Ramelteon

Pictured: Red and white Takeda sign on a brick wall/iStock, jetcityimage Takeda’s work in its orexin franchise may soon reach a new high point as the oral candidate TAK-816 will imminently have a readout in Phase II to treat narcolepsy. Back in 2021, the Japanese pharma put the kibosh on another orexin candidate, TAK-994, due to issues around safety. But with a readout expected soon, Elena Koundourakis, who has led Takeda’s orexin program for more than three years, spoke to BioSpace in San Francisco to talk about what’s to come for its orexin program. This interview has been edited for brevity. BSp: What has been your involvement in Takeda’s orexin program? EK: I’ve been with the company a long time, but I came to orexin after various roles in oncology, GI, and vaccines because I saw the promise of the biology. I knew at the time that orexin was being developed by Takeda since 2017 [as an] IV for narcolepsy, type one and type two. Still, I knew that orexin had been implicated in sleep-wake from a biological perspective, regulation of sleep-wake, respiration, metabolism. BSp: What is the previous history of this drug? EK: It has the potential to serve [an] unmet need in several indications, so that attracted me. . . . We had experience in the sleep field with ramelteon [Rozerem], which was launched in Japan and the U.S. [It] didn’t do extremely well, but it helped us from a chemistry perspective to make the target druggable in terms of having a selective orexin 2 agonist that can penetrate the blood-brain barrier and then modulate the receptor, which is intact in patients with narcolepsy type 1. The peptide is lost . . . but the receptors are intact. So the idea is that you can modulate the receptor, then influence the signaling downstream of the receptor and restore, if you like, the physiological function of patients in narcolepsy. The cardinal symptom is excessive daytime sleepiness, so they often fall asleep throughout the day. BSp: What went wrong with the other orexin program, and how is Takeda aiming to bounce back? EK: We bounced back big time. Because it was the first time we were going from an IV to an oral [drug], we had a lot of question marks. When you try to improve the pathophysiology of a narcoleptic patient who in the morning is somewhat sleepy but not really sleepy, and then in the afternoon is sleepy, and then it gets better later in the afternoon. Still, then they are having disrupted nighttime sleep. It is an oral compound, which you dose maybe once a day or two times a day—it’s hard, right? We weren’t sure if, with the oral TAK-994 at that time, [we could] address all the symptoms. . . . So we have had a very active backup programs. [After toxicity issues ended the program] everybody working on 994 started working on TAK-861. BSp: Even though 994 didn’t progress, results were still posted in the New England Journal of Medicine. What were the most surprising results? EK: The most surprising result that we found was how well it worked. It was like a complete normalization of wakefulness; they wouldn’t fall asleep. Their wakefulness would be like yours and mine—maybe not during J.P. Morgan. Then there’s the complete suppression of cataplexy, like zero cataplectic attacks, which was incredible. . . . So it’s a functional cure, basically. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Topline results from Phase IV study demonstrate Qelbree is safe and well-tolerated, and significantly improved efficacy outcomes when added to a stimulant medication in pediatric patients with ADHDFinal long-term data show Qelbree consistently improved symptoms and executive function in adults with ADHD, with safety and tolerability similar to the short-term pivotal adult Phase III trial ROCKVILLE, Md., Sept. 09, 2023 (GLOBE NEWSWIRE) -- Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, announces the presentation of two posters at Psych Congress 2023 with new data showing improved efficacy in children ages 6 years and older with ADHD when Qelbree is added to a stimulant, as well as in adults with ADHD who undergo long-term treatment with Qelbree. “While ADHD is recognized as one of the most common psychiatric diagnoses, affecting approximately 16.1 million individuals in the United States, patients are in need of alternative or additional options to stimulants that allow them to manage their symptoms with a safe and tolerable treatment option,” says Jonathan Rubin, Chief Medical Officer and Senior Vice President of Research & Development. “The new Qelbree data presented during Psych Congress 2023 reinforce the efficacy and safety of our novel nonstimulant treatment in addition to existing stimulant therapy in children ages 6 and older with ADHD