap to differences in TYK2 selectivity and duration of IL-23 blockade.

She now considers next-generation oral TYK2 inhibitors a first-line option after topical therapy.

Zasocitinib, an investigational next-generation tyrosine kinase 2 (TYK2) inhibitor, may allow clinicians to aim for completely clear skin with an oral agent for 

, according to Linda Stein Gold, MD, director of dermatology clinical research at Henry Ford Health in Detroit, Michigan.

Stein Gold, principal investigator of the phase 3 LATITUDE Atlas trial, discussed head-to-head data presented at the 

2026 European Academy of Dermatology and Venereology (EADV) Congress

 in Vienna, Austria, in an interview with 

Why zasocitinib outperformed deucravacitinib in plaque psoriasis

Why Zasocitinib Outperformed Deucravacitinib in New Plaque Psoriasis Data

In LATITUDE Atlas, 36.5% of patients receiving zasocitinib achieved a 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 16, compared with 13.9% receiving deucravacitinib (

 < .001), according to Takeda.¹ Stein Gold noted the trial was the first head-to-head comparison of 2 drugs sharing the same mechanism of action, and the first to use PASI 100 as its primary endpoint. Based on the data so far, she said zasocitinib appears to perform similarly to traditional biologics.

What Explains the Efficacy Gap Between 2 TYK2 Inhibitors?

Despite their shared mechanism, Stein Gold described the 2 agents as quite different. She cited more than 1 million-fold greater selectivity for TYK2 over Janus kinase (JAK) 1, 2, and 3 with zasocitinib, compared with roughly 87-fold with deucravacitinib, a distinction aimed at avoiding off-target metabolic or hematologic effects.¹ She also pointed to the duration of interleukin (IL)-23 blockade, which extends over 24 hours with zasocitinib versus just under 5 hours with deucravacitinib.

Higher rates of complete clearance with zasocitinib emerged as early as week 8.² Stein Gold explained oral agents have historically taken time to show an effect, which has required considerable reassurance for patients. Visible improvement within the first several weeks gives patients confidence to continue treatment, even before their skin is fully clear.

In the pivotal LATITUDE PsO 3001 and 3002 studies, up to 93% of week 24 responders maintained skin clearance through week 52 or week 40, and patients reported improvements in itch and quality of life as early as week 2.¹ Stein Gold emphasized itch as a central component of psoriasis for many patients, contributing to poor sleep and diminished quality of life. The goal, in her view, is for patients to live as people with psoriasis rather than living their lives around the disease.

Patients want to gain control of their disease and keep it, Stein Gold added, and they need confidence their medication can deliver both over time.

Where Does Zasocitinib Fit in Psoriasis Treatment?

Stein Gold noted clinicians have not always presented an oral option to patients with moderate to severe plaque psoriasis, since no oral drug previously combined adequate efficacy, tolerability, and safety. With next-generation TYK2 inhibitors and other recently approved oral agents, she now offers these medications as a first-line option for patients not responding to topical therapy. Zasocitinib remains under review by the US Food and Drug Administration and the European Medicines Agency.¹

The most common adverse events across the LATITUDE program were upper respiratory tract infection, nasopharyngitis, and acne.¹ Stein Gold observed acne occurred more often with zasocitinib than with placebo and slightly more often than with deucravacitinib, although most cases were mild to moderate and many resolved without treatment. She recommended counseling patients up front about the possibility of acne, noting dermatologists can manage it, often with topical therapy alone.

Editor’s note: This summary has been edited for grammar and clarity using artificial intelligence tools. Financial disclosures reported for Stein Gold include AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Organon Health, Eli Lilly, Johnson & Johnson, Novartis, Pfizer, and UCB.

Takeda. Zasocitinib delivered superior efficacy versus deucravacitinib in phase 3 LATITUDE psoriasis studies. News release. Published September 30, 2026. Accessed October 6, 2026. 

https://www.takeda.com/newsroom/news-releases/2026/zasocitinib-superior-efficacy/

HCPLive. EADV 2026: Zasocitinib tops deucravacitinib for PASI 100 in plaque psoriasis. Published September 30, 2026. Accessed October 6, 2026. 

https://www.hcplive.com/view/eadv-2026-zasocitinib-tops-deucravacitinib-for-pasi-100-in-plaque-psoriasis

Videos

Linda Stein Gold, MD, discusses LATITUDE Atlas data showing zasocitinib achieved higher PASI 100 rates than deucravacitinib in psoriasis.

