Ryan Livingston joined the MJH Life Sciences team in March of 2025, shortly after graduating from TCNJ with a bachelor’s degree in English. He enjoys creative writing, reading, and scuba diving. He can be reached at rlivingston@mjhlifesciences.com.

Image Credit: US Food and Drug Administration

Announced by Outlook Therapeutics on December 31, 2025, the 

 has issued a Complete Response Letter (CRL) to ONS-5010 for the treatment of 

wet age-related macular degeneration (AMD)

In the CRL, the FDA determined that the additional mechanistic and natural history data provided in the resubmission failed to alter the previous review conclusion, which stated that confirmatory evidence of efficacy must be submitted to support the application. According to the release, the FDA has not yet indicated what type of confirmatory evidence would be acceptable.

"We are disappointed and disagree with this decision, but we remain fully committed to taking all necessary steps to receive approval in the United States," Bob Jahr, chief executive officer of Outlook Therapeutics, said in a statement. "We continue to believe strongly in the clinical need and commercial potential of the first on-label bevacizumab product for patients in the United States that is specifically formulated, manufactured, and packaged for intravitreal use."

ONS-5010 is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to all isoforms of human vascular endothelial growth factor (VEGF) with high affinity, neutralizing VEGF’s biologic activity through a steric blocking of its binding to its receptors on endothelial cells. This reduces endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.

ONS-5010 has previously received regulatory approval in the European Union and the United Kingdom in 2024 for the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet AMD.

ONS-5010 has had a long regulatory road in the US, having received a Complete Response Letter from the FDA in August of 2023 after their first Biologics License Application (BLA). At the time, despite the pivotal NORSE TWO trial achieving its safety and efficacy endpoints, the FDA concluded it was unable to approve the BLA on account of several Chemistry Manufacturing and Controls (CMC) issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.

On April 8, 2025, Outlook Therapeutics announced the FDA’s acceptance of a new BLA, which allows ONS-5010 – under the brand name LYTENAVA – 12 years of regulatory exclusivity after regulatory approval. This resubmission was based on the NORSE EIGHT trial results, as well as the additional CMC data requested by the FDA.

On August 28, 2025, however, the FDA issued another CRL, citing a lack of substantial evidence of effectiveness. Outlook Therapeutics conducted a Type A meeting, after which a third BLA was submitted on November 3, 2025. The submission contains the same data from NORSE TWO and NORSE EIGHT, as well as a response to the CRL crafted from the official minutes of the Type A meeting.

NORSE EIGHT was a randomized, controlled, parallel group, masked, non-inferiority study investigating the difference in best-corrected visual acuity (BCVA) and retinal thickness between ONS-5010 and ranibizumab. After analysis, investigators announced on January 16, 2025, that ONS-5010 demonstrated noninferiority to ranibizumab at week 12.

ONS-5010 did not, however, meet its primary non-inferiority endpoint by week 8, as suggested in the special protocol assessment with the FDA. Investigators did note the consistent BCVA improvement across all time points, the generally good tolerability, and the safety and efficacy results compared to NORSE ONE, NORSE TWO, and NORSE THREE.

According to the press release, Outlook Therapeutics continues to explore all available pathways for approval while expanding into additional markets in Europe, where it has already received several regulatory approvals.

"Our goal has always been to provide wet AMD patients and their physicians with a safe, consistent, FDA-approved alternative to compounded Avastin manufactured in the United States, and that goal has not changed," Jahr said.

Outlook Therapeutics. Outlook Therapeutics Provides Regulatory Update on US Food and Drug Administration Review of ONS-5010/LYTENAVA (bevacizumab-vikg) for the Treatment of Wet AMD. December 31, 2025. Accessed December 31, 2025.

 https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeutics-provides-regulatory-update-us-food-and-0

Outlook Therapeutics. Outlook Therapeutics Announces Acceptance of Biologics License Application by US FDA for ONS-5010 as a Treatment for Wet AMD. November 13, 2025. Accessed December 24, 2025. 

https://ir.oncobiologics.com/news-releases/news-release-details/outlook-therapeutics-announces-acceptance-biologics-license

Outlook Therapeutics. Outlook Therapeutics Announces Acceptance of Biologics License Application by U.S. FDA for ONS-5010 as a Treatment for Wet AMD. April 8, 2025. Accessed December 24, 2025. 

https://ir.oncobiologics.com/news-releases/news-release-details/outlook-therapeuticsr-announces-acceptance-biologics-license-0

Campbell P. FDA Issues CRL for Ophthalmic Bevacizumab in Wet AMD. 

