Axsome Therapeutics Presents New Data from the EVOLVE Open-Label Trial Demonstrating Effects of AUVELITY® on Cognitive and Physical Functioning in Patients with Major Depressive Disorder at the American College of Neuropsychopharmacology (ACNP) 2022 Annual Meeting

Improvement in cognitive and physical functioning, measured by the CPFQ patient-rated scale, starting at week 1 and sustained over 12 months

Improvement in disability, measured by the SDS, starting at week 1 and sustained over 12 months

NEW YORK, Dec. 07, 2022 (GLOBE NEWSWIRE) -- 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 treatment with AUVELITY® (dextromethorphan HBr-bupropion HCl) resulted in rapid, substantial, and durable improvements in cognitive and physical functioning in the EVOLVE open-label trial in major depressive disorder (MDD). Treatment with AUVELITY also resulted in reduced disability. These new data were presented yesterday at the American College of Neuropsychopharmacology (ACNP) 2022 Annual Meeting being held in Phoenix, Arizona.

In the trial, AUVELITY rapidly, durably, and substantially improved symptoms of depression including cognitive and physical functioning, and reduced disability in patients with MDD who had received one or more prior antidepressants. The change in cognitive and physical functioning was assessed using the Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ), a patient-rated scale used to measure cognitive and executive dysfunction in mood and anxiety disorders. The mean CPFQ score at baseline was 28.4. Mean improvements from baseline to weeks 1, 2, and 6 in CPFQ scores were -2.0 points, -4.4 points, and -7.5 points, respectively (p<0.001 for all). Improvements on the CPFQ were sustained through month 6 (-9.5 points, p<0.001) and month 12 (-8.5 points, p<0.001). Disability was assessed using the Sheehan Disability Scale (SDS), a patient-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. The mean SDS score at baseline was 17.5. Mean improvements from baseline to weeks 1, 2, and 6 in SDS scores were -2.9 points, -5.0 points, and -8.3 points, respectively (p<0.001 for all). Improvements on the SDS were sustained through month 6 (-10.1 points, p<0.001) and month 12 (-10.8 points, p<0.001).

EVOLVE (Evaluation of NMDA Modulation for Depressive Episodes) was an open-label, U.S. trial in which 146 patients with MDD who had received one or more prior antidepressants were treated with AUVELITY twice daily for up to 15 months. The primary endpoint was the change from baseline to week 6 on the Montgomery-?sberg Depression Rating Scale (MADRS) total score. Statistical analysis was performed comparing the measures at each timepoint to baseline values as pre-specified (significance level of 0.05, two-sided). AUVELITY was generally well tolerated with long-term treatment and exhibited a safety profile consistent with that observed in previously reported trials. The most common adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), dizziness (5.5%), and insomnia (5.5%).

Details of the poster presentation are as follows:

Title: Improvements in Cognitive and Physical Functioning Outcomes in Depressed Patients Treated with AXS-05 (Dextromethorphan-Bupropion): Results from the EVOLVE Open-label, Long-Term Study
Poster Number: T122
Session: Poster Session II, December 6, 2022

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.¹ 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.² Nearly two-thirds of diagnosed and treated patients do not experience adequate treatment response with available first-line treatment,³ 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 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 for use 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:

• suicidal thoughts or actions
• new or worsening depression or anxiety
• agitation or restlessness
• trouble sleeping (insomnia)
• acting aggressive, being angry violent
• an extreme increase in activity and talking (mania)
• panic attacks
• new or worsening irritability
• acting on dangerous impulses
• other unusual changes in behavior or mood
  

Do not take Auvelity if you:

• have or had a seizure disorder.
• have or had an eating disorder like anorexia or bulimia.
• have recently and suddenly stopped drinking alcohol or use medicines called benzodiazepines, barbiturates, or anti-seizure medicines, and you have recently suddenly stopped taking them.
• are taking a monoamine oxidase inhibitor (MAOI), have stopped taking an MAOI in the last 14 days, or are being treated with the antibiotic linezolid or intravenous methylene blue. Ask your HCP or pharmacist if you are unsure whether you take an MAOI. Do not start taking an MAOI until you have stopped taking Auvelity for at least 14 days.
• are allergic to dextromethorphan, bupropion, or any other ingredients in Auvelity.
  

