Clenbuterol Hydrochloride

Robert Barrie The results from a global Phase III trial funded by Novo Nordisk found significant symptom improvement in patients with preserved ejection fraction (HFpEF). Image credit: Shutterstock/JHVEPhoto. Data published in The New England Journal of Medicine has demonstrated that Novo Nordisk ’s blockbuster weight loss drug Wegovy (2.4mg subcutaneous semaglutide) can reduce heart-failure-related symptoms in people with obesity. The results from a global Phase III trial funded by Novo Nordisk found significant symptom improvement in patients with preserved ejection fraction (HFpEF) – a condition that comprises roughly half of all heart failure cases. Recommended Reports Reports LOA and PTSR Model - Clenbuterol Hydrochloride in Mild Cognitive Impairment GlobalData Reports LOA and PTSR Model - Levetiracetam Er in Mild Cognitive Impairment GlobalData View all Companies Intelligence Novo Nordisk AS Saint Luke's Mid America Heart Institute View all In the randomised, placebo-controlled trial (NCT04788511), Wegovy was administered as a 2.4mg weekly dose in 529 patients. After a year, it led to an estimated mean difference of 7.8 points in the Kansas City Cardiomyopathy Questionnaire clinical summary score – a patient-reported outcome for heart failure symptoms and limitations, compared to placebo. Along with leading to a larger reduction in body weight (13.3% versus 2.6%), Wegovy also vastly increased the distance patients were able to walk in six minutes compared to placebo – 21.5 metres versus 1.2 metres. The authors of the paper noted that one of the limitations of the study was that it focused on symptoms, physical limitations, and exercise function and could not take into account the efficacy in more serious instances such as hospitalisations. Lack of patient diversity was also a factor to consider for drawing widespread implications of the results, with the number of non-White participants being low. The findings, which were also presented at the European Society of Cardiology (ESC) Congress in Amsterdam on 25 August, hint that semaglutide – also sold at a different dose under the brand name Ozempic – could be used in an expanded indication for heart failure. Novo Nordisk is not attempting to hide the expansive plans for its prize asset. The company has already unveiled positive results from a Phase III trial investigating Wegovy in some 17,600 adults with cardiovascular disease . In the last few years, Novo Nordisk has had to contend with undeliverable demand for Wegovy . The company has moved to increase infrastructure capabilities to roll out the drug, including a recent manufacturing contract with life science giant Thermo Fisher . The drug is the main driver of the company’s sales, helping set an expected growth of 24% – 30% for 2023 . GlobalData predicts the obesity market to be worth $37.1bn by 2031, with Wegovy expected to be the top-selling drug. “As clinicians, we have limited treatment options to offer our patients living with HFpEF and obesity. Yet this is a condition that seriously impacts patients’ day-to-day experience, due to debilitating symptoms and functional limitations,” said Dr. Mikhail Kosiborod, lead study investigator and cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, US. “Today’s news heralds a possible fundamental paradigm shift in how cardiologists approach HFpEF in people with obesity.”

Additional Phase 1 Data with CST-2032/CST-107 Reinforce Potential of Adrenoceptor Agonist Class of Drugs in Patients with Cognitive Impairment GOTHENBURG, Sweden--(BUSINESS WIRE)-- CuraSen Therapeutics, Inc., a clinical-stage company developing small molecule drugs to treat neurodegenerative symptoms and disease progression, announced that it will present Phase 2 clinical data showing improvements in cognition and mood in Parkinson’s disease patients treated with CST-103/CST-107, a novel combination therapy that restores adrenergic stimulus to the brain. Additionally, the company will present promising Phase 1 data with a second program, CST-2032/CST-107, in healthy participants and patients with mild cognitive impairment (MCI). Data will be shared in two oral presentations at the International Alzheimer’s Disease and Parkinson’s Disease (AD/PD’23) conference, being held March 28 - April 1, 2023, in Gothenburg, Sweden. Presentation details are below. CST-103, also known as clenbuterol, and CST-2032 are oral, brain-permeant, beta2 adrenoceptor (β2-AR) agonists, and CST-107, known as nadolol, is a brain-sparing β-AR blocker. In these studies, clenbuterol and CST-2032 are co-administered with nadolol to minimize known peripheral cardiometabolic side effects of β2-AR agonists. The company is developing fixed-dose combinations for both drugs. “For the first time, we have been able to show improved outcomes in cognition and mood with adrenergic agonism in patients with neurodegenerative disease, by safely restoring a stimulus to the brain that is lost early in the pathologic process. With its strong safety