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Edward Chen, MD, is a professor of surgery at Thomas Jefferson University and the chief of cardiac surgery at Jefferson Abington Hospital.

 care has been on an upward trajectory in 2026, with recent guideline updates and trial readouts providing new perspectives on the myriad issues within this specialty.

, Edward Chen, MD, professor of surgery at Thomas Jefferson University and chief of cardiac surgery at Jefferson Abington Hospital, discussed his perspective on the growth of aortic surgery and his expertise in its application.

Updates and Evolution in Aortic Disease Care, With Edward Chen, MD

“Over the last 25 years since I started my training in cardiac surgery, taking care of the patient after the operation has really led to significant improvement in the outcomes of these types of operations,” Chen told 

. “Whereas before it might have been a coin flip, and it would be hard to know if someone’s going to do well, now, with the right patient selection and thorough evaluation of all of the variables, we can be very confident that many of these patients can go on to not only normal recovery, but a normal life.”

Chen’s statements on this patient-first approach mirror the recently published European Society for Vascular Surgery (ESVS) 2026 Clinical Practice Guidelines, published in February 2026, which emphasize the importance of the patient-centered treatment process. In the guidelines, the authors suggest that clinicians expand their focus to include patient perspectives while tailoring interventions to fit life expectancy and functional status. Additionally, the document pushes for further inclusion of multidisciplinary care, centralizing treatment in high-volume centers and prioritizing team-based decision making in regard to care.

Aortic disease care is also evolving through ongoing clinical trials, including the ARISE III trial at Stanford University. The program focuses on a less invasive alternative for certain high-risk patients with de novo Type A aortic dissections, evaluating the efficacy and safety of a new investigational stent graft device. The trial began in May of 2026 and is currently ongoing with plans to conclude in 2030. ARISE III currently aims to enroll 112 patients across the US.

Jefferson Health is also participating in an ongoing trial investigating the efficacy and safety of the Navitor Transcatheter Aortic Valve Implantation (TAVI) system, which is in development by Abbott. Roughly 1500 patients will be enrolled in the trial at ≤80 sites in the US and ≤15 internationally. The device will be investigated in both patients with symptomatic, severe native aortic stenosis at intermediate or low risk of surgical mortality and in patients with symptomatic heart disease due to failure of a surgical or transcatheter bioprosthetic aortic valve at high or greater surgical risk.

Chen also discussed his move to Jefferson Health and his upcoming projects within the organization, highlighting several potential targets for research.

“A lot of this work involves looking at aortic root surgery outcomes related to valve repair, aortic arch operations, various methods for protection – not just what I do, but also what my colleagues do in microval repair, coronary artery bypass, transplantation, and so on,” Chen said. “There’s a wide breadth of research going on here, and really, I’m only just scratching the surface of what’s being done.”

Editors’ Note: Chen reports no relevant disclosures.

Wanhainen A, Gombert A, Antoniou GA, et al. European Society for Vascular Surgery (ESVS) 2026 Clinical Practice Guidelines on the Management of Descending Thoracic and Thoraco-Abdominal Aortic Diseases - Editor's Choice. 

Nichols L. Stanford Continues to Advance Ascending Aorta Treatments Through National ARISE III Clinical Trial. 

Stanford Department of Cardiothoracic Surgery

. July 30, 2026. Accessed October 6, 2026. 

https://med.stanford.edu/ctsurgery/about-the-department/news/2026/stanford-continues-to-advance-ascending-aorta-treatments.html

Abbott Medical Devices. ENVISION IDE Trial: Safety and Effectiveness of NAVITOR in Transcatheter Aortic Valve Implantation (ENVISION). ClinicalTrials.gov Identifier: NCT05932615. Updated September 11, 2026. Accessed October 6, 2026. 

https://clinicaltrials.gov/study/NCT05932615#contactlocation

Chen discusses his experience with aortic and cardiac surgery, as well as ongoing research into ways to optimize and improve care.

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...

Structural Heart Disease

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Hisamitsu Hayashi, PhD, in the Graduate School of Pharmaceutical Sciences associate professors at the University of Tokyo.

