Dexmethylphenidate Hydrochloride

Twelve Required Registration Batches Completed New Drug Application Being Prepped for Submission June 25, 2024 -- In alignment with U.S. Food and Drug Administration (FDA) requirements, Cingulate Inc. (NASDAQ: CING), a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, announced today that it has completed the manufacturing of its twelve registration batches for its lead asset CTx-1301 (dexmethylphenidate) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Registration batches are required by the U.S. Food and Drug Administration (FDA) to be manufactured before submitting a new drug application (NDA) using the actual equipment, dosage strengths and procedures that will be used to commercialize the drug product candidate. “This achievement brings us one step closer to compliance with the FDA’s guidance for submission of an NDA, and is an important chemical, manufacturing and control (CMC) inflection point for CTx-1301, as these pivotal batches are used to demonstrate that we have a reliable manufacturing process and acceptable shelf life for our product,” said Cingulate Chief Operating Officer Laurie Myers. Cingulate, which recently announced it had received confirmation from and agrees with the FDA on the requirements necessary for filing an NDA for CTx-1301, has begun NDA preparation and expects to submit its application in the first half of 2025. ADHD is a chronic neurobiological and developmental disorder that affects millions of children and often continues into adulthood. The condition is marked by an ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development. In the U.S., approximately 6.4 million children and adolescents (11 percent) aged under the age of 18 have been diagnosed with ADHD. Among this group, approximately 80 percent receive treatment, with 65-90 percent demonstrating clinical ADHD symptoms that persist into adulthood. Adult ADHD prevalence is estimated at approximately 11 million patients (4.4 percent), almost double the size of the child and adolescent segment combined. However, only an estimated 20 percent receive treatment. Cingulate’s lead candidate, CTx-1301, utilizes Cingulate’s proprietary PTR drug delivery platform to create a breakthrough, multi-core formulation of the active pharmaceutical ingredient dexmethylphenidate, a compound approved by the FDA for the treatment of ADHD. Dexmethylphenidate is part of the stimulant class of medicines and increases norepinephrine and dopamine activity in the brain to affect attention and behavior. While stimulants are the gold standard of ADHD treatment due to their efficacy and safety, the long-standing challenge continues to be providing patients with an entire active-day duration of action. CTx-1301 is designed to precisely deliver three releases of medication at the predefined time, ratio, and style of release to optimize patient care in one tablet. The result is a rapid onset and entire active-day efficacy, with the third dose being released around the time when other extended-release stimulant products begin to wear off. Cingulate is developing ADHD and anxiety disorder product candidates capable of achieving true once-daily dosing using Cingulate’s innovative PTR drug delivery platform technology. It incorporates a proprietary Erosion Barrier Layer (EBL) providing control of drug release at precise, pre-defined times with no release of drug prior to the intended release. The EBL technology is enrobed around a drug-containing core to give a tablet-in-tablet dose form. It is designed to erode at a controlled rate until eventually the drug is released from the core tablet. The EBL formulation, Oralogik™, is licensed from BDD Pharma. Cingulate intends to utilize its PTR technology to expand and augment its clinical-stage pipeline by identifying and developing additional product candidates in other therapeutic areas in addition to Anxiety and ADHD where one or more active pharmaceutical ingredients need to be delivered several times a day at specific, predefined time intervals and released in a manner that would offer significant improvement over existing therapies. To see Cingulate’s PTR Platform, click here. Cingulate Inc. (NASDAQ: CING), is a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, designed to improve the lives of patients suffering from frequently diagnosed conditions characterized by burdensome daily dosing regimens and suboptimal treatment outcomes. With an initial focus on the treatment of attention deficit/hyperactivity disorder (ADHD), Cingulate is identifying and evaluating additional therapeutic areas where PTR technology may be employed to develop future product candidates, including to treat anxiety disorders. The content above comes from the network. if any infringement, please contact us to modify.

