Aliza Narva, JD, BSN, MSN, director of ethics at the Hospital of the University of Pennsylvania.

Dominic Sisti, PhD, is an associate professor in the Department of Medical Ethics & Health Policy and the director of the Scattergood Program for the Applied Ethics of Behavioral Health Care. Sisti is also the host of 

, our monthly multimedia series on medical ethics in modern healthcare. 

In this Q&A, Dominic Sisti, PhD, from Penn Medicine, speaks with Aliza Narva, JD, MSN, the director of ethics at the Hospital of the University of Pennsylvania, about her path from law and nursing to clinical ethics consultation and how ethics services function in practice at Penn Medicine.

Narva discusses the interdisciplinary process behind ethics consults, including chart review, engagement with care teams, and conversations with patients and families. She also outlines common sources of ethical conflict, particularly end-of-life decision-making and clinician moral distress, and reflects on a complex, prolonged ICU case that shaped her perspective on balancing policy, compassion, and family dynamics.

This Q&A is a snippet from our latest episode of Medical Ethics Unpacked, all about clinical ethics consultations. Watch the episode here: 

Medical Ethics Unpacked: Clinical Ethics Consultation in Practice

Sisti: Why did you gravitate towards ethics consultation after receiving your JD from Pennsylvania Law School and your bachelor’s and master’s degrees in nursing from Penn?

It started with having a humanities undergraduate degree. Before I went to law school, I was an American studies major at Occidental College in Los Angeles, and I really was focused on and interested in civil rights. I had this idea in undergrad that I would go to law school, and I would end up studying constitutional law and practicing, and that is not what happened to me. Like so many people who go to law school, I ended up coming out with massive debt and sort of got funneled into a large corporate firm where I felt really bored but also anxious, which was a particularly bad combination for me. After a couple of years of practicing corporate law, it became clear to me that I was going to need to do a different thing.

I started to go back to parts of my undergrad education that I had really loved, and then I had worked for 2 years after college in a women's health clinic, and I had really loved that healthcare environment. It was largely run by nurses and nurse practitioners and was really focused on the individual needs of patients, who were folks who often felt very marginalized.

I decided I was going to go back to school. I thought I would go straight through and become a nurse practitioner. Like so many people, I really didn't have a clear idea of what clinical nurses do. I sort of thought of them in this sort of stereotypical way of little lady helpers with little paper hats, and I was obviously quite wrong.

During nursing school, I really fell in love with clinical nursing and being in a hospital, just how dynamic it is. You have this group of people who are all focused on doing the right thing for patients; it really was that same theme of thinking about individual rights, making sure that people are not getting marginalized.

During orientation, [I] met our clinical ethicist, and was like, Yep, that's it. That's the thing I really do. She mentored me. I was able to have her shadow me for years, read my notes, and educate me. I got additional ethics training…and learned the mediation approach to ethics consultation, which is the model that we use here, and it all felt very consistent with that initial inspiration, even in college, of really trying to think about, how are we making sure that individuals who may not have access to the things they need have the best chance of getting what they need.

Sisti: What do you do when you get an ethics consultation request? Do you have a standard process, and what's the result?

A lot of what we do in our model is very traditional in terms of ethics consultation. We typically have one person who's covering the service we offer consultation, 24/7, just with the caveat of like, if it's not an emergency, consider not calling at 3 in the morning. There's always someone who is going to call you back if you have a question.

Whoever's covering will spend a little bit of time talking to the person, [asking] what's going on? What do you think is the ethical issue?

What we will typically do is spend some time in the patient's chart. What is this person's history? Why are they here? What has their experience been? Who are the key players in their health journey?

We really like to make sure we're talking to the clinical team, so not just the person who called, but also the other members. If the resident called, I want to talk to the attending. I want to talk to the nurse. I want to talk to [a] social [worker]. Maybe respiratory therapy is really involved. I'm going to want to talk to that person. And then, really, the standard of practice is also to talk to patients and families.

