The U.S. Food and Drug Administration announced the proposal to exclude semaglutide, tirzepatide, and liraglutide on the 503B bulks list, finding no clinical need for outsourcing facilities to compound these drugs from bulk substances.
The 503B bulks list identifies bulk drug substances that outsourcing facilities may use in compounding under the conditions of section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act). In most cases, outsourcing facilities cannot compound drugs using bulk drug substances unless the substance appears on the 503B bulks list, or the compounded drug is on the FDA’s drug shortage list at the time of compounding, distribution, and dispensing.
After evaluating the nominations for these three substances, the FDA did not identify a clinical need for outsourcing facilities to compound semaglutide, tirzepatide, and liraglutide from bulk drug substances.
“When FDA-approved drugs are available, outsourcing facilities cannot lawfully compound using bulk drug substances unless there is a clear clinical need,” said FDA Commissioner Marty Makary, M.D., M.P.H. “This action reflects our responsibility to protect patients and preserve the integrity of the drug approval process while continuing to provide a transparent, science-based pathway for public input.”
The FDA carefully reviewed the nominations it received and did not identify sufficient evidence to include semaglutide, tirzepatide and liraglutide on the 503B bulks list. A determination of clinical need is based on patient safety and medical necessity under the law.
The FDA is now inviting interested parties to submit comments electronically through the docket by June 29, 2026. The agency will consider submitted comments before making a final determination.
The U.S. Food and Drug Administration has approved an expanded use for Auvelity (dextromethorphan hydrobromide and bupropion hydrochloride) extended-release tablets to treat agitation associated with dementia due to Alzheimer’s disease in adults. The drug is the first FDA-approved treatment for this condition that is not an antipsychotic. FDA initially approved Auvelity in 2022 to treat major depressive disorder in adults.
Bupropion
Dextromethorphan
"This approval represents a significant advancement in our ability to help patients and families dealing with one of the most challenging aspects of Alzheimer's disease," said FDA Commissioner Marty Makary, M.D., M.P.H. "With today’s action, patients and their families have access to an additional important treatment for complications of this devastating disease."
Agitation is a common and distressing symptom in patients with Alzheimer's disease dementia, characterized by excessive motor activity, or verbal or physical aggression. It can significantly impact quality of life for patients and caregivers.
"Auvelity was found to be efficacious for treating agitation in Alzheimer’s disease in two randomized trials and now represents an additional option to address one of the most difficult sequelae of the disease, especially as it progresses,” said Tracy Beth Hoeg, M.D., Ph.D., Acting Director of the FDA’s Center for Drug Evaluation and Research. "We hope this approval will provide meaningful benefit to patients, their families, and caregivers."
The first randomized study (NCT 03226522) was a five-week trial in which participants received either Auvelity or a placebo. The primary endpoint was the change from baseline to week five in the total score of the Cohen-Mansfield Agitation Inventory (CMAI), a survey that assesses the frequency of manifestations of agitated behaviors in elderly patients, based on caregiver reports. Auvelity was significantly superior to placebo in The Cohen-Mansfield Agitation Inventory score improvements.
The second randomized study (NCT 04947553) was a withdrawal study in participants who responded to Auvelity. Upon reaching a sustained clinical response to Auvelity, patients were randomly assigned to continue treatment with Auvelity or switch to placebo. The primary endpoint was time to relapse. Participants who continued Auvelity treatment had a significantly longer time to relapse of agitation symptoms compared to patients receiving the placebo.
The most common side effects include dizziness, upset stomach, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction, and uncontrolled sweating. Auvelity has a Boxed Warning about increased risk of suicidal thoughts and behaviors in adolescents and young adults taking antidepressants. Health care providers should monitor patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during initial treatment. The medicine can cause seizures, with risk increasing with dose. It can also cause elevated blood pressure and hypertension, and may activate mania or hypomania (irritable mood) in susceptible patients.
Before starting Auvelity, health care providers should assess blood pressure, screen for personal or family history of bipolar disorder, and determine if patients are taking other medications containing bupropion or dextromethorphan.
The FDA granted breakthrough therapy designation and priority review designation for this action. The approval of Auvelity for agitation associated with dementia due to Alzheimer's disease was granted to Axsome Therapeutics.
Today, the U.S. Food and Drug Administration is announcing that it issued a “safe to proceed” letter to Revolution Medicines, allowing the sponsor to initiate an expanded access treatment protocol (EAP) for its experimental pancreatic cancer drug, daraxonrasib.
