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

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

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

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

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

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

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

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

New P2 trial • Brain Cancer • Oncology • NF2

A MULTI-CENTER, OPEN-LABEL, SINGLE-ARM PHASE II STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FCN-159 IN ADULTS WITH HISTIOCYTIC NEOPLASMS (EHA 2024) - "The preliminary study results showed that treatment of FCN-159 was remarkableefficacious for patients with histiocytic neoplasms, including all the genotypes and disease subtypes. FCN-159was well tolerated and adverse events were manageable, without new safety signal observed."

Clinical • P2 data • Atopic Dermatitis • Dermatitis • Dermatology • Dyslipidemia • Immunology • Musculoskeletal Pain • Oncology • Respiratory Diseases • ARAF • ARRB1 • BRAF • CXCR1

FCN-159, a MEK1/2 inhibitor, in patients with advanced melanoma harboring NRAS or NF1 mutations: A phase 1B dose-expansion study. (ASCO 2024) - P1 | "FCN-159 showed encouraging efficacy data with well tolerated safety profile in patients with NRAS-mutant advanced melanoma, especially those who failed in previous anti-PD-1 therapy."

Clinical • IO biomarker • Metastases • P1 data • Dermatology • Herpes Zoster • Infectious Disease • Melanoma • Oncology • Pneumonia • Respiratory Diseases • Retinal Disorders • Solid Tumor • Varicella Zoster • NF1 • NRAS

Efficacy and safety of FCN-159, a MEK1/2 inhibitor in pediatric participants with neurofibromatosis type 1: Results from a phase 2 trial. (ASCO 2024) - P2 | "FCN-159 demonstrated good tolerability and exhibited notable anti-tumor activity in pediatric pts with NF1-related PN."

Clinical • P2 data • Dermatitis • Dermatology • Genetic Disorders • Infectious Disease • Neurofibromatosis • Pain • Pediatrics • Pneumonia • Respiratory Diseases • Solid Tumor • NF1

Fosun Pharma: Registration application for new drug Fumatinib tablets of holding subsidiary accepted [Google translation] (Sina Corp) - "Fosun Pharma announced on the evening of May 24 that the drug registration application for Fumaitinib tablets (project code: FCN-159) independently developed by its holding subsidiary Shanghai Fosun Pharmaceutical Industry Development Co., Ltd. for the treatment of adult dendritic cell and tissue cell tumors was recently accepted by the National Medical Products Administration."

China filing • Oncology • Solid Tumor

Fosun Pharma’s MEK1/2 inhibitor plans to be included in priority review [Google translation] (163.com) - "On April 15, the official website of the Center for Drug Evaluation (CDE) of China’s State Food and Drug Administration announced that Fosun Pharma’s FCN-159 tablets are planned to be included in priority review, with the indications being the treatment of adult dendritic cell and histiocytic tumors . Public information shows that FCN-159 tablets are a MEK1/2 selective inhibitor developed by Fosun Pharma....Adult dendritic cell tumor is a rare malignant tumor that mainly affects bones, but can also affect lungs, skin, brain, liver and other organs. Histiocytic tumor is a malignant tumor originating from the body's interstitial and supporting tissues, such as muscle, bone, cartilage, fat, nerves, blood vessels, etc. It is a rare disease that usually occurs in middle-aged people."

Non-US regulatory • Priority review • Solid Tumor

MEK Inhibitor FCN-159 To Treat Advanced Melanoma With NRAS-aberrant (Ia) and NRAS-mutant (Ib)or NF1-mutant(1b) (clinicaltrials.gov) - P1 | N=79 | Suspended | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. | Phase classification: P1a/1b ➔ P1 | N=37 ➔ 79 | Trial completion date: Mar 2023 ➔ Apr 2024 | Recruiting ➔ Suspended | Trial primary completion date: Sep 2022 ➔ Apr 2023

Enrollment change • Metastases • Phase classification • Trial completion date • Trial primary completion date • Trial suspension • Melanoma • Oncology • Solid Tumor • NF1 • NRAS

FCN-159 in Adult Patients With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas (clinicaltrials.gov) - P3 | N=162 | Recruiting | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

A phase II study to explore the efficacy and safety of FCN-159 in recurrent or progressive pediatric low-grade glioma (pLGG) with MAPK pathway-activated (ESMO 2023) - "FCN-159 is well tolerated and easily manageable, without new safety signal observed. Long-term efficacy and safety follow-up are ongoing."

Clinical • P2 data • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • BRAF • KIAA1549 • 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. | Not yet recruiting ➔ Recruiting

Enrollment open • Langerhans Cell Histiocytosis • Pediatrics • ARAF • BRAF • HRAS • KRAS • MAP2K1 • MAP2K2 • NRAS