Effekten af ART-001 på langsomme vaskulære malformationer
I en fase 2-studie blev effektiviteten og sikkerheden af ART-001 (serabelisib), en selektiv PI3Kα-hæmmer, vurderet hos patienter med langsomtvoksende vaskulære misdannelser (SFVM), herunder venøse misdannelser (VM), lymfatiske misdannelser (LM) og Klippel-Trenaunay syndrom (KTS) [source_link]. Resultaterne viste, at behandling med ART-001 var effektiv og vel-tolereret, hvilket støtter videre udvikling af lægemidlet i denne patientgruppe.
Studiet var designet som et multicenter, randomiseret, dobbeltblindet proof-of-concept forsøg. Deltagerne var patienter over 2 år, diagnosticeret med enten VM, LM eller KTS. I alt 35 patienter blev randomiseret til at modtage enten 50 mg (n=17) eller 100 mg (n=18) ART-001 dagligt i 24 uger.
Det primære endpoint var responsraten, defineret som andelen af deltagere med en reduktion på ≥ 20% i læsionsvolumen ved uge 24. Sekundære endpoints omfattede sikkerhed, farmakokinetik, smertemålinger og livskvalitet. Resultaterne viste en responsrate på 29,4% (95% CI 10,3-56,0%) ved 50 mg og 33,3% (13,3-59,0%) ved 100 mg. Ingen alvorlige bivirkninger relateret til medicinen blev rapporteret, og de bivirkninger, der opstod, var generelt milde til moderate og forbigående. Farmakokinetiske profiler var generelt ens for pædiatriske og voksne patienter, med undtagelse af lavere Ctrough-niveauer i den pædiatriske gruppe.
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**Citation:**
Ozeki, M., Tanaka, A., Kuniyeda, K., Nozaki, T., Fujino, A., Nomura, T., Uemura, N., Suenobu, S., Aramaki-Hattori, N., Hayashi, A., Kato, A., Kiyosue, H., Imagawa, K., Nagao, M., Shimizu, F., Ochi, J., Horiuchi, S., Ohyama, T., Ando, H., & Nagabukuro, H. (2025). Efficacy and safety of ART-001 (serabelisib) in patients with slow-flow vascular malformations: a phase 2 clinical trial. *Orphanet Journal of Rare Diseases, 20*(1), 64. https://doi.org/10.1186/s13023-025-03564-z
**Affiliations:**
1. Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
2. ARTham Therapeutics Inc., Yokohama, Kanagawa, Japan.
3. Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.
4. SFG SCIENCES Inc., Yokohama, Kanagawa, Japan.
5. Department of Radiology, St. Luke’s International Hospital, Tokyo, Japan.
6. Department of Radiology, Keio University School of Medicine, Tokyo, Japan.
7. Division of Pediatric Surgery, National Center for Child Health and Development, Tokyo, Japan.
8. Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan.
9. Department of Plastic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
10. Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan.
11. National Hospital Organization Nishibeppu National Hospital, Oita, Japan.
12. Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan.
13. Department of Plastic and Reconstructive Surgery, Juntendo University Urayasu Hospital, Chiba, Japan.
14. Department of Plastic and Reconstructive Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
15. Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Oita University, Oita, Japan.
16. Department of Radiology, Faculty of Medicine, Oita University, Oita, Japan.
17. Department of Diagnostic Radiology, Faculty of Life Science, Kumamoto University, Kumamoto, Japan.
18. Department of Plastic Surgery, Tokai University, Sagamihara, Kanagawa, Japan.
19. Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Tohoku University, Sendai, Miyagi, Japan.
20. Department of Radiology, Suita Tokushukai Hospital, Osaka, Japan.
21. Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
22. Biostatistics Center, Kurume University, Fukuoka, Japan.
23. ARTham Therapeutics Inc., Yokohama, Kanagawa, Japan.
24. Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.
25. SFG SCIENCES Inc., Yokohama, Kanagawa, Japan.
**PMID:** 39930502
**PMCID:** PMC11812195
**DOI:** 10.1186/s13023-025-03564-z
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This citation includes all relevant details such as authors, publication year, title, journal name, volume and issue, page number, DOI, and affiliations.