. August 30, 2023. Accessed December 24, 2025. 

https://www.hcplive.com/view/fda-issues-crl-for-ophthalmic-bevacizumab-in-wet-amd

Outlook Therapeutics. Outlook Therapeutics Re-Submits Biologics License Application for ONS-5010. November 3, 2025. Accessed December 24, 2025. 

https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeutics-re-submits-biologics-license-application

Harp M. Outlook Therapeutics completes analysis of 12-week safety and efficacy results of NORSE EIGHT. 

 January 16, 2025. Accessed December 24, 2025. 

https://www.ophthalmologytimes.com/view/outlook-therapeutics-completes-analysis-of-12-week-safety-and-efficacy-results-of-norse-eight

Articles

The FDA issued a Complete Response Letter to Outlook Therapeutics for ONS-5010, a bevacizumab formulation for wet AMD, citing insufficient confirmatory evidence of efficacy. Despite previous regulatory approvals in Europe, the US approval process has faced challenges, including Chemistry Manufacturing and Controls issues and unmet efficacy endpoints. The NORSE EIGHT trial showed non-inferiority to ranibizumab at week 12 but not at week 8. Outlook Therapeutics remains committed to pursuing US approval and expanding in European markets, emphasizing the clinical need for an FDA-approved alternative to compounded Avastin.

The CRL notes that additional mechanistic and natural history data have not altered the previous review conclusions.

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Age-Related Macular Degeneration

age-related macular degeneration condition center page is a comprehensive resource for clinical news and insights on retina disease. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for patients with AMD.

FDA Issues Complete Response Letter for ONS-5010 for Wet AMD

Announced by Axsome Therapeutics, Inc., on December 31, 2025, the 

 has accepted – and granted Priority Review to – the supplemental New Drug Application (sNDA) for AXS-05 for the treatment of agitation in 

“Up to 76% of people with Alzheimer’s disease experience agitation, representing a significant unmet medical need for patients and their caregivers, and currently there is a dearth of approved treatments,” Herriot Tabuteau, MD, chief executive officer of Axsome Therapeutics, said in a statement. “We look forward to continuing to work with the FDA for the remainder of the review.”

AXS-05 is a novel oral N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor under development for Alzheimer’s disease and smoking cessation. The medication utilizes a proprietary dextromethorphan and bupropion formulation and dose, along with Axsome’s metabolic inhibition technology, to modulate component delivery. It has already received FDA approval for major depressive disorder in adults.

The sNDA was submitted following positive results from a series of phase 3 clinical trials, including ACCORD/ACCORD-2 and ADVANCE-2. ACCORD was a double-blind, multi-center, randomized-controlled trial consisting of a 9-week open-label period followed by a 26-week double-blind period. A total of 178 participants with a mean Cohen Mansfield Agitation Inventory (CMAI) baseline total score of 70.9 were enrolled in the open-label phase and were treated with AXS-05. During this phase, AXS-05 treatment was associated with improvements from baseline in CMAI scores at all timepoints from Week 1 (6.7 points; 

A total of 108 responders, defined as those with ≥30% improvement from baseline in CMAI total score and with Patient Global Impression of Change (PGI-C) score improvements ≤3 lasting ≥4 consecutive weeks, were then randomly assigned in a 1:1 ratio to either AXS-05 (n = 53) or placebo (n = 55). During the second phase, AXS-05 delayed time to relapse of agitation symptoms compared to placebo (HR, 0.276; 

 = .014), representing a 3.6-fold lower risk. It also displayed improved relapse prevention (7.5%) compared to placebo (25.9%; 

ADVANCE-2 was a multi-center, double-blind, placebo-controlled, randomized study investigating AXS-05's safety and efficacy compared to placebo. Investigators enrolled patients with a diagnosis of probable Alzheimer’s disease based on the 2011 National Institute on Aging-Alzheimer Association (NIA-AA) criteria and a diagnosis of clinically significant agitation resulting from probable Alzheimer’s disease according to the International Psychogeriatric Association (IPA) provisional definition of agitation. Patients who had dementia of a non-Alzheimer’s type were excluded.

