Ruoxinlin (toludesvenlafaxine extended release) / Luye Group - LARVOL DELTA

CLASS 1 INNOVATIVE ANTIDEPRESSANT RUOXINLIN APPROVED FOR MARKETING IN MACAO (HKEXnews) - "The board of directors (the 'Board') of Luye Pharma Group...announces that Ruoxinlin (Toludesvenlafaxine Hydrochloride Extended-Release Tablets), the Group’s innovative drug for treating Major Depressive Disorder ('MDD'), has been approved for marketing in Macao by the Pharmaceutical Administration Bureau of the Macao SAR Government....The results of the Phase 3 clinical study of Ruoxinlin demonstrated that it is able to treat MDD in a comprehensive and stable manner....At the end of 2024, following successful negotiations, Ruoxinlin was included in the China’s National Reimbursement Drug List for Basic Medical Insurance, Work-Related Injury Insurance and Maternity Insurance (2024 Version) for the first time."

Approval • Reimbursement • Major Depressive Disorder

Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Venlafaxine Hydrochloride Sustained-release Tablets in Patients With Major Depression Disorder (clinicaltrials.gov) - P=N/A | N=84 | Completed | Sponsor: First Affiliated Hospital of Zhejiang University | Recruiting ➔ Completed

Trial completion • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Uncovering the Elusive Structures and Mechanisms of Prevalent Antidepressants. (PubMed, Adv Ther (Weinh)) - "In this study, we apply microcrystal electron diffraction (MicroED) to reveal the atomic 3D structures for the first time of five of the most prevalent antidepressants (reboxetine, pipofezine, ansofaxine, phenelzine, bifemelane) directly from the commercially available powder of the active ingredients. Their modes of binding are investigated by molecular docking, revealing the essential contacts and conformational changes into the biologically active state. This study underscores the combined use of MicroED and molecular docking to uncover elusive drug structures and mechanisms to aid in further drug development pipelines."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Psychiatry

Ansofaxine suppressed NSCLC progression by increasing sensitization to combination immunotherapy. (PubMed, Int Immunopharmacol) - "The findings suggest that Ansofaxine may represent a promising therapeutic approach for NSCLC patients with comorbid depression, potentially enhancing both mental well-being and cancer-related outcomes."

IO biomarker • Journal • CNS Disorders • Depression • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Psychiatry • Solid Tumor • CD8 • PD-L1 • PTPN1

Luye Pharma’s Antidepressant Drug LY03005 Completes Primary Endpoint Observation for a Phase III Clinical Trial in China (Luye Press Release) - "Luye Pharma Group announced today that the enrollment and follow-up of patients in a phase III clinical trial, an efficacy and safety comparative study of LY03005 with placebo, has been completed...The clinical trial study involved the enrolment of 558 patients, all of whom have completed the study following observations in changes of the ten-item Montgomery-Åsberg depression rating scales (MADRS) total score from baseline as the primary endpoint under blind state....'We are expediting the development and launch of this drug as quickly as we can.'"

Trial primary completion date • CNS Disorders • Depression

Toludesvenlafaxine- An Innovative Agent or Just Another „me, too” drug? (ISBD 2024) - "The available data are derived from industry-sponsored research, therefore independent data are needed to validate the preliminary efficacy and good tolerability of toludesvenlafaxine in patients with MDD."

CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Efficacy and dose-response relationships of antidepressants in the acute treatment of major depressive disorders: a systematic review and network meta-analysis. (PubMed, Chin Med J (Engl)) - "Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit."

Journal • Retrospective data • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

To Evaluate the Long-term Efficacy and Safety of Toludevenlafaxine Hydrochloride Sustained-release Tablets (clinicaltrials.gov) - P4 | N=736 | Not yet recruiting | Sponsor: Luye Pharma Group Ltd.

New P4 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Venlafaxine Hydrochloride Sustained-release Tablets in Patients With Major Depression Disorder (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: First Affiliated Hospital of Zhejiang University | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

PET/CT Study of Dopamine Transporter (DAT) Binding with the Novel Triple Reuptake Inhibitor Toludesvenlafaxine in Rats and Humans (ASCP 2024) - "These results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine. Learning Objectives PoM exploratory clinical research by combining PET/CT and microdialysis; to assess Dopamine Transporter occupancy in the Healthy Adult Brain Using 11C-CFT PET"

Preclinical • CNS Disorders

Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Desvenlafaxine Succinate Sustained-release Tablets Targeting Anhedonia in Patients With Major Depression Disorder (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: Jiangsu Province Nanjing Brain Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

PET/CT study of dopamine transporter (DAT) binding with the triple reuptake inhibitor toludesvenlafaxine in rats and humans. (PubMed, Eur J Nucl Med Mol Imaging) - P1 | "These results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine."

