luvometinib (FCN-159) / Fosun Pharma - LARVOL DELTA

Shanghai Fosun Pharmaceutical announced that its subsidiary’s drug registration application for Luvometinib Tablets, intended for treating pediatric patients with Langerhans cell histiocytosis, has been accepted by China’s National Medical Products Administration and prioritized for review. (TipRanks)

China filing • Priority review • Langerhans Cell Histiocytosis

A single center, single arm, prospective clinical study initiated by a researcher on the efficacy and safety of FCN-159 table (ChiCTR) - P=N/A | N=20 | Completed | Sponsor: Beijing Childrens Hospital,Capital Medical University; Beijing Childrens Hospital,Capital Medical University

New trial • Genetic Disorders • Neurofibromatosis • Pediatrics • Solid Tumor

Update on the phase II study: to explore the efficacy and safety of luvometinib (FCN-159) in recurrent or progressive pediatric low-grade glioma with MAPK pathway-activated (ESMO 2025) - P2 | "Table: 661MO Efficacy Evaluable set (ES) FCN-159 (n=37) KIAA1549-BRAF (n=23) BRAF V600E (n=11) NF1 mut (n=3) Total (n=37) Confirmed ORR (CR+PR+MR), n(%) 10 (43.5) 8 (72.7) 2 (66.7) 20 (54.1) Median DOR, months [95% confidence interval (CI)] - (-, -) - (9.232, -) - (-, -) - (14.850, -) Median PFS, months (95% CI) - (-, -) - (11.072, -) - (-, -) - (17.511, -) Median Time to Response (TTR), months (range) 3.710 (1.84, 11.17) 1.890 (1.71, 11.07) 2.695 (1.87, 3.52) 3.595 (1.71, 11.17) Safety Full analysis set (FAS) FCN-159 (n=38) Any grade TEAEs, n(%) 37 (97.4) ≥ grade 3 TEAEs, n(%) 7 (18.4) TEAEs Leading to dose interruption, n(%) 27 (71.1) TEAEs Leading to dose reduction, n(%) 0 TEAEs Leading to discontinuation, n(%) 0 Conclusions The updated data showed that FCN-159 exhibited promising efficacy for pLGG with a manageable safety profile and no new safety signal observed. A phase III randomized controlled trial to evaluate FCN-159 in pLGG is recruiting."

Clinical • P2 data • Brain Cancer • Glioma • Oncology • Solid Tumor • BRAF • KIAA1549 • NF1

Phase 1 Study of Luvometinib Use in Pediatric Patients with Neurofibromatosis Type 1-Related Unresectable Plexiform Neurofibromas. (PubMed, Target Oncol) - P1/2 | "Luvometinib had a manageable safety profile in pediatric patients with unresectable NF1-related PN. Encouraging preliminary efficacy was observed, particularly among patients receiving the RP2D of 5 mg/m2, supporting further investigation of luvometinib in this setting."

Journal • P1 data • Genetic Disorders • Neurofibromatosis • Oncology • Pain • Pediatrics • Solid Tumor • NF1

Luvometinib in patients with Langerhans cell histiocytosis, Erdheim-Chester disease, and other histiocytic neoplasms: a single-arm, multicentre, phase 2 study. (PubMed, EClinicalMedicine) - P2 | "Luvometinib demonstrated high and durable responses and a manageable safety profile in patients with histiocytic neoplasms. Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd."

Journal • P2 data • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Langerhans Cell Histiocytosis • Oncology • Rare Diseases

Shanghai Fosun Pharmaceutical (Group) Co., Ltd…announced that its self-developed innovative drug Luvometinib Tablets has gained Breakthrough Therapy Designation by the Saudi Food and Drug Authority (SFDA) for the treatment of adult patients with Langerhans cell histiocytosis (LCH) and histiocytic neoplasms. (Market Screener)

Breakthrough therapy • Langerhans Cell Histiocytosis

Luvometinib: First Approval. (PubMed, Drugs) - "In May 2025, luvometinib was approved in china for the treatment of adult patients with Langerhans cell histiocytosis (LCH) and histiocytic neoplasms and for the treatment of paediatric patients aged ≥ 2 years with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection. This article summarizes the milestones in the development of luvometinib leading to this first approval for the treatment of adult patients with LCH/histiocytic tumours and children and adolescents aged ≥ 2 years with NF1 with symptomatic, inoperable PN."