For US clinicians managing progressive familial intrahepatic cholestasis (PFIC), approved drug therapy targets the itch, not the disease. The 

 has approved the ileal bile acid transporter (IBAT) inhibitor odevixibat (Bylvay) to treat pruritus in patients aged ≥3 months with PFIC.¹ Yet most patients still develop fibrosis and end-stage 

PFIC is a heterogeneous group of autosomal recessive disorders of childhood in which defects in hepatocellular transport genes disrupt bile formation.² Estimated incidence ranges from 1 in 50,000 to 1 in 100,000 births, and PFIC accounts for 10% to 15% of childhood cholestasis cases and 

10% to 15% of pediatric liver transplant indications

PFIC1, caused by ATP8B1 mutations, and PFIC2, caused by ABCB11 mutations affecting the bile salt export pump (BSEP), usually appear in the first months of life with jaundice and severe pruritus.² Serum gamma-glutamyltransferase (GGT) activity is normal in both, a key clue distinguishing them from PFIC3, and diagnosis is confirmed through genetic testing.² PFIC1 can carry extrahepatic features including short stature, sensorineural deafness, diarrhea, and pancreatitis, while patients with PFIC2, particularly those with biallelic truncating mutations, face an estimated 15% risk of hepatocellular carcinoma or cholangiocarcinoma.²

A different approach now has regulatory backing. In August 2026, sodium phenylbutyrate (Buphenyl), a longstanding urea cycle disorder therapy, gained approval in Japan for PFIC types 1 and 2 based on a series of clinical studies and an investigator-initiated trial.³ Rather than targeting pruritus, the drug increases functional BSEP at the canalicular membrane to restore bile acid export.

Hisamitsu Hayashi, PhD, associate professor in the Laboratory of Molecular Pharmacokinetics at the University of Tokyo Graduate School of Pharmaceutical Sciences, led the laboratory work identifying the drug's effect on BSEP. Following PFIC Awareness Day on October 5, Hayashi spoke with HCPLive in a written interview about early diagnosis, the evidence for a disease-directed therapy, and how it could complement IBAT inhibitors.

Q&A: Restoring bile acid export in PFIC types 1 and 2

HCPLive: What should clinicians know about PFIC types 1 and 2, and what unmet needs remain for patients?

 PFIC types 1 and 2 are rare inherited cholestatic liver diseases caused by defects in ATP8B1 and ABCB11, respectively. Both typically present in infancy or childhood with cholestasis and severe pruritus, but importantly, they are progressive liver diseases. Over time, patients may develop fibrosis, cirrhosis, and ultimately require liver transplantation.

Pruritus has an enormous impact on quality of life, but controlling pruritus does not necessarily mean that progression of the underlying liver disease has been controlled. Therefore, we need to consider both symptom control and preservation of the native liver.

Now that medical treatment options are emerging, I think early diagnosis is becoming increasingly important. Rather than waiting until patients have advanced fibrosis or hepatic decompensation, we should aim to establish the molecular diagnosis and intervene as early as possible, when there may still be an opportunity to preserve liver function.

This also makes genetic diagnosis increasingly relevant, because PFIC is biologically heterogeneous and treatment response may depend on the underlying disease subtype and molecular defect.

HCPLive: How does sodium phenylbutyrate work in PFIC, and are some patients, such as those with particular genetic variants, more likely to respond?

 BSEP is located at the canalicular membrane of hepatocytes and exports bile acids from the liver into bile. Sodium phenylbutyrate increases the amount of functional BSEP at this membrane, in part by stabilizing BSEP that has reached the cell surface.

In PFIC2, some ABCB11 variants produce BSEP proteins that retain transport activity but have reduced expression at the canalicular membrane. For those patients, increasing the amount of functional BSEP at the membrane provides a clear mechanistic rationale for treatment.

However, sodium phenylbutyrate is not simply a mutation-specific chaperone. We originally found that it also increases the membrane expression and transport capacity of wild-type BSEP. This is particularly relevant to PFIC1, where ABCB11 itself is not mutated, but ATP8B1 deficiency can lead to secondary impairment of BSEP function. Enhancing functional wild-type BSEP may therefore improve bile acid excretion even when BSEP is not the primary genetic defect.

