Axsome Therapeutics Announces FDA Approval of AUVELITY(TM), the First and Only Oral NMDA Receptor Antagonist for the Treatment of Major Depressive Disorder in Adults
6:45 am ET August 19, 2022 (Globe Newswire)
AUVELITY is the first and only rapid-acting oral treatment approved with labeling of statistically significant improvement in depressive symptoms compared to placebo starting at one week
AUVELITY uses the first new oral mechanism of action approved for major depressive disorder in over 60 years
[This bodes well for AVXL since we too will be introducing a "new oral mechanism of action" for CNS diseases to the FDA. Also note that AUVELITY is an oral NMDA receptor antagonist that also causes Sigma-1 Receptor agonist activity!]
AUVELITY was developed with FDA Breakthrough Therapy designation and evaluated by the FDA under Priority Review
Company to host webcast today at 8:00 AM ET
Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has approved AUVELITY (dextromethorphan HBr -bupropion HCl) extended-release tablets for the treatment of major depressive disorder (MDD) in adults. AUVELITY is the first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week. The rapid antidepressant effects of AUVELITY were sustained at all subsequent timepoints. AUVELITY is the first and only oral N-methyl D-aspartate (NMDA) receptor antagonist approved for the treatment of MDD. Axsome anticipates AUVELITY to be commercially available in the U.S. in the fourth quarter of 2022.
Experience the interactive Multimedia News Release here: link
Maurizio Fava, MD, Psychiatrist-In-Chief, Department of Psychiatry, Massachusetts General Hospital, Executive Director, Clinical Trials Network & Institute, Associate Dean for Clinical & Translational Research, and Slater Family Professor of Psychiatry, Harvard Medical School said, "The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile. Auvelity, which was granted Breakthrough Therapy designation by the FDA, represents the first new oral non-monoamine-based mechanism of action approved to treat major depressive disorder in over sixty years. Nearly two thirds of patients treated with currently available antidepressants do not adequately respond, and those that do may not achieve clinically meaningful responses for up to six to eight weeks. Given the debilitating nature of depression, the efficacy of Auvelity observed at one week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition."
Michael Pollock, Chief Executive Officer of the Depression and Bipolar Support Alliance (DBSA), a leading national patient advocacy organization focusing on depression and bipolar disorder said, "The mental health crisis in the United States is one of the most pressing health issues facing our country today. Over 20 million American adults experienced major depressive disorder each year prior to the COVID-19 pandemic. These numbers increased dramatically during the pandemic with approximately thirty percent of adults in the U.S. or more than 80 million Americans experiencing elevated symptoms of depression. The need for new treatment options, particularly those with new mechanisms of action, could not be clearer and more urgent for those living with, or impacted by, major depressive disorder."
Dan V. Iosifescu, MD, Professor of Psychiatry at the New York University School of Medicine, and Director of the Clinical Research Division at the Nathan Kline Institute for Psychiatric Research said, "Major depressive disorder is disabling and potentially life-threatening, causes profound distress for patients and their families, and leads to substantial healthcare resource utilization. Auvelity's oral NMDA receptor antagonist and sigma-1 receptor agonist activity, which targets glutamatergic neurotransmission, provides clinicians a long sought after new mechanistic approach which may benefit the millions of patients living with this serious condition. In clinical trials, Auvelity has demonstrated rapid and statistically significant improvement in depressive symptoms as early as Week 1, and increased rates of remission at Week 2 compared with placebo. This early benefit with Auvelity was maintained and increased with continued treatment, and was accompanied by a favorable safety and tolerability profile."