Sisti: If you had to summarize your top 3 kinds of issues, what are the general ethical conflicts that you see that often come up?

We have a ton of stuff that comes up at [the] end of life. The patient may no longer be able to advocate for themselves, and there's disagreement about what the next step should be in treatment. Are we going to withhold life-sustaining therapies? Are we going to escalate care for this person to the ICU? Is dialysis appropriate?

Another thing that comes up a lot is moral distress. Clinicians…often [feel] morally constrained from doing the thing that they think is the right thing to do or… uncertain about what the right thing is to do. That is definitely a completely appropriate time to call an ethics consult because the ethics consultant is there to help you think through, what are my ethical obligations? Who is the surrogate decision maker?

Sisti: Is there a particular case that stands out from your career that's been either haunting you or you feel proud of?

There was a case a couple of years ago, now maybe 7 years ago. Nothing about this is especially unique, except for her length of stay. There was a woman who suffered from an arrest [and] was in a persistent vegetative. She was in the neuro ICU for a year and a half, and I was new in this role and… thinking about a lot of the literature out [at] the time. [I] was thinking about policies related to how…you respond to potentially inappropriate requests for care from families. What do we do when families are asking for things that just aren't medically indicated? It may not be that they're actually physiologically futile, but they probably aren't going to do the thing that families want them to do. I think I was less generous then. I was very into this policy.

This patient…was 65 years old. She had two adult sons, she had a husband, she was really a matriarch in her community. She had another very rare disease, a neurological disease that had taken like 15 years to diagnose, which predated this terrible arrest. And so, this husband had this traumatic experience, and he really wanted to keep going.

There were meetings and meetings and meetings…with him, and he felt like even just having her heart beating would be all that she would want. It was tricky because I really saw the impact on the patient and her body. She was in the ICU for a long time, so her body just started to really fall apart. I saw the impact on the team and on the staff and how distressed folks felt, continuing to provide these aggressive treatments, keeping her intubated, giving her feeds through the pig tube. She was on dialysis at times. It was a lot.

I wasn't at the point where I could appreciate or understand that the history that they'd had as a family was really explaining the story of where they were now and why he didn't want to let go. Her very long time to get this diagnosis of this rare disease was really informing his goals and wishes.

Questions and answers are edited for clarity.

Articles

In a Q&A with Dominic Sisti, Narva discusses ethics consult workflows, common conflicts, and lessons from complex ICU cases.



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Clinical Ethics Consultation in Practice, With Aliza Narva, JD, MSN

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.

Ravulizumab (Ultomiris) reduced proteinuria as early as week 10 and met its primary endpoint at week 34 in a prespecified interim analysis of the phase 3 I CAN trial, demonstrating a statistically significant and clinically meaningful reduction in proteinuria among adults with 

AstraZeneca announced positive topline results based on the change from baseline in 24-hour urine protein-creatinine ratio (UPCR) at week 34, supporting terminal C5 complement inhibition as a potential disease-modifying approach in IgAN. The trial’s second primary endpoint, change in estimated glomerular filtration rate (eGFR), will be assessed at week 106.

“Many people living with IgAN continue to progress to kidney failure, ultimately requiring dialysis or a transplant—outcomes that can place profound burden on patients’ daily lives—despite advances in care,” said Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, United Kingdom, and I CAN trial investigator. “The interim I CAN results demonstrate that blocking terminal complement activation, a central driver of kidney inflammation in IgAN, with Ultomiris may play a promising role in reducing proteinuria. We look forward to understanding the full clinical impact of Ultomiris in treating this disease following study completion at two years.”

Ravulizumab inhibits complement protein C5, preventing its cleavage into C5a and C5b-9—key drivers of inflammation and kidney damage. By targeting terminal complement activation, the therapy may reduce inflammation and slow the progression of kidney injury in IgAN.

The global, phase 3, randomized, double-blind, placebo-controlled I CAN (ALXN1210-IgAN-320) trial is evaluating ravulizumab in approximately 510 adults with biopsy-confirmed IgAN across 28 countries. Participants were required to be on stable background therapy consistent with standard of care for at least 3 months prior to screening and were randomized 1:1 to receive ravulizumab or placebo.

