An interventional, Phase 3 extension study to investigate long-term safety and tolerability of tolebrutinib in participants with relapsing multiple sclerosis, primary progressive multiple sclerosis, or nonrelapsing secondary progressive multiple sclerosis - LTS17043

Start Date20 May 2024

Sponsor / Collaborator-

NCT06372145 / RecruitingPhase 3

An Interventional, Phase 3 Extension Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Relapsing Multiple Sclerosis, Primary Progressive Multiple Sclerosis, or Nonrelapsing Secondary Progressive Multiple Sclerosis

This is a Phase 3 extension, global, multicenter study to assess the long-term safety and tolerability of tolebrutinib in adult participants (aged ≥18 years) with RMS, PPMS, or NRSPMS who were previously enrolled in the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 tolebrutinib pivotal trials (GEMINI 1 [EFC16033], GEMINI 2 [EFC16034], HERCULES [EFC16645], or PERSEUS [EFC16035]).
SUBSTUDY: ToleDYNAMIC substudy

Start Date16 Apr 2024

Sponsor / Collaborator

Sanofi

CTR20220329 / TerminatedPhase 3

一项在成人全身型重症肌无力受试者中评价tolebrutinib（SAR442168）的有效性和安全性的III 期、随机、双盲、安慰剂对照、平行组研究

[Translation] A Phase III, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of tolebrutinib (SAR442168) in adult subjects with generalized myasthenia gravis

主要目的，双盲（DB）期：根据MG-ADL 评分，在接受标准治疗（SoC）的全身型重症肌无力（gMG）受试者中评价服用tolebrutinib每天1 次对比安慰剂的有效性。开放标签扩展（OLE）期在接受SoC 的gMG 受试者中评价服用tolebrutinib每天1 次的长期安全性和耐受性。次要目的，DB 期：根据其他有效性测量值，评价服用tolebrutinib每天1 次与安慰剂相比的有效性：接受SoC 的gMG 受试者的量表，如QMG、MGII、MG-QoL15 和MGADL；在接受SoC 的gMG 受试者中评价服用tolebrutinib每天1 次的安全性和耐受性。OLE 期：在接受SoC 的gMG 受试者中评价服用tolebrutinib每天1 次的安全性。

[Translation]

Primary Objective, Double-Blind (DB) Phase: To evaluate the efficacy of tolebrutinib once daily compared with placebo in subjects with generalized myasthenia gravis (gMG) receiving standard of care (SoC) based on MG-ADL scores. Open-label Extension (OLE) Phase To evaluate the long-term safety and tolerability of tolebrutinib once daily in gMG subjects receiving SoC. Secondary Objectives, DB Phase: To evaluate the efficacy of tolebrutinib once daily compared with placebo based on other efficacy measures: scales such as QMG, MGII, MG-QoL15, and MGADL in gMG subjects receiving SoC; to evaluate the safety and tolerability of tolebrutinib once daily in gMG subjects receiving SoC. OLE Phase: To evaluate the safety of tolebrutinib once daily in gMG subjects receiving SoC.

Start Date01 Jun 2022

Sponsor / Collaborator

Sanofi-Aventis Recherche et Développement SA

[+1]

100 Clinical Results associated with Tolebrutinib

100 Translational Medicine associated with Tolebrutinib

100 Patents (Medical) associated with Tolebrutinib

307

Literatures (Medical) associated with Tolebrutinib

01 Nov 2024·ANNALS OF HEMATOLOGY

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis

Article

Author: Zheng, Yuan-Jun ; Wang, Ya-Ru ; Wang, Wen-Jun ; Geng, Ye ; Yang, Lin-Hua ; He, Jian-Xia ; Bai, Si-Jun ; Qin, Li-Yuan ; Zhang, Cai-Xia ; Gao, Yi-Nan

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

25 Oct 2024·MEDICINE

BTKi combined with chemical immunotherapy in the initial treatment of aggressive mantle cell lymphoma: A retrospective study

Article

Author: Li, Zhenling ; Ju, Qianqian

To explore the safety and efficacy of Bruton’s tyrosine kinase inhibitor (BTKi) combined with immunological therapy in untreated patients with aggressive mantle cell lymphoma. A retrospective study was conducted on 9 previously untreated patients who received BTKi combined with immunological therapy, which means using immunological therapy and BTKi at the same time. The median age of the patients was 61 years, 7 were males, and the median follow-up time was 14 months. Among the 7 evaluable patients, the median follow-up was 14 months, and the objective remission rate was 100% (complete remission rate 86%, partial remission rate 14%), while the median progression-free survival and overall survival were not achieved. No patients were dead. The progression-free survival rate of 6 patients in the low-risk group was 100%. The combination of BTKi and chemoimmunotherapy has shown excellent therapeutic results in untreated patients of aggressive mantle cell lymphoma. At the same time, it also can prolong the survival time of high-risk patients. The combined therapy has acceptable safety in previously untreated patients. Hematological toxicity is the most common side effect and infection is the second one. A rash reaction was seen occasionally. There are no heart-related adverse events in the study. There are no new adverse effects caused by the combined treatment.

01 Oct 2024·Journal of Managed Care & Specialty Pharmacy

Real-world comparison of health care costs of venetoclax-obinutuzumab vs Bruton’s tyrosine kinase inhibitor use among US Medicare beneficiaries with chronic lymphocytic leukemia in the frontline setting

Article

Author: Puckett, Justin T. ; Emechebe, Nnadozie ; Jawaid, Dureshahwar ; Manzoor, Beenish S. ; Kamal-Bahl, Sachin ; Huntington, Scott F. ; Ravelo, Arliene ; Doshi, Jalpa A.

BACKGROUND:

Bruton's tyrosine kinase inhibitors (BTKis) and the BCL-2 inhibitor venetoclax in combination with obinutuzumab (VEN-O) are both recommended as frontline therapy in chronic lymphocytic leukemia (CLL). However, VEN-O is a 12-month fixed-duration therapy generating durable remissions whereas BTKis are continuous treat-to-progression treatments.

OBJECTIVE:

To examine costs before and after the fixed-duration treatment period for VEN-O relative to that observed for BTKis in a national sample of older US adults with CLL in the frontline setting.

