Etovopivat showed a 27% reduction in vaso-occlusive crisis events and ~4-month delay to first vaso-occlusive crisis event on top of standard of care in patients with sickle cell disease, according to topline results from the phase 3 HIBISCUS trial.

Novo Nordisk announced the results on April 20, 2026, with etabopivat meeting both co-primary endpoints, substantially reducing vaso-occlusive crisis events and improving haemoglobin response, 48.7% of people on treatment achieved an increase of >1g/dL after 24 weeks compared to 7.2% with placebo.

“Sickle cell disease severely impacts the lives of millions of people. We are very excited that etavopivat has the potential to be a first and best-in-class therapy and transform the lives of people with sickle cell disease, who currently have limited therapeutic options,” said Martin Holst Lange, executive vice president, chief scientific officer and head of Research and Development at Novo Nordisk, in a company statement. “Novo Nordisk remains committed to collaborating with sickle cell disease communities around the world to drive innovation, advance health equity and improve access to treatment and care.”

↑ ATP → improved RBC health and membrane stability

↓ 2,3-DPG → increased hemoglobin–oxygen affinity

Etavopivat is an investigational, once-daily, orally bioavailable, selective Pyruvate kinase red blood cell (RBC) isozyme (PKR) activator. By activating PKR, it enhances glycolysis, leading to increased adenosine triphosphate (ATP) levels (improving RBC health/membrane stability) and decreased 2,3-diphosphoglycerate (2,3-DPG) levels, which increases hemoglobin-oxygen affinity and reduces sickle RBC sickling.

, etavopivat was well-tolerated in people with sickle cell disease and daily use resulted in improvements in vaso-occlusive crises, improvements in fatigue and hemolysis, and increases in hemoglobin levels compared to placebo.

In the randomized, double-blind phase 3 HIBISCUS trial, 400mg etavopivat was evaluated for efficacy and safety compared with placebo. The trial included 385 people ≥ 12 years of age with sickle cell disease.

 385 patients aged ≥12 years with sickle cell disease

 Randomized, double-blind, placebo-controlled

Further, as an exploratory analysis, etavopivat significantly reduced the risk of blood transfusion. Further, as an exploratory analysis, etavopivat significantly reduced the risk of blood transfusion.

The US Food and Drug Administration (FDA) has granted etavopivat Fast Track, Rare Pediatric Disease and Orphan Drug designations. Additionally, etavopivat was granted Orphan Drug designation by the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products of the European Medicines Agency for the treatment of patients with SCD.

In the second half of 2026, the company plans to submit for the first regulatory approval of etavopivat, while detailed results from HIBISCUS will be presented at a scientific conference in 2026.

Novo Nordisk A/S. Novo Nordisk: Etavopivat is the first in a new class of drugs to meet both co-primary endpoints in the phase 3 HIBISCUS trial, substantially reducing vaso-occlusive crisis events and improving haemoglobin response in sickle cell disease. GlobeNewswire News Room. Published April 20, 2026. Accessed April 20, 2026. https://www.globenewswire.com/news-release/2026/04/20/3276770/0/en/novo-nordisk-etavopivat-is-the-first-in-a-new-class-of-drugs-to-meet-both-co-primary-endpoints-in-the-phase-3-hibiscus-trial-substantially-reducing-vaso-occlusive-crisis-events-and.html

Wu G, Dhayakar P. Hibiscus 2 (Trial-in-Progress): A global, Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of etavopivat in adolescents and adults with sickle cell disease. 

. 2025;146(Supplement 1):2976-2976. doi:https://doi.org/10.1182/blood-2025-2976

Articles

Topline phase 3 data indicate once-daily oral etavopivat, a selective RBC pyruvate kinase (PKR) activator, met both co-primary endpoints in sickle cell disease, delivering a 27% reduction in vaso-occlusive crisis (VOC) events and delaying time to first VOC by roughly four months on background standard of care. Hemoglobin response was notable, with 48.7% achieving >1 g/dL increase at 24 weeks versus 7.2% on placebo. Exploratory analyses suggested reduced transfusion risk. Regulatory momentum includes multiple FDA designations and EU orphan status, with a first filing planned in 2H 2026.

Etavopivat reduced VOC events by 27% and improved hemoglobin response in the phase 3 HIBISCUS trial in sickle cell disease.

Clinical

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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.

Phase 3 HIBISCUS: Etavopivat Cuts VOC Events, Improves Hemoglobin in SCD

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

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

Integrating Comparative Evidence to Optimize Psoriasis Treatment Decisions

In the final episode, "Integrating Comparative Evidence to Optimize Psoriasis Treatment Decisions," the panelists explore how the full body of available evidence, including comparative analyses, long term extension studies, real world data, and clinical experience, can be integrated into practical treatment decision making for plaque psoriasis.