Journal • Genetic Disorders • Langerhans Cell Histiocytosis • Neurofibromatosis • Oncology • Pediatrics • Rare Diseases • Solid Tumor • NF1

Phase II Study of FCN-159 in NF2 Nerve Sheath Tumors (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer

THE EFFICACY AND SAFETY OF LUVOMETINIB (FCN-159) IN PEDIATRIC PATIENTS WITH REFRACTORY/RELAPSED LANGERHANS CELL HISTIOCYTOSIS: A MULTI-CENTER, OPEN-LABEL, SINGLE-ARM PHASE II STUDY (EHA 2025) - P2 | "Current first-line treatment recommended by Histiocyte Society for children with multifocal disease is vinblastine and prednisone. For patients with risk-organ involvement, additional 6-mercaptopurine is also used as maintenance therapy...While cobimetinib has been approved for the treatment of adult patients, it has not yet been approved for pediatric patients... The preliminary study results showed that luvometinib was highly efficacious for pediatric patients with refractory/relapsed LCH. In addition, luvometinib was well tolerated, without TRAEs-induced discontinuation reported. Trial Information: NCT05997602, CTR20232238."

Clinical • P2 data • Anemia • Dermatitis • Dermatology • Genetic Disorders • Hematological Disorders • Immunology • Infectious Disease • Langerhans Cell Histiocytosis • Neurofibromatosis • Pediatrics • Rare Diseases • Solid Tumor • ARAF • BRAF • CD1a

Follow-up Study to Evaluate the Safety and Efficacy of FCN-159 in Pediatric Participants With Neurofibromatosis Type 1 (clinicaltrials.gov) - P1/2 | N=65 | Not yet recruiting | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

New P1/2 trial • Genetic Disorders • Neurofibromatosis • Pediatrics • Solid Tumor

Global R&D | Updated data on luvometinib (FCN-159) for the treatment of NF1 in children were published at ASCO 2025 [Google translation] (Fosun Pharma Press Release) - P1/2 | N=160 | NCT04954001 | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. | "As of September 23, 2024, this multicenter, open-label Phase 2 clinical study included 46 pediatric patients aged 2-18 years (exclusive) with NF1-related PN treated with luvometinib (5 mg/m2 once daily). The median follow-up was 25.1 months. Among the 43 evaluable patients, the investigator-assessed and confirmed objective response rate (ORR) was 60.5% (95% CI: 44.4-75.0), 26 achieved partial response (PR), 17 had stable disease (SD), and no disease progression. Median duration of response (DOR) and median progression-free survival (PFS) were not reached. Of the 43 evaluable patients, BIRC assessed and confirmed an ORR of 44.2% (95% CI: 29.1-60.1), 19 achieved PR, 24 achieved SD, and no disease progression."

P2 data • Neurofibromatosis

FCN-159 Monotherapy Versus Chemotherapy by Investigator's Choice in Pediatric Low-grade Glioma Patients With BRAF Alteration (clinicaltrials.gov) - P3 | N=102 | Not yet recruiting | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Monotherapy • New P3 trial • Brain Cancer • Glioma • Oncology • Pediatrics • Solid Tumor • BRAF

Updated data of efficacy and safety of luvometinib (FCN-159) in pediatric participants with neurofibromatosis type 1 from a multi-center, open-label, single-arm phase 2 study. (ASCO 2025) - P1/2 | "Overall, luvometinib was well-tolerated and demonstrated promising anti-tumor activity in pediatric participants with NF1-related PN. Long-term efficacy and safety follow-up are ongoing. Clinical trial information: NCT04954001."

Clinical • P2 data • Anemia • Dermatitis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Immunology • Infectious Disease • Neurofibromatosis • Pain • Pediatrics • Pneumonia • Respiratory Diseases • Solid Tumor • NF1

Novel Therapies for Neurofibromatosis Type 1-Associated Inoperable Plexiform Neurofibromas: A Systematic Literature Review (ISPOR 2025) - "These reported on a total of 21 unique studies on 11 emerging therapies: 6 MEK inhibitors (selumetinib, mirdametinib, trametinib, binimetinib, FCN-159, tunlametinib) and 5 targeted anti-cancer agents (cabozantinib, tipifarnib, sorafenib, sirolimus, everolimus)... The promising results of MEK inhibitors in therapeutic trials for NF1 demonstrate that targeting the MAPK/ERK pathway is an attractive therapeutic avenue for unresectable PNs. Because selumetinib is only approved for children, future reimbursement will require advanced studies establishing MEK inhibitor efficacy in adults."

Review • Brain Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • NF1

A single center, single arm, prospective clinical study initiated by a researcher on the efficacy and safety of FCN-159 in the treatment of pediatric patients with type 1 neurofibromatosis associated with symptomatic and inoperable plexiform neurofibromatosis: Mid-term study report. (ASCO 2025) - "In this study, 79% of pediatric NF1-PNs showed a trend toward tumor shrinkage or atrophy within the first 14 months of treatment with FCN-159.Patients had significantly lower mean pain scores, but adverse effects were also common.Subsequent, more substantial studies are still needed to evaluate the effectiveness and long-term adverse effects of FCN-159."