METHODS:

This retrospective analysis used Medicare Parts A, B, and D claims from 2016 to 2021. Fee-for-service Medicare beneficiaries aged 66 years or older initiating frontline CLL treatment with VEN-O or a BTKi treatment between June 1, 2019, and June 30, 2020 (index date = first prescription fill date), were included in the sample. Mean cost measures were captured for both groups over 2 fixed time periods calculated from the index date: Month 0 to 12 (proxy for VEN-O on-treatment period) and Month 13 to 18 (proxy for VEN-O off-treatment period). A difference-in-difference approach was used. Multivariate generalized linear models estimated changes in adjusted mean monthly costs during Month 0 to 12 vs Month 13 to 18, for the VEN-O group relative to the BTKi group.

RESULTS:

The final sample contained 193 beneficiaries treated with VEN-O and 1,577 beneficiaries treated with BTKis. Risk-adjusted all-cause monthly total costs were similar for VEN-O patients ($13,887) and BTKi patients ($14,492) between Month 0 and 12. Moreover, during Month 13 to 18, the mean monthly all-cause total costs declined by 67% for VEN-O ($13,887 to $4,462) but only by 10% for BTKi ($14,492 to $13,051). Hence, the relative reduction in costs across the 2 periods was significantly larger for VEN-O (-$9,425) vs BTKi (-$1,441) patients (ie, difference in difference = -$7,984; P < 0.001). Similar patterns were observed for CLL-related costs, with the substantially larger reductions in CLL-related total monthly costs (-$9,880 VEN-O vs -$1,753 BTKi; P < 0.001) for the VEN-O group primarily driven by the larger reduction in CLL-related monthly prescription costs (-$9,437 VEN-O vs -$2,020 BTKi; P < 0.001).

CONCLUSIONS:

This real-world study of older adults with CLL found a large reduction in monthly Medicare costs in the 6 months after completion of the fixed-duration treatment period of VEN-O, largely driven by the reduction in CLL-related prescription drug costs. A similar decline in costs was not observed among those treated with BTKis. Our study highlights the substantial economic benefits of fixed-duration VEN-O relative to treat-to-progression therapies like BTKis in the first-line CLL setting.

156

News (Medical) associated with Tolebrutinib

17 Nov 2024

·www.prnewswire.com

Ascentage Pharma Announces a New Drug Application for Its Novel Bcl-2 Inhibitor Lisaftoclax Accepted and Recommended Priority Review Designation by CDE of China NMPA

ROCKVILLE, Md. and SUZHOU, China, Nov. 17, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily for malignancies, today announced that a New Drug Application (NDA) for its inhouse developed investigational novel Bcl-2 selective inhibitor, lisaftoclax (APG-2575), for the treatment of patients with relapsed or refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has been accepted and recommended the Priority Review designation by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA). This NDA, the first for a domestically developed Bcl-2 inhibitor in China, could potentially lead lisaftoclax to become the second Bcl-2 inhibitor approved anywhere in the world. This NDA is based on results from a pivotal registrational Phase II study in China (APG2575CC201) that evaluated the efficacy and safety of lisaftoclax in patients with r/r CLL/SLL. The primary endpoint of the study is the overall response rate (ORR). CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. It primarily affects older populations and is among the most common leukemia subtypes in the Western World, with over 100,000 new diagnoses reported globally each year1. In China, where the incidence rate of CLL/SLL is lower than that of the western countries, the disease is occurring at a rapidly rising rate, with a younger age of onset and higher aggressiveness2. SLL and CLL are two different manifestations of the same disease and approximately 20% of all SLL cases would progress to CLL3. Treatments such as immunotherapies and Bruton's tyrosine kinase inhibitors (BTKis) have significantly improved patients' responses to initial treatment. However, due to the limitations of existing treatment options, the poor prognosis of patients, severe impact on patients' quality of life and high complexity of the disease, patients with r/r CLL/SLL are in desperate need for new treatment options that are safe and effective. The introduction of Bcl-2 inhibitors has further revolutionized the treatment of CLL/SLL. Bcl-2 is an apoptosis suppressor factor that regulates cell survival by controlling mitochondrial membrane permeability. It suppresses apoptosis by inhibiting the release of cytochrome C from mitochondria or by binding to apoptotic activators to inhibit the activity of caspase. The overexpression of Bcl-2, found in a variety of hematologic malignancies, particularly CLL/SLL, is a key mechanism by which tumor cells evade apoptosis. However, the development of Bcl-2 as a therapeutic target is challenging mainly because its mechanism of action is based on the protein-protein interaction (PPI). The binding interface of Bcl-2 is relatively large, making it difficult for small-molecule inhibitors to exert blocking effects. Additionally, the Bcl-2 protein is located on the mitochondrial membrane, and mitochondria, with its double-membrane structure, is among the most complex and challenging cellular components. Drugs must first penetrate the cell membrane before they can further act on the mitochondrial membrane. In nearly 40 years since the discovery of this target, only one Bcl-2 inhibitor has been approved globally, a reality highlighting the immense difficulty and challenges in this field of research and development. In western countries, the treatment of CLL/SLL has entered a new era of chemotherapy-free and fixed-duration regimens, while no Bcl-2 inhibitor has been approved in China in this therapeutic area. Therefore, patients in China have an urgent unmet need for such novel therapies that can offer both efficacy and safety. Lisaftoclax is a novel, investigational orally administered small-molecule Bcl-2 selective inhibitor being developed by Ascentage Pharma to treat patients with malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. Lisaftoclax is the first Bcl-2 inhibitor in China and the second anywhere globally that has demonstrated compelling clinical benefit and entered a pivotal registrational study. Lisaftoclax has broad therapeutic potential for a variety of hematologic malignancies and solid tumors, particularly as a single agent and in combinations in CLL/SLL. Lisaftoclax is a potential drug that may offer patients a safe, effective, and easy to use treatment option. Lisaftoclax is being evaluated in multiple registrational Phase III studies, including a global registrational Phase III study of lisaftoclax in combination with a BTKi in previously treated patients with CLL/SLL (cleared by the US FDA); a global registrational Phase III study of lisaftoclax in combination with acalabrutinib for the first-line treatment of treatment-naïve patients with CLL/SLL; a global registrational Phase III study of lisaftoclax in combination with azacitidine (AZA) for the first-line treatment of elderly/unfit treatment-naïve patients with acute myeloid leukemia (AML) who were intolerant of standard induction chemotherapies; and a global registrational Phase III study of lisaftoclax in combination with AZA for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS). "Ascentage Pharma's founding team has over 20 years of deep experience in developing apoptosis-targeted therapies and has made significant strides with the Bcl-2 target," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "To date, only one Bcl-2 inhibitor has been approved globally, which is a reality underscoring the immense difficulty and challenges in this field of research and development. This NDA submission for lisaftoclax could potentially pave the way for lisaftoclax to become the first approved China-developed Bcl-2 inhibitor, thus marking another major milestone that is a culmination of the Ascentage Pharma's deep commitment and perseverant work in the past 15 years." Dr. Yang continued, "Globally, r/r CLL/SLL represents an area of urgent unmet clinical needs. To have successfully advanced lisaftoclax to this point, it is a true testament to Ascentage Pharma's robust capabilities in global pharmaceutical innovation. Moving forward, we will accelerate the global development of lisaftoclax in other indications to bring benefit to patients as quickly as possible. Remaining steadfastly committed to our mission of addressing unmet clinical needs in China and around the world, we will strive to develop more novel therapeutics for patients in need." References: 1. Yao, Y., Lin, X., Li, F., et al. The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019. Biomed Eng Online. 2022 Jan 11;21(1):4. DOI: 10.1186/s12938-021-00973-6 2. Liu Peng. Practice guidelines for the diagnosis and treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma in Zhongshan Hospital, Fudan University (v1.2018). [J]. Chin J Clin Med, 2018, 25(1): 157-160. DOI 10.12015/j. issn. 1008-6358. 2018. 20180 3. Li Jianyong, Qiu Lugui. Hematology Committee of Chinese Medical Association; Hematological Oncology Committee of China Anti-Cancer Association; Chinese Working Group for Chronic Lymphocytic Leukemia. The guidelines for diagnosis and treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma in China (2022). Zhonghua Xue Ye Xue Za Zhi. 2022 May 14;43(5):353-358. DOI: 10.3760/cma.j.issn.0253-2727.2022.05.001 About Ascentage Pharma Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. The company has built a rich pipeline of innovative drug candidates that includes novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 13 registrational studies (completed/ ongoing/planned). Olverembatinib, the company's first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute and the University of Michigan. The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development. SOURCE Ascentage Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Phase 3Orphan DrugBreakthrough TherapyFast Track