Biologically, this suggests that treatment response may depend on how much recoverable BSEP function remains. However, we do not yet have a validated genotype-based predictor of response, and the Japanese approval is not restricted to particular variants.

The effect on wild-type BSEP also raises the possibility that this mechanism could be relevant to other cholestatic conditions in which canalicular BSEP function is secondarily reduced. That is scientifically interesting, but at present this remains a research question; the approved indication is PFIC types 1 and 2.

HCPLive: How do you see sodium phenylbutyrate fitting alongside current options such as IBAT inhibitors, biliary diversion, and liver transplant?

 I think an important point is that the approved indications and therapeutic roles are different.

In Japan, IBAT inhibitors are approved specifically for the treatment of cholestatic pruritus associated with PFIC, not for PFIC itself as the approved indication. The approved indications are also pruritus-focused in the US, although regulatory labeling differs across regions.

Sodium phenylbutyrate, by contrast, is approved for PFIC types 1 and 2 themselves. It acts in the liver by increasing functional BSEP expression at the canalicular membrane and enhancing bile acid export from hepatocytes. From the current regulatory and clinical perspective, I therefore view sodium phenylbutyrate as a therapy directed at the underlying disease mechanism, whereas IBAT inhibitors are positioned primarily as treatments for cholestatic pruritus.

That distinction does not mean that IBAT inhibitors have no effect on disease biology. By reducing intestinal bile acid reabsorption and the circulating bile acid pool, they may have broader biological effects. But their approved indication in PFIC is cholestatic pruritus, whereas sodium phenylbutyrate is approved for PFIC1 and PFIC2 themselves.

Because they act at different points in bile acid physiology, these treatments may ultimately be complementary rather than competing. Future studies should determine how best to select, sequence, or potentially combine them according to disease subtype, genotype, residual BSEP function, and disease stage.

Biliary diversion remains an important option when medical therapy is insufficient, and liver transplantation remains essential for patients with advanced or decompensated liver disease. This is also why early diagnosis and early intervention are becoming increasingly important: once irreversible liver damage has developed, the opportunity for medical therapy to preserve the native liver becomes much more limited.

HCPLive: What did the clinical evidence supporting the approval show, and which outcomes do you think are most meaningful for patients?

 The multicenter investigator-initiated study enrolled 6 patients with PFIC2. The primary endpoint was change in liver histology at 24 weeks. Histological improvement was observed in 3 of the 6 patients, and liver biochemical parameters generally improved during treatment. PMDA [Pharmaceuticals and Medical Devices Agency] considered these findings meaningful in the context of a progressive disease in which spontaneous histological improvement would not generally be expected.

What I find particularly important is the long-term follow-up. Four patients who continued treatment were still receiving sodium phenylbutyrate as of March 2026 and had survived with their native livers for approximately 6.5 to 8 years. In our nationwide survey of Japanese patients with PFIC2, the historical disease course was characterized by frequent progression to liver transplantation at a young age. Against that background, the duration of native liver survival observed in the treated patients appears substantially longer than the clinical course we had historically observed in Japanese patients with PFIC2. Of course, this is not a controlled comparison, and the number of patients is very small, so we have to be cautious.

For PFIC1, the evidence came from an exploratory study in 3 patients. Pruritus improved during treatment and worsened again after discontinuation, providing supportive evidence of clinical benefit, although histological changes were not clearly demonstrated during the short treatment period.

For patients and families, I think the most meaningful outcomes are not laboratory values alone. They are relief from severe pruritus, preservation of growth and quality of life, prevention of progressive liver injury, and ultimately the ability to remain well with one's native liver for as long as possible.

HCPLive: Can you walk us through the path from your lab's initial sodium phenylbutyrate findings to its approval?

 Our starting point was not drug repurposing itself, but understanding the disease mechanism.

We were studying how impaired BSEP expression and function at the canalicular membrane contribute to cholestasis in PFIC. Our pathophysiological studies showed that some PFIC2-associated BSEP variants retain transport activity but have impaired trafficking to, or reduced stability at, the canalicular membrane. This led us to ask whether restoring functional BSEP expression at the hepatocyte membrane could become a therapeutic strategy.