Ultimately, a total of 408 patients were enrolled and randomly assigned in a 1:1 ratio to either AXS-05 or placebo for ≤5 weeks, both in the form of tablets taken twice daily. During the trial, AXS-05 failed to demonstrate statistical significance in changing the CMAI total score from baseline to Week 5 (AXS-05, 13.8 points; placebo, 12.6 points). However, the results from this endpoint did numerically favor AXS-05.

AXS-05 was safe and well-tolerated in both studies, and it was not associated with an increased risk of falls, cognitive decline, or sedation. Additionally, AXS-05 led to no deaths in the clinical program.

According to the press release, the FDA has established a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2026.

Axsome Therapeutics. Axsome Therapeutics Announces FDA Acceptance and Priority Review of Supplemental New Drug Application for AXS-05 for the Treatment of Alzheimer’s Disease Agitation. December 31, 2025. Accessed December 31, 2025. 

https://www.globenewswire.com/news-release/2025/12/31/3211743/33090/en/Axsome-Therapeutics-Announces-FDA-Acceptance-and-Priority-Review-of-Supplemental-New-Drug-Application-for-AXS-05-for-the-Treatment-of-Alzheimer-s-Disease-Agitation.html?_gl=1*10bx1vl*_up*MQ..*_ga*MTMwMTY4NzU1OC4xNzY3MTk1NDM2*_ga_ERWPGTJ5X8*czE3NjcxOTU0MzUkbzEkZzAkdDE3NjcxOTU0OTgkajYwJGwwJGgw

Cummings J, Grossberg G, Andersson C, et al. Efficacy and Safety of AXS-05 in Agitation Associated with Alzheimer’s Disease: Results from ACCORD, a Phase 3, Double-blind, Placebo-controlled, Relapse Prevention Trial (PL5.004). 

. April 9, 2024. Accessed December 31, 2025. 

https://www.neurology.org/doi/10.1212/WNL-.0000000000205634

Axsome Therapeutics, Inc. A Study to Assess the Efficacy and Safety of AXS-05 in Subjects With Alzheimer’s Disease Agitation (ADVANCE-2). ClinicalTrials.gov Identifier: NCT05557409. Updated November 26, 2025. Accessed December 31, 2025. 

https://clinicaltrials.gov/study/NCT05557409

Axsome Therapeutics. Axsome Therapeutics Announces Successful Completion and Results of Phase 3 Clinical Program of AXS-06 in Alzheimer’s Disease Agitation. 

. December 30, 2024. Accessed December 31, 2025. 

https://www.biospace.com/press-releases/axsome-therapeutics-announces-successful-completion-and-results-of-phase-3-clinical-program-of-axs-05-in-alzheimers-disease-agitation

The FDA has accepted and granted Priority Review to Axsome Therapeutics' supplemental New Drug Application for AXS-05, targeting agitation in Alzheimer's disease. AXS-05, an NMDA receptor antagonist and sigma-1 agonist, showed promising results in phase 3 trials, including ACCORD and ADVANCE-2. While ACCORD demonstrated significant improvements in agitation symptoms, ADVANCE-2 did not achieve statistical significance but favored AXS-05 numerically. The drug was well-tolerated, with no increased risk of falls or cognitive decline. The FDA's target action date for the application is April 30, 2026.

The novel oral NMDA receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor has indicated its efficacy and safety across 3 clinical trials.

Geriatrics

Geriatric medicine condition center page is a comprehensive resource for clinical news and insights on frequent geriatric-related diseases and conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for sleep disorder, dementia, Alzheimer's disease, and more.

Dementia and Alzheimer Disease

Alzheimer Disease condition center page, resources on the topics of medical news and expert insight into Alzheimer's can be found. Content includes articles, interviews, videos, podcasts, and breaking news on dementa and Alzheimer disease research, treatment, and drug development.

FDA Accepts, Grants Priority Review to AXS-05 sNDA for Alzheimer’s Disease Agitation

Announced by parent company Corcept Therapeutics on December 31, 2025, the 

 has issued a Complete Response Letter (CRL) regarding relacorilant's New Drug Application (NDA) for hypercortisolism.

