5 August FDA Approvals Marked by Novelty, Pushback

August's FDA approvals were marked by both novelty and controversy. The novel approvals included a first-in-class mRNA flu vaccine, the first orexin agonist for narcolepsy type 1 (NT1), and the first oral therapy for dermatomyositis.

The month also tested the agency's approach to contested therapies, with both Moderna's flu vaccine and Replimune's oncolytic immunotherapy for melanoma receiving approval only after initial FDA pushback, complete response letters, or a rocky advisory committee vote.

Learn more about these 5 August FDA approvals:

FDA Approves Moderna’s mRNA Flu Vaccine After Phase 3 Success

After months of scrutiny following the FDA’s refusal to file the initial New Drug Application (NDA) in mid-February 2026, the agency approved Moderna’s Biologics License Application for mRNA-1010 (mFLUSIVA), its mRNA-based flu vaccine, for adults 50 years and older on August 5.¹ The approval of the first mRNA-based flu vaccine was supported by a unanimous recommendation from the Vaccines and Related Biological Products Advisory Committee and trial data demonstrating superior efficacy.

Specifically, the approval was based on findings from a phase 3, double-blinded, active-controlled trial (NCT06602024) that assessed the efficacy and safety of mRNA-1010 in adults aged 50 to 64 years. Of the 40,805 participants analyzed, approximately half received mRNA-1010. RT-PCR-confirmed, protocol-defined influenza-like illness occurred in 2% of participants who received mRNA-1010 and 2.8% of those who received the standard comparator, corresponding to a relative vaccine efficacy of 26.6% (95% CI, 16.7%-35.4%).

Although solicited adverse reactions occurred more frequently in the mRNA-1010 group than in the standard-comparator group, the overall safety profile of mRNA-1010 was consistent with earlier findings, with no new safety concerns identified.

The approval comes amid continued debate surrounding mRNA vaccine technology and shifting federal policies toward mRNA vaccine development. The FDA’s initial refusal to file the NDA application earlier this year was followed by an agreement to review it ahead of the 2026–2027 influenza season, after Moderna committed to conducting a confirmatory postmarketing study. The FDA’s decision also came as HHS announced plans to halt or scale back 22 investigational mRNA vaccine programs, underscoring the broader regulatory uncertainty surrounding the technology.

“Flu remains a significant public health challenge, and mFLUSIVA provides an important new option for America's seniors,” Stéphane Bancel, CEO of Moderna, said in a news release.² “This approval also reflects the ongoing potential of our mRNA platform to help address important public health challenges through continued scientific innovation.”

FDA Approves First Orexin Agonist for Narcolepsy Type 1

That same day, the FDA approved oveporexton (Orzeyful; Takeda), an oral orexin receptor 2 (OX2R) agonist, for the treatment of narcolepsy type 1 (NT1, narcolepsy with cataplexy) in adults.³ The decision made oveporexton the first approved therapy indicated to address the underlying orexin deficiency driving NT1, a rare, chronic neurological disease caused by a loss of orexin-producing neurons, rather than managing its symptoms individually.

In patients with NT1, oveporexton selectively stimulates OX2R to restore orexin signaling, promoting wakefulness and reducing abnormal rapid eye movement sleep phenomena, including cataplexy. The approval was supported by the global phase 3 FirstLight (NCT06470828) and RadiantLight (NCT06505031) trials, which demonstrated statistically significant improvements in excessive daytime sleepiness, cataplexy, and health-related quality of life vs placebo. Oveporexton was generally well tolerated, with the most common adverse effects being insomnia, urinary urgency, urinary frequency, and excessive salivation.

“As the first and only approved orexin therapy to treat the broad spectrum of the disease, Orzeyful can enable a different kind of conversation in the doctor’s office about treatment options,” Emmanuel Mignot, MD, PhD, principal US investigator for the Orzeyful phase 3 program, said in a statement.⁴

FDA Grants Accelerated Approval for Replimune’s RP1 Plus Nivolumab in Advanced Melanoma

The next day, August 6, the FDA granted accelerated approval for Replimune Group’s RP1 (vusolimogene oderparepvec-wtpg), to be sold as Tudriqev.⁵ The novel oncolytic immunotherapy combined with nivolumab is used to treat adults with unresectable advanced cutaneous melanoma who experienced disease progression on an anti-PD-1 antibody-based regimen. Continued approval for this indication may be contingent on the verification of clinical benefit in a confirmatory trial, according to company officials.