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:

• greatly increased energy
• racing thoughts
• unusually grand ideas
• talking more or faster than usual
• severe trouble sleeping
• reckless behavior
• excessive happiness or irritability

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:

• agitation
• hallucinations
• confusion
• coma
• fast heartbeat
• blood pressure changes
• dizziness
• sweating
• flushing
• high body temperature (hyperthermia)
• shaking (tremors), stiff muscles, or muscle twitching
• loss of coordination
• seizures
• nausea, vomiting, diarrhea
  

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 possible 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 the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
• It is important to tell your HCP if you are taking:
  • other medicines containing bupropion or dextromethorphan
  • medicines to treat depression, anxiety, psychotic or thought disorders, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants
  • theophylline
  • corticosteroids
  • oral diabetes medicines or use insulin to control your blood sugar
  • medicines to control appetite (anorectic)
  • nicotine medicines to help you stop smoking
  • street (illicit) drugs
  • benzodiazepines, sedative-hypnotic (sleep medicines), or opiates
• If you are unsure if you take any of these medicines, ask your HCP. They can tell you if it is safe to take Auvelity with your other medicines.
• Tell your HCP if you are pregnant or plan to become pregnant. Auvelity may harm your unborn baby if you take it during pregnancy. Auvelity is not recommended during pregnancy. Your HCP will prescribe another treatment for females who plan to become pregnant.
• One of the ingredients in Auvelity passes into your breast milk. Do not breastfeed during treatment with Auvelity and for 5 days after the final dose.

Tell your HCP about all your medical conditions, including if you:

• have problems with your liver or kidneys.
• have diabetes, heart disease, or high blood pressure.
• have a history of seizure, stroke, eating disorder, head injury, or have a tumor in your brain or spinal cord.
• have a history of alcohol or drug abuse.
• have a history of seizure, eating disorder, or abuse alcohol or drugs.
• have low blood sugar, low blood sodium levels, or a history of falls.
• you take certain other medicines that could interact with Auvelity.
• have or had a condition known as bipolar disorder, a family history of bipolar disorder, suicide, or depression.
• have high pressure in the eye (glaucoma).
  

Review the list below with your HCP. Auvelity may not be right for you if:

• you drink a lot of alcohol.
• you abuse prescription or street drugs.
• you are pregnant or plan to become pregnant.
• you are breastfeeding or plan to breastfeed.

HOW TO TAKE

• Auvelity is available by prescription only.
• Take Auvelity exactly as instructed by your HCP.
• Take Auvelity 1 time a day for 3 days, then increase your dose to 2 times a day (taken at least 8 hours apart). Do not take more than 2 Auvelity tablets in 24 hours.
• If you miss a dose, do not take an extra dose. Wait and take your next dose at the regular time. Do not take more than 1 dose of Auvelity at a time.
• Do not change your dose or stop taking Auvelity without talking to your HCP.
• Swallow Auvelity tablets whole. Do not crush, chew, or divide the tablets.
• Do not give Auvelity to other people.
• If you take too much Auvelity call your HCP or seek medical advice promptly.

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 10/2022

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.

Forward Looking Statements

Certain matters discussed in this press release are "forward-looking statements". We may, in some cases, use terms such as "predicts," "believes," "potential," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company's statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the continued commercial success of our Sunosi and Auvelity products and the success of our efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the success, timing and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of our ongoing clinical trials, and the number or type of studies or nature of results necessary to support the filing of a new drug application ("NDA") for any of our current product candidates; our ability to fund additional clinical trials to continue the advancement of our product candidates; the timing of and our ability to obtain and maintain U.S. Food and Drug Administration ("FDA") or other regulatory authority approval of, or other action with respect to, our product candidates; whether issues identified by FDA in the complete response letter may impact the potential approvability of the Company's NDA for AXS-07 for the acute treatment of migraine in adults with or without aura, pursuant to our special protocol assessment for the MOMENTUM clinical trial; the Company's ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company's research and development programs and collaborations; the success of the Company's license agreements; the acceptance by the market of the Company's products and product candidates, if approved; the Company's anticipated capital requirements, including the amount of capital required for the continued commercialization of Sunosi and Auvelity and for the Company's commercial launch of its other product candidates, and the potential impact on the Company's anticipated cash runway; unforeseen circumstances or other disruptions to normal business operations arising from or related to COVID-19; and other factors, including general economic conditions and regulatory developments, not within the Company's control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance.

Axsome Contact:
Mark Jacobson
Chief Operating Officer
Axsome Therapeutics, Inc.
22 Cortlandt Street, 16^th Floor
New York, NY 10007
Tel: 212-332-3243
Email: [email protected]
www.axsome.com

References

1. U.S. Department of Health and Human Services. Key Substance Use and Mental Health Indicators in the United States: Results from the 2020 National Survey on Drug Use and Health. Published October 2021.
2. Baune BT, et al. Neuropsychiatr Dis Treat 2021;17:2995-3006.
3. Wardenaar KJ, et al. J. Affect. Disord 2012; 136:1198-1203.