Neurofibrosarcoma

– GOMEKLI is the first and only medicine approved for both adults and children with NF1-PN – – Approval based on positive data from Phase 2b ReNeu trial, which showed GOMEKLI treatment resulted in robust ORR, deep and durable reductions in tumor volume, and a manageable safety profile – – SpringWorks granted rare pediatric disease priority review voucher by the FDA – Feb. 11, 2025 -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, announced today that the U.S. Food and Drug Administration (FDA) has approved GOMEKLI™ (mirdametinib), SpringWorks’ MEK inhibitor, for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.1 With the approval, SpringWorks was granted a rare pediatric disease priority review voucher (PRV) by the FDA. “The NF1-PN patient community has a great need for more treatment options. With today’s approval, we are honored to serve both adults and children with NF1-PN and provide them with a therapy that has the potential to shrink their tumors and offer meaningful symptomatic relief,” said Saqib Islam, Chief Executive Officer of SpringWorks. “We are grateful to each clinical trial participant, their families, the investigators, and the patient advocacy groups involved in the journey towards making GOMEKLI available in the U.S. I am proud that we are delivering on our commitment to patients with devastating diseases with our company’s second FDA approval in less than 18 months.” NF1 is a genetic disorder that currently affects approximately 100,000 children and adults in the United States.2,3 Patients with NF1 have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PNs, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment.2,4 There are approximately 40,000 people in the United States living with NF1-PN, the majority of whom are adults that have not had an approved medicine until GOMEKLI.5 Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors, an aggressive and potentially fatal disease.6 Surgical removal can be challenging due to the infiltrative tumor growth pattern of plexiform neurofibromas along nerves, and up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.7,8,9 “Patients with NF1-PN often face significant challenges with their health and have had limited treatment options to manage this devastating condition,” said Christopher Moertel, M.D., Medical Director Pediatric Neuro-Oncology and Neurofibromatosis Programs and Kenneth and Betty Jayne Dahlberg Professor of Pediatrics, University of Minnesota, and lead investigator of the ReNeu trial. “It was very encouraging in the ReNeu trial to see that GOMEKLI provided deep and durable responses, with a manageable safety profile that enabled patients to stay on therapy. This approval represents an important advance, especially for adults who previously did not have an approved treatment.” GOMEKLI was approved under Priority Review and SpringWorks received a rare pediatric disease priority review voucher from the FDA. GOMEKLI was previously granted Orphan Drug and Fast Track designations for the treatment of NF1-PN. The FDA approval of GOMEKLI is based on results from the Phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN ≥2 years of age (58 adults and 56 pediatric patients).10 GOMEKLI met the primary endpoint of confirmed objective response rate (ORR), as assessed by blinded independent central review, demonstrating a 41% ORR (N= 24/ 58) in adults and 52% in children (N=29/56).10 Tumor volume reductions were deep and durable; the median best percentage change in target PN volume was -41% (range: -90 to 13%) in adults and -42% (range: -91 to 48%) in children.10 Eighty-eight percent of adults and 90% of children with a confirmed response had a response of at least 12 months duration, and 50% and 48%, respectively, had a response of at least 24 months duration.10 Patients in both cohorts also experienced early and sustained significant improvements from baseline in pain, and quality of life, as assessed across multiple patient-reported outcome tools.10 GOMEKLI demonstrated a manageable safety and tolerability profile.1 The most common adverse events (>25%) reported in adults receiving GOMEKLI were rash, diarrhea, nausea, musculoskeletal pain, vomiting and fatigue.1 The most common adverse events (>25%) occurring in children were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea.1 Please see additional Important Safety Information below, including Warnings & Precautions