Ravulizumab was administered intravenously, beginning with a loading dose followed by weight-based maintenance dosing every 8 weeks for a total treatment duration of 106 weeks.

The primary endpoints are change from baseline in proteinuria (UPCR) at week 34 and change in eGFR at week 106, assessed at the interim and final analyses, respectively. Key secondary endpoints include ≥50% reduction in UPCR at week 34, change in UPCR at week 10, time to sustained ≥30% decline in eGFR, and time to first composite kidney event through week 106.

The safety profile observed in the trial was consistent with the known profile of ravulizumab, with no new safety concerns identified.

AstraZeneca indicated it plans to seek accelerated approval in key markets and will present full data from the trial at an upcoming medical meeting.

Phase 2 data previously presented at Kidney Week 2023

 showed greater proteinuria reduction with ravulizumab (40.3%) compared with placebo (10.9%) at 26 weeks, with a treatment effect of 33.1% (90% CI, 14.7-47.5; P = .0012). 

 in patients aged ≥1 month, as well as several other complement-mediated conditions.

Ultomiris demonstrated statistically significant and clinically meaningful reduction of proteinuria in adults with immunoglobulin A nephropathy in I CAN Phase III trial. Astrazeneca.com. Published April 21, 2026. Accessed April 21, 2026. 

https://www.astrazeneca.com/media-centre/press-releases/2026/i-can-phiii-interim-analysis-met-primary-endpoint.html

Valentine A. I CAN - ALXN1210-IgAN-320 Study. Igan.org. Published September 4, 2024. Accessed April 21, 2026. 

https://igan.org/clinical-trial/alxn1210-igan-320-study

Ravulizumab achieved a statistically significant, clinically meaningful reduction in proteinuria in adults with biopsy-confirmed IgA nephropathy, with effects evident by week 10 and meeting the interim primary endpoint at week 34 (24-hour UPCR change). Findings support terminal complement inhibition via C5 blockade as a potential disease-modifying strategy. The ongoing global phase 3, double-blind I CAN trial will evaluate the second primary endpoint, eGFR change, at week 106, alongside kidney-outcome time-to-event secondary endpoints. No new safety signals emerged.

Ravulizumab reduced proteinuria by week 10 and met the primary endpoint in the phase 3 I CAN trial in IgA nephropathy.


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Ravulizumab Reduces Proteinuria as Early as Week 10 in Phase 3 I CAN Trial for IgAN

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.

Avrom S. Caplan, MD/Ananta Khurana, MD, DNB

Credit: NYU Grossman School of Medicine/X

: it is a warning about what can occur when a pathogen outpaces clinician awareness, infrastructure, and the treatment armamentarium.

, represents a newly identified dermatophyte species with evidence of a spread from the Indian subcontinent to many countries around the world, including Europe and the US.

 It is a notable cause of the severe, highly contagious, and often antifungal-resistant skin infection known as ringworm.

, has been identified as genotype VIII within the 

 species complex via Internal Transcribed Spacer (ITS) region sequencing of ribosomal DNA, first described in 2019.

 is a type of fungi requiring keratin to grow and infecting patients’ hair, skin, and nails. The dermatophyte has also attained near-epidemic prevalence on the Indian subcontinent, displacing formerly prevalent dermatophyte species in this location. It is also emerging in the US, representing a notable problem for dermatologists and clinicians of all types.

The dermatophyte’s spread is notable as it is attributable to 2 significant issues faced by dermatologists: misdiagnosis and treatment resistance. This set of compounding issues was discussed in a set of interviews with the 

 team and a pair of clinicians, both of whose research has contributed to the medical community’s increasing awareness of the spread of treatment-resistant skin infections.