The expanded access treatment protocol is for patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). The FDA received the expanded access request from Revolution Medicines on April 28 and signed it on April 30.
FDA regulations allow expanded access to investigational drugs for treatment purposes for larger populations under a treatment protocol or treatment investigational new drug application. Per EAP guidelines, requests for expanded access must be submitted to the sponsor by physicians licensed in the U.S. on behalf of eligible patients.
“Granting the request two days after receiving the expanded access application reflects the FDA’s strong commitment to facilitate early access to therapies for serious and life-threatening conditions, including pancreatic cancer,” said FDA Commissioner Marty Makary, M.D., M.P.H. “Having taken care of many patients with metastatic cancer, I am hopeful that today’s action will improve the lives of patients suffering from this disease.”
Daraxonrasib is a RAS inhibitor designed to inhibit a protein (RAS) that is mutated in most pancreatic cancer tumors.
The company said on April 13 that it intends to submit a new drug application for daraxonrasib under the Commissioner’s National Priority Voucher (CNPV) pilot program. The FDA granted a national priority voucher to daraxonrasib, also called RMC-6236, in October 2025.
As more people look for ways to stay younger for longer, the supplement industry has moved beyond creams and cosmetic fixes to something more ambitious: products that claim to slow aging by acting on cellular processes.
Nicotinamide mononucleotide ("NMN" and "β-NMN"
Among the most heavily marketed compounds are NAD+, NMN and resveratrol, often described as supporting cellular repair, energy production and healthy aging. But what do they actually do, where are they being used, and how strong is the evidence?
To make sense of the claims, it helps to separate three things: the molecule NAD+, the compounds sold to raise it, and the products, such as supplements, creams and serums, that contain them.
Nicotinamide adenine dinucleotide, or NAD+, is a coenzyme found in all living cells. A coenzyme is a helper molecule that allows enzymes to carry out chemical reactions in the body. NAD+ plays an essential role in energy metabolism, DNA repair, inflammation and the activity of a family of proteins involved in cellular stress responses.
NAD+ levels tend to decline with age, although this decline is complex and may vary between tissues. Lower NAD+ availability has been linked to reduced mitochondrial function, meaning reduced activity in the cell structures that help produce energy. This is one of the biological changes associated with aging.
NAD+ in creams and serums
NAD+ has begun appearing in skincare creams and serums, but the evidence is even less developed here than it is for supplements.
While NAD+ is important for skin-cell energy and repair, it remains unclear whether topical NAD+ in ordinary creams can penetrate the skin in sufficient amounts to produce meaningful anti-aging effects.
Better-established ingredients, such as sunscreen, retinoids and niacinamide, currently have much stronger evidence for improving visible signs of skin aging.
NAD+ precursors as supplements
Nicotinamide adenine dinucleotide (NAD)
Because NAD+ itself is not thought to be absorbed efficiently when swallowed, much research has focused on NAD+ precursors. Precursors are compounds the body can convert into another substance. In this case, they are compounds the body can convert into NAD+. Two of the best known are nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR).
In animal studies, NAD+ precursors have produced promising results. Older mice given these compounds have shown improvements in energy metabolism, insulin sensitivity and aspects of physical function. Some studies have also reported improvements in healthspan and lifespan-related measures in animal models, although these findings vary by model and do not translate neatly into humans. These results have helped drive enormous commercial interest, but turning promising mouse studies into meaningful benefits for people has proved far harder.
Human clinical trials suggest that NMN and NR can raise NAD+ levels, or related markers of NAD+ activity, in blood and tissues. However, the strongest evidence is for changes in blood, while evidence for meaningful effects in specific tissues is still limited.
Some small studies have reported possible benefits for metabolic health, including insulin sensitivity in specific groups. Others have explored potential effects on muscle mass, but recent reviews have not found convincing evidence that NMN or NR preserve muscle mass or function in older adults.
When researchers look at outcomes that matter more directly to everyday aging, such as strength, cognition, frailty or biological age, the picture is much less clear. Biological age is a contested estimate of how old the body appears at a cellular or molecular level. One major problem is that aging unfolds over a long period, while most supplement trials last only weeks or months.
Resveratrol
Resveratrol is another compound often promoted for anti-aging, but it is different from NMN and NR. It is not an NAD+ precursor. It belongs to a group of natural plant chemicals called polyphenols and is found in red grapes, berries and peanuts.
In laboratory and animal studies, resveratrol has been associated with lower levels of inflammation and improved mitochondrial function, meaning better activity in the parts of cells that help produce energy.