AUVELITY was studied in a comprehensive clinical program which included more than 1,100 patients with depression. The efficacy of AUVELITY in the treatment of MDD was demonstrated in the GEMINI placebo-controlled study, and confirmatory evidence which included the ASCEND study comparing AUVELITY to bupropion sustained-release tablets. In the GEMENI study, AUVELITY was statistically significantly superior to placebo in improvement of depressive symptoms as measured by the change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at Week 6, the study's primary endpoint. To evaluate speed of onset of action, the change in MADRS total score from baseline to Week 1 and from baseline to Week 2 were pre-specified secondary efficacy endpoints. The difference between AUVELITY and placebo in change from baseline in MADRS total score was statistically significant at Week 1 and at Week 2. In the ASCEND study, AUVELITY was statistically significantly superior to bupropion sustained-release tablets 105 mg twice daily on the primary outcome measure. The primary outcome measure of the ASCEND study was calculated by assessing the change from baseline in MADRS total scores from Week 1 to Week 6 and then taking the average of those scores. In the placebo-controlled clinical study, the most common (incidence greater-than or equal to5% for AUVELITY and more than twice as frequently as placebo) adverse reactions were dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.
The FDA granted Breakthrough Therapy designation for AUVELITY for the treatment of MDD in March 2019. This designation is granted to candidate drugs that show potential for benefit above that of available therapies based on preliminary clinical data, and it provides the sponsor with added focus from and greater interactions with FDA staff during the development of the candidate drug. The AUVELITY New Drug Application (NDA) was evaluated by the FDA under Priority Review, which is granted by the FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.
AUVELITY uses the first new oral mechanism of action in more than 60 years for MDD. AUVELITY works on the NMDA receptor, an ionotropic glutamate receptor, and on the sigma-1 receptor in the brain via its dextromethorphan component. The bupropion component of AUVELITY is an aminoketone which increases blood levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6 (CYP2D6), which catalyzes a major biotransformation pathway for dextromethorphan. The exact mechanism of action of AUVELITY in the treatment of MDD is unclear. The blood levels of AUVELITY are determined by the distinct pharmacokinetic interaction between its components which has been found to be non-linear at steady state. AUVELITY is protected by a robust patent estate extending out at least to 2037-2040.
Herriot Tabuteau, MD, Chief Executive Officer of Axsome said, "The approval of Auvelity is the culmination of the tremendous and focused research and development activities conducted by the Axsome team and our collaborators. We are extremely proud to deliver this Breakthrough Therapy-designated new treatment to the millions of patients living with depression at a time when it is most needed, given the recent sharp increase in depression prevalence. We are thrilled to contribute to potentially fundamental advances in neuropsychiatry by providing clinicians the first rapid-acting oral antidepressant demonstrated with FDA labeling, and the first oral glutamatergic medicine approved for depression. Auvelity and the rest of the Axsome neuroscience portfolio reflect our steadfast commitment to developing and delivering potentially life-changing medicines to people living with serious central nervous system disorders."
For patients who need help getting started on AUVELITY, the Auvelity On My Side patient support program will offer comprehensive patient support services, including the Auvelity On My Side Savings Card to help make treatment more affordable for eligible commercially-insured patients. Additionally, Auvelity On My Side will include a samples program, prior authorization support, as well as other patient support tools. All programs will be available immediately upon launch.
Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients. Auvelity is not approved for use in children.
A Media Snippet accompanying this announcement is available by clicking on the image or link below:
Axsome Therapeutics, Inc. (AUVELITY): Media Snippet (AUVELITY)
Webcast Information
Axsome will host a webcast and conference call today at 8:00 AM Eastern to discuss the approval of AUVELITY. To access the live webcast please click here. The live webcast can also be accessed on the "Webcasts & Presentations" page of the "Investors" section of the Company's website at axsome.com. A replay of the webcast will be available for approximately 30 days following the live event. To participate in the live conference call, please dial (877) 405-1239 or for international toll-free access numbers, please click here.
About Major Depressive Disorder (MDD)
Major depressive disorder (MDD) is a debilitating, chronic, biologically-based disorder characterized by low mood, inability to feel pleasure, feelings of guilt and worthlessness, low energy, and other emotional and physical symptoms, and which impairs social, occupational, educational, or other important functioning. In severe cases, MDD can result in suicide. According to the U.S. Department of Health and Human Services, an estimated 21 million U.S. adults experienced MDD each year. According to the World Health Organization (WHO), depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease. Nearly two-thirds of diagnosed and treated patients do not experience adequate treatment response with available first-line treatment, highlighting the need for new therapies.