and in a long-term setting in adults with ADHD.” Results from Phase IV Safety Trial of Concomitant Use with Psychostimulants in Children and Adolescents with ADHD When added to existing psychostimulants, Qelbree demonstrated a favorable safety and tolerability profile as well as a significant improvement in ADHD symptoms in pediatric patients (6-17 years), regardless of timing of dosing. In an eight-week, Phase IV, open-label study, children (ages 6-11) and adolescents (ages 12-17) took psychostimulants at least five days a week in the morning throughout the duration of the study, and received Qelbree once-daily in the morning through week four and then switched to evening dosing through week eight; children received 100mg per day of Qelbree at week one and were optimized to 100-400mg per day, and adolescents received 200mg per day of Qelbree at week one and were optimized to 200-600mg per day. Results showed significant symptom improvement from baseline ADHD-RS-5 and CGI-S scores following both morning and evening dosing of Qelbree in combination with the morning psychostimulant. At baseline (N=56), mean (standard deviation) ADHD-RS-5 and CGI-S scores were 37.2 (8.35) and 4.4 (0.56), respectively, and improved at week four (N=54) by -13.5 (9.7) and -0.9 (0.92), respectively, and at week eight (N=48) by -18.2 (9.99) and -1.4 (1.10), respectively. Reported adverse events (AEs) of the combination therapy included headache (17.9%), decreased appetite (12.5%), and upper respiratory tract infection (10.7%), and 3.6% of patients discontinued the combination treatment due to an AE. “Approximately 10%-30% of individuals living with ADHD experience inadequate response or have difficulty tolerating stimulant medications, which indicates a clear need for alternative or additional treatment options,” says Ann Childress, M.D., President of the Center for Psychiatry and Behavioral Medicine in Las Vegas, NV. “These data demonstrate Qelbree’s ability to enhance efficacy when co-administered with stimulants, including significant improvement during evening hours when the effects of stimulants often wear off following their morning dose. This study illustrates the versatility of Qelbree to address patient needs, including standalone usage and combination therapy, regardless of dosing time.” Final Results from Long-term, Phase III, Open-label Extension Trial in Adults with ADHD Conclusive outcomes from a long-term, open-label extension (OLE) trial of the double-blind pivotal Phase III study that led to the U.S. Food and Administration (FDA)-approval of Qelbree in adults with ADHD, found that adult patients (N=159) saw an improvement in ADHD symptoms and executive function with safety and tolerability similar to the initial trial. Adults received 200mg of Qelbree every day for one week, increased to 400mg, and then optimized over twelve weeks up to 600mg per day (200-600mg per day). Patients in this open-label trial received Qelbree for 265 (254.9) days. Patients ADHD symptoms improved from 37.9 (6.34) to 19.7 (12.16) on the Adult ADHD Investigator Symptom Rating Scale (AISRS), representing average symptom reduction of -18.2 (11.54). Patients executive function improved from 70.4 (10.94) to 58.3 (16.19) on the BRIEF-A Global Executive Composite scale, representing improvement in executive function of -12.9 (13.48). The treatment related adverse events (TRAEs) seen in this long-term trial were consistent with those seen in the short-term pivotal adult trial. The most commonly occurring TRAEs reported with the use of Qelbree were insomnia (11.3%), nausea (9.4%), headache (5.7%), and fatigue (10.1%). AEs led to discontinuation in 17.6% of patients. “ADHD is a 24/7 disorder that often persists into adulthood, and it can be difficult to find the right treatment regimen,” says Andrew J. Cutler, M.D., Clinical Associate Professor of Psychiatry at SUNY Upstate Medical University, and Chief Medical Officer, Neuroscience Education Institute. “These data are encouraging as they underscore the compelling advantage of long-term medication adherence and benefits with Qelbree for our ADHD patients, including sustained improvement in ADHD symptoms, robust response, reduced severity and improved executive function.” INDICATION Qelbree® (viloxazine extended-release capsules) is a prescription medicine used to treat ADHD in adults and children 6 years and older. IMPORTANT SAFETY INFORMATION ABOUT QELBREEQelbree may increase suicidal thoughts and actions, in children and adults with ADHD, especially within the first few months of treatment or when the dose is changed. Tell your doctor if you or your child have (or if there is a family history of) suicidal thoughts or actions before starting