The difficulty is that resveratrol has poor oral bioavailability. This means much of what is swallowed is broken down or modified before it can reach tissues in the form and concentration used in laboratory experiments. This creates a large gap between what resveratrol can do in cells in a dish and what a supplement is likely to do in the human body. So far, human trials have not shown convincing evidence that resveratrol slows aging, and findings on cardiovascular and anti-inflammatory benefits remain mixed.
Resveratrol may interact with some medications, especially anticoagulant and antiplatelet drugs, often described as blood-thinning medicines. High doses can also cause side effects such as gastrointestinal symptoms. Anyone taking regular medication, managing a chronic condition, pregnant or breastfeeding should seek medical advice before taking high-dose supplements.
So, are NAD+, NMN and resveratrol the elixir of youth? No. The key distinction is between biological plausibility and proven benefit. These compounds are not biologically implausible: they act on real pathways involved in energy production, stress responses and cellular maintenance. But affecting a pathway is not the same as slowing aging in a person.
In humans, the evidence so far suggests possible benefits in limited contexts, but major questions remain about long-term safety, optimum doses and who is most likely to benefit. The science is plausible, but the marketing often turns "this affects a process associated with aging" into "this supplement will keep you young."
For now, the best-supported ways to support healthy aging remain far less glamorous: regular exercise, good sleep, a balanced diet, avoiding smoking, limiting alcohol and managing long-term health conditions. Supplements may eventually prove useful, but at present, the evidence for staying younger for longer is much stronger for everyday habits than for anti-aging products.
Scientific Knowledge on the Subject: AD109 (aroxybutynin 2.5 mg/atomoxetine 75 mg), an investigational, first-in-class, once-daily oral tablet, is designed to target the neuromuscular dysfunction underlying obstructive sleep apnea (OSA) by increasing upper airway muscle tone during sleep. In the phase 2b MARIPOSA trial, AD109 demonstrated significant improvement in the apnea–hypopnea index (AHI) in adults with mild-to-severe OSA over 4 weeks. An earlier phase 2 study suggested that AD109 may reduce AHI from the first dose. AD109 efficacy/safety beyond 4 weeks remain unknown.
What This Study Adds to the Field: SynAIRgy, a part of one of the largest clinical development efforts conducted for an OSA pharmacotherapy, is one of 2 phase 3 registrational trials evaluating the efficacy/safety of AD109. SynAIRgy is a randomized, double-blind, placebo-controlled, parallel-arm trial conducted in 646 participants with mild-to-severe OSA who were intolerant to or refused positive airway pressure therapy. SynAIRgy demonstrated significant improvements in airway obstruction and oxygenation across mild-to-severe OSA participants, supporting the potential for AD109 to be a new oral treatment option for patients with mild-to-severe OSA. Given existing OSA therapy limitations, AD109 may fill a large unmet medical need in providing patients with a pharmacologic therapy targeting the neuromuscular dysfunction underlying OSA pathogenesis.
Among adults with osteogenesis imperfecta, teriparatide plus zoledronic acid does not reduce fracture risk compared with standard care, according to a study published online May 14 in the Journal of the American Medical Association.
Jannie Dahl Hald, Ph.D., from Aarhus University Hospital in Denmark, and colleagues examined whether the parathyroid hormone analogue teriparatide followed by zoledronic acid reduces the risk for fractures in adults with osteogenesis imperfecta in a multicenter randomized clinical trial. Participants were randomly assigned to receive 20 μg of teriparatide daily by subcutaneous injection for two years, followed by 5 mg zoledronic acid infusion (176 participants), or to standard care, in which bisphosphonates and other bone-targeted medicines could be used (174 participants).
Most of the participants had type I osteogenesis imperfecta caused by pathogenic variants in the type 1 collagen genes. The researchers found that 36.9 and 36.4 percent of patients in the teriparatide plus zoledronic acid group and the standard care group, respectively, had incident fractures. There was significantly more of an increase in lumbar spine and total hip bone mineral density with teriparatide plus zoledronic acid than standard care. Teriparatide plus zoledronic acid was favored in several quality-of-life measures. The groups reported similar adverse events.
"We have been using drugs to increase bone density for decades in the hope that they might prevent fractures but the TOPaZ trial clearly shows that these medicines simply do not work," lead author Stuart Ralston, M.D., from the University of Edinburgh Institute of Genetics and Cancer in the United Kingdom, said in a statement.