About AUVELITY
AUVELITY is a novel, oral, NMDA receptor antagonist with multimodal activity approved for the treatment of MDD in adults. AUVELITY is a proprietary extended-release oral tablet containing dextromethorphan HBr (45 mg) and bupropion HCl (105 mg). The dextromethorphan component of AUVELITY is an antagonist of the NMDA receptor (an ionotropic glutamate receptor) and a sigma-1 receptor agonist. These actions are thought to modulate glutamatergic neurotransmission. The bupropion component of AUVELITY is an aminoketone and CYP2D6 inhibitor which serves to increase the increase and prolong the blood levels of dextromethorphan. The exact mechanism of action of Auvelity in the treatment of depression is unclear. AUVELITY received Breakthrough Therapy designation from the FDA for the treatment of MDD.
INDICATION AND IMPORTANT SAFETY INFORMATION
WHAT IS AUVELITY (aw-VEHL-ah-tee)? It is a prescription oral medicine used to treat adults with major depressive disorder (MDD). It is not known if Auvelity is safe and effective in children.
Auvelity is not approved for uses other than the treatment of MDD. The ingredients in Auvelity, bupropion and dextromethorphan, are the same ingredients found in some other medicines approved for other uses.
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT AUVELITY?
Auvelity and other antidepressant medicines may increase suicidal thoughts and actions in some children, adolescents, and young adults, especially within the first few months of treatment or when the dose is changed. Auvelity is not for use in children.
You should pay close attention to any new or sudden changes in mood, behavior, thoughts, or feelings or if you develop suicidal thoughts or actions. This is very important when starting or changing the dose of an antidepressant medicine.
Call your healthcare provider (HCP) or get emergency help right away if you or your loved one have any of the following symptoms, especially if they are new, worse, or worry you:
Do not take Auvelity if you:
Auvelity may cause serious side effects. Ask your HCP how to recognize the serious side effects below and what to do if you think you have one:
Seizures. There is a risk of seizures during treatment with Auvelity. The risk is higher if you take higher doses of Auvelity, have certain medical problems, or take Auvelity with certain other medicines. Do not take Auvelity with other medicines unless your healthcare provider tells you to.
If you have a seizure during treatment with Auvelity, stop taking Auvelity and call your HCP right away. Do not take Auvelity again if you have a seizure.
Increases in blood pressure (hypertension). Some people may get high blood pressure during treatment with Auvelity. Your HCP should check your blood pressure before you start taking and during treatment with Auvelity.
Manic episodes. Manic episodes may happen in people with bipolar disorder who take Auvelity. Symptoms may include:
Unusual thoughts or behaviors. One of the ingredients in Auvelity (bupropion) can cause unusual thoughts or behaviors, including delusions (believing you are someone else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that people are against you), or feeling confused. If this happens to you, call your HCP.
Eye problems (angle-closure glaucoma). Auvelity may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your HCP if you have eye pain, changes in your vision, or swelling or redness in or around the eye.
Dizziness. Auvelity may cause dizziness which may increase your risk for falls.
Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take Auvelity with certain other medicines. Call your HCP or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms:
COMMON SIDE EFFECTS
The most common side effects of Auvelity include dizziness, headache, diarrhea, feeling sleepy, dry mouth, sexual function problems, and excessive sweating.
These are not all the side effects of Auvelity. Tell your doctor if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.
BEFORE USING
Tell your HCP about all your medical conditions, including if you:
Review the list below with your HCP. Auvelity may not be right for you if:
HOW TO TAKE
LEARN MORE
For more information about Auvelity, call 866-496-2976 or visit Auvelity.com.
This summary provides basic information about Auvelity but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other HCP about Auvelity and how to take it. Your HCP is the best person to help you decide if Auvelity is right for you.
AUV CON BS 08/2022
Please see full Prescribing Information, including Boxed Warning for suicidal thoughts and behaviors, and Medication Guide.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical company developing and delivering novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are committed to developing products that meaningfully improve the lives of patients and provide new therapeutic options for physicians. For more information, please visit the Company's website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.
