Ganglioglioma

MONDAY, June 17, 2024 -- Patients with neuroglial tumors are ideal epilepsy surgical candidates, with good long-term outcomes observed, according to a study published online May 22 in Frontiers in Neurology . Attila Rácz, M.D., Ph.D., from the University Hospital Bonn in Germany, and colleagues evaluated long-term outcomes and potential influencing factors among 107 patients who underwent surgery for neuroglial tumors (2001 to 2020) at a single institution. The researchers found that 75 percent of the patients who underwent surgery achieved complete freedom from seizures at 12 months and 56 percent achieved complete freedom from seizures at the last follow-up visit (70.4 months; median: 40 months). For both 12-month follow-up outcomes and the longest available outcomes, completeness of resection was a crucial factor, while there was no consistent impact on postsurgical outcomes for lobar tumor localization, histology (ganglioglioma versus dysembryoplastic neuroepithelial tumor), history of bilateral tonic-clonic seizures prior to surgery, invasive diagnostics, side of surgery (dominant versus nondominant hemisphere), age at epilepsy onset, age at surgery, or epilepsy duration. Patients who underwent lesionectomy and lesionectomy with hippocampal resection showed similar outcomes. "Neuroglial tumors present as excellent surgical substrates in treating structural epilepsy," the authors write. "To achieve an optimal postsurgical outcome, a complete lesion resection should be pursued whenever possible." Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

CDK5, or cyclin-dependent kinase 5, is a crucial enzyme found in the human body that plays a significant role in various physiological processes. It is primarily involved in the development and maintenance of the central nervous system, including neuronal migration, synaptic plasticity, and neurotransmitter release. CDK5 also regulates cell cycle progression, neuronal survival, and differentiation. Dysregulation of CDK5 has been implicated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease, and epilepsy. Understanding the role of CDK5 in these conditions can provide valuable insights for the development of targeted therapies and interventions to treat and manage these disorders. CDK5 Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 10 Sep 2023, there are a total of 8 CDK5 drugs worldwide, from 18 organizations, covering 24 indications, and conducting 19 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The current competitive landscape of target CDK5 indicates a strong focus on its development by companies such as Merck KGaA, AbbVie, Inc., and Cothera Bioscience, Inc. Merck KGaA leads the way with drugs in Phase 3 and the inactive stage.  Indications being targeted include various types of cancers and neurological disorders. Small molecule drugs are progressing rapidly, indicating a focus on developing orally available drugs with high specificity for CDK5.  The United States and the European Union are the leading countries/locations in the development of CDK5 inhibitors. Overall, the future development of target CDK5 shows promising potential for the treatment of various diseases, but further research and clinical trials are needed to bring these drugs to market. The multi-target CDK5 inhibitor ZTR enters Phase I clinical trialsThe drug ZTR is a small molecule drug that targets CDK2, CDK5, CDK7, and CDK9. It falls under the therapeutic areas of neoplasms, immune system diseases, nervous system diseases, digestive system disorders, hemic and lymphatic diseases, skin and musculoskeletal diseases, and other diseases. ZTR is indicated for the treatment of various types of cancers including acute myeloid leukemia, cholangiocarcinoma, chondrosarcoma, colorectal cancer, diffuse intrinsic pontine glioma, diffuse large B-cell lymphoma, ganglioglioma, glioblastoma, hepatocellular carcinoma, small cell carcinoma, and triple negative breast cancer. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. The drug is developed by Cothera Bioscience, Inc, which is the originator organization. Currently, ZTR is in Phase 1. This indicates that the drug is still in the early stages of clinical trials and further research and testing are required before it can be approved for commercial use. ZTR's targeting of CDK2, CDK5, CDK7, and CDK9 suggests that it may have potential in inhibiting the growth and proliferation of cancer cells. CDKs, or cyclin-dependent kinases, are enzymes that play a crucial role in cell cycle regulation. By targeting multiple CDKs, ZTR may have a broader spectrum of activity against different types of cancers. The therapeutic areas of ZTR cover a wide range of diseases, indicating its potential for treating various medical conditions. Neoplasms, immune system diseases, nervous system diseases, digestive system disorders, hemic and lymphatic diseases, and skin and musculoskeletal diseases are all areas where ZTR may have therapeutic benefits. This suggests that the drug may have a versatile mechanism of action that could be applicable to different disease pathways. However, it is important to note that the information provided is limited to the objective facts about ZTR. Further research and clinical trials are needed to determine the drug's efficacy, safety profile, and potential side effects. The current phase of development, Phase 1, indicates that ZTR is still in the early stages of evaluation and it will be some time before it can progress to later phases and potentially be approved for commercial use. The selective CDK5 inhibitor MRT3-007 is in the preclinical research stageThe drug MRT3-007 is a small molecule drug that targets CDK5, a protein involved in cell cycle regulation. It is being developed by ManRos Therapeutics SA, an organization specializing in biomedicine. The drug is primarily intended for the treatment of neoplasms, a broad term encompassing various types of tumors. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Specifically, MRT3-007 is indicated for the treatment of pheochromocytoma, a rare tumor that develops in the adrenal glands. Pheochromocytomas are typically noncancerous, but they can cause symptoms such as high blood pressure, rapid heartbeat, and excessive sweating. The drug aims to address the underlying mechanisms of pheochromocytoma by targeting CDK5, which plays a role in cell proliferation and survival. As of the latest available information, MRT3-007 is in the preclinical phase, which means it is still undergoing laboratory testing and has not yet been tested in humans. Preclinical studies are crucial for evaluating the drug's safety, efficacy, and potential side effects before proceeding to clinical trials. The development of small molecule drugs like MRT3-007 involves the design and synthesis of chemical compounds that can interact with specific targets in the body. These drugs are typically administered orally and can penetrate cells to modulate the activity of target proteins. Small molecule drugs have been widely used in the pharmaceutical industry and have proven effective in treating various diseases. In summary, MRT3-007 is a small molecule drug being developed by ManRos Therapeutics SA for the treatment of pheochromocytoma, a type of neoplasm. It targets CDK5, a protein involved in cell cycle regulation, and is currently in the preclinical phase of development. Further research and clinical trials will be necessary to determine the drug's safety and efficacy in humans.