Qelbree. Monitor your or your child’s moods, behaviors, thoughts, and feelings during treatment with Qelbree. Report any new or sudden changes in these symptoms right away. You should not take Qelbree if you or your child:Take a medicine for depression called a monoamine oxidase inhibitor (MAOI) or have stopped taking an MAOI in the past 14 days. Also, you or your child should avoid alosetron, duloxetine, ramelteon, tasimelteon, tizanidine, and theophylline. Qelbree can increase blood pressure and heart rate. Your or your child’s doctor will monitor these vital signs. Qelbree may cause manic episodes in patients with bipolar disorder. Tell your doctor if you or your child show any signs of mania. Do not drive or operate heavy machinery until you know how Qelbree will affect you or your child. Qelbree may cause you or your child to feel sleepy or tired. The most common side effects of Qelbree in patients 6 to 17 years are sleepiness, not feeling hungry, feeling tired, nausea, vomiting, trouble sleeping, and irritability, and in adults, insomnia, headache, sleepiness, tiredness, nausea, decreased appetite, dry mouth, and constipation. These are not all the possible side effects of Qelbree. Please see full Prescribing Information, including Boxed Warning, for Qelbree here. About Supernus Pharmaceuticals, Inc. Supernus Pharmaceuticals is a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases. Our diverse neuroscience portfolio includes approved treatments for epilepsy, migraine, ADHD, hypomobility in Parkinson’s disease (PD), cervical dystonia, chronic sialorrhea, dyskinesia in PD patients receiving levodopa-based therapy, and drug-induced extrapyramidal reactions in adult patients. We are developing a broad range of novel CNS product candidates including new potential treatments for hypomobility in PD, epilepsy, depression, and other CNS disorders. For more information, please visit www.supernus.com. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements do not convey historical information but relate to predicted or potential future events that are based upon management's current expectations. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. In addition to the factors mentioned in this press release, such risks and uncertainties include, but are not limited to, the Company’s ability to sustain and increase its profitability; the Company’s ability to raise sufficient capital to fully implement its corporate strategy; the implementation of the Company’s corporate strategy; the Company’s future financial performance and projected expenditures; the Company’s ability to increase the number of prescriptions written for each of its products; the Company’s ability to increase its net revenue; the Company’s ability to commercialize its products including Qelbree; the Company’s ability to enter into future collaborations with pharmaceutical companies and academic institutions or to obtain funding from government agencies; the Company’s product research and development activities, including the timing and progress of the Company’s clinical trials, and projected expenditures; the Company’s ability to receive, and the timing of any receipt of, regulatory approvals to develop and commercialize the Company’s product candidates; the Company’s ability to protect its intellectual property and operate its business without infringing upon the intellectual property rights of others; the Company’s expectations regarding federal, state and foreign regulatory requirements; the therapeutic benefits, effectiveness and safety of the Company’s product candidates; the accuracy of the Company’s estimates of the size and characteristics of the markets that may be addressed by its product candidates; the Company’s ability to increase its manufacturing capabilities for its products and product candidates; the Company’s projected markets and growth in markets; the Company’s product formulations and patient needs and potential funding sources; the Company’s staffing needs; and other risk factors set forth from time to time in the Company’s filings with the Securities and Exchange Commission made pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934, as amended. The Company undertakes no obligation to update the information in this press release to reflect events or circumstances after the date hereof or to reflect the occurrence of anticipated or unanticipated events. CONTACT: Jack A. Khattar, President and CEO Timothy C. Dec, Senior Vice President and CFOSupernus Pharmaceuticals, Inc.Tel: (301) 838-2591 Or MEDIA CONTACT:Alice SofieldMobile: (703) 861-5654Email: Alice.Sofield@BCW-Global.com INVESTOR CONTACT:Peter VozzoICR WestwickeOffice: (443) 213-0505Email: peter.vozzo@westwicke.com