13 Nov 2024

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75+ Key Companies Charting New Frontiers in Multiple Sclerosis Therapeutic Space | DelveInsight

Multiple sclerosis (MS) is a chronic neurological disorder affecting the central nervous system (CNS), particularly the brain, spinal cord, and optic nerves. Continuous research has led to new drug developments, particularly disease-modifying therapies (DMTs) that slow MS progression. Monoclonal antibodies, oral therapies, and infusion treatments are among the most promising options and drives the multiple sclerosis market. LAS VEGAS, Nov. 13, 2024 /PRNewswire/ -- DelveInsight's ' Multiple Sclerosis Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline multiple sclerosis therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the multiple sclerosis pipeline domain. Key Takeaways from the Multiple Sclerosis Pipeline Report DelveInsight's multiple sclerosis pipeline report depicts a robust space with 75+ active players working to develop 80+ pipeline therapies for multiple sclerosis treatment. Key multiple sclerosis companies such as Mapi Pharma, Novartis, Immunic, Biocad, Apimeds, Genentech (Roche), AB Science, Celltrion, Clene Nanomedicine, InnoCare Pharma, Oryzon Genomics, GeNeuro SA, AbbVie, BrainStorm Cell Therapeutics, NeuroSense Therapeutics, Denali Therapeutics Inc., Sanofi, MediciNova, Biogen, Tiziana Life Sciences, Antisense Therapeutics, RemeGen, Atara Biotherapeutics, Contineum Therapeutics, Eli Lilly and Company, Axsome Therapeutics, Accure therapeutics, Stem Cell Medicine Ltd., Ever Supreme Bio-Technology Co., Ltd., ImCyse, Lucid Psycheceuticals, Immune Response BioPharma, Guangzhou Lupeng Pharmaceutical, Kyowa Kirin, Nura Bio, Bristol-Myers Squibb, ImStem Biotechnology, Hoffmann-La Roche, LAPIX Therapeutics, Motric Bio, Immunophage Biotech, NervGen, FibroBiologics, Kyverna Therapeutics, GlaxoSmithKline, PolTREG, Cyxone, Biohaven Pharmaceuticals, HuniLife Biotechnology, GlobeStar Therapeutics, Anokion, Medsenic, ZyVersa Therapeutics, Alumis Inc., Axoltis Pharma, Barricade Therapeutics, BioNxt Solutions, Eikonoklastes Therapeutics, 4D Pharma, Gossamer Bio, Pasithea Therapeutics, Synaptogenix, Monte Rosa Therapeutics, Immix Biopharma, f5 Therapeutics, Autobahn Therapeutics, Biosenic, Polpharma Biologics, Find Therapeutics, TeraImmun, AptaTargets, Trethera, Aditxt, SetPoint Medical, Sarepta Therapeutics, Nucleome Therapeutics, Vaccinex Inc., and others are evaluating new multiple sclerosis drugs to improve the treatment landscape. Promising multiple sclerosis pipeline therapies such as GA Depot, Remibrutinib, Tolebrutinib, IMU 838, BCD-132, Apitox, Fenebrutinib, SAR 441344, CT-P53, CNM-Au8, Orelabrutinib, Vafidemstat, Temelimab, Elezanumab, NurOwn (MSC-NTF cells), PrimeC, SAR4433820, Ibudilast, BIIB091, Foralumab, ATL1102, RC18, ATA188, PIPE-307, Pirtobrutinib, LY3541860, Solriamfetol, Act-01, SCM-010, UMSC01, IMCY-0141, Lucid-MS, NeuroVax, LP-168, NB-4746, CC-97540, IMS-001, RO7121932, BMS-986196, LPX-TI641, MTR-601, IPG-11406, IPG-1094, NVG-291, CYMS-101, KYV-101, PIPE-791, GSK 3888130B, PTG-007, T 20K, BHV-8000, HuL001, Amethyst™, ANK 700, Arscimed, A-005, NX210c, Research programme: CAR-TREG, TASIN-1, Cladribine ODF, ET-101, MRx0002, GB7208, PAS-002, Bryostatin-1, MRT-6160, NXC-201, Research Program: Cytokine reduction, ABX-002, Arsenic trioxide, LL-341070, PB018, FTX 101, TI-235, TRE 515, NT-0007, NT-0002, NVG300, and others are under different phases of multiple sclerosis clinical trials. In October 2024, Immunic, Inc. reported favorable results from the non-binding interim futility analysis of its Phase 3 ENSURE trial, which is evaluating its lead candidate, vidofludimus calcium (IMU-838), a nuclear receptor-related 1 (Nurr1) activator, for the treatment of relapsing multiple sclerosis (RMS). In October 2024, Immunic, Inc. announced a positive outcome of the non-binding, interim futility analysis of its Phase III ENSURE program, investigating lead asset, nuclear receptor related 1 (Nurr1) activator, vidofludimus calcium (IMU-838), for the treatment of relapsing multiple sclerosis (RMS). Based on the outcome of the interim futility analysis, an unblinded Independent Data Monitoring Committee (IDMC) has recommended that the trials are not futile and should continue as planned. In September 2024, Roche, secured FDA approval for an injectable form of its blockbuster multiple sclerosis treatment, Ocrevus, reducing patient treatment time and potentially helping the company stay ahead of increasing competition. In September 2024, Sanofi announced the outcomes of Phase III clinical trials of its investigational oral brain-penetrant BTK inhibitor, tolebrutinib, aimed at treating multiple sclerosis (MS). These studies, namely HERCULES, GEMINI 1, and GEMINI 2, have provided mixed results, with the HERCULES trial meeting its primary endpoint while the GEMINI trials did not. The HERCULES study focused on the efficacy and safety of tolebrutinib in individuals with non-relapsing secondary progressive MS (nrSPMS) compared to a placebo. In August 2024, Abata Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for ABA-101 for the treatment of patients with progressive multiple sclerosis (MS). The FDA recently cleared ABA-101's Investigational New Drug (IND) application, and initiation of a first-in-human (FIH) Phase I study is imminent. In August 2024, TG Therapeutics announced that the FDA has cleared an investigational new drug (IND) application submitted by TG Therapeutics for azercabtagene zapreleucel (azer-cel), an investigational allogeneic chimeric antigen receptor T-cell (CAR-T) therapy, for a phase 1 clinical trial in patients with progressive multiple sclerosis (MS). In January 2024, Kyverna Therapeutics, Inc. announced it received fast-track designation by the U.S. Food and Drug Administration (FDA) for its autologous, fully human CD19 chimeric antigen receptor (CAR) T-cell product candidate, KYV-101, to be used for the treatment of multiple sclerosis (MS). Request a sample and discover the recent advances in multiple sclerosis treatment drugs @ Multiple Sclerosis Pipeline Report The multiple sclerosis pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage multiple sclerosis drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the multiple sclerosis clinical trial landscape. Multiple Sclerosis Overview Multiple sclerosis is a chronic autoimmune disorder that affects the central nervous system, leading to the deterioration or permanent damage of myelin, the protective sheath surrounding nerve fibers. While the exact cause of multiple sclerosis remains unclear, it is believed to involve a combination of