"We are surprised and disappointed by this outcome," Joseph Belanoff, MD, chief executive officer of Corcept, said in a statement. "Our commitment to patients suffering from the effects of hypercortisolism is unwavering."

The FDA acknowledged that Corcept's pivotal GRACE trial met its primary endpoint and that the company's GRADIENT trial provided confirming evidence. However, the FDA also determined that it was unable to determine a favorable benefit-risk assessment without additional evidence of effectiveness.

Relacorilant is a selective cortisol modulator, designed to bind to glucocorticoid receptors without interacting with other hormone receptors. Corcept is currently investigating relacorilant in several different disorders, including ovarian and prostate cancer.

The NDA submission was based on results from the pivotal GRACE trial and the phase 3 GRADIENT trial, as well as a phase 2 trial in hypercortisolism and a long-term extension. GRACE was a 2-part, phase 3, double-blind, placebo-controlled, randomized-withdrawal study examining the safety, efficacy, and pharmacokinetics of relacorilant in patients with 

 with impaired glucose tolerance and/or uncontrolled 

The first phase of GRACE was an open-label period where patients with hypercortisolism and either hypertension, hyperglycemia, or both received relacorilant for 22 weeks. Investigators excluded patients with non-endogenous hypercortisolism, uncontrolled and clinically significant hypothyroidism or hyperthyroidism, poorly controlled hypertension, poorly controlled diabetes mellitus, or renal insufficiency.

The second phase was a double-blind, randomized, withdrawal period, allowing investigators to measure blood pressure control maintenance. In this phase, patients who met response criteria were randomly assigned in a 1:1 ratio to either continue relacorilant or switch to placebo therapy for 12 weeks.

Ultimately, investigators found that loss of blood pressure control was 83% less likely to occur in the relacorilant arm compared to placebo (odds ratio [OR], 0.17; 

 = .02), along with similar blood pressure trends favoring relacorilant over placebo in 24-hour systolic and diastolic blood pressure.

GRADIENT was a randomized, double-blind, placebo-controlled study assessing the efficacy and safety of relacorilant to treat hypercortisolism in patients with cortisol-secreting adrenal adenoma or hyperplasia associated with diabetes mellitus/impaired glucose tolerance and/or uncontrolled systolic hypertension. Investigators included patients with a lack of cortisol suppression based on dexamethasone suppression testing, suppressed or low early-morning adrenocorticotropic hormone levels, and a radiologically confirmed adrenal lesion. Patients were excluded if they had severe uncontrolled hypertension, poorly controlled diabetes mellitus, 

, significantly abnormal liver test results, or uncontrolled hypo- or hyperthyroidism.

Patients were randomly assigned in a 1:1 ratio to either oral relacorilant or placebo for 22 weeks. Primary outcomes included change in average 24-hour systolic blood pressure and the number of patients with ≥1 treatment-emergent adverse event. Secondary endpoints included change in average heart rate, average diastolic blood pressure, and area under the concentration-time curve of blood glucose, among others.

Patients receiving relacorilant exhibited substantial and clinically significant improvements in mean systolic blood pressure at 22 weeks compared to baseline, while those receiving placebo saw no significant reduction. Additionally, 5 patients receiving placebo required rescue therapy, compared to 1 receiving relacorilant.

"I am confident we will find a way to get relacorilant to the patients it could help," Belanoff said in the statement. "We will meet with the FDA as soon as possible to discuss the best path forward."

Corcept Therapeutics. Corcept Receives Complete Response Letter for Relacorilant as a Treatment for Patients with Hypercortisolism. 

. December 31, 2025. Accessed December 31, 2025. 

https://www.businesswire.com/news/home/20251231309474/en/Corcept-Receives-Complete-Response-Letter-for-Relacorilant-as-a-Treatment-for-Patients-with-Hypercortisolism

Corcept Therapeutics. A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome (GRACE). ClinicalTrials.gov Identifier: NCT03697109. Updated July 16, 2025. Accessed December 23, 2025. 

https://clinicaltrials.gov/study/NCT03697109

Campbell P. Full GRACE Results Shed Further Light on Effects of Relacorilant in Hypercortisolism. 