The approval followed a tumultuous regulatory path, which included 2 complete response letters and disapproval from the FDA staff ahead of a July 30, 2026, advisory panel vote. Despite this, the Cellular, Tissue, and Gene Therapies Advisory Committee voted 10-3 to recommend approval for the therapy after testimony from melanoma physicians, patients, and patient advocates.

Both the recommendation and the approval were based on data from the IGNYTE clinical trial (NCT03767348), which evaluated RP1 and nivolumab in patients with confirmed progression on an anti-PD-1-containing regimen. Among 140 enrolled patients, the confirmed overall response rate was 32.9%, with a median duration of response of 33.7 months. Overall survival rates at 1 and 2 years were 75.3% (95% CI, 66.9% to 81.9%) and 63.3% (95% CI, 53.6% to 71.5%), respectively, with biomarker analysis demonstrating broad immune activation associated with response. Regarding safety, treatment-related adverse event rates were 77.1% for grades 1 and 2, 9.3% for grade 3, 3.6% for grade 4, and 0% for grade 5.

“Advanced melanoma patients have few options after anti–PD-1 therapy and face high morbidity and poor survival outcomes,” Michael K. Wong, MD, PhD, primary investigator of the IGNYTE study, said in a statement.⁶ “With the approval of Tudriquev, we have a potent oncolytic immunotherapy that can be used in a broad population, including BRAF-naive or pretreated and adjuvant relapsed patients.”

FDA Approves Novel Iberdomide Regimen in RRMM

Another myeloma treatment regimen received accelerated approval a week later on August 13: iberdomide (Zenbexus; Bristol Myers Squibb) plus daratumumab/hyaluronidase-fihj and dexamethasone (IberDd).⁷ The regimen, used to treat patients with relapsed/refractory multiple myeloma who have received at least 1 line of therapy, is a combination of a cereblon E3 ligase modulator (CELMoD), a CD-38–directed monoclonal antibody, and a corticosteroid.

The approval was supported by data from the ongoing phase 3 EXCALIBER-RRMM trial (NCT04975997), which compared IberDd with the daratumumab, bortezomib (Velcade), and dexamethasone (DVd) regimen. The trial’s coprimary end points are minimal residual disease (MRD)-negative CR and PFS, with additional outcomes including overall survival, overall response rate, duration of response, time to progression, time to next treatment, and health-related quality of life.

The trial enrolled 939 patients, with the first 420 patients comprising the primary efficacy population. Among these patients, MRD-negative complete response occurred in 41% of those receiving IberDd compared with 21% of those receiving DVd, nearly doubling the rate with IberDd (P < .0001).

“We are very excited to have a new treatment available, because especially with iberdomide, with dara and dex, it is a drug which actually works in patients who have even failed IMiDs [immunomodulatory drugs], who have failed lenalidomide and pomalidomide,” Prerna Mewawalla, MD, director of stem cell transplant and cellular therapy at Allegheny Health Network and associate professor of medicine at Drexel University College of Medicine, told The American Journal of Managed Care^®.⁸

FDA Approves Brepocitinib as First Oral Drug for Dermatomyositis

To round out the month, on August 27, the FDA approved brepocitinib (Lisraya; Roivant) for adults with dermatomyositis, a condition that causes progressive muscle weakness alongside extensive, painful, and pruritic skin lesions and significantly impairs their quality of life through physical disability, cutaneous disfigurement, and dependence on chronic high-dose steroids.

The decision makes brepocitinib, a once-daily tablet that works as a Janus kinase 1 and tyrosine kinase 2 inhibitor, blocking immune signaling pathways implicated in the disease's pathogenesis, the first approved oral medicine designed to target the disease itself rather than dampen the immune system broadly.