genetic predisposition, environmental factors, and possibly viral infections. Common symptoms of multiple sclerosis include fatigue, difficulty walking, numbness or tingling in the limbs, muscle weakness, and vision problems, which can vary significantly among individuals and may evolve over time. Diagnosis typically involves a combination of neurological examinations, magnetic resonance imaging (MRI) to detect lesions in the brain and spinal cord, and sometimes lumbar puncture to analyze cerebrospinal fluid for inflammatory markers. While there is no cure for multiple sclerosis, treatment options aim to manage symptoms, reduce the frequency and severity of relapses, and slow disease progression. This may include disease-modifying therapies (DMTs), corticosteroids for acute exacerbations, and symptomatic treatments such as physical therapy, pain management, and lifestyle modifications. Early diagnosis and a tailored treatment plan are crucial for improving the quality of life for those living with multiple sclerosis. Find out more about multiple sclerosis treatment drugs @ Drugs for Multiple Sclerosis Treatment A snapshot of the Multiple Sclerosis Pipeline Drugs mentioned in the report: Learn more about the emerging multiple sclerosis pipeline therapies @ Multiple Sclerosis Clinical Trials Multiple Sclerosis Therapeutics Assessment The multiple sclerosis pipeline report proffers an integral view of the multiple sclerosis emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Multiple Sclerosis Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous, Parenteral, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Immunomodulators, MHC class II gene modulators, Agammaglobulinaemia tyrosine kinase inhibitors, Dihydroorotate dehydrogenase inhibitors, Nuclear receptor subfamily 4 group A member 2 agonists, CD20 antigen inhibitors, Energy metabolism stimulants; Immunomodulators, Lysine-specific demethylase 1 inhibitors, Monoamine oxidase B inhibitors, Protein-arginine deiminase inhibitors, Immunostimulants Key Multiple Sclerosis Companies: Mapi Pharma, Novartis, Immunic, Biocad, Apimeds, Genentech (Roche), AB Science, Celltrion, Clene Nanomedicine, InnoCare Pharma, Oryzon Genomics, GeNeuro SA, AbbVie, BrainStorm Cell Therapeutics, NeuroSense Therapeutics, Denali Therapeutics Inc., Sanofi, MediciNova, Biogen, Tiziana Life Sciences, Antisense Therapeutics, RemeGen, Atara Biotherapeutics, Contineum Therapeutics, Eli Lilly and Company, Axsome Therapeutics, Accure therapeutics, Stem Cell Medicine Ltd., Ever Supreme Bio-Technology Co., Ltd., ImCyse, Lucid Psycheceuticals, Immune Response BioPharma, Guangzhou Lupeng Pharmaceutical, Kyowa Kirin, Nura Bio, Bristol-Myers Squibb, ImStem Biotechnology, Hoffmann-La Roche, LAPIX Therapeutics, Motric Bio, Immunophage Biotech, NervGen, FibroBiologics, Kyverna Therapeutics, GlaxoSmithKline, PolTREG, Cyxone, Biohaven Pharmaceuticals, HuniLife Biotechnology, GlobeStar Therapeutics, Anokion, Medsenic, ZyVersa Therapeutics, Alumis Inc., Axoltis Pharma, Barricade Therapeutics, BioNxt Solutions, Eikonoklastes Therapeutics, 4D Pharma, Gossamer Bio, Pasithea Therapeutics, Synaptogenix, Monte Rosa Therapeutics, Immix Biopharma, f5 Therapeutics, Autobahn Therapeutics, Biosenic, Polpharma Biologics, Find Therapeutics, TeraImmun, AptaTargets, Trethera, Aditxt, SetPoint Medical, Sarepta Therapeutics, Nucleome Therapeutics, Vaccinex Inc., and others are evaluating new multiple sclerosis drugs to improve the treatment landscape. Key Multiple Sclerosis Pipeline Therapies:GA Depot, Remibrutinib, Tolebrutinib, IMU 838, BCD-132, Apitox, Fenebrutinib, SAR 441344, CT-P53, CNM-Au8, Orelabrutinib, Vafidemstat, Temelimab, Elezanumab, NurOwn (MSC-NTF cells), PrimeC, SAR4433820, Ibudilast, BIIB091, Foralumab, ATL1102, RC18, ATA188, PIPE-307, Pirtobrutinib, LY3541860, Solriamfetol, Act-01, SCM-010, UMSC01, IMCY-0141, Lucid-MS, NeuroVax, LP-168, NB-4746, CC-97540, IMS-001, RO7121932, BMS-986196, LPX-TI641, MTR-601, IPG-11406, IPG-1094, NVG-291, CYMS-101, KYV-101, PIPE-791, GSK 3888130B, PTG-007, T 20K, BHV-8000, HuL001, Amethyst™, ANK 700, Arscimed, A-005, NX210c, Research programme: CAR-TREG, TASIN-1, Cladribine ODF, ET-101, MRx0002, GB7208, PAS-002, Bryostatin-1, MRT-6160, NXC-201, Research Program: Cytokine reduction, ABX-002, Arsenic trioxide, LL-341070, PB018, FTX 101, TI-235, TRE 515, NT-0007, NT-0002, NVG300, and others are under different phases of multiple sclerosis clinical trials. Dive deep into rich insights for new drugs for multiple sclerosis treatment, visit @ Multiple Sclerosis Drugs Table of Contents For further information on the multiple sclerosis pipeline therapeutics, reach out @ Multiple Sclerosis Treatment Drugs Related Reports Multiple Sclerosis Market Multiple Sclerosis Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key multiple sclerosis companies including Immune Response BioPharma, Inc., Clene Nanomedicine, Genzyme, ImStem Biotechnology, Rho, Inc., Bristol-Myers Squibb, TG Therapeutics, Inc., Hoffmann-La Roche, Atara Biotherapeutics, Immunic AG, Celgene, Anokion SA, Sanofi, Actelion, Biogen, Supernus Pharmaceuticals, Inc., GeNeuro SA, HuniLife Biotechnology, Inc., Emerald Health Pharmaceuticals, RemeGen Co., Ltd., Antisense Therapeutics, Biocad, AB Science, Genentech, Novartis, Pipeline Therapeutics, ASLAN Pharmaceuticals, GlaxoSmithKline, Lucid Psycheceuticals, Voronoi, Hanmi Pharmaceutical, Mapi Pharma, f5 Therapeutics, Autobahn Therapeutics, AstraZeneca, ZyVersa Therapeutics, RedHill Biopharma, Gossamer Bio, Sarepta Therapeutics, BrainStorm Cell Limited, CytoDyn, Pear Therapeutics, Solstice Neurosciences, ProJenX, among others. Multiple Sclerosis Epidemiology Forecast Multiple Sclerosis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted multiple sclerosis epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Relapsing Multiple Sclerosis Pipeline Relapsing Multiple Sclerosis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key relapsing multiple sclerosis companies, including ASLAN Pharmaceuticals, GlaxoSmithKline, Lucid Psycheceuticals, Voronoi, Hanmi Pharmaceutical, among others. Relapsing-Remitting Multiple Sclerosis Pipeline Relapsing-Remitting Multiple Sclerosis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key RRMS companies, including TG Therapeutics, Novartis, Sanofi, Cinnagen, Polpharma Biologics, Immunic, Mapi Pharma, Biocad, Apimeds, Genentech (Roche), Merck, Immune Response BioPharma, Clene Nanomedicine, InnoCare Pharma, Oryzon Genomics, GeNeuro SA, AbbVie, Emerald Health Pharmaceuticals, GlaxoSmithKline, RedHill Biopharma, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Clinical ResultFast TrackCell TherapyImmunotherapy