. June 7, 2024. Accessed December 23, 2025. 

https://www.hcplive.com/view/full-grace-results-shed-further-light-on-effects-of-relacorilant-in-hypercortisolism

Corcept Therapeutics. A Study of the Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas (GRADIENT). ClinicalTrials.gov Identifier: NCT04308590. Updated September 4, 2025. Accessed December 23, 2025. 

https://clinicaltrials.gov/study/NCT04308590

Corcept Therapeutics. Corcept Therapeutics Announces Third Quarter Financial Results, Positive Results from Phase 3 GRADIENT Trial in Patients With Cushing’s Syndrome and Provides Corporate Update. October 30, 2024. Accessed December 23, 2025. 

https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-announces-third-quarter-financial-results-3

The FDA issued a Complete Response Letter for relacorilant's NDA for hypercortisolism, despite positive results from pivotal trials. The GRACE and GRADIENT trials demonstrated relacorilant's efficacy in managing hypercortisolism, particularly in patients with concurrent type 2 diabetes and hypertension. However, the FDA requires additional evidence to assess the benefit-risk profile. Relacorilant, a selective cortisol modulator, showed significant improvements in blood pressure control compared to placebo. Corcept Therapeutics remains committed to advancing relacorilant's approval and plans to engage with the FDA to determine the next steps.

The FDA has issued a CRL for selective cortisol modulator relacorilant, citing a need for more evidence of effectiveness.

Endocrinology

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FDA Issues Complete Response Letter for Relacorilant for Hypercortisolism

Announced by parent company Vanda Pharmaceuticals Inc. on December 30, 2025, the 

 has approved tradipitant under the brand name NEREUS for the prevention of vomiting induced through 

“This approval underscores the strong scientific evidence in the antiemetic effects of NEREUS in motion sickness,” Mihael Polymeropoulos, MD, president, chief executive officer, and chairman of the board of Vanda Pharmaceuticals, said in a statement. “For the first time in over 40 years, patients have access to a novel therapy grounded in modern neuropharmacology, offering effective prevention without the limitations of existing options.”

Motion sickness is prevalent in daily life, with roughly 25-30% of adults exhibiting symptoms during common modes of travel, including cars, planes, or boats. Around 1 in 3 individuals worldwide are highly susceptible, and although most cases are mild, roughly 5-15% of the population experiences recurrent and severe symptoms which can impact quality of life significantly. The condition arises from a sensory conflict between visual, vestibular, and proprioceptive inputs, which causes the release of substance P and the activation of NK-1 receptors in the central nervous system.

The FDA’s decision was based on data from 2 pivotal phase 3 trials, Motion Syros and Motion Serifos, both of which were provocation studies conducted on boats. Motion Syros was a randomized, double-blind, placebo-controlled study involving patients aged 18-75 years with a history of motion sickness. Investigators excluded patients with nausea-inducing disorders other than motion sickness, a body mass index (BMI) >40, and a history of intolerance and/or hypersensitivity to NK-1 receptor antagonists.

A total of 365 participants were enrolled in the trial and randomly assigned in a 1:1:1 ratio to either 170 mg (n = 120) or 85 mg (n = 123) of tradipitant, or placebo (n = 120). Patients embarked on a series of 4-hour boat trips in variable sea conditions, during which symptoms of vomiting and nausea were evaluated with questionnaires every 30 minutes. The primary efficacy endpoint was the percentage of vomiting during vehicle travel.

Ultimately, Motion Syros saw substantially lower vomiting incidence in both dosing arms of tradipitant compared to placebo, which stayed consistent across all boat groups (170 mg tradipitant, 18.3%; 85 mg tradipitant, 19.5%; placebo, 44.3%; 

 <.0001). Additionally, tradipitant prevented severe nausea and vomiting as compared to placebo (18.03% vs 37.7%; 

Motion Serifos was another randomized, double-blind, placebo-controlled study with the same inclusion and exclusion criteria as Motion Syros. A total of 316 patients were included and randomly assigned in a 1:1:1 ratio to the same doses of tradipitant and placebo. Ultimately, investigators noted substantially lower vomiting among patients receiving tradipitant compared to placebo (170 mg tradipitant, 10.4%; 85 mg tradipitant, 18.3%; placebo, 37.7%) and greater prevention of severe nausea and vomiting among tradipitant recipients versus placebo (13.3% vs 33%; 

“We are proud of this historic milestone and grateful to the Vanda researchers, patients, investigators, and regulators who contributed to this achievement,” Polymeropoulos said.