Treatment with targeted therapies Tafinlar + Mekinist resulted in 47% ORR versus chemotherapy (11%) and reduced risk of progression or death by 69%, showing significant efficacy improvement in patients ages 1 to 17 years old with BRAF V600 low-grade gliomas (LGG) requiring first systemic treatment1 If approved, Tafinlar + Mekinist may offer a potential new standard-of-care for pediatric patients with this brain cancer who are in need of a more efficacious and convenient option that can be administered orally and may also improve quality of life1 Results add to body of evidence demonstrating efficacy and safety of Tafinlar + Mekinist across multiple BRAF V600 solid tumors Data highlighted as part of ASCO official press briefing and will form basis of upcoming regulatory submissions Basel, June 6, 2022 — Novartis today announced Tafinlar® (dabrafenib) + Mekinist® (trametinib) significantly improved efficacy in patients ages 1 to 17 years old with BRAF V600 pediatric low-grade glioma (pLGG) requiring first systemic treatment compared to chemotherapy, the current standard-of-care for these patients1. In this study, patients randomized to receive Tafinlar + Mekinist experienced a statistically significant overall response rate (ORR) of 47% (CI: 35-59%) compared to 11% (CI: 3-25%, p<0.001) for those randomized to receive chemotherapy. A new liquid formulation of Tafinlar + Mekinist that can be easier to administer than chemotherapy was used in this trial. The data will be highlighted today as part of an official press briefing and oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA2002). “These results show dabrafenib and trametinib demonstrate an improvement over chemotherapy for children and adolescents with BRAF V600 low-grade gliomas,” said Eric Bouffet, MD, FRCPC, Senior Associate Scientist Emeritus at The Hospital for Sick Children (SickKids) in Toronto, Canada. “This work highlights the importance of testing for mutations like BRAF in patients with low-grade gliomas.” LGG is the most common pediatric brain cancer and BRAF V600 mutations are present in 15-20% of pLGGs2,5. Currently, standard chemotherapy is associated with poor outcomes and a high burden of care6. Additional results from the Phase II/III trial showed at a median follow-up of 18.9 months, median progression-free survival (PFS) was 20.1 months with Tafinlar + Mekinist (CI: 12.8 months-not estimable) compared to 7.4 months with chemotherapy (CI: 3.6-11.8 months, hazard ratio=0.31 [CI: 0.17-0.55] [p<0.001])1. Additionally, tumors shrank or remained stable in 86% of patients in the Tafinlar + Mekinist arm (n=73; CI: 76-93%) compared to 46% of patients in the chemotherapy arm (n=37; CI: 30-63%). After one year of follow-up, nearly all patients on Tafinlar + Mekinist (89%) had a reduction in tumor size compared with baseline versus 70% of patients in the chemotherapy arm. Results from a quality-of-life analysis favored Tafinlar + Mekinist compared to chemotherapy at all time points1. “These young patients and their families experience a heavy burden of care as BRAF V600 low-grade glioma poses a risk of neurological impairment and current standard-of-care treatment is intravenous and associated with frequent trips to the cancer clinic or hospital,” said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development at Novartis. “Tafinlar + Mekinist has shown unprecedented efficacy, and we will work with health authorities to bring these children the possibility of a more effective and easier to administer liquid oral treatment option as quickly as possible.” The safety profile of Tafinlar + Mekinist was generally consistent with established safety observed in previous studies. Patients in the Tafinlar + Mekinist arm had fewer grade 3 or higher adverse events (AEs; 47% vs 94%) and fewer discontinuations due to AEs (4% vs 18%) than patients in the chemotherapy arm evaluated for safety (n=33)1. The most frequent AEs in the Tafinlar + Mekinist arm were pyrexia, headache and vomiting1. In a separate single-arm cohort of this study evaluating pediatric patients with relapsed or refractory BRAF V600 high-grade gliomas (HGG), treatment with Tafinlar + Mekinist showed an independently assessed ORR of 56.1% [CI: 39.7%-71.5%] and generally consistent safety results4. These data were presented in a poster discussion at the 2022 ASCO Annual Meeting (Abstract #2009). Tafinlar + Mekinist was granted Breakthrough Therapy