relating to ocular toxicity, left ventricular dysfunction, dermatologic adverse reactions, and embryo-fetal toxicity.1 “We are excited to celebrate the extraordinary milestone of our partners and long-term friends at SpringWorks for the NF1-PN community. This FDA approval shows the power of collaboration to advance innovative science for drugs that may otherwise not have been taken forward,” said Annette Bakker, Ph.D., Chief Executive Officer of the Children’s Tumor Foundation. "When industry, researchers, and organizations like ours driving treatment innovation join forces, scientific progress moves faster, and patients gain access to the therapies they need. Every treatment approval is hard-won, built on research, persistence, and partnership. Today, that work delivers a critical new option for NF patients of all ages.” “NF1-PN is a complex, devastating disease that affects not only individual patients, but entire families. Treatment advances are crucial to achieving better outcomes for patients and this FDA approval offers hope for NF patients and their families,” said Kim Bischoff, Executive Director, NF Network. SpringWorks is dedicated to helping patients with NF1-PN access GOMEKLI and to providing support throughout their treatment journey. The SpringWorks CareConnections™ program is a comprehensive patient support program that offers personalized support services and resources to eligible GOMEKLI patients, including insurance coverage information and access support, financial assistance and personalized educational and emotional support. Physicians and patients can contact 1-844-CARES-55 (1-844-227-3755) or visit www.springworkstxcares.com for more information. GOMEKLI is available in 1 and 2 mg capsules and in a 1mg tablet for oral suspension, which dissolves easily in water. GOMEKLI is expected to be available through a specialty pharmacy and specialty distributor network in the United States within two weeks. SpringWorks’ Marketing Authorization Application for mirdametinib for the treatment of children and adults with NF1-PN was validated by the European Medicines Agency (EMA) and is currently under review; a decision is expected from the European Commission in 2025. Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.11,12 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals, and there are approximately 100,000 patients living with NF1 in the United States.2,3 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.13 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.14 NF1 patients have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.2,4,6 NF1-PNs are most often diagnosed in the first two decades of life.2 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.15,16 Surgical removal of these tumors can be challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.6 Up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.7,8,9 GOMEKLI™ is an oral, small molecule MEK inhibitor approved in the United States for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection. SpringWorks is a commercial-stage biopharmaceutical company dedicated to improving the lives of patients with severe rare diseases and cancer. We developed and are commercializing OGSIVEO® (nirogacestat) as the first and only FDA-approved medicine for adults with desmoid tumors and GOMEKLI™ (mirdametinib) as the first and only FDA-approved medicine for both adults and children with neurofibromatosis type 1 associated plexiform neurofibromas (NF1-PN). We are also advancing a diverse portfolio of novel targeted therapy product candidates for patients with both solid tumors and hematological cancers. References GOMEKLI. Prescribing Information. SpringWorks Therapeutics, Inc. Prada C, Rangwala F, Martin L, et al. Pediatric Plexiform Neurofibromas: Impact on Morbidity and Mortality in Neurofibromatosis Type 1. J Pediatr. 2012;160(3):461-467. doi:10.1016/j.jpeds.2011.08.051. Ferner R. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. The Lancet Neurology. 2007;6(4):340-351. doi:10.1016/s1474-4422(07)70075-3. Miller DT, et al. Health supervision for children with neurofibromatosis Type 1. Pediatrics. 2019;143(5):e20190660. Data on File. Kamaludin, Siti Nurhazwani et al. “Plexiform neurofibromatosis with peripheral malignant nerve sheath tumor and scoliosis - more surveillance imaging needed?.” Radiology case reports vol. 17,7 2388-2393. 