The approval was based on the results of the phase 3 VALOR trial (NCT05437263), which randomized 241 adults 1:1:1 to once-daily brepocitinib 30 mg, brepocitinib 15 mg, or placebo over 52 weeks. The 30-mg dose met the trial's primary end point, a composite Total Improvement Score that tracks 6 domains including muscle strength, physical function, and skin and overall disease activity, and it also met all 9 key secondary end points. Patients taking brepocitinib 30 mg were more than 4 times as likely to achieve improvement in overall disease activity as those on placebo. Patients on brepocitinib also achieved clinically meaningful gains in everyday function, including pain and activities such as climbing stairs, dressing, and running errands.

A secondary analysis reported skin-specific outcomes, further demonstrating the treatment’s effects. Among patients with moderate to severe skin disease at baseline, 45.7% of those on brepocitinib 30 mg achieved “clear” or “almost clear” skin by week 52, vs 21.8% on placebo. Also, 43.5% reached functional skin remission vs 20.8% on placebo.

“For too long, patients with dermatomyositis have faced a significant unmet need for effective treatments, often relying on therapies meant for other diseases,” said Nikolay Nikolov, MD, director of the Office of Immunology and Inflammation in the FDA’s Center for Drug Evaluation and Research. “Today’s approval is a meaningful step forward, giving patients and their health care providers an approved oral therapy proven to help manage this rare and debilitating disease.”

References

1. McCrear S. FDA approves Moderna’s mRNA flu vaccine after phase 3 success. AJMC. August 6, 2026. Accessed September 11, 2026. https://www.ajmc.com/view/fda-approves-moderna-s-mrna-flu-vaccine-after-phase-3-success
2. Moderna receives US FDA approval for influenza vaccine mFLUSIVA. News release. Moderna. August 5, 2026. Accessed September 11, 2026. https://feeds.issuerdirect.com/news-release.html?newsid=4801915282452025&symbol=MRNA
3. Grossi G. FDA approves first orexin agonist for narcolepsy type 1. AJMC. August 21, 2026. Accessed September 11, 2026. https://www.ajmc.com/view/fda-approves-first-orexin-agonist-narcolepsy-type-1
4. FDA approves Takeda's Orzeyful (oveporexton), the first and only medicine to treat the underlying cause of narcolepsy type 1. News release. Takeda. August 5, 2026. Accessed September 11, 2026. https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-narcolepsy/
5. Caffrey M. After wild ride, FDA grants accelerated approval for Replimune’s RP1 plus nivolumab in advanced melanoma. AJMC. August 6, 2026. Accessed September 11, 2026. https://www.ajmc.com/view/after-wild-ride-fda-grants-accelerated-approval-for-replimune-s-rp1-plus-nivolumab-in-advanced-melanoma
6. Replimune announces FDA accelerated approval of Tudriqev in combination with nivolumab for unresectable advanced cutaneous melanoma after progression on an anti-PD-1 based regimen. News release. Replimune. August 6, 2026. Accessed September 11, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-accelerated-approval-tudriqevtm
7. Shaw ML. FDA clears lerodalcibep-liga autoinjector, widens LDL-C indication. AJMC. August 17, 2026. Accessed September 11, 2026. https://www.ajmc.com/view/fda-clears-lerodalcibep-liga-autoinjector-widens-ldl-c-indication
8. Mewawalla P, Shaw ML. Iberdomide approval elevates MRD’s role in myeloma: Prerna Mewawalla, MD. AJMC. August 13, 2026. Accessed September 11, 2026. https://www.ajmc.com/view/iberdomide-approval-elevates-mrd-s-role-in-myeloma-prerna-mewawalla-md
9. Joszt L. FDA approves brepocitinib as first oral drug for dermatomyositis. AJMC. August 27, 2026. Accessed September 11, 2026. https://www.ajmc.com/view/fda-approves-brepocitinib-as-first-oral-drug-for-dermatomyositis
10. FDA approves first oral drug indicated to treat dermatomyositis in adults. News release. FDA. August 27, 2026. Accessed September 11, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-drug-indicated-treat-dermatomyositis-adults