designation by the US Food and Drug Administration for the treatment of pediatric patients one year of age and older with LGG with a BRAF V600E mutation who require systemic therapy. About the TADPOLE trialThis global Phase II/III, multicenter, open-label trial is evaluating patients aged 1 to 17 with BRAF V600 LGG (n=110) or relapsed or refractory HGG (n=41)1. Tafinlar + Mekinist is administered orally either as new liquid formulations, or as capsules and tablets, respectively. The primary endpoint in both cohorts is overall response rate. Secondary outcome measures include duration of response, progression-free survival, overall survival and other endpoints1. About pediatric gliomas Gliomas are the most common pediatric central nervous system tumor type, representing about half of all pediatric brain cancers5,7,8. Gliomas are classified as either low-grade (grades 1 and 2) or high-grade (grades 3 and 4)7. Pediatric low-grade gliomas positive for the BRAF V600E mutation have been associated with worse survival outcomes (OS/PFS) and are found in approximately 15-20% of pLGG2,3. BRAF mutations are found in approximately 3% to 7% of people with HGG (all ages combined)9,10. BRAF mutations have been identified as drivers of cancer growth across a wide range of solid tumors and often have limited treatment options11,12. About Tafinlar + MekinistThe combination of Tafinlar + Mekinist, the worldwide targeted therapy leader in BRAF/MEK-inhibition research and patients reached, may help to slow tumor growth by blocking signals associated with the BRAF and MEK kinases, which are implicated in the growth of various types of cancer11-15. Tafinlar + Mekinist has been studied in more than 6,000 BRAF-positive patients in more than 20 ongoing and completed trials and has been prescribed to more than 200,000 patients worldwide15. Tafinlar + Mekinist is currently not approved for pediatric patients with LGG or HGG. These results will form the basis of regulatory discussions with global health authorities. DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About NovartisNovartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com. Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnewsFor Novartis multimedia content, please visit https://www.novartis.com/news/media-libraryFor questions about the site or required registration, please contact media.relations@novartis.com References Bouffet, E MD. Primary analysis of a phase II trial of dabrafenib plus trametinib (dab + tram) in BRAF V600–mutant pediatric low-grade glioma (pLGG). 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract #LBA2002.Lassaletta A, et al. J Clin Oncol. 2017;35:2934-2941Mistry M, et al. J Clin Oncol. 2015;33:1015-1022Hargrave, D MD. Dabrafenib + trametinib (dab + tram) in relapsed/refractory (r/r) BRAF V600–mutant pediatric high-grade glioma (pHGG): Primary analysis of a phase II trial. 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract #2009.Ostrom QT, et al. Neuro Oncol. 2021;23(12 suppl 2):iii1-iii105Oberheim Bush NA, Chang S. Treatment Strategies for Low-Grade Glioma in Adults. J Oncol Pract. 2016 Dec;12(12):1235-1241. doi: 10.1200/JOP.2016.018622. PMID: 27943684.ESMO/Anticancer Fund. Glioma Guide for PatientsLouis DN, et al. Acta Neuropathol. 2016;131:803-82Ballester LY, Fuller GN, Powell SZ, Sulman EP, Patel KP, Luthra R, et al. Retrospective analysis of molecular and immunohistochemical characterization of 381 primary brain tumors. J Neuropathol Exp Neurol. 2017 Mar 1;76(3):179-88Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol. 2011 Mar;121(3):397-405Turski ML, et al. Mol Cancer Ther. 2016;15:533-547Pratilas C, et al. Curr Top Microbiol Immunol. 2012;355:82-98Tafinlar [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022.Mekinist [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022.Data on file. # # # Novartis Media RelationsE-mail: media.relations@novartis.com Anja von TreskowNovartis External Communications+41 79 392 8697 (mobile)anja.von_treskow@novartis.com Julie MasowNovartis US External Communications+1 862 579 8456julie.masow@novartis.comDan ConnellyNovartis Oncology Communications+1 862 210 0217 (mobile)daniel.connelly@novartis.com Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com Central North America Samir Shah+41 61 324 7944Sloan Simpson+1 862 345 4440Nicole Zinsli-Somm+4 16 132 43809Alina Levchuk+1 862 778 3372Isabella Zinck+41 61 324 7188Parag Mahanti+1 973-876-4912