This nearly four-month delay was observed on top of the standard of care, highlighting the drug’s potential to reduce the frequency and severity of painful VOC events in people with sickle cell disease (SCD).

The Phase 3 HIBISCUS trial showed that etavopivat significantly delayed the time to first vaso-occlusive crisis (VOC), with patients experiencing their first crisis at 38.4 weeks compared to 20.9 weeks for those receiving placebo, according to Novo Nordisk officials.

The trial enrolled 385 participants aged 12 years and older who were treated over a 52-week period with a once-daily 400-mg oral dose of etavopivat, a pyruvate kinase-R (PKR) activator. The drug’s mechanism works by preventing the sickling of red blood cells, which is the underlying cause of vaso-occlusive crises, according to company statements and published trial data. Both co-primary endpoints of the study were met, with etavopivat demonstrating a 27% reduction in annualized VOC rate and a superior hemoglobin response compared to placebo.

Specifically, 48.7% of patients treated with etavopivat achieved a hemoglobin increase greater than 1 gram per deciliter at 24 weeks, compared to 7.2% in the placebo group, representing a 41.2% adjusted rate difference, Novo Nordisk reported. This hemoglobin improvement is a key measure of treatment efficacy and supports the drug’s potential to improve oxygen delivery and reduce the complications associated with sickle cell disease.

Clinical safety data from the HIBISCUS trial indicated that etavopivat was well tolerated, with a safety profile consistent with previous studies of the drug. No major safety concerns emerged that would impede the regulatory approval process, according to company officials. The inclusion of adolescents aged 12 years and older alongside adults provided a broad assessment of the drug’s safety and efficacy across a wide age range.

Novo Nordisk acquired etavopivat in September 2022 as part of its $1.1 billion purchase of Forma Therapeutics, the original developer of the drug candidate. The acquisition added etavopivat to Novo Nordisk’s pipeline as a first-in-class oral treatment for sickle cell disease, designed to improve patient convenience and compliance with a once-daily tablet formulation. Company leadership has described etavopivat as a potential “first and best-in-class therapy” for SCD.

The company plans to submit regulatory filings for etavopivat in the third or fourth quarter of 2026, with FDA approval expected in the second half of that year, Novo Nordisk said. Detailed results from the HIBISCUS trial are scheduled to be presented at a scientific conference in 2026.

Analysts from Truist Securities noted that the trial results create “separation amongst PK class candidates,” although no direct head-to-head comparisons have been conducted between etavopivat and competing drugs such as mitapivat. Mitapivat, another PKR activator, showed a 40.6% hemoglobin response rate in its Phase 3 data released in November 2025. Cross-trial comparisons remain inconclusive, according to market analysts, but the data put pressure on other drugmakers developing therapies for sickle cell disease.

Sickle cell disease is a genetic blood disorder characterized by the sickling of red blood cells, which can block blood vessels and cause severe pain in bones, chest, back, or joints. Vaso-occlusive crises are a major cause of morbidity and reduced quality of life for millions of patients worldwide. Current therapeutic options are limited, creating a significant unmet medical need for effective and well-tolerated treatments.

Novo Nordisk’s development of etavopivat aims to address this gap by providing a novel oral therapy that targets the underlying pathophysiology of SCD. The company’s acquisition of Forma Therapeutics and subsequent Phase 3 success represent a strategic effort to expand treatment options for this patient population.

The approval marks the first time the FDA has authorized an oral glucagon-like peptide-1 (GLP-1) receptor agonist specifically for weight management in adults, officials said. The FDA’s decision was based on data from the OASIS 4 clinical trial, which included 307 participants randomized in a 2:1 ratio to receive either the 25 mg semaglutide oral tablet or placebo, alongside lifestyle interventions involving diet and physical activity, according to Novo Nordisk. The trial’s 64-week treatment period incorporated a 12-week dose escalation protocol, with participants achieving an average weight loss of approximately 17% if they remained on the 25 mg dose throughout the study. When accounting for all participants regardless of adherence, the average weight loss was about 14%, company records show.

Participants achieving an average weight loss of approximately 17% if they remained on the 25 mg dose throughout the study.

The OASIS 4 trial excluded individuals with diabetes and included a seven-week off-treatment follow-up phase, according to the FDA’s review documents. The safety profile observed was consistent with known semaglutide side effects, including gastrointestinal symptoms such as nausea, vomiting, diarrhea, constipation, and abdominal pain, the agency noted. Reports of altered skin sensation were more frequent at higher doses but generally resolved over time, officials added. The FDA has issued a boxed warning highlighting the risk of thyroid C-cell tumors based on rodent studies, although the relevance to humans remains unknown, according to prescribing information.

Novo Nordisk plans to launch the oral Wegovy tablet in the United States in early January 2026, with an initial 1.5 mg starting dose priced at $149 per month, company representatives confirmed. The 25 mg once-daily dose will be available following the dose escalation period outlined in the clinical trial. The tablets are produced domestically in the U.S., ensuring a robust supply at launch, according to company sources. Novo Nordisk emphasized that concomitant use of oral Wegovy with other semaglutide products or GLP-1 receptor agonists is not recommended due to potential safety concerns and lack of additional benefit, the FDA prescribing information states.

Timothy Garvey, MD, a professor at the University of Alabama at Birmingham, commented on the approval, saying it equips healthcare professionals with more options to tailor weight management treatments for patients. “Oral Wegovy expands the delivery formats of semaglutide, providing additional flexibility for patients and clinicians,” Garvey said in a statement provided by Novo Nordisk. The company highlighted that the approval broadens patient choices in managing excess weight and underscores the ability to meet diverse patient needs with efficacious therapies.

Wegovy is indicated for adults with obesity or overweight who have at least one weight-related comorbidity, such as hypertension or type 2 diabetes, and is intended to be used in conjunction with a reduced-calorie diet and increased physical activity, according to FDA labeling. The medication is also approved to reduce the risk of major cardiovascular events in certain adults and carries an accelerated approval for treating metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis. Healthcare providers are advised to monitor blood glucose levels in patients with diabetes before and during treatment with Wegovy tablets.

The FDA’s approval of the oral semaglutide tablet adds to the existing portfolio of semaglutide products, which includes injectable formulations previously approved for weight management and diabetes treatment. The original approval for Wegovy injection dates back to 2017, and the oral tablet represents an extension of that indication, officials said. The prescribing information now covers both the injectable and oral formulations, providing guidance on dosing, safety, and contraindications.

Regulatory authorities emphasized that the oral Wegovy tablet is currently approved only in the United States. The approval followed a separate authorization of Wegovy HD injection (7.2 mg) under the Critical to New Product Vitality (CNPV) program, which expedites review of innovative therapies addressing critical health priorities, according to FDA announcements. The CNPV program aims to facilitate faster access to treatments that improve affordability and patient outcomes.

Post-approval monitoring will continue to assess the safety profile of oral semaglutide, including reports of skin reactions that the FDA is investigating further. The agency also advises against combining oral Wegovy with other GLP-1 receptor agonists to minimize risks. As the medication becomes available, healthcare professionals will have an additional therapeutic option to support patients in achieving and maintaining weight loss, officials said.