The panel opens by outlining the distinct role each type of evidence plays in clinical practice. Comparative studies including MAICs, network meta-analyses, and head to head trials are valued for helping clinicians identify which therapy is most likely to work best for a given patient when all else is equal. Long term extension studies are primarily used to provide patients with reassurance around safety, offering years of accumulated clinical trial safety data with no new emerging signals. Real world data is highlighted as particularly valuable for informing drug persistence and helping clinicians select a therapy that patients are likely to stay on long term, reducing the burden of frequent switching for both the patient and the clinical team. The panel also acknowledges the role of anecdotal clinical experience, noting that when personal observations align with what is seen across clinical trial and real world data, it creates a compelling and well supported basis for treatment recommendations.

The discussion then turns to how community practice dermatologists can apply comparative evidence in their daily practice, with the panel emphasizing the importance of understanding what MAICs are and how to interpret them in the absence of head to head trial data. The panel acknowledges that real world evidence takes time to generate, making other data sources particularly important when evaluating newer agents.

The episode concludes with a summary of the strengths of the IL-23 inhibitor class, including superior efficacy, infrequent dosing, and a strong safety profile, and reinforces that each piece of evidence, from phase three trials to real world analyses, contributes to a complete picture that enables truly holistic and patient centered treatment decisions.

Thank you for watching this Peer Exchange series on psoriasis. Please subscribe to our newsletter for information on upcoming video series.

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Video Series

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. 

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

Medical Ethics Unpacked: Clinical Ethics Consultation in Practice

, Dominic Sisti, PhD, a bioethicist from Penn Medicine, speaks with Aliza Narva, JD, BSN, MSN, director of ethics at the Hospital of the University of Pennsylvania, about the practical realities of clinical ethics consultation. Co-host Steve Levine, MD, from Compass Pathways, was unable to join the recording, and Sisti leads the discussion solo with Narva on how ethics teams function within complex hospital environments.

Narva describes clinical ethics consultation as a structured, case-based process that typically begins with a clinician identifying uncertainty or discomfort in care. Requests most often come from residents and nurses. From there, ethicists review the medical record, speak with members of the care team, and, when feasible, include patients and families. She notes that consults frequently reflect communication gaps across teams rather than purely ethical disagreements.

The conversation highlights differences between traditional consultation models and mediation-based approaches. Traditional models often emphasize policy, prior cases, and ethical literature to determine an appropriate recommendation. In contrast, the mediation model focuses on bringing stakeholders together to clarify values and surface assumptions driving disagreement. Narva suggests that many cases shift once all parties are in the same conversation.

Common consult themes include end-of-life decision-making, surrogate disputes, and clinician moral distress. She emphasizes that ethics consultants are often called when clinicians feel constrained or uncertain about next steps.

The discussion also touches on system-level challenges, including pandemic-era visitation policies and their downstream effects on communication and trust. Narva reflects on how rapidly changing policies during COVID-19 exposed tensions between safety, access, and patient-centered care.

Narva stresses that ethics consultants do not issue binding decisions. Their role is to clarify ethical considerations, support communication, and help teams identify workable paths forward within clinical and institutional constraints.

“Ethics consultants don’t have any powers. We’re consultants,” Narva says. “I’m there to outline what our ethical obligations are, do some creative thinking… and make suggestion[s]…but I can’t sign anyone’s permission slip.”

Aliza Narva, JD, discusses how clinical ethics consultation works in practice, from bedside dilemmas to mediation-based approaches and clinician support.

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Medical Ethics Unpacked

Medical Ethics Unpacked is a regular multimedia series hosted by Dominic Sisti, PhD, and Steve Levine, MD, spotlighting a spectrum of topics within the field of medical ethics. Throughout the year, hosts will sit down for an in-depth discussion on a specific ethical dilemma within modern healthcare, with some episodes also featuring a special guest. 

Check back throughout the year for discussions on a variety of topics, including data privacy in health apps, euthanasia and medical assistance in dying, reproductive rights and technologies, and more!

Evaluating IL-23 Inhibitors with Long-Term Data and Real-World Evidence

In this episode, "Evaluating IL-23 Inhibitors with Long-Term Data and Real-World Evidence," the expert dermatologists explore the distinct but complementary roles of long term extension studies and real world evidence in evaluating the durability and safety of biologic therapies for plaque psoriasis.

The panel opens by examining the value and limitations of long term extension studies. While these studies are considered valuable primarily for identifying emerging safety signals and assessing whether adverse events accumulate over time, the panel expresses some skepticism about their ability to accurately reflect long term durability of response. This is because patients who remain in long term extension studies tend to be those who are already responding well, creating an inherently enriched population that does not capture patients who may have struggled to respond early on.

The discussion then shifts to real world evidence, with the panel outlining the key sources of this data including patient registries such as CorEvitas and various country specific registries, as well as claims based data. Registries are noted as semi real world in nature given their lack of strict entry criteria compared to clinical trials, while claims based data offers insight into how long patients persist on a given therapy, though often without accompanying efficacy data unless linked to electronic medical records.

The panel emphasizes that real world data is critical because clinical trials represent a best case scenario, with carefully screened patients, controlled comorbidities, and a high level of clinical support including dedicated nursing staff, medication delivery, and appointment reminders that do not reflect everyday practice. In contrast, real world patients may have uncontrolled comorbidities, complex medication regimens, and limited support, making adherence more challenging. When comparing drug classes in real world analyses, IL-23 inhibitors are noted to generally outperform IL-17 inhibitors, TNF inhibitors, and newer oral agents in keeping patients on therapy over time.

The last episode in this series, "Integrating Comparative Evidence to Optimize Psoriasis Treatment Decisions," features the panelists advancing their conversation on psoriasis and focusing on how clinicians can synthesize MAIC analyses, long term extension studies, real world data, and anecdotal clinical experience into a holistic framework for making individualized treatment decisions and optimizing long term outcomes for patients with plaque psoriasis.

Roy Beck, MD, PhD, is the founder of the Jaeb Center for Health Research.

INHALE-1: Afrezza Safe but Not Superior to Rapid-Acting Analogue in Children, With Roy Beck, MD, PhD

Although it failed to reach the prespecified criteria for HbA1c noninferiority, inhaled technosphere insulin (TI) was proven safe and associated with greater treatment satisfaction than rapid-acting analogue (RAA) insulin in the INHALE-1 study.

These data were presented at the International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) in Barcelona, Spain, by Roy Beck, MD, PhD, founder of the aeb Center for Health Research and lead investigator on the study. 

 spoke with Beck to discuss the pulmonary safety findings from this phase 3 trial.

“It’s advisable to have pulmonary function tests, and it can be done in the office,” Beck told 

. “Maybe 6 months after they’ve started treatment, and if they’re doing okay, then maybe after another 6 months. And then if they’re okay, maybe once a year, unless someone’s getting symptoms. But we did not identify any risk.”

INHALE-1 was a phase 3, open-label, randomized clinical trial evaluating TI’s efficacy and safety in combination with basal insulin versus RAA - including insulin lispro, insulin glulisine, and insulin aspart in combination with basal insulin – in pediatric patients with 

. The trial included 26 weeks of randomized treatment with either TI or RAA, all patients entered an extension period of TI treatment until week 52.

Patients were eligible for INHALE-1 if they were ≥4 and <18 years old with a clinical diagnosis of T1DM or T2DM and had been using insulin for ≥6 months for T1DM or ≥3 months for T2DM. Additionally, patients were required to have an HbA1c ≥7% and ≤11% and be receiving an average prandial dose of insulin ≥2 units per meal, among other criteria. Patients were excluded if they had a history of recent blood transfusions, asthma, serious complications of diabetes, or respiratory tract infection within 14 days of screening, among other criteria.

Patients were then randomly assigned in a 1:1 ratio to either the TI or RAA group. Randomization was stratified by diabetes subtype, baseline HbA1c (<8.5% or ≥8.5%), and age (4 to <13 years or 13 to <18 years). Both groups continued using basal insulin, typically once daily in the evening with either insulin glargine, insulin degludec, or insulin detemir. The primary outcome was change in HbA1c by 26 weeks, with secondary outcomes including binary HbA1c metrics, CGM metrics, and others. Investigators also examined pulmonary function testing as a safety endpoint.

A total of 313 participants were screened and 230 were randomized to the TI group (n = 117) or the RAA group (n = 113). Mean age was 12.6 years (standard deviation [SD], +/- 3 years). 225 patients presented with T1DM and 5 presented with T2DM. In intent-to-treat analysis, mean baseline HbA1c was 8.22 +/- 0.87 and 8.41 +/- 1.38 at 26 weeks with TI and 8.21 +/- 0.96 and 8.21 +/- 1.1, respectively, with RAA (adjusted difference, 0.18; 95% CI, -0.07 to 0.43; noninferiority 

However, despite not meeting the prespecified criteria for HbA1c noninferiority, only 2 severe hypoglycemic events occurred in the TI group and 1 in the RAA group. Treatment was also shown to be safe without affecting pulmonary function compared with RAA, and the TI group reported greater treatment satisfaction (

 = .004) and had less gain in weight and BMI percentile (

“Both the parents and the children expressed greater satisfaction with treatment based on the specific validated survey that was used, even if they didn’t show a benefit in their glucose levels,” Beck said. “I think, possibly because of fewer injections, there’s a greater treatment satisfaction. We actually have a study that’s ongoing now that’s looking at whether starting pediatric patients newly diagnosed with type 1 diabetes on inhaled insulin rather than injections will benefit their adherence.”

Editors’ Note: Beck reports that his institution has received funding on his behalf from Insulet, Tandem Diabetes Care, Beta Bionics, Abbott, Dexcom, Sequel Med Tech, and others.

Haller MJ, Kanapka L, Monzavi R, et al. INHALE-1: A Multicenter Randomized Trial of Inhaled Technosphere Insulin in Children With Type 1 Diabetes. Diabetes Care. 2026;49(1):179-187. 

MannKind Corporation. Afrezza INHALE-1 Study in Pediatrics (INHALE-1). ClinicalTrials.gov Identifier: NCT04974528. Updated May 6, 2025. Accessed April 17, 2026. 

https://clinicaltrials.gov/study/NCT04974528

Beck discusses the recently presented results of INHALE-1, in which technosphere insulin failed to prove noninferiority to RAA but had no pulmonary effects.

Endocrinology

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Howard Trachtman, MD, is an adjunct clinical professor of pediatrics at the University of Michigan.

Listen to our conversation with Trachtman about sparsentan's recent FDA approval for FSGS.

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FSGS Drug Development No Longer a ‘Graveyard’: What Comes After Sparsentan’s Approval

In a Q&A from AAD 2026, Elmariah highlights a variety of significant results highlighted in a poser session from the RELIEVE-PN study regarding dupilumab for prurigo nodularis.

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RELIEVE-PN: Prurigo Nodularis Improves Over 6 Months on Dupilumab, With Sarina Elmariah, MD, PhD, MPH

Stay updated with the latest healthcare breakthroughs, including FDA actions and new topline clinical trial data, in this week’s essential news roundup.

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

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The HCPFive: Top News for Healthcare Providers from the Week of 04/12

Tozorakimab significantly reduced moderate-to-severe exacerbations in COPD regardless of blood eosinophil count.

COPD

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Reducing COPD Exacerbations With Tozorakimab, With Frank Sciurba, MD

At AAD, April W. Armstrong, MD, MPH, discussed recent innovations in the atopic dermatitis treatment space, highlighting long-term safety data and more.

Atopic Dermatitis

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What's New in Atopic Dermatitis Management, With April Armstrong, MD, MPH

Nancy Reau, MD, is Professor of Internal Medicine, Richard B. Capps Chair of Hepatology, Associate Director of Solid Organ Transplantation, and Section Chief of Hepatology at Rush University Medical Center.

Experts discuss how metabolic and hormonal factors in women influence MASLD risk, progression, and potential long-term outcomes.

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MASLD and Women’s Health: The Roles of PCOS and Pregnancy

Beck discusses a recent analysis of the phase 4 trial comparing TI and degludec against standard treatment, highlighting the need for individualized titration.

INHALE-3 Analysis Supports Need for Increased Technosphere Insulin Doses, With Roy Beck, MD, PhD

Marie-José van Tol, PhD, from the University of Groningen.

Research suggests preventive cognitive therapy reduced relapse risk in recurrent depression by improving positive affect and anhedonia, van Tol explained in an interview.

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Preventive Therapy Targeting Positive Affect May Reduce MDD Relapse, With Marie-José van Tol, PhD

Hanna describes the "freedom" patients with sickle cell disease reported after being treated with reni-cel, a one-time edited gene therapy. 

Strategic Alliance Partnership

One-Time Gene-Editing Therapy Gives Patients “Freedom” From Pain Crisis

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.

View slated expert interviews and 7 clinical trials to watch at AACE Annual Meeting 2026.

Latest News

Phase 3 HIBISCUS: Etavopivat Cuts VOC Events, Improves Hemoglobin in SCD

Integrating Comparative Evidence to Optimize Psoriasis Treatment Decisions

Medical Ethics Unpacked: Clinical Ethics Consultation in Practice

Evaluating IL-23 Inhibitors with Long-Term Data and Real-World Evidence

INHALE-1: Afrezza Safe but Not Superior to Rapid-Acting Analogue in Children, With Roy Beck, MD, PhD