In the course of that work, we discovered that sodium phenylbutyrate has a previously unrecognized pharmacological action that is completely different from its established nitrogen-scavenging effect in urea cycle disorders: it increases functional BSEP expression at the canalicular membrane and enhances bile acid transport.

We then moved step by step from mechanistic studies to translational research. We demonstrated the effect in experimental models and human liver samples, conducted exploratory clinical studies in both PFIC1 and PFIC2, and subsequently performed a multicenter investigator-initiated clinical trial in patients with PFIC2.

The development therefore followed a path from understanding disease biology, to discovering a new pharmacological action, to testing that mechanism in patients. Approximately 20 years after the initial discovery, sodium phenylbutyrate was approved in Japan in August 2026 for both PFIC types 1 and 2.

This long path required sustained collaboration among patients and families, clinicians, researchers, public funding agencies, and industry, and ultimately led to the regulatory submission by OrphanPacific.

HCPLive: What should US clinicians take away from this approval, and what research is needed next?

 I hope there are 2 major take-home messages.

The first is the importance of basic research into disease mechanisms. This development began with a very fundamental question: why does bile acid transport fail in PFIC? By studying the molecular and cellular mechanisms of the disease, we discovered an unexpected pharmacological action of an existing drug. That basic discovery eventually became a treatment for patients more than 2 decades later.

To me, this is an important example of how deep mechanistic research can reveal therapeutic opportunities that would not necessarily emerge from conventional drug screening or from the known pharmacology of an existing drug.

The second lesson is that successful development in rare diseases requires a sustainable ecosystem that extends beyond a single drug.

Based on what we learned during the development of sodium phenylbutyrate, we established CIRCLe, a research and clinical-development platform for rare disorders and undiagnosed conditions presenting with liver abnormalities in Japan. CIRCLe has already supported the development and post-marketing evaluation of IBAT inhibitors in Japan.

We are now also collaborating with other pharmaceutical companies on drug-development projects involving a broader range of rare and undiagnosed disorders with diverse liver manifestations, extending well beyond PFIC and cholestatic disease. CIRCLe is also expanding internationally through collaborations with medical institutions outside Japan.

We hope CIRCLe can serve not only as a platform for one disease or one therapeutic area, but as an infrastructure that helps accelerate the development of new treatments for rare disorders and undiagnosed conditions involving the liver more broadly.

For sodium phenylbutyrate itself, the next priorities include international validation, better understanding of genotype-response relationships, long-term evaluation of native liver survival, and determining how this therapy should be used alongside IBAT inhibitors and other emerging treatments.

Ultimately, our goal is not simply to develop one successful drug. It is to create an environment in which the knowledge gained from one successful development can make the next treatment easier to bring to patients.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Disclosures for Hayashi were not available at the time of publication.

Walter K. FDA approves odevixibat for PFIC. HCPLive. Published July 20, 2021. Accessed October 6, 2026. 

https://www.hcplive.com/view/fda-approves-odevixibat-pfic

Davit-Spraul A, Gonzales E, Baussan C, et al. Progressive familial intrahepatic cholestasis. 

OrphanPacific. Notice regarding approval of a partial change to the marketing authorization for sodium phenylbutyrate for progressive familial intrahepatic cholestasis (PFIC) types 1 and 2. Published August 24, 2026. Accessed October 6, 2026. 

https://en.cmicgroup.com/news-events/notice-regarding-approval-of-a-partial-change-to-the-marketing-authorization-for-sodium-phenylbutyrate-for-progressive-familial-intrahepatic-cholestasis-pfic-types-1-and-2/

Articles

Approved US PFIC drugs treat pruritus. The researcher behind a therapy targeting BSEP on diagnosis, data, and what comes next.

Hepatology

RDR Alert®

The Rare Disease Report page is a resource for medical news and expert insights on rare diseases. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for sickle cell disease, multiple myeloma, and more.

Targeting the Disease Mechanism in PFIC, With Hisamitsu Hayashi, PhD

Florence Schleich, MD, PhD, a respiratory physician at the University of Liège in Belgium.