Journal • Preclinical

A Study to Evaluate Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets in Generalized Anxiety Disorder. (clinicaltrials.gov) - P3 | N=555 | Recruiting | Sponsor: Luye Pharma Group Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry

Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Venlafaxine Hydrochloride Sustained-release Tablets in Patients With Major Depression Disorder (clinicaltrials.gov) - P=N/A | N=80 | Not yet recruiting | Sponsor: First Affiliated Hospital of Zhejiang University

New trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Desvenlafaxine Succinate Sustained-release Tablets Targeting Anhedonia in Patients With Major Depression Disorder (clinicaltrials.gov) - P=N/A | N=80 | Not yet recruiting | Sponsor: Jiangsu Province Nanjing Brain Hospital

New trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Ansofaxine hydrochloride inhibits tumor growth and enhances Anti-TNFR2 in murine colon cancer model. (PubMed, Front Pharmacol) - " We treated CT26, HCT116, MCA38 and SW620 colon cancer cells with fluoxetine (0-50 µM), ansofaxine hydrochloride (0-50 µM) and amitifadine hydrochloride (0-150 µM) to examine their effects on cell proliferation and apoptosis. In summary, our data reveal the role of ansofaxine hydrochloride in modulating the anti-tumor immunity. Our results support that exhausted CD8T is an important potential mechanism by which ansofaxine hydrochloride activates anti-tumor immunity and enhances anti-tumor effects of anti-TNFR2."

Journal • Preclinical • CNS Disorders • Colon Cancer • Colorectal Cancer • Depression • Gastrointestinal Cancer • Oncology • Psychiatry • Solid Tumor • Transplantation • CD4 • CD8 • TNFRSF1B

Assessing Dopamine Transporter Occupancy in the Patients With Depression Brain With Toludesvenlafaxine Hydrochloride Extended-Release Tablets Using 11C-CFT Positron Emission Tomography (PET) (clinicaltrials.gov) - P4 | N=15 | Recruiting | Sponsor: Shanghai Mental Health Center | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Assessing Dopamine Transporter Occupancy in the Patients With Depression Brain With Toludesvenlafaxine Hydrochloride Extended-Release Tablets Using 11C-CFT Positron Emission Tomography (PET) (clinicaltrials.gov) - P4 | N=15 | Not yet recruiting | Sponsor: Shanghai Mental Health Center

New P4 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Study to Evaluate Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets in Generalized Anxiety Disorder. (clinicaltrials.gov) - P3 | N=555 | Not yet recruiting | Sponsor: Luye Pharma Group Ltd.

New P3 trial • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry

A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to verify the efficacy and safety of ansofaxine (LY03005) for major depressive disorder. (PubMed, Transl Psychiatry) - P3 | "The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407."

Clinical • Journal • P3 data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

The effect of triple reuptake inhibitor toludesvenlafaxine on neurological function in cerebral ischemic rats. (PubMed, Front Pharmacol) - "The application of the specific CREB inhibitor, compound 666-15, could reverse the anti-ischemic cerebral injury of Tdv in MCAO/R rats. Tdv ameliorated cerebral ischemic injury through reducing neuronal apoptosis and increasing the expression of BDNF via the activation of CREB pathway."

IO biomarker • Journal • Preclinical • Cardiovascular • BAX • BCL2 • BDNF • CASP3

Efficacy and Safety of Toluedesvenlafaxine Hydrochloride Extended-release Tablets in Somatic Symptoms of Depression (clinicaltrials.gov) - P4 | N=60 | Not yet recruiting | Sponsor: Shanghai Mental Health Center

New P4 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry

Efficacy, Tolerability, and Safety of Toludesvenlafaxine for the Treatment of Major Depressive Disorder-A Narrative Review. (PubMed, Pharmaceuticals (Basel)) - "In conclusion, this review highlights the favorable clinical results of toludesvenlafaxine in only two short-term trials that enrolled patients with major depressive disorder (MDD) (efficacy and tolerability were good for up to eight weeks), indicating the need for more good quality, larger-sample, and longer-term trials. Exploring new antidepressants, such as TRI, can be considered a priority for clinical research due to the high rates of TRD, but also due to the significant percentages of relapse in patients with MDD."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Efficacy and Safety of LY03005 in Major Depressive Disorder: A Multicenter, Randomized, Double-Blind, Phase 3 Trial (APA 2022) - P3 | "In in vitro study, LY03005 showed IC50 values of 31.4 nM, 586.7 nM, and 733.2 nM for serotonin, norepinephrine, and dopamine reuptake transporters; and in vivo studies revealed that parts of LY03005 were metabolized into desvenlafaxine. There were no significant differences in Sexual Experience Scale (ASEX), changes of body weight, somnolence, and insomnia among the three groups. Conclusion : LY03005 160 and 80 mg are safe and effective for MDD and can comprehensively improve the depressive symptoms."

Clinical • P3 data • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder • Xerostomia

Epigenetic Mechanism of 5-HT/NE/DA Triple Reuptake Inhibitor on Adult Depression Susceptibility in Early Stress Mice. (PubMed, Front Pharmacol) - "Hypermethylation and downregulation of oxytocin receptor (Oxtr) in the hippocampal tissues along with increased protein expression of Dnmt1 and Dnmt3a in mice that experienced the "two-hit" stress compared to those that only experienced adulthood social defeat stress, and LPM570065 could reverse these changes. Combined, these results suggest that methylation specificity of the gene Oxtr in the hippocampus may play an important role in early life stress-induced susceptibility to depression and that the5-HT/NE/DA triple reuptake inhibitor LPM570065 may reduce depression susceptibility via the reversal of the methylation of the gene Oxtr."

Journal • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • DNMT1 • DNMT3A