Clinical • Genetic Disorders • Infectious Disease • Neurofibromatosis • Pain • Pediatrics • Solid Tumor • NF1

Global R&D | Fosun Pharma's self-developed innovative drug FCN-159 tablets is included in the breakthrough therapy program for the treatment of Langerhans' histiocytosis in children [Google translation] (Sina Corp) - "On May 12, 2025, Fosun Pharma...announced that its independently developed Class 1 new drug FCN-159 tablets (luvometinib tablets) for the treatment of Langerhans' histiocytosis in children has been included in the breakthrough therapy drug program of the National Medical Products Administration."

Breakthrough therapy • Rare Diseases

FCN-159-008: A phase II multicenter, open-label, single-arm study to evaluate the efficacy and safety of FCN-159 in adolescent and adult patients with extracranial arteriovenous malformation (ChiCTR) - P2 | N=35 | Not yet recruiting | Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Shanghai Fosun Pharmaceutical (Group) Limited by Shar

New P2 trial • Cardiovascular • CNS Disorders • Giant Cell Arteritis • BRAF • EPHB4 • KRAS • MAP2K1 • MAP2K2 • NRAS • PTEN • RASA1 • SMAD4

An Exploratory Study to Evaluate the Efficacy and Safety of FCN-159 in Patients With Brain Arteriovenous Malformations (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Xuanwu Hospital, Beijing

New P2 trial • Cardiovascular • CNS Disorders

Fosun Pharma Announces 2024 Annual Results (PRNewswire) - "In 2024, Fosun Pharma further focused on the business development of innovative drugs and high-value devices, achieving operating revenue of RMB41.07 billion and net profit attributable to shareholders of RMB2.77 billion, representing an increase of 16.08% YoY. Fosun Pharma continuously optimize supply chain management to enhance operational efficiency, recording an operating cash flow of RMB4.48 billion with an increase of 31.13% YoY, surpassing the growth rate of operating profit...During the Reporting Period, the gross margin minus the selling and distribution expense ratio improved by 2.45 percentage points YoY; and, excluding the impact of newly acquired enterprises during the Reporting Period and the same period last year, administrative expenses declined by RMB355 million."

Commercial • Breast Cancer • Gastric Cancer • Neurofibromatosis • Non Small Cell Lung Cancer • Small Cell Lung Cancer

FCN-159 in Adult Patients with Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas (clinicaltrials.gov) - P3 | N=167 | Active, not recruiting | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

To Evaluate the Efficacy, Safety, and PK Characteristics of FCN-159 in Pediatric Patients With Refractory/Recurrent LCH (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. | Trial completion date: Jul 2026 ➔ May 2027 | Trial primary completion date: Jul 2024 ➔ May 2025

Trial completion date • Trial primary completion date • Langerhans Cell Histiocytosis • Pediatrics • ARAF • BRAF • HRAS • KRAS • MAP2K1 • MAP2K2 • NRAS

…blockbuster new drugs expected to be approved for marketing in China in 2025 [Google translation] (Sohu.com) - "Fosun Pharma's FCN-159: This is a MEK1/2 selective inhibitor used to treat adult dendritic cell and histiocytic tumors, as well as plexiform neurofibromas (PN) associated with neurofibromatosis type 1 (NF1) in children. The drug's marketing application has been accepted by the CDE and is expected to be approved in 2025."

China approval • Neurofibromatosis • Solid Tumor

Study to Evaluate the Safety, Tolerability, PK Characteristics and Anti-tumor Activity of FCN-159 in Adult and Pediatric Participants With Neurofibromatosis Type 1 (clinicaltrials.gov) - P1/2 | N=160 | Active, not recruiting | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. | Phase classification: P2 ➔ P1/2

Phase classification • Genetic Disorders • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • NF1

A single-center, open, single-arm phase II clinical study: evaluation of the efficacy and safety of FCN-159 in selected NF2-associated nerve sheath tumors (ChiCTR) - P2 | N=30 | Not yet recruiting | Sponsor: Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

New P2 trial • Brain Cancer • Oncology

Fosun Pharma Announces 2024 Interim Results (PRNewswire) - "During the Reporting Period, the New Drug Application (NDA) of self-developed selective MEK1/2 inhibitor (project code: FCN-159) for two indications was accepted by NMPA in May and June 2024, both of which were included in the priority review procedure."

China filing • Priority review • Solid Tumor