Asthma exacerbations persisting in patients with severe asthma on biologic therapy reflect distinct inflammatory phenotypes, and identifying the phenotype should come before treatment escalation, according to a presentation at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain.¹

“In routine clinical practice, we still see a significant proportion of patients who continue to experience exacerbations despite receiving biologics,” said Florence Schleich, MD, PhD, a respiratory physician at the University of Liège in Belgium, in an interview with HCPLive. "For these patients, it's really important to try to understand the underlying mechanisms for these residual exacerbations, to avoid inappropriate treatment escalation and to prevent future exacerbations.”

Residual Asthma Exacerbations on Biologics Vary by Mechanism

Exacerbation Phenotypes on Mepolizumab, Benralizumab, and Tezepelumab

According to Schleich, residual exacerbations on mepolizumab, an anti-interleukin (IL)-5 antibody, split roughly evenly between eosinophilic events and infection-driven, more neutrophilic events. In the prospective observational MEX study of 145 patients with severe eosinophilic asthma receiving mepolizumab, a fractional exhaled nitric oxide (FeNO) level of ≤20 ppb or ≥50 ppb was the most useful discriminator of exacerbation phenotype.²

Non-eosinophilic events in MEX were associated with low FeNO and elevated C-reactive protein, consistent with infection.² MEX investigators also cautioned against switching biologics for treatment failure without first profiling the inflammatory phenotype of ongoing exacerbations.²

Exacerbations on benralizumab (Fasenra), an anti-IL-5 receptor α antibody, follow a different pattern. In the multicenter, prospective BenRex cohort study across 15 UK severe asthma centers, airway neutrophilia was present in 55% of exacerbations with available sputum, and new acquisition of 

 occurred in 18.2% of sampled cases.³ BenRex investigators concluded eosinophilic inflammation is not involved in exacerbations on benralizumab, pointing instead to viral pathogens, airway neutrophilia, and sputum microbiome alteration.³

The newest data, from the TezEx study of exacerbations on tezepelumab (Tezspire), an anti-thymic stromal lymphopoietin (TSLP) antibody, surprised her most. TezEx is a retrospective and prospective observational study collecting blood, nasal, and sputum samples at exacerbation and at 1-year stable state in patients with severe asthma receiving tezepelumab.⁴ According to Schleich, 60% of residual exacerbations on tezepelumab were eosinophilic, and airway eosinophilic inflammation did not correlate with FeNO in these patients.¹,⁴

Choosing Biomarkers and Addressing Comorbidities in Residual Exacerbations

Why do patients with severe asthma still experience exacerbations on biologics?

Residual exacerbations are heterogeneous, ranging from persistent eosinophilic events to infection-driven, neutrophilic events, and can also stem from uncontrolled comorbidities such as nasal polyps, bronchiectasis, or obesity.

Which biomarker best identifies eosinophilic exacerbations on a biologic?


It depends on the agent: FeNO is most useful during anti-IL-5 or anti-IL-5 receptor therapy, whereas blood eosinophil count better reflects airway eosinophilia in patients receiving tezepelumab.

Exacerbations on benralizumab were largely non-eosinophilic, with airway neutrophilia in 55% of sampled events and evidence of viral infection and sputum microbiome alteration.

Schleich described FeNO and blood eosinophil count as strong predictors of future exacerbation risk and of response before biologic initiation. Once a patient is on treatment, their utility depends on the agent. Blood eosinophils offer little information during anti-IL-5 or anti-IL-5 receptor therapy because these agents reduce or deplete them, leaving FeNO as the more practical marker, with values between 20 ppb and 50 ppb remaining indeterminate and potentially warranting sputum analysis.¹

"With tezepelumab, FeNO is not helpful anymore, and you should look at the blood eos count, which is still correlated with the presence of eosinophilic inflammation in the sputum," Schleich said. "The biomarkers you will use to predict the exacerbation will change according to the treatment the patient receives."

Beyond phenotyping, Schleich urged clinicians to evaluate uncontrolled comorbidities in patients who continue to exacerbate, including chronic rhinosinusitis with nasal polyps, bronchiectasis, and obesity. She cited ORACLE2 data presented at ERS 2026, drawn from more than 7000 patients with moderate to severe asthma, in which a body mass index (BMI) above 25 kg/m² was already associated with increased exacerbation risk.¹ For infection-driven exacerbations, particularly in patients with chronic bronchitis, purulent sputum, or concomitant bronchiectasis, she said macrolides could provide additional benefit on top of biologic therapy.¹

Schleich F. Asthma: why do asthma exacerbations persist, even in well-treated patients on biologics? Presented at: European Respiratory Society Congress 2026; September 2026; Barcelona, Spain.