06 Nov 2024

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ASH 2024 | Results From Three Clinical Studies of Ascentage Pharma's Bcl-2 Inhibitor Lisaftoclax Selected for Presentations, Including an Oral Report

ROCKVILLE, Md. and SUZHOU, China, Nov. 6, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for malignancies, today announced that the latest results from three clinical studies of one of the company's key drug candidate, lisaftoclax (APG-2575), have been selected for presentations, including an Oral Report, at the 66th American Society of Hematology (ASH) Annual Meeting. This is the third consecutive year in which clinical results on lisaftoclax have been selected by the ASH Annual Meeting. In 2024, results from multiple clinical and preclinical studies on four of the company's investigational drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at the ASH Annual Meeting. Developed by Ascentage Pharma, lisaftoclax is a novel orally available Bcl-2 inhibitor with clinical benefits for an array of hematologic malignancies and solid tumors. At this year's ASH Annual Meeting, Ascentage Pharma will present an Oral Report featuring the latest results from a Phase I/II study of lisaftoclax in patients with relapsed/refractory multiple myeloma (R/R MM) or immunoglobulin light-chain (AL) amyloidosis. Furthermore, the latest data of lisaftoclax combinations in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and myelodysplastic syndrome (MDS) will also be released in Poster Presentations at the meeting. The ASH Annual Meeting is one of the largest gatherings of the international hematology community, aggregating the latest scientific research in the pathogenesis and clinical treatment of hematologic diseases. The 66th ASH Annual Meeting will take place on December 7-10, 2024, local time, both online and in-person in San Diego, CA (United States). "Lisaftoclax is the first Bcl-2 inhibitor in China and the second globally that has demonstrated clinical benefits and entered pivotal registrational studies," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Currently, the drug candidate is being evaluated in four registrational Phase III studies. For the clinical results of lisaftoclax to be once again selected by the ASH meeting, it underscores the clinical benefit of this drug in hematologic malignancies. Furthermore, multiple studies of four of our investigational drug candidates have been selected for presentations at the meeting this year, highlighting Ascentage Pharma's robust capabilities in global innovation and investigational clinical development. We are eager to share detailed data at the event. Moving forward, we will continue to accelerate our clinical development programs in efforts to bring more treatment options to patients as soon as possible." An overview of presentations featuring Ascentage Pharma's drug candidates at ASH 2024: Abstracts on lisaftoclax selected for presentations at the 2024 ASH Annual Meeting are as follows: (for details on the abstracts featuring olverembatinib, please refer to a separate press release published at the same time) Oral Presentation Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (pts) with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light- Chain (AL) Amyloidosis Format: Oral Presentation Abstract#: 1022 Session: 654. Multiple Myeloma: Pharmacologic Therapies: Into the Future: New Drugs and Combinations in Multiple Myeloma Time: Monday, December 9, 2024, 4:45 PM First Author: Dr. Sikander Ailawadhi, Mayo Clinic, Jacksonville, FL Highlights: Background: MM is characterized by the proliferation of abnormal clonal plasma cells, causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. The treatment of MM involves immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies to achieve disease remission. AL amyloidosis comprises disorders of abnormal extracellular deposition of misfolded proteins in various organs with resultant damage, and the key strategy of treatment is to prolong the time to or reverse organ dysfunction. However, many patients will relapse from the standard triplet or quadruplet therapies, necessitating additional treatments with novel mechanisms of action. Lisaftoclax is a novel investigational Bcl-2 inhibitor that has shown strong antitumor activity in earlier studies. This presentation reports clinical trial data on lisaftoclax combined with novel therapeutic regimens in patients with R/R MM or R/R AL amyloidosis. Introduction: This is a multicenter, open-label Phase I/II study. Enrolled Patients and Study Methods: Eligible patients had an ECOG performance status ≤ 2, ≥ 1 prior line of therapy, and adequate organ function. Patients with R/R AL amyloidosis had confirmed symptomatic organ involvement. Lisaftoclax was administered orally daily in repeated 28-day cycles. Pomalidomide, daratumumab, and lenalidomide were administered per label use. Dexamethasone 40 mg (20 mg, patients > 75 years old) was administered on days 1, 8, 15, and 22 of 28-day cycles. This study evaluated the safety and efficacy of lisaftoclax combined with pomalidomide and dexamethasone (Pd; Arm A) or daratumumab, lenalidomide, and dexamethasone (DRd; Arm B) in R/R MM, and lisaftoclax combined with the Pd regimen in R/R AL amyloidosis (Arm C). As of May 29, 2024, 52 patients were enrolled, including 42 with R/R MM and 10 with AL amyloidosis. The median (range) age of all patients was 69.5 (24-88) years, of whom 63.5% were male and 63.5% were ≥ 65 years of age. The enrolled patients were heavily pretreated, with a median (range) number of prior therapy lines of 3 (1-19). In Arm A (n=35), lisaftoclax was administered orally at dose assigned: 400 mg (n=3); 600 mg (n=4); 800 mg (n=15); 1,000 mg (n=7); and 1,200 mg (n=6). In Arm B (n=7), all patients were treated with lisaftoclax 600 mg. In Arm C (n=10), lisaftoclax was administered at 400 mg (n=1); 600 mg (n=4); 800 mg (n=3); and 1,000 mg (n=2). Efficacy Results: In Arm A, out of 31 evaluable patients, 3 (9.7%) achieved complete remission (CR), 7 (22.6%) reached very good partial remission (VGPR), and 9 (29.0%) achieved partial response (PR). The overall response rate (ORR) was 61.3% (n=19), and 10 (32.3%) achieved≥VGPR. In Arm B, of 4 evaluable patients, 2 (50%) achieved CR and 2 (50%) achieved ≥ VGPR. In Arm C, of 7 assessed patients, 1 (14.3%) achieved CR, 4 (57.1%) achieved VGPR, 1 (14.3%) achieved PR, and 5 (71.4%) achieved ≥ VGPR, for an ORR of 6 (85.7%); 2 patients had cardiac responses. Safety Results: Among 49 patients in the safety population, 34 (69.4%) reported any-grade lisaftoclax treatment-related AEs (TRAEs; ≥ 5% incidence), including neutropenia (20.4%), thrombocytopenia (6.1%), leukopenia (10.2%), nausea (16.3%), abdominal distension (10.2%), diarrhea (12.2%), and constipation (8.2%). A total of 11 patients experienced grade ≥ 3 TRAEs, including neutropenia (14.3%) and febrile neutropenia (2%), and 3 patients experienced lisaftoclax-related serious AEs (1 each): febrile neutropenia, acute kidney injury, and diarrhea with electrolyte imbalance. In Arm B, 1 pt experienced a dose-limiting toxicity (prolonged QT interval). Pharmacokinetic analyses showed no drug-drug interaction (DDI) in all patients treated with lisaftoclax at all doses in combination with other therapeutic agents used in 3 arms. Conclusions: These findings suggest that lisaftoclax improves the depth of response in patients with R/R MM or AL amyloidosis when combined with Pd or DRd. These combination therapies demonstrated a favorable safety profile with no DDIs, particularly in hematologic side effects. Poster Presentations Lisaftoclax (APG-2575) Demonstrates Activity and Safety When Given With Accelerated Ramp-up and Then Combined With Acalabrutinib or Rituximab in Patients (pts) With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Including Those With Prior Exposure to Venetoclax Format: Poster Presentation Abstract#: 4614 Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III Time: Monday, December 9, 2024; 6:00 PM - 8:00 PM First Author: Dr. Matthew Davids, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA Highlights: Background: Bcl-2 inhibition with venetoclax (ven) was a major advance in CLL treatment, but the 5-week dose ramp-up to mitigate the risk of tumor lysis syndrome (TLS) and DDIs challenge treatment optimization. Lisaftoclax is an investigational, oral Bcl-2i with a short half-life, allowing it to be ramped-up on a daily schedule. Introduction: This poster presents updated clinical data of lisaftoclax alone or combined with acalabrutinib or rituximab in patients with treatment-naïve (TN; lisaftoclax-acalabrutinib arm), relapsed/refractory, or prior ven-treated CLL/SLL. Enrolled Patients and Study Methods: From March 20, 2020, to June 27, 2024, 176 patients were enrolled: 46 in monotherapy and 39 and 91 in the rituximab and acalabrutinib combination cohorts, respectively; 87.5% (154/176) of patients were R/R and 12.5% (22/176) were TN. The median (range) age was 63 (34-80) years; 67% were male; 25.6% had del(17p) and/or TP53 mutation; and 70.6% had unmutated IGHV. Median (range) duration of treatment with lisaftoclax was 16.5 (1-54; monotherapy), 24 (3-39; rituximab), and 27 (1-43; acalabrutinib) months. In R/R patients, the median (range) number of prior lines of therapy was 2 (1-15), and 14 (9%) patients had been treated with ven. Patients who had received prior treatment with ven had a median (range) age of 65 (51-78); and 79% were male. Of evaluable patients, 50% had del(17p), 36% had TP53 mut, 64% had del(11q), 38% had complex karyotype (≥ 3 abnormalities), and 92% had unmutated IGHV; 57% were BTKi naïve; and the median (range) number of prior therapies was 3 (1-6). Patients were treated with a rapid 4- to 6-day daily ramp-up of lisaftoclax from 20 mg to a target dose of 400, 600, or 800 mg, receiving daily oral lisaftoclax alone or, plus continuous acalabrutinib or 6 cycles of rituximab in 28-day cycles, starting on Cycle 1 Day 8 (C1D8) until disease progression, complete response by C24, or unacceptable toxicity. Blood samples were collected for pharmacokinetic (PK) and exposure-response (E-R) analyses. Efficacy Results: The ORR for lisaftoclax plus acalabrutinib in 87 patients was 96.6%, and the median duration of response (DOR; 95% CI, 23-NR) and median progression-free survival (PFS; 95% CI, 34-NR) were not reached. The 12- and 18-month PFS rates were 89% and 86%, respectively. Fourteen R/R CLL ven-exposed patients received lisaftoclax plus acalabrutinib: of whom 9 had progressed on ven, 3 relapsed after completing ven, and 2 discontinued due to ven intolerance. Median (range) duration of treatment was 16 (3-25) months. Safety profile was similar to that of other study cohorts. ORR was 85.7% (12/14) in the ven-exposed patients; ORR was 100% (8/8) in the ven-exposed but BTKi-naïve patients; ORR was 66.7% (4/6) in the ven- and BTKi-exposed patients; The median DOR and PFS were not reached. The 12- and 18-month PFS rates were 84% and 73%, respectively. Safety Results: Incidence and severity of TEAEs were similar across cohorts. Common (>10%) any-grade TEAEs in all cohorts combined were neutropenia (59 [33.5%]), diarrhea (38 [21.6%]), anemia (27 [15.3%]), and thrombocytopenia (26 [14.8%]). Grade ≥ 3 treatment-emergent AEs (TEAEs) were neutropenia in 15 (32.6%), 10 (25.6%), and 22 (24%) patients and anemia in 10 (21.7%), 5 (12.8%), and 12 (13.2%) patients in monotherapy, rituximab, and acalabrutinib combination cohorts, respectively. Comprehensive E-R analyses indicated that lisaftoclax had similar systemic exposure as monotherapy or when combined with acalabrutinib or rituximab; lisaftoclax had no DDI when combined with acalabrutinib or rituximab. No discontinuations were attributed to lisaftoclax TRAEs. Forty-four (95.7%) patients in monotherapy discontinued treatment. Most discontinuations were due to progressive disease (n = 41 [23.3%]) and AEs (n = 13 [7.4%]); 9 (5.1%) patients withdrew consent; 7 (4%) achieved complete response or MRD negativity after ≥ 24 cycles; 5 (2.8%) died; and 18 (10.2%) discontinued for other reasons. Clinical (n = 2) and laboratory (n = 3) TLS was observed in 5 (2.8%) patients on lisaftoclax (by Howard/Cairo-Bishop criteria), with cases rapidly resolving to resume lisaftoclax safely. Conclusions: The presented data suggest that lisaftoclax combined with acalabrutinib is effective for patients with prior ven exposure, including those with progression on ven. In this updated analysis with longer follow-up, no DDIs or new safety findings were observed in TN or R/R CLL/SLL patients treated with lisaftoclax monotherapy or combinations. Patients with prior ven exposure continue to be accrued in order to further evaluate this promising signal. A global registrational phase III study is recruiting. Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in Combination with Azacitidine in Treatment of Patients with Myelodysplastic Syndrome (MDS) Format: Poster Presentation Abstract#: 3202 Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster II Time: Sunday, December 8, 2024, 6:00 PM - 8:00 PM First Author: Prof. Huafeng Wang, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Highlights: Background: Hypomethylating agents (HMAs) remain the standard of care in higher-risk MDS. However, its clinical efficacy is limited, and patients who have failed or are resistant to HMAs have a poor prognosis, leaving them in need of new therapeutic options. Introduction: Preclinical data have shown that novel investigational Bcl-2 inhibitor lisaftoclax combined with an HMA can synergistically induce apoptosis in cancer cells in AML and MDS. Reported here are the follow-up safety and efficacy data from a Phase Ib/II clinical trial evaluating lisaftoclax combined with azacitidine in adults (≥18 years) with MDS. Enrolled Patients and Study Methods: This study enrolled patients with higher-risk MDS (IPSS-R score > 3.5; blasts > 5%), including those with TN or R/R disease. Lisaftoclax at an assigned dose (400, 600, or 800 mg) was administered orally once daily from Days 1 to 14 and combined with azacitidine (75 mg/m2/day) on Days 1 to 7 in repeated 28-day cycles. A daily ramp-up was used before the first cycle to prevent TLS. The primary objectives of the study were to assess the efficacy and safety of the combination regimen in patients with MDS and establish the recommended Phase III dose for lisaftoclax. Complete response (CR) and marrow CR (mCR) rates were evaluated in accordance with 2006 International Working Group (IWG) criteria. As of July 1, 2024, 49 patients were enrolled: 8 had R/R MDS (lisaftoclax 600 mg [n=5] and 800 mg [n=3]) and 41 had TN MDS (lisaftoclax 400 mg [n=16], 600 mg [n=23], and 800 mg [n=2]). The median (range) age was 66 (22-83) years, and 55.1% of patients were male. IPSS-R risk categories were intermediate (12/49 [24.5%]), high (24/49 [49.0%]), and very high (13/49 [26.5%]). Among the 39 patients with genetic mutational profile data, 9 (23.1%) had TP53 mutations; 11 (28.2%) had TET2 mutations; 10 (25.6%) had ASXL1 mutations; and 10 (25.6%) had RUNX1 mutations. At baseline, 70.8% of patients reported grade ≥ 3 anemia; 54.2% had grade ≥ 3 neutropenia; and 45.8% had grade ≥ 3 thrombocytopenia. Efficacy Results: Lisaftoclax dose reduction occurred in 4 (8.2%) patients. Neither 60-day mortality nor TLS was reported. In 8 patients with R/R MDS, the median (range) duration of treatment (DOT) was 3.2 (1.2-9.4) months. The overall response rate (ORR=CR[12.5%]+marrow CR[62.5%]) was 75.0% (95% CI, 34.9-96.8). In 40 efficacy-evaluable patients with TN MDS, the median DOT (range) was 4.5 (0.5-12.1) months; the ORR was 77.5% (95% CI, 61.5-89.2); and the CR rate was 25.0% per IWG 2006 criteria. Furthermore, the ORR and CR rate in 23 patients with TN MDS treated with lisaftoclax 600 mg combined with azacitidine were 73.9% and 30.4%, respectively; because these patients had a relatively longer median DOT (6.01 months), we conducted further analyses per IWG 2023 criteria. The composite CR rate (CR2023 = CR [52.2%] + CRL [17.4%]) was 69.6%, and the median time to CR (range) was 2.84 (1.1-8.7) months. Both the median progression-free survival and overall survival rates were not reached. Safety Results: All patients treated with lisaftoclax combined with azacitidine reported TEAEs. Of these, 93.8% were grade ≥ 3 AEs and 35.4% were serious AEs. Common grade ≥ 3 nonhematologic TEAEs (≥ 10% incidence) included pneumonia (24.4%) and hypokalemia (10.2%). Common grade ≥ 3 hematologic TEAEs included leukocyte count decreased (75.5%), neutropenia (69.4%), thrombocytopenia (65.3%), anemia (24.5%), and febrile neutropenia (18.4%). Grade ≥ 3 infections were reported in 46.9% of patients, of which 26.5% were treatment related. Treatment delays between cycles due to AEs occurred in 11 (22.4%) patients, with a median delay time (range) of 12 (1-63) days. A total of 95.9% of patients reported TRAEs, of which 87.8% were grade ≥ 3 AEs and 28.6% were serious AEs. Common grade ≥ 3 hematologic TRAEs included leukocyte count decreased (71.4%), neutropenia (65.3%), thrombocytopenia (65.3%), anemia (20.4%), and febrile neutropenia (12.2%). Conclusions: The clinical data support an emerging role for lisaftoclax in combination with azacitidine for treatment of patients with higher-risk TN or R/R MDS. The combination therapy was efficacious and well tolerated, resulting in no 60-day mortality, few dose modifications, and low infection rates, supporting further clinical development of this combination in patients with higher-risk MDS. * Olverembatinib is an investigational drug that has not been approved for any indication outside China; lisaftoclax (APG-2575), APG-2449 and APG-5918 are investigational drugs that have not been approved in any country and region. About Ascentage Pharma Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. The company has built a rich pipeline of innovative drug candidates that includes novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 13 registrational studies (completed/ ongoing/planned). Olverembatinib, the company's first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute and the University of Michigan. The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development. SOURCE Ascentage Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Clinical ResultASHImmunotherapyPhase 2