pro impressive effect sizes in key domains, we look forward to testing this fast-acting combination treatment in a longer-term study in Parkinson’s patients later this year,” said Anthony Ford, PhD, chief executive officer, CuraSen Therapeutics. “These data, coupled with promising Phase 1 results from our second program, CST-2032/nadolol, validate our novel approach to providing meaningful treatment options to neurodegenerative patients with high unmet needs.” Clenbuterol is an established drug that has been used in pulmonology for decades, while CST-2032 was discovered and developed at CuraSen, with properties providing the ability to differentiate and de-risk the two products in distinct neurodegenerative patient populations and outcome measures. Phase 2 Proof-of-Concept Study with Clenbuterol/Nadolol in Parkinson’s Disease Parkinson’s disease is a progressive, neurodegenerative disease that is associated with slow movement, tremor, rigidity and imbalance, as well as non-motor complications such as cognitive impairment, depression, pain, dysautonomia and sleep disorders. The Phase 2 trial was an exploratory, randomized, double-blinded, crossover study in 25 patients with Parkinson’s disease with cognitive deficits. An additional 13 patients were enrolled with mild cognitive impairment without a PD diagnosis. Patients received either the once-daily clenbuterol (80 µg)/nadolol (1 mg) combination treatment or matched placebo, with 14 days treatment on each period and at least 14 days of washout between periods. All PD subjects had impaired cognition at baseline with evidence of impaired cerebral noradrenergic signaling, as assessed by neuromelanin MRI of the locus coeruleus. The study took place at sites in the UK, Australia, New Zealand and Belgium. Results in PD patients showed: Statistically significant improvements in several quantitative test measures of episodic memory, attentiveness and depressive emotional bias in patients treated with clenbuterol/nadolol, with several effect sizes (Cohen’s d) in the range 0.3-0.6 which are predictive of clinically meaningful results in a larger, longer trial Rapid onset of drug effect - improvements observed as early as one day after treatment and in some cases, persisting beyond the two weeks of daily treatment No serious or severe adverse events attributed to study drug; most adverse events observed were mild CuraSen’s next Phase 2 study with clenbuterol/nadolol is anticipated later this year and will enroll Parkinson’s patients with significant non-motor symptoms with a similar combination dosing plan in a 12-week parallel design. Phase 1 Study with CST-2032/Nadolol in Mild Cognitive Impairment (MCI) The Phase 1 study with CST-2032/nadolol included 79 healthy volunteers and patients with MCI. The study involved single-ascending and multiple-ascending dose cohorts. Results showed that treatment with CST-2032/nadolol: Was safe and well tolerated Increased cerebral blood flow, a biomarker for target engagement, in brain regions involved in memory, alertness and arousal Led to performance changes in cognitive tasks associated with memory Offered clear guidance on optimal combination dose levels of each substance for Phase 2 assessment Based on the strength of these data, CuraSen has initiated a Phase 2a exploratory, randomized, placebo-controlled, double-blinded crossover study with CST-2032/CST-107 in up to 60 patients with MCI or mild dementia due to either Alzheimer’s or Parkinson’s disease. The trial is taking place at 20 centers in the U.S. and New Zealand, with results anticipated later in 2023. Oral Presentation Details Abstract #: 368 Title: “Effects of a Beta-2 Adrenoceptor Agonist on Cognition in Parkinson’s Disease Patients with REM Sleep Behavior Disorder” Date/Time: Sat, April 1, 3:15-3:30 pm CET; 9:15 am-9:30 am ET Session: #4450 - Advances in PD and LBD Diagnosis and Drug Development Presenter: Gabriel Vargas, MD, PhD, chief medical officer, CuraSen Therapeutics Abstract #: 338 Title: "A Phase 1 Safety, Pharmacokinetics and Pharmacodynamic Study of CST-2032: A Novel, Selective, CNS Penetrating Beta-2 Adrenoceptor Agonist for the Treatment of Cognitive Impairment” Date/Time: Sat, April 1, 6:25-6:40 pm CET; 12:25-12:40 pm ET Session: #4540 - SOC Drugs and Other Targeted Therapies in AD Presenter: Professor Thomas Lodeweyckx, MD, KU Leuven, Belgium About CuraSen Therapeutics CuraSen is developing novel treatments for neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and other related orphan conditions. CuraSen’s drugs are designed to activate certain receptor populations in the brain to compensate for critical neuronal and glial functions that have otherwise been lost early in degeneration and represent a unique approach in the field, addressing core symptoms and the progression of pathology. The company is evaluating CST-103 and CST-2032, both selective β2-ARs agonists, in combination with CST-107, a β-AR blocker, in multiple Phase 2 clinical studies. For more information, please visit .