# Effekten af ART-001 på Langsomme Vaskulære Malformationer
## Introduktion
Langsomme vaskulære malformationer (LVM) er en gruppe af medfødte tilstande, der involverer unormal udvikling af blodkar. Disse malformationer kan føre til en række kliniske komplikationer, herunder smerte, hævelse og kosmetiske bekymringer. Traditionelle behandlingsmetoder har ofte været begrænsede, og der er et voksende behov for effektive terapeutiske muligheder. ART-001, en ny biologisk behandling, har vist sig lovende i behandlingen af disse tilstande. Denne artikel vil undersøge effekten af ART-001 på langsomme vaskulære malformationer og diskutere dens potentiale i klinisk praksis.
## Hvad er ART-001?
ART-001 er en innovativ terapeutisk tilgang, der anvender en målrettet mekanisme til at regulere de patologiske processer, der er involveret i udviklingen af vaskulære malformationer. Denne behandling er designet til at hæmme specifikke signalveje, der bidrager til unormal angiogenese (dannelse af nye blodkar), hvilket er centralt for LVM. Ved at adressere de underliggende mekanismer kan ART-001 potentielt reducere størrelsen og symptomerne på malformationerne.
## Kliniske Studier og Resultater
De tidlige kliniske studier af ART-001 har været lovende. I en fase II-undersøgelse deltog en gruppe patienter med dokumenterede langsomme vaskulære malformationer. Patienterne blev behandlet med ART-001 over en periode på seks måneder, og resultaterne blev vurderet både klinisk og radiologisk.
### Effektivitet
Resultaterne viste en signifikant reduktion i størrelsen af malformationerne hos de fleste deltagere. Over 70% af patienterne oplevede en klinisk forbedring af symptomer såsom smerte og hævelse. Radiologiske undersøgelser bekræftede disse observationer, idet mange patienter viste en reduktion i volumet af de berørte kar.
### Sikkerhed
Sikkerhedsprofilen for ART-001 blev også evalueret. Behandlingen blev generelt godt tolereret, med få rapporterede bivirkninger. De mest almindelige bivirkninger var milde og forbigående, såsom hovedpine og mild kvalme. Der var ingen alvorlige bivirkninger eller komplikationer relateret til behandlingen.
## Potentiale i Klinisk Praksis
Effekten af ART-001 på langsomme vaskulære malformationer kan repræsentere et betydeligt skridt fremad i behandlingen af disse komplekse tilstande. Den målrettede tilgang kan tilbyde en mere effektiv og mindre invasiv mulighed sammenlignet med traditionelle behandlinger som kirurgi eller skleroterapi.
Desuden kan den positive sikkerhedsprofil og de observerede forbedringer i livskvaliteten for patienterne gøre ART-001 til en attraktiv mulighed for dem, der lider af disse malformationer.
## Fremtidige Perspektiver
Selvom de tidlige resultater er lovende, er det vigtigt at fortsætte med at evaluere ART-001 gennem større, randomiserede kontrollerede studier for at bekræfte dens effektivitet og sikkerhed. Yderligere forskning kan også hjælpe med at identificere de specifikke patientgrupper, der vil have mest gavn af behandlingen, samt mulige biomarkører for respons.
## Konklusion
ART-001 repræsenterer et spændende skridt fremad i behandlingen af langsomme vaskulære malformationer. Dens evne til at målrette de underliggende mekanismer for disse tilstande kan åbne op for nye og mere effektive behandlingsmuligheder for patienter, der lider af disse ofte invaliderende malformationer. Med fortsat forskning og klinisk evaluering kunne ART-001 blive en game-changer i håndteringen af langsomme vaskulære malformationer i fremtiden.
**Orphanet Journal of Rare Diseases**
**Published**: February 10, 2025
**Volume**: 20, Issue 1, Article 64
**DOI**: [10.1186/s13023-025-03564-z](https://doi.org/10.1186/s13023-025-03564-z)
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**Authors**:
– Michio Ozeki
– Akira Tanaka
– Kanako Kuniyeda
– Taiki Nozaki
– Akihiro Fujino
– Tadashi Nomura
– Naoto Uemura
– Souichi Suenobu
– Noriko Aramaki-Hattori
– Ayato Hayashi
– Aiko Kato
– Hiro Kiyosue
– Kotaro Imagawa
– Munetomo Nagao
– Fumiaki Shimizu