According to the press release, Vanda Pharmaceuticals plans to launch tradipitant commercially in the coming months.

Vanda Pharmaceuticals Inc. Vanda Pharmaceuticals Announces FDA Approval of NEREUS (tradipitant) for the Prevention of Vomiting Induced by Motion: A Historic Scientific Milestone in the Prevention of Motion Sickness. 

. December 30, 2025. Accessed December 31, 2025. 

https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-announces-fda-approval-of-nereus-tradipitant-for-the-prevention-of-vomiting-induced-by-motion-a-historic-scientific-milestone-in-the-prevention-of-motion-sickness-302650965.html

Polymeropoulos VM, Kiely L, Bushman ML, et al. Motion Syros: tradipitant effective in the treatment of motion sickness; a multicenter, randomized, double-blind, placebo-controlled study. Front Neurol. 2025;16:1550670. Published 2025 Mar 4. 

Vanda Pharmaceuticals Inc. Vanda Pharmaceuticals Reports Positive Results from a Second Phase III Study of Tradipitant in Motion Sickness. May 16, 2024. Accessed December 31, 2025. 

https://edge.prnewswire.com/c/link/?t=0&l=en&o=4587679-1&h=246048005&u=https%3A%2F%2Fvandapharmaceuticalsinc.gcs-web.com%2Fnode%2F15956%2Fpdf&a=here

The FDA has approved tradipitant, branded as NEREUS, for preventing motion sickness-induced vomiting, marking the first novel therapy in over 40 years. Motion sickness affects 25-30% of adults, with severe cases impacting quality of life. Tradipitant's approval was based on two phase 3 trials, Motion Syros and Motion Serifos, which demonstrated significant reductions in vomiting and severe nausea compared to placebo. Vanda Pharmaceuticals plans to launch tradipitant commercially soon, highlighting a significant advancement in motion sickness management.

The FDA has approved oral neurokinin-1 receptor antagonist tradipitant for the prevention of motion sickness, marking the first approval in decades.

Internal Medicine

Internal Medicine condition center page, resources on the topics of medical news and expert insight into internal medicine can be found. Content includes articles, interviews, videos, podcasts, and breaking news on internal medicine research, treatment, and drug development.

FDA Approves Tradipitant (NEREUS) for the Prevention of Vomiting Induced by Motion

Chelsie Derman is an associate editor for 

who covers psychiatry, sleep medicine, geriatrics, migraine, and allergy. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

The past year brought several important updates in 

US Food & Drug Administration (FDA) approvals

, trial results, and guideline changes with direct implications for clinical practice. These updates affected the management of obstructive sleep apnea (OSA), narcolepsy, restless legs syndrome (RLS), and idiopathic hypersomnia (IH), giving clinicians additional evidence-based treatment options.

Clinical research highlighted alternative therapies, optimized treatment strategies, and novel mechanisms of action for sleep disorders. Check out the top 7 sleep health news stories from 2025.

FDA Rejects Pitolisant NDA for Idiopathic Hypersomnia

Harmony Biosciences received a Refusal to File (RTF) from the FDA for its supplemental New Drug Application (NDA) seeking approval of pitolisant (WAKIX) to treat excessive daytime sleepiness in adults with IH. The Phase 3 INTUNE study did not meet its primary endpoint during the randomized withdrawal phase, though open-label data showed clinically meaningful improvements on the Epworth Sleepiness Scale, with most patients maintaining normal wakefulness for over a year.

Pitolisant, already approved for narcolepsy-related sleepiness and cataplexy, is a selective H₃ receptor antagonist. Harmony plans to conduct a pivotal phase 3 trial for an enhanced formulation, Pitolisant HD, targeting a 2028 PDUFA date.

Pitolisant Shows Benefit for IH in Phase 3 Open-Label Trial, with Bruce Corser, MD

FDA Grants Approval of Hypoglossal Nerve Stimulation System for Obstructive Sleep Apnea Treatment

The FDA has approved Nyxoah’s Genio hypoglossal nerve stimulation system for adults with moderate to severe OSA and an apnea-hypopnea index (AHI) of 15–65. The leadless, bilateral stimulation system features a wearable, nonimplanted battery compatible with MRI.