McDowell PJ, Diver S, Yang F, et al. The inflammatory profile of exacerbations in patients with severe refractory eosinophilic asthma receiving mepolizumab (the MEX study): a prospective observational study. 

Logan J, Martin K, Gillespie L, et al. Asthma exacerbation profile of benralizumab for severe eosinophilic asthma (the BenRex study): a multicentre, prospective cohort study. 

The inflammatory profile of exacerbations in patients with severe asthma receiving tezepelumab: the TezEx study. ClinicalTrials.gov identifier: NCT06666504. Accessed October 6, 2026. 

https://clinicaltrials.gov/study/NCT06666504

Florence Schleich, MD, PhD, explains how exacerbation phenotypes and useful biomarkers shift across anti-IL-5, anti-IL-5R, and anti-TSLP therapies.

Pulmonology

Infectious Disease condition center page is a comprehensive resource for clinical news and insights on respiratory health. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for asthma, COPD, interstitial lung disease, COVID-19, and more.

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Despite advancements in diabetes technology in recent years, hypoglycemia is still among the most substantial dangers faced by patients with 

. However, ongoing research into investigational treatments, such as cadisegliatin, is actively working to combat this risk.

Addressing the Lingering Challenge of Hypoglycemia in T1D, With John Buse, MD, PhD

While continuous glucose monitors (CGM) and automated insulin delivery (AID) systems are substantially simplifying the process of monitoring and managing this risk, hypoglycemia remains a major barrier to achieving full glucose control. In an exclusive interview with 

, John Buse, MD, PhD, the Verne S. Caviness Distinguished Professor of Medicine and director of the Diabetes Care Center and North Carolina Translational and Clinical Sciences Institute at the University of North Carolina School of Medicine, discussed the lingering issues of CGM and AID technology and their impact on hypoglycemia.

“Current state-of-the-art therapy are these AID systems, these pumps, and they integrate information from CGMs with an algorithm to help the patient manage their diabetes and select insulin doses,” Buse told 

. “The problem is that when you inject insulin subcutaneously, it first enters what we call the peripheral circulation, whereas Mother Nature intended insulin to go to the liver.”

Buse went on to discuss major issues in insulin delivery, the first of which was the intrinsic difference between subcutaneous versus naturally produced insulin. Typically, AIDs infuse insulin through the skin, which introduces it to the full circulatory system. However, naturally produced insulin is administered directly to the liver. To get the same glucose-canceling effect as natural insulin, AIDs must provide enough to filter through the entire body while still impacting the liver.

Additionally, the sensors used in CGMs typically have an unavoidable lag of around 10-15 minutes. Insulin introduced via injection takes roughly that long to permeate the endothelium and occupy the interstitial space in which the CGM needle is implanted. Buse explains that this can create a gap in timing of 20-30 minutes, meaning that the AID systems cannot respond quickly to overcorrection or rapid changes in activity level. Ultimately, clinicians have no way to prevent this insulin from causing hypoglycemia in the event of a rapid correction in glucose.

To address these issues, parent company vTv Therapeutics has developed cadisegliatin, a novel oral small molecule glucokinase activator, as a potential first-class adjunctive treatment for T1D. Previous trials have displayed cadisegliatin’s effect on the liver, increasing the activity of glucokinase independently of insulin.

Currently, clinicians have officially completed enrollment in the phase 3 CATT1 trial, which aims to investigate cadisegliatin’s efficacy in adults with T1D currently taking multiple daily insulin injections or continuous subcutaneous insulin infusions, along with CGM. Patients will be randomly assigned to either cadisegliatin 800 mg once daily, twice daily, or placebo. The primary endpoint will measure the incidence of level 2 and 3 hypoglycemic events, while secondary endpoints will include changes in HbA1c, time in target glucose range, and the incidence of diabetic ketoacidosis between groups.

“There are other mechanisms that are trying to accomplish similar things, but using fundamentally different biology. As an example, cadisegliatin is in development to activate glucokinase, the rate-limiting step in glucose metabolism in the liver,” Buse said. “This should provide for greater shortage of glucose in the liver and for better glucose uptake, particularly in the post-prandial state, which may provide a different way of reducing hypoglycemia.”