KP1077 was well tolerated and showed meaningful clinical improvements in patient-reported assessments of daytime sleepiness, sleep inertia, and brain fog Additional data presented on pharmacokinetics of morning and nighttime doses of KP1077 European Commission has granted Orphan Drug Designation for KP1077 for the treatment of idiopathic hypersomnia CELEBRATION, Fla., June 03, 2024 (GLOBE NEWSWIRE) -- Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) (Zevra, or the Company), a rare disease therapeutics company, today announced that final positive results from its placebo-controlled, double-blind Phase 2 clinical trial (NCT05668754) evaluating the safety and tolerability of KP1077 (serdexmethylphenidate or SDX) in patients with idiopathic hypersomnia (IH) were presented in a poster at SLEEP 2024, the 38th annual joint meeting of the American Academy of Sleep Medicine and the Sleep Research Society, held in Houston, TX, June 1-5, 2024. In addition, a second poster describing the pharmacokinetics of SDX when administered in the morning and at night was also presented. “We are encouraged by the positive results of the Phase 2 clinical trial, which serve as further support of KP1077 as a strong candidate to treat patients struggling with idiopathic hypersomnia,” said Adrian Quartel, MD, FFPM, Chief Medical Officer of Zevra. “We believe that KP1077 has great potential to provide a differentiated treatment option for patients underserved by currently available therapies.” This proof-of-concept study was designed to demonstrate safety and tolerability and was not powered to demonstrate statistical significance. However, the trial included several important secondary and exploratory endpoints, such as change in Epworth Sleepiness Scale (ESS) total score, the IH Severity Scale (IHSS), the Sleep Inertia Visual Analog Scale (SIVAS), and a new scale to assess the symptoms and severity of brain fog. These data gathered from the secondary endpoints will help inform the study design for a potential Phase 3 clinical trial of KP1077. “The results of the Phase 2 clinical trial support the safety and tolerability of KP1077 as measured by the primary endpoint of the study,” stated Christopher Drake, PhD, FAASM, DBSM, Principal Investigator of the study. “The clinically meaningful impact for both the safety and efficacy were well demonstrated by patients showing significant improvements in IH symptom severity such as sleep inertia, excessive daytime sleepiness (EDS), and patient-reported IH-specific outcomes.” Key Takeaways from Phase 2 Clinical Trial of KP1077 for Idiopathic Hypersomnia: KP1077 was well tolerated at all dose levels evaluated in the trial, including the highest dose of 320 mg daily, regardless of the dosing regimen: once daily (QD) or twice daily (BID). Adverse events (AEs) were similar to other methylphenidate productsMost common AEs included insomnia, headache, anxiety, decreased appetite, and nauseaMost AEs occurred during the titration period, were mild, and did not lead to early discontinuation KP1077 produced clinically meaningful improvements in EDS as assessed by change from baseline in the ESS during both the 5-week open-label (OL) titration period which was maintained during the 2-week double-blind withdrawal period for both dosing regimens. Mean total ESS scores decreased by approximately 9 points after 5 weeks of OL treatment. At the end of 7 weeks of treatment, patients administered KP1077 showed clinically meaningful benefits in change from baseline for the ESS, IHSS, SIVAS, and Brain Fog Scale (BFS): Mean total ESS score decreased by 9.4 (QD) and 8.8 (BID)Mean total IHSS score decreased by 16.1 (QD) and 12.3 (BID)Mean SIVAS score decreased by 25.9 (QD) and 17.2 (BID)Mean total BFS symptom score decreased by 23.8 (QD) and 22.3 (BID) The study successfully fulfilled the objectives of providing key information for the design of a pivotal efficacy trial, and the results of the secondary efficacy endpoints were supportive of initiating a Phase 3 trial of KP1077. Separately, the pharmacokinetics of morning and nighttime dose of KP1077 was studied. These data are also being presented in a poster at SLEEP 2024. Key Takeaways from Pharmacokinetics of Morning and Nighttime Doses of KP1077 Based on the Phase 2 trial results, the Company believes that: Peak exposure of SDX-derived d-MPH after a nighttime dose of SDX occurs during the next morning leading to higher exposure at awakening compared to a morning dose.The delay in exposure is likely due to a longer intestinal transit time and lower intestinal activity during the nighttime sleeping hours.The delay in exposure supports nighttime dosing of SDX in patients with IH who suffer from EDS and sleep inertia (difficulty waking up in the morning). The results from each study were discussed during two poster presentations in Hall A3, Poster Presentation Session P-13: Title: Safety and Efficacy of KP1077 in a Phase 2, Double-blind, Randomized Trial in Patients with Idiopathic HypersomniaDate/Time: June 3, 2024, 10 a.m. to 11:45 a.m. CDT Title: Pharmacokinetics of Morning and Nighttime Doses of KP1077, an Investigational Treatment for Idiopathic HypersomniaDate/Time: June 3, 2024, 10 a.m. to 11:45 a.m. CDT Representatives from Zevra Therapeutics are also available during exhibit hours at Booth #1421 for additional discussion. Zevra proudly supports the Hypersomnia Foundation’s mission to raise awareness, educate, and uplift the voices of those living with idiopathic hypersomnia and was proud to participate in the inaugural Idiopathic Hypersomnia Day (IH Day) on June 1, 2024. IH Day, held in Houston during the Hypersomnia Foundation’s BeyondSleepy Conference, served as the kickoff to Idiopathic Hypersomnia Awareness Week, which runs through June 7, 2024. About the KP1077 Phase 2 Trial The Phase 2 clinical trial was a double-blind, placebo-controlled, randomized-withdrawal, dose-optimizing, multi-center study that evaluated the safety and efficacy of KP1077 for the treatment of IH. Part 1 of the trial consisted of a 5-week open-label dose titration phase during which patients were optimized to one of