DREAM trial data demonstrated significant reductions in AHI and Oxygen Desaturation Index (ODI), with 82% of participants achieving an AHI < 15. Efficacy was consistent across supine and nonsupine positions, addressing a key challenge in OSA treatment. Safety was favorable, with few device-related serious adverse events.

On December 17, 2025, SleepRes announced that the FDA had cleared its Kricket Positive Airway Pressure (PAP) device for obstructive sleep apnea in patients who weigh > 66 pounds. KPAP technology is designed to reduce CPAP-related discomfort by synchronizing therapy with a patient’s natural breathing and airway dynamics.

The device offers the KPAP algorithm alongside traditional CPAP and automatic PAP modes. SleepRes plans to launch Kricket for use at home, in hospitals, or other institutions in the first half of 2026.

RLS Guidelines Advise Against Dopamine Agonists, With John Winkelman, MD, PhD

At SLEEP 2025, John W. Winkelman, MD, PhD, highlighted the American Academy of Sleep Medicine’s updated guidelines advising against dopamine agonists for restless legs syndrome (RLS) due to augmentation risks.

The guidelines now favor iron therapies—oral or intravenous—and alpha-2-delta ligands such as gabapentin, gabapentin enacarbil, and pregabalin. Winkelman emphasized a gradual transition strategy, addressing aggravating factors like serotonergic antidepressants, sleep apnea, and alcohol, before slowly tapering dopamine agonists over 6–12 months, ensuring safer, more effective RLS management for long-term patient outcomes.

Axsome Presents Positive Phase 3 Data for AXS-12 in Narcolepsy at SLEEP 2025

Axsome Therapeutics presented positive phase 3 ENCORE and SYMPHONY data at SLEEP 2025, showing roboxetine (AXS-12) significantly reduced cataplexy attacks and improved daytime functioning in patients with narcolepsy.

Roboxetine, a selective norepinephrine reuptake inhibitor and cortical dopamine modulator with FDA Orphan Drug Designation, enhanced wakefulness, cognition, and overall patient function. ENCORE results showed a lower mean weekly cataplexy frequency versus placebo during a randomized-withdrawal period.

Aroxybutynin and Atomoxetine (AD109) Reduces Obstructive Sleep Apnea Burden in Phase 3 SynAIRgy

Phase 3 SynAIRgy data demonstrated that the combination therapy AD109—aroxybutynin plus atomoxetine—significantly reduced AHI scores and improved oxygen desaturation and hypoxic burden in adults with OSA. Conducted over 26 weeks in 639 participants intolerant of positive airway pressure therapy, AD109 improved AHI4 events by 55.6% versus placebo and enhanced fatigue and sleep impairment scores.

The oral regimen, combining an antimuscarinic and norepinephrine reuptake inhibitor, was well-tolerated, with manageable adverse events. These results support Apnimed’s plans to submit an FDA New Drug Application for AD109, offering a promising treatment for OSA.

Tirzepatide Shows Consistent Benefit for OSA Regardless of Baseline Severity

A post-hoc analysis of the Phase 3 SURMOUNT-OSA trials showed that tirzepatide provided consistent benefits in adults with moderate to severe OSA and obesity, regardless of baseline OSA severity or use of PAP therapy. The analysis revealed significant improvements compared to the placebo in AHI, sleep apnea–specific hypoxic burden, systolic blood pressure, C-reactive protein, and body weight across all severity subgroups. Tirzepatide increased the likelihood of achieving clinically meaningful AHI reductions in nearly all groups, with no consistent association between baseline severity and treatment response.

Phase 3 Data Shows Iptacopan Eases Fatigue in C5i-Experienced, -Naïve PNH Patients

Phase 3 trials APPLY-PNH and APPOINT-PNH demonstrate that iptacopan, a first-in-class oral selective complement factor B inhibitor, significantly improves fatigue, quality of life, and hematologic outcomes in patients with paroxysmal nocturnal hemoglobinuria (PNH). In C5 inhibitor-experienced and C5i-naïve patients, iptacopan monotherapy increased hemoglobin and reduced lactate dehydrogenase.

APPLY-PNH showed 51% of C5i-experienced patients achieved meaningful fatigue improvement versus 11% with prior therapy. APPOINT-PNH reported 56% of C5i-naïve patients reached fatigue improvement thresholds.