The experts were Avrom S. Caplan, MD, an assistant professor of dermatology in the Ronald O. Perelman Department of Dermatology at the NYU Grossman School of Medicine, and Ananta Khurana, MD, DNB, from the Department of Dermatology at the Atal Bihari Vajpayee Institute of Medical Sciences (ABVIMS) and Dr. Ram Manohar Lohia (RML) Hospital in New Delhi, India.

Through a combination of recent data and these experts’ insights, this feature explores the rise of treatment-resistant dermatoses across the world, centering on 

 as a key example, as well as what clinicians need to understand about treatment resistance and why it matters.

"It is something which everyone has to know and understand, before it becomes endemic in more regions of the world,” Khurana expressed. Caplan concurred, noting the dermatophyte has been hiding in plain sight for longer than the medical community has realized.

Recognizing Infection, Clinical Presentation, and Red Flags

Dermatophytoses impact approximately 25% of the global population, according to research authored in part by Caplan.

 Dermatophytes are made up of over 30 species of common and contagious filamentous fungi known to invade keratinized tissues and lead to superficial infections.

Consequently, clinicians, and especially dermatologists, may have to focus more deeply on infections such as these, keeping both antifungal resistance and misdiagnosis in mind as the issue becomes more visible around the world.

“If we're not aware as clinicians of the potential that someone might have this particular dermatophyte, we might be fooled into thinking they have a different dermatologic condition, such as eczema or psoriasis, and then the patient might have a delay in treatment,” Caplan noted in his interview.

 is now documented in about 40 countries across multiple continents, according to Khurana, and its spread has been strongly linked to travel and migration patterns.

 Cases in the US have been confirmed in multiple states, with 9 of 11 patients identified in a 2023 cohort study having reported prior travel to Bangladesh.

 Diagnostic delays were also observed, ranging from 3 - 42 months in this study.

The dermatophyte causes inflammatory, intensely itchy, commonly widespread dermatophytosis impacting those with the condition in their groin, gluteal region, trunk, and face. Patients of all ages and genders can be affected.

"The kind of extent of infection we see in patients now was not so common before,” Khurana said. “And a lot of patients come with very prominent facial involvement, face, neck, and extension into the scalp."

In the Morbidity and Mortality Weekly Report by the US Centers for Disease Control and Prevention (CDC), the highly transmissible infection is characterized by inflamed, widespread, pruritic plaques on the body, known as tinea corporis.

 Plaques are found in the pubic region, crural fold, the adjacent thigh, or face.

"One of the things I hear from patients most is how itchy it is,” Caplan added. “It can be sort of maddeningly itchy, and it can be pretty widespread across the body."

The diagnosis of resulting tinea infections poses a challenge, given their similar appearance to other conditions with comparable lesions. Researchers have noted eczema’s similar appearance to tinea corporis and alopecia areata’s similarity to tinea capitis, for example.

Caplan noted the importance of looking into t. Indotineae as a possibility, noting additional exploration may be needed when “someone has been treated for eczema or psoriasis for quite some time, and it's not getting better, and then we start to pick up some more clinical clues.”

Additionally, both Khurana and Caplan urged attention if a family member has the infection or if a patient has traveled to a country in which the dermatophyte is widespread.

Research has suggested that culture and physiological characteristics of the infection cannot confirm identification at the species level.

 Such a situation, therefore, could require species-level confirmation via molecular methods.

The Resistance Picture: What Clinicians Should Understand

One of the biggest concerns surrounding the spread of 

 is the dermatophyte’s resistance to terbinafine, an antifungal commonly known by the brand name Lamisil. Terbinafine is typically the first-line treatment for tinea.

“There had been actually articles before, in the early 2000s, which said that it is very unlikely that dermatophytes will ever become resistant to terbinafine, because the mode of action of that resistance in acquiring a single gene mutation in the target enzyme would be a very rare occurrence,” Khurana explained.

Khurana noted it had been established that dermatophytes would not have the ability to resist antifungal drugs such as terbinafine. She pointed to the well-documented observation that the dermatophyte is, in fact, developing resistance.

Those who are resistant to terbinafine are often treated next with oral itraconazole. However, data has suggested 

 is often resistant to azole antifungals such as itraconazole and fluconazole.

 Its use as an alternative option has seen success, but questions about resistance remain.

"If we are actually seeing terbinafine resistance and itraconazole resistance, that's really worrisome,” Caplan noted. “Now there's a lot of debate and discussion about whether we're actually seeing itraconazole resistance or not. But talking to colleagues anecdotally, it sounds like there are some countries where people are now reaching for other antifungals beyond itraconazole to treat this infection."

 carries predominantly in vitro genetic resistance to terbinafine through point mutations in the enzyme squalene epoxidase (SQLE).

 There is also no established clinical breakpoint for antifungal treatment of dermatophytes. Additionally, in vitro antifungal susceptibility tests (AFST) do not necessarily correspond to patients’ clinical responses, leading to additional treatment issues.

In the current treatment landscape, there is still a lack of consensus on the most impactful therapeutic approach for infections resulting from 

, including antifungal agents, duration of treatment, dosing regimens, and infection control measures needed to diminish continued dermatophyte transmission.

Adapting Treatment Strategies and Looking to the Future

Knowledge about how to confront treatment-resistant dermatophytes is increasingly becoming necessary for clinicians. When it comes to addressing suspected or confirmed 

, both Khurana are in agreement: shifting to itraconazole directly rather than defaulting to terbinafine may be warranted.

While terbinafine at higher-than-standard doses retains utility and has data supporting its utilization, the pair noted it may not fully overcome resistance and should be reserved for select cases or where itraconazole is contraindicated.

Another important aspect worth considering is counseling patients on their duration of treatment. Khurana urged caution to clinicians who might assume itraconazole failures are immediate evidence of treatment resistance.

“Currently, the organism is sensitive to itraconazole, and clinically, itraconazole does work well,” Khurana said. “Mostly when the patients say they have taken itraconazole and not responded, it's mostly to do with compliance with the long treatment durations, or if a good formulation has not been used."

Caplan echoed this sentiment, pointing to the need for close follow-up to confirm not only patients’ initial response to treatment, but also their level of clearance. He highlighted the value of ensuring patients have consistent access to their medication and are taking it correctly.

When considering what follows itraconazole, both experts believe the answer is not escalation. Third-generation azoles such as posaconazole and voriconazole must be preserved for invasive and systemic fungal infections. Implementing them for widespread community tinea would be both clinically inappropriate and could be seen as a failure of stewardship.

The experts noted the antifungal pipeline is limited, with very few new treatments in development. This, they suggested, means clinicians should resist their impulse to move to other drugs out of frustration or uncertainty.

“We don't have a lot of antifungals in the pipeline, and so we need to preserve what we have,” Caplan explained. “Also, we need to think about what's called antifungal stewardship, [which means] not using antifungals inappropriately, so that we're not contributing to any potential resistance."

Overall, Khurana and Caplan are 2 of many experts who have pointed to the explosion of antifungal-resistant dermatophyte infections as an alarming global health issue.

 In the interest of preventing such easily transmissable infections, clinicians may wish to maintain a high level of awareness of resistant dermatophyte infections.

Additionally, the maintenance of the aforementioned antifungal stewardship measures may be critical for stemming the tide of these infections. Dermatologists may be in a position to lead efforts in the coming years to prevent the rising spread of treatment-resistant dermatophytes in the US and around the world.

Uhrlaß S, Verma SB, Gräser Y, Rezaei-Matehkolaei A, Hatami M, Schaller M, Nenoff P. Trichophyton indotineae-An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide-A Multidimensional Perspective. J Fungi (Basel). 2022 Jul 21;8(7):757. 

Tamer F, Polat M. Evaluation of Clinical Studies of Patients With Dermatophyte Infections Caused by Trichophyton indotineae: Treatment Response and Resistance to Antifungal Medications. Dermatol Pract Concept. 2025 Oct 1;15(4):e20255517. 

Caplan AS, Todd GC, Zhu Y, et al. Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae. JAMA Dermatol. 2024;160(7):701–709. 

Dellière S, Jabet A, Abdolrasouli A. Current and emerging issues in dermatophyte infections. PLoS Pathog. 2024 Jun 13;20(6):e1012258. 

Caplan AS, Chaturvedi S, Zhu Y, et al. Notes from the Field: First Reported U.S. Cases of Tinea Caused by Trichophyton indotineae — New York City, December 2021–March 2023. MMWR Morb Mortal Wkly Rep 2023;72:536–537. DOI: 

Marbaniang YV, Leto D, Almohri H, Hasan MR. Treatment and diagnostic challenges associated with the novel and rapidly emerging antifungal-resistant dermatophyte, Trichophyton indotineae. J Clin Microbiol. 2025 Jun 11;63(6):e0140724. 

. Epub 2025 Jun 11. PMID: 40497720; PMCID: PMC12153305.

Hui ST, Gifford H, Rhodes J. Emerging Antifungal Resistance in Fungal Pathogens. Curr Clin Microbiol Rep. 2024;11(2):43-50. 

. Epub 2024 Mar 18. PMID: 38725545; PMCID: PMC11076205.

Hill RC, Caplan AS, Elewski B, Gold JAW, Lockhart SR, Smith DJ, Lipner SR. Expert Panel Review of Skin and Hair Dermatophytoses in an Era of Antifungal Resistance. Am J Clin Dermatol. 2024 May;25(3):359-389. 

. Epub 2024 Mar 18. PMID: 38494575; PMCID: PMC11201321.

Trichophyton indotineae, a newly defined dermatophyte within the T. mentagrophytes/T. interdigitale complex, is spreading globally and emerging in the US, driven by travel and migration. Clinically, it produces intensely pruritic, inflammatory, often extensive tinea corporis with frequent groin, trunk, and facial involvement, and is commonly misdiagnosed as eczema or psoriasis, delaying effective therapy for months. The major threat is antifungal resistance, particularly terbinafine via SQLE mutations, with uncertain but concerning azole resistance patterns, limited diagnostic certainty without molecular methods, and few pipeline alternatives.

There is an antifungal-resistant dermatophyte spreading globally, and experts are urging clinicians to become more aware.

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When First-Line Fails: The Rising Threat of Treatment-Resistant Dermatoses

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 US Food and Drug Administration has accepted Cristcot’s New Drug Application (NDA) under section 505(b)(2) of the Federal Food, Drug and Cosmetic Act for its next-generation hydrocortisone acetate (ngHCA) 90-milligram suppository administered using the Company’s patented, FDA-approved Sephure® suppository applicator for the treatment of patients with ulcerative colitis (UC) of the rectum.

 Topical corticosteroid (hydrocortisone acetate suppository)

As described in an April 21, 2026, press release, the NDA is supported by positive results from the Company’s phase 3 pivotal trial, which achieved its primary endpoint of clinical remission based on the Modified Mayo Score of 0-2 at Day 29. With the acceptance, the FDA has set a PDUFA target date in October 2026. If approved, ngHCA would be the first and only FDA-approved hydrocortisone acetate (HCA) suppository.

“The FDA’s acceptance of our NDA brings us one step closer to addressing the significant treatment gap for the roughly 1.3 million ulcerative colitis patients in the U.S.,” Jennifer Davagian, Cristcot Founder and Chief Executive Officer, said in a statement. “While the clinical use of HCA in treating UC is well characterized, there is significant unmet need with no FDA approved rectal suppository for the most stubborn symptoms associated with rectal disease involvement. ngHCA is designed to address the limitations of currently available UC therapies and the gap in treating rectal disease.”

ngHCA, Cristcot’s investigational hydrocortisone acetate (HCA) 90 mg suppository formulation, is a novel corticosteroid therapy delivering a small volume suppository administered using the Sephure® suppository applicator. Unlike other corticosteroid treatments, the advanced HCA formulation allows for rapid, sustained release with optimal bioavailability, and very limited systemic exposure. The innovative delivery system is designed to overcome the treatment barriers associated with currently available therapies and enhance patient compliance.

CESSA trial results were presented at the American College of Gastroenterology 2025 Annual Scientific Meeting and showed the trial achieved its primary endpoint of clinical remission at day 29 and secondary endpoint of clinical response at day 15, both using modified Mayo Score criteria, demonstrating statistically significant improvements for patients treated with the ngHCA 90 mg suppository compared to those who received placebo.

Clinical and endoscopic remission was achieved by 21.2% (

= .0005) of study participants in the ngHCA QD (once-daily) arm versus 1.5% of patients in the placebo arm. Additional secondary efficacy analyses showed treatment with ngHCA QD resulted in greater improvement in rectal bleeding and stool frequency scores at day 15 and day 29 versus placebo.

Safety results showed ngHCA was well tolerated with no treatment-related serious adverse events (SAEs). Treatment-related adverse events (TEAEs) were reported by 4.5% of patients in the QD treatment group and 7.6% in the placebo group, with the majority being mild and moderate in severity. Of note, compliance was very high, with 100% of subjects in the ngHCA QD group having > 90% adherence with the required dosing.

Cristcot. Cristcot Announces FDA Acceptance of NDA for Next-Generation Hydrocortisone Acetate (ngHCA) for Treatment of Ulcerative Colitis (UC) of the Rectum. April 21, 2026. Accessed April 21, 2026. 

https://cristcot.com/news/cristcot-announces-fda-acceptance-of-nda-for-next-generation-hydrocortisone-acetate-nghca-for-treatment-of-ulcerative-colitis-uc-of-the-rectum

Cristcot. Cristcot to Present Data on Novel Ulcerative Colitis Treatment at the American College of Gastroenterology 2025 Annual Meeting. October 26, 2025. Accessed April 21, 2026. 

https://cristcot.com/news/26-october-2025

FDA accepted Cristcot’s 505(b)(2) NDA for a next-generation hydrocortisone acetate 90‑mg rectal suppository delivered via the FDA-approved Sephure® applicator for ulcerative colitis involving the rectum, with an October 2026 PDUFA date. Phase 3 CESSA data support filing, showing Day 29 clinical remission by Modified Mayo Score and earlier clinical response at Day 15. The small-volume formulation is intended to provide rapid, sustained local release with limited systemic exposure. Tolerability was favorable, and adherence exceeded 90% in all treated patients.

If approved, the novel corticosteroid therapy would be the first and only FDA-approved hydrocortisone acetate suppository.

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FDA Accepts NDA For Next-Generation Hydrocortisone Acetate in Ulcerative Colitis of the Rectum

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.

 has accepted Genentech's supplemental Biologics License Application (sBLA) for obinutuzumab (Gazyva) for the treatment of systemic lupus erythematosus (SLE), the company announced on April 20, 2026. 

The filing is based on results from the phase 3 ALLEGORY trial, which demonstrated a statistically significant improvement in disease activity compared with placebo. An FDA decision is expected by December 2026. 

"The FDA's sBLA acceptance for Gazyva brings us one step closer to providing a highly effective new treatment option for people living with this unpredictable and potentially life-threatening disease," said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech.¹

If approved, obinutuzumab would become the first anti-CD20 therapy indicated for SLE, a chronic autoimmune disease affecting more than 3 million people worldwide. The drug is already approved in the US and European Union for adults with active lupus nephritis, as well as for several hematological malignancies in approximately 100 countries.¹

The ALLEGORY study (NCT04963296) is a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that enrolled approximately 300 adults with SLE receiving standard therapy. Participants were randomized 1:1 to receive obinutuzumab or placebo for 52 weeks, followed by an open-label extension period with obinutuzumab for up to 104 additional weeks.¹

The trial met its primary endpoint: 76.7% of patients treated with obinutuzumab plus standard therapy achieved a 4-point or greater improvement on the SLE Responder Index (SRI-4) at 52 weeks, compared with 53.5% in the placebo group (adjusted difference, 23.1%; 95% CI, 12.5-33.6; 

Obinutuzumab was also superior to placebo across all key secondary endpoints, including British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response at 52 weeks and sustained glucocorticoid reduction to 7.5 mg/day or less from week 40 through 52.¹

The remission rate at 52 weeks, as defined by the Definition of Remission in SLE (DORIS) criteria, more than doubled among obinutuzumab-treated patients (33.8% vs 13.8%; adjusted difference, 19.9%; 95% CI, 10.6-29.2). The Lupus Low Level Disease Activity State (LLDAS) rate also more than doubled (57.6% vs 25.0%; adjusted difference, 32.6%; 95% CI, 22.3-43.0). 

Of note, patients receiving obinutuzumab were significantly less likely to experience a disease flare through week 52, as measured by the BILAG index (hazard ratio, 0.58; 95% CI, 0.40-0.82; 

Safety findings were reported as consistent with the known profile of obinutuzumab, with no new safety signals identified. Key established risks include infusion-related reactions, infections, hepatitis B reactivation, progressive multifocal leukoencephalopathy, neutropenia, and thrombocytopenia.¹

SLE remains a challenging disease to manage, with diagnosis often delayed 2 to 6 years. Repeated flares drive cumulative organ damage, and approximately half of patients develop lupus nephritis within 5 years.¹ Current treatment relies heavily on glucocorticoids, antimalarials, and immunosuppressants, with belimumab (Benlysta) and anifrolumab (Saphnelo) representing the only targeted biologic therapies approved for SLE.² The steroid-sparing effect demonstrated in the ALLEGORY trial is clinically relevant, as long-term glucocorticoid use contributes substantially to morbidity in this population.

Obinutuzumab is a humanized, glycoengineered type II anti-CD20 monoclonal antibody that induces direct B-cell death and enhanced antibody-dependent cellular cytotoxicity. It differs mechanistically from rituximab, the most widely used anti-CD20 agent off-label in lupus, which failed to meet primary endpoints in prior randomized SLE trials.³ Whether obinutuzumab's glycoengineered properties account for superior B-cell depletion and the positive results observed in ALLEGORY warrants further investigation.

The ALLEGORY trial's 52-week primary endpoint provides a limited window for evaluating a chronic disease. Long-term durability data from the open-label extension period will be important. Detailed subgroup analyses, including outcomes by race and ethnicity, populations disproportionately affected by SLE, have not yet been fully reported. The ALLEGORY data have also been submitted to the European Medicines Agency for review.¹ Results were published in the 

 in March 2026 and presented at SLEuro 2026.¹

Genentech. FDA accepts application for Genentech's Gazyva for the treatment of the most common form of lupus. Press release. April 20, 2026. Accessed April 21, 2026. 

https://www.businesswire.com/news/home/20260420770652/en/CORRECTING-and-REPLACING-FDA-Accepts-Application-for-Genentechs-Gazyva-for-the-Treatment-of-the-Most-Common-Form-of-Lupus

Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. 

Rovin BH, Furie R, Latinis K, et al; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. 

Genentech’s sBLA for obinutuzumab in systemic lupus erythematosus has been accepted by the FDA, with a December 2026 action date. In the phase 3 ALLEGORY trial (~300 adults on standard therapy), adding obinutuzumab significantly improved SRI-4 responses at week 52 versus placebo and achieved superiority across key secondary endpoints, including BICLA response and sustained glucocorticoid tapering. Remission (DORIS) and LLDAS rates more than doubled, and flare risk was reduced. Safety aligned with the established anti-CD20 profile.

The FDA accepted Genentech's sBLA for obinutuzumab in SLE based on positive phase 3 ALLEGORY trial results, with a decision expected by December 2026.

FDA Accepts sBLA for Obinutuzumab (Gazyva) in Systemic Lupus Erythematosus

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