four doses of KP1077 (80, 160, 240, or 320 mg/day). Part 2 of the trial entailed a two-week randomized, double-blind, withdrawal phase, during which two-thirds of the trial participants continued to receive their optimized dose while the remaining one-third received placebo. Participants were assigned into two evenly divided cohorts. The first cohort received a single daily dose just before bedtime, and the second cohort received half the daily dose shortly after awakening and the second half prior to bedtime. Zevra enrolled 66 adult patients with IH in 24 centers in the U.S. into the open-label titration phase of the study and 50 of those patients continued into the double-blind phase. The primary endpoint was the safety and tolerability of KP1077. The major secondary efficacy endpoint was the change in Epworth Sleepiness Scale (ESS) total score. Additional secondary endpoints included the IH Severity Scale (IHSS), the Sleep Inertia Visual Analog Scale (SIVAS), and a new scale to assess the symptoms and severity of brain fog. About Idiopathic Hypersomnia Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness (EDS). Patients with IH experience daytime lapses into sleep, or an irrepressible need to sleep that persists even with adequate or prolonged nighttime sleep. Additionally, those with IH have extreme difficulty waking, otherwise known as sleep inertia, severe brain fog, and often fall asleep unintentionally or at inappropriate times. These symptoms of IH often lead to further, even more debilitating problems such as memory lapses, difficulty maintaining focus, and depression. It is estimated, based on claims data, that approximately 37,000 patients in the United States are currently diagnosed with IH, although the total patient population may be much larger due to some patients who have not yet been diagnosed, have been misdiagnosed, or are not currently seeking treatment. About KP1077 KP1077 (serdexmethylphenidate or SDX) is Zevra’s proprietary prodrug of d-methylphenidate (d-MPH) and its sole active pharmaceutical ingredient (API). KP1077 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA), and by the European Commission, for the treatment of IH. The U.S. Drug Enforcement Agency (DEA) has classified SDX, the sole API in KP1077, as a Schedule IV controlled substance based on evidence suggesting SDX has a lower potential for abuse when compared to d-MPH, a Schedule II controlled substance. In addition, KP1077 has intellectual property protection through 2037 and potentially beyond. About Zevra TherapeuticsZevra Therapeutics is a rare disease company combining science, data, and patient needs to create transformational therapies for diseases with limited or no treatment options. Our mission is to bring life-changing therapeutics to people living with rare diseases. With unique, data-driven development and commercialization strategies, the Company is overcoming complex drug development challenges to make new therapies available to the rare disease community. Expanded access programs are made available by Zevra Therapeutics and its affiliates and are subject to the Company's Expanded Access Program (EAP) policy as published on its website. Participation in these programs is subject to the laws and regulations of each jurisdiction under which each respective program is operated. Eligibility for participation in any such program is at the treating physician's discretion. For more information, please visit www.zevra.com or follow us on X (formerly Twitter) and LinkedIn. About American Academy of Sleep MedicineEstablished in 1975 as the Association of Sleep Disorders Centers, the American Academy of Sleep Medicine (AASM) is the only professional society dedicated exclusively to the medical subspecialty of sleep medicine. As the leading voice in the sleep field, the AASM sets standards and promotes excellence in sleep medicine health care, education, and research. The AASM has a combined membership of 11,000 accredited member sleep centers and individual members, including physicians, scientists, and other health care professionals. About the Sleep Research SocietyThe Sleep Research Society (SRS) is an organization for scientific investigators who educate and research sleep and circadian science. The SRS serves its members and the field of sleep research through training and education, and by providing forums for the collaboration and the exchange of ideas. Cautionary Note Concerning Forward-Looking Statements This press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that do not relate solely to historical or current facts, including without limitation statements regarding the promise and potential impact of our preclinical or clinical trial data, the initiation, timing, design, or results of any clinical trials or readouts, the potential benefits of any of our products or product candidates for any specific disease indication or at any dosage, and upcoming events or Zevra’s participation at such events. Forward-looking statements are based on information currently available to Zevra and its current plans or expectations. They are subject to several known and unknown uncertainties, risks, and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. These and other important factors are described in detail in the "Risk Factors" section of Zevra’s Annual Report on Form 10-K for the year ended December 31, 2023, Zevra’s quarterly report for the three months ended March 31, 2024, and Zevra’s other filings with the Securities and Exchange Commission. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. Although we believe the expectations reflected in such forward-looking statements are reasonable, we cannot assure that such expectations will prove correct. These forward-looking statements should not be relied upon as representing our views as of any date after the date of this press release. Zevra Contact Nichol Ochsner +1 (732) 754-2545 nochsner@zevra.com Russo Partners Contacts Adanna G. Alexander, Ph.D. +1 (646) 942-5603 adanna.alexander@russopartnersllc.com Ignacio Guerrero-Ros, Ph.D. +1 (646) 942-5604 ignacio.guerrero-ros@russopartnersllc.com