Recent advancements in sleep medicine have introduced new FDA approvals, trial results, and guideline updates, impacting the management of sleep disorders like obstructive sleep apnea (OSA), narcolepsy, restless legs syndrome (RLS), and idiopathic hypersomnia (IH). Notable developments include the FDA's rejection of pitolisant for IH, approval of the Genio hypoglossal nerve stimulation system for OSA, and clearance of the Kricket PAP device. Updated RLS guidelines now advise against dopamine agonists, favoring iron therapies and alpha-2-delta ligands. Positive trial data for AXS-12, AD109, and tirzepatide highlight promising treatment options for narcolepsy and OSA.

From FDA decisions to late-phase trial readouts and updated practice guidelines, 2025 delivered clinically actionable insights across sleep conditions.

Sleep

On the HCPLive sleep page, resources on the topics of medical news and expert insight into sleep medicine can be found. Content includes articles, interviews, videos, podcasts, and breaking news on sleep apnea, insomnia, narcolepsy, and more.

Obstructive Sleep Apnea

​​Sleep in 2025: Year in Review

Catch up on the most impactful headlines in hormonal disorders from all of 2025 with our Year in Review.

Hormonal Disorders

Hormonal Disorders in 2025: Year in Review

Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

The fibromyalgia year in review highlights FDA approvals, data, and advances in 2025.

Fibromyalgia

On the HCPLive fibromyalgia page, resources on the topics of medical news and expert insight into fibrositis can be found. Content includes articles, interviews, videos, podcasts, and breaking news on fibromyalgia, and more.

Rheumatology

Rheumatology condition center page is a comprehensive resource for clinical news and insights on rheumatologic disease. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for arthritis, gout, nr-AxSpA, and more.

Fibromyalgia in 2025: Year in Review

Videos

Experts discuss groundbreaking innovations in cardiovascular disease prevention, highlighting personalized medicine and new therapies for effective treatment.

Video Series

Emerging Innovations in Post-Event Lipid Management for ASCVD

Engaging patients in their treatment journey enhances adherence to therapies, ultimately improving health outcomes and managing cholesterol effectively.

Sustaining Long-Term Adherence to PCSK9 Therapy in ASCVD

This Year In Medicine

Reframing Fibromyalgia Care in 2025: Restricted Impact of TNX-102 SL’s Approval

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.

C3G treatment advances in 2025 with FDA approvals of iptacopan and pegcetacoplan, offering disease-modifying options


Nephrology

The HCPLive nephrology page is a resource for medical news and expert insights on kidney disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in nephrology, and more.

C3 Glomerulopathy

The HCPLive C3 glomerulopathy page is a resource for medical news and expert insights on C3G. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in C3G, and more.

C3 Glomerulopathy in 2025: Year in Review

FDA clears first human umbilical cord–derived sheet device, Theracor, for wound Care


FDA Grants 510(k) Clearance to First Umbilical Cord–Derived Sheet Formulation for Wound Care

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.

In this end-of-year reel, HCPLive has showcased several key highlights from the Skin of Color Savvy podcast in 2025.

Skin of Color Savvy: The Art and Science of Treating Patients of Color

Hosted by Skin of Color Society and produced by HCPLive, 

 delves into the latest research, clinical insights, and culturally intelligent care practices in dermatology with leading experts. 

Whether it’s groundbreaking research, practice-changing insights, or highlights from the SOCS community, this twice-monthly program provides dermatologists and care providers with expert perspectives on treating patients with skin of color.

Podcasts

podcasts page features a feed of medical news and interview podcast series, including DocTalk, Lungcast, Derm Discussions, and Heart Trials.

Dermatology

The HCPLive dermatology page is a resource for medical news and expert insights on skin disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for dermatologic conditions, and more.

Skin of Color Savvy: Highlights from 2025

The FDA grants breakthrough therapy designation for ulizacaltamine for the treatment of essential tremor. 


Latest News

FDA Issues Complete Response Letter for ONS-5010 for Wet AMD

FDA Accepts, Grants Priority Review to AXS-05 sNDA for Alzheimer’s Disease Agitation

FDA Issues Complete Response Letter for Relacorilant for Hypercortisolism

FDA Approves Tradipitant (NEREUS) for the Prevention of Vomiting Induced by Motion

​​Sleep in 2025: Year in Review

Sleep in 2025: Year in Review