100 Deals associated with Tolebrutinib

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Indication	Highest Phase	Country/Location	Organization	Date
Myasthenia Gravis	Phase 3	US	Sanofi	03 Dec 2021
Myasthenia Gravis	Phase 3	CN	Sanofi	03 Dec 2021
Myasthenia Gravis	Phase 3	JP	Sanofi	03 Dec 2021
Myasthenia Gravis	Phase 3	BR	Sanofi-Aventis Recherche et Développement SA	03 Dec 2021
Myasthenia Gravis	Phase 3	BR	Sanofi (China) Investment Co. Ltd.	03 Dec 2021
Myasthenia Gravis	Phase 3	CA	Sanofi	03 Dec 2021
Myasthenia Gravis	Phase 3	DE	Sanofi-Aventis Recherche et Développement SA	03 Dec 2021
Myasthenia Gravis	Phase 3	DE	Sanofi (China) Investment Co. Ltd.	03 Dec 2021
Myasthenia Gravis	Phase 3	HU	Sanofi	03 Dec 2021
Myasthenia Gravis	Phase 3	IT	Sanofi	03 Dec 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2024	Not Applicable	Small Lymphocytic Lymphoma	-	BTKi (Ibrutinib)	wbvnsxpent(ncsocjyjvn) = A quarter of all pts experienced a non-fatal bleed, resulting in <15% of the pts discontinuing and >50% pts interrupting their BTKi tx nxxrkljphy (diakgmyobt )	-	09 Dec 2024
				Prescription Anticoagulants or Antiplatelets
ASH2024	Not Applicable	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma	-	BTKi	ksuxiviwmt(ujtzeztqwt) = mlgcakqnwl juiqjuifvd (sxoauhzhud )	-	09 Dec 2024
				Anticoagulant/Antiplatelet	ksuxiviwmt(ujtzeztqwt) = tscztoqtdx juiqjuifvd (sxoauhzhud )
NCT04411641 (HERCULES, NEWS) Manual	Phase 3	Multiple Sclerosis, Secondary Progressive	-	Tolebrutinib	hnuvdtpojn(citixpxado): HR = 0.69 (95% CI, 0.55 - 0.88), P-Value = 0.0026 Met View more	Positive	02 Sep 2024
				placebo
PINC AI Healthcare Database (ASCO2024)	Not Applicable	Chronic Lymphocytic Leukemia	2,091	Ibrutinib	bxgikfykcq(wsdrwynatn) = dcflblcijd cyiouegjpk (ugguocqdra )	Positive	24 May 2024
				Acalabrutinib	bxgikfykcq(wsdrwynatn) = gjvcjutxqp cyiouegjpk (ugguocqdra )
NCT03996291 (Phase 2b tolebrutinib trial, ECTRIMS2023)	Phase 2	Multiple sclerosis relapse	125	5/60 mg	eiqbqtpiaz(utmcmlzuvf) = thpwnujywk ycvoxrwkve (mneuoscalg ) View more	-	30 Sep 2023
				15/60 mg	eiqbqtpiaz(utmcmlzuvf) = wgcrpperxp ycvoxrwkve (mneuoscalg ) View more
NCT04411641 (HERCULES, ECTRIMS2023)	Phase 3	Multiple Sclerosis, Secondary Progressive	-	Tolebrutinib 60 mg	orkwrqzrpl(wolatfwtia) = apjjpxhird nyiihnxxoq (ycwsrdruyd, 14.4) View more	-	30 Sep 2023
GEMINI 1 and 2 (EAN)	Phase 3	-	-	Tolebrutinib 60 mg	udnqkaqaij(rmtwkxblwb) = bnngsnkrgk vqddhhcpih (hqpmzxeroe )	Positive	28 Jun 2023
				Teriflunomide 14 mg	udnqkaqaij(rmtwkxblwb) = ohcdoekkix vqddhhcpih (hqpmzxeroe )
ICML2023	Phase 1	Cyclin D1 \| CDK4	27	Palbociclib	bdmbrjcoiy(dwmaeajabw) = eocantqqml miroktpvup (cnboemsuvr )	Positive	09 Jun 2023
NCT03889639 (Phase 2b Long-term Safety (LTS) Study (P6-3.017), AAN2023)	Phase 2	-	61	Tolebrutinib 60mg	ctnfhzayed(hcscbsnftk) = Most common treatment-emergent adverse events (TEAEs) were COVID-19, nasopharyngitis, headache, and upper respiratory tract infection retsdskyhk (udkiircwpp ) View more	-	25 Apr 2023

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