6 May. 2022, doi:10.1016/j.radcr.2022.03.111. Needle M, Cnaan A, Dattilo J, et al. Prognostic signs in the surgical management of plexiform neurofibroma: The Children’s Hospital of Philadelphia experience, 1974-1994. J Pediatr. 1997;131(5):678-682. doi:10.1016/s0022-3476(97)70092-1. Ejerskov, C., Farholt, S., Nielsen, F.S.K. et al. Clinical Characteristics and Management of Children and Adults with Neurofibromatosis Type 1 and Plexiform Neurofibromas in Denmark: A Nationwide Study. Oncol Ther 11, 97–110 (2023). https://doi.org/10.1007/s40487-022-00213-4. Wolkenstein, P. et al. (2023) ‘French cohort of children and adolescents with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas: Cassiopea study’, European Journal of Medical Genetics, 66(5), p. 104734. doi:10.1016/j.ejmg.2023.104734. Moertel CL, Fisher MJ, Weiss BD, et al. ReNeu: A pivotal, Phase IIb trial of mirdametinib in adults and children with symptomatic neurofibromatosis type 1-associated plexiform neurofibroma. J Clin Oncol. 2024;JCO.24.01034. doi.org/10.1200/JCO.24.01034. Yap YS, McPherson JR, Ong CK, et al. The NF1 gene revisited - from bench to bedside. Oncotarget. 2014;5(15):5873-5892. doi:10.18632/oncotarget.2194. Rasmussen S, Friedman J. NF1 Gene and Neurofibromatosis 1. Am J Epidemiol. 2000;151(1):33-40. doi:10.1093/oxfordjournals.aje.a010118. Weiss BD, Wolters PL, Plotkin SR, et al. NF106: A neurofibromatosis clinical trials consortium Phase II trial of the MEK inhibitor mirdametinib (PD-0325901) in adolescents and adults with NF1-related plexiform neurofibromas. J Clin Onc. 2021;JCO.20.02220.doi.org/10. 1200/JCO.20.02220. Lee: Lee TJ, et al. Incidence and prevalence of neurofibromatosis type 1 and 2: a systematic review and meta-analysis. Orphanet J Rare Dis. 2023;18(1):292. doi:10.1186/s13023-023-02911-2. Gross A, Singh G, Akshintala S, et al. Association of plexiform neurofibroma volume changes and development of clinical morbidities in neurofibromatosis 1. Neuro Oncol. 2018;20(12):1643-1651. doi:10.1093/neuonc/noy067. Nguyen R, Dombi E, Widemann B, et al. Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1. Orphanet J Rare Dis. 2012;7(1):75. doi:10.1186/1750-1172-7-75. The content above comes from the network. if any infringement, please contact us to modify.

The US Food and Drug Administration (FDA) has approved SpringWorks Therapeutics’ Gomekli (mirdametinib) to treat neurofibromatosis type 1 (NF1), a rare genetic disorder affecting approximately 100,000 people in the US. The drug has been specifically authorised to treat adult and paediatric patients aged two years and older who have symptomatic plexiform neurofibromas (PN) that cannot be removed surgically. NF1 causes a variety of symptoms across multiple organ systems, including abnormal pigmentation, skeletal deformities, tumour growth and neurological complications. Around 40,000 NF1 patients in the US have PNs, which are tumours that grow along the peripheral nerve sheath and can cause severe disfigurement, pain and functional impairment. PNs can also develop into malignant peripheral nerve sheath tumours, an aggressive and potentially fatal disease. SpringWorks’ Gomekli is an oral small molecule MEK inhibitor and the first and only FDA-approved therapy for both adults and children with NF1-PN. The FDA’s decision on the drug was supported by results from the phased 2b ReNeu trial, which demonstrated an objective response rate of 41% and 52% in adult and paediatric NF1-PN patients, respectively. Tumour volume reductions were deep and durable, SpringWorks said, with 50% of adults and 48% of children in response for at least 24 months, and patients in both cohorts also experienced early and sustained improvements in pain and quality of life. SpringWorks’ chief executive officer, Saqib Islam, said: “The NF1-PN patient community has a great need for more treatment options. With [this] approval, we are honoured to serve both adults and children with NF1-PN and provide them with a therapy that has the potential to shrink their tumours and offer meaningful symptomatic relief.” Alongside the approval, the FDA has awarded SpringWorks a priority review voucher (PRV), which the company can redeem to have any drug reviewed under the regulator’s priority review pathway. Under the PRV programme, which was created to encourage the development of new drug and biological products for the prevention and treatment of certain rare paediatric diseases, SpringWorks may also sell or transfer the voucher to another company.