In a press statement, vTv Therapeutics stated that topline results from CATT1 are expected in mid 2027.

Editors’ Note: Buse reports relevant disclosures with Corcept, Dexcom, GentiBio, Novo Nordisk, Amgen, AstraZeneca, Boehringer-Ingelheim, Corcept Therapeutics, and others.

van Beers CA, DeVries JH. Continuous Glucose Monitoring: Impact on Hypoglycemia. J Diabetes Sci Technol. 2016;10(6):1251-1258. Published 2016 Nov 1. 

vTv Therapeutics. vTv Therapeutics Announces Completion of Enrollment in Phase 3 CATT1 Study of Cadisegliatin in Type 1 Diabetes (T1D). October 5, 2026. Accessed October 6, 2026. 

https://ir.vtvtherapeutics.com/news-releases/news-release-details/vtv-therapeutics-announces-completion-enrollment-phase-3-catt1

Buse discusses the shortcomings of current CGM and AID technologies, as well as how current research aims to address them and further reduce hypoglycemia risk.

Endocrinology

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This page also hosts content previously published by EndocrinologyNetwork. 


Type 1 Diabetes

Alex Hillenbrand is an assistant editor for 

. She earned her BA in English from Lafayette College in 2023 and went on to write for pop culture, entertainment, and sports media outlets before joining MJH Life Sciences in 2025. In her free time, Alex enjoys cooking, going on walks, and meeting new people. Contact her at mjhlifesciences.com.

Hematology in September 2026: ASH raises ferritin thresholds for iron deficiency, plus marstacimab in hemophilia and curative SCD care.

Hematology

Sickle Cell

Sickle Cell condition center page, resources on the topics of medical news and expert insight into sickle cell disease can be found. Content includes articles, interviews, videos, podcasts, and breaking news on sickle cell research, treatment, and drug development.

Anemia

3 Hematology Headlines You Missed in September 2026

Strong recommendations cover carvedilol or banding for varices, semiannual HCC surveillance, vaccines, and smoking cessation.

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.

ACG Guideline Sets 18 Preventive Care Recommendations for Cirrhosis

April Armstrong, MD, MPH, discusses 1-year RELIEVE-AD-PEDs data on rapid, sustained dupilumab disease control in adolescents with atopic dermatitis.

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.

RELIEVE-AD-PEDs: Dupilumab Sustains Adolescent Atopic Dermatitis Control at 1 Year

Eyal Kristal, MD, from the pediatric allergy and immunology clinic at Saban Children's Hospital, Soroka University Medical Center in Israel.

A cohort of 1.3 million Israeli children found a small composite signal, but investigators say penicillin allergy delabeling practice should not change.

Delayed Penicillin Rash and Later Autoimmunity, With Eyal Kristal, MD

Gerald Appel, MD, is a professor of clinical medicine, director of clinical nephrology, and director of the Glomerular Disease Center at Columbia University.

Discover which therapeutic targets and multicenter trial designs Columbia experts see as the next step for fibrillary glomerulonephritis research.

Video Series

Designing the Next Fibrillary GN Trial: B-Cell Agents and T-Cell Engagers

Explore how proteinuria targets and treatment decisions for non-responders differ across IgA nephropathy, lupus nephritis, and membranous nephropathy.

Managing Non-Responders in Glomerular Disease: Proteinuria Targets by Disease

Understand how nonspecific therapy lowers cardiovascular risk in fibrillary glomerulonephritis and why transplant recurrence may be lower than reported.

Fibrillary GN: Cardiovascular Protection and Recurrence After Kidney Transplant

Discover the four-drug conservative regimen one Columbia nephrologist uses to slow fibrillary glomerulonephritis progression without immunosuppression.

Latest News

Why Zasocitinib Outperformed Deucravacitinib in New Plaque Psoriasis Data

Updates and Evolution in Aortic Disease Care, With Edward Chen, MD

Targeting the Disease Mechanism in PFIC, With Hisamitsu Hayashi, PhD

Residual Asthma Exacerbations on Biologics Vary by Mechanism

Addressing the Lingering Challenge of Hypoglycemia in T1D, With John Buse, MD, PhD