Poster Includes Preclinical Data on Novel Direct Pan-RAS Inhibitors CARLSBAD, Calif., April 10, 2024 (GLOBE NEWSWIRE) -- Qualigen Therapeutics, Inc. (“Qualigen” or “the Company,” Nasdaq: QLGN) today announces a poster presentation on its preclinical Novel Direct Pan-RAS Inhibitors was presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 held April 5 – 10 in San Diego, California. “We continue to see cancers developing resistance to current clinical agents that target a particular K-RAS mutation, and we remain optimistic that a more broad-based Pan-RAS inhibitor may help resolve these issues”, commented Michael Poirier, Qualigen’s Chairman and Chief Executive Officer. “The data show that our Pan-RAS inhibitors can interfere with K-RAS, H-RAS and N-RAS activity and signaling, on both mutant and wild type RAS. This suggests there could be a viable window for Pan-RAS inhibitors in patients with RAS driven tumors, as well as a potentially broader application to cancers not usually associated with RAS, such as certain classes of Ovarian, Breast, and NF1 loss driven Malignant Peripheral Nerve Sheath Tumors (MPNST).” The Annual AACR Conference is a focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine. Highlights from this Poster Abstract #3320 - “Novel Direct Pan-RAS Inhibitors" - Howard Donninger, Rachel Ferril, Becca von Baby, Joe Burlison, Mike Sabo, Tariq Arshad, Rob Monsen, John Trent, and Geoffrey J. Clark - Results demonstrated the compounds' role as Pan-RAS inhibitors. These compounds effectively target and disrupt the activity and signaling of various RAS mutations, including K-RAS, H-RAS, and N-RAS, impacting both mutant and wild type variants. Encouragingly, in vivo studies indicate minimal toxicity associated with these compounds, likely due to their selective suppression of RAS signaling at the administered doses. These results hint at a promising therapeutic potential for Pan-RAS inhibitors in clinical settings, emphasizing their significance in cancer treatment strategies. About Pan-RAS Qualigen Therapeutics has collaborated with Dr. Geoff Clark and Dr. Joe Burlison at the University of Louisville, Kentucky to develop a series of potentially highly potent compounds to take forward into preclinical development. Lead compounds are believed to suppress or block the interaction of endogenous RAS with c-RAF, and thereby influence the K-RAS, H-RAS, and N-RAS effector pathways. RAS acts as a “hub” that activates multiple effector pathways, hence blocking any single pathway may be ineffective for many RAS-driven tumor types, including pancreatic, lung, and colorectal cancers. This approach could potentially enable a differentiated, pan-RAS strategy for inhibiting the MAPK, PI3K, and RAL pathways implicated in cancer cell proliferation, survival, and differentiation. About Qualigen Therapeutics, Inc. Qualigen Therapeutics, Inc. is an early-clinical-stage biotechnology company. Until the sale of its diagnostic business in 2023, Qualigen had a 20+ year history developing, marketing and selling medical devices in the United States and internationally. Our investigational QN-302 compound is a small molecule selective transcription inhibitor with strong binding affinity to G4s prevalent in cancer cells; such binding could, by stabilizing the G4s against “unwinding,” help inhibit cancer cell proliferation. QN-302 is currently in a Phase 1a clinical trial. The preclinical compounds within Qualigen’s family of PAN-RAS oncogene protein-protein interaction inhibitor small molecules are believed to inhibit or block the binding of mutated RAS genes’ proteins to their effector proteins, thereby leaving the proteins from the mutated RAS unable to cause further harm. In theory, such mechanism of action may be effective in the treatment of about one quarter of all cancers, including certain forms of pancreatic, colorectal, and lung cancers. For more information about Qualigen Therapeutics, Inc., please visit www.qlgntx.com. Contact: Michael PoirierQualigen Therapeutics, Inc.760.452.8111mpoirier@qlgntx.com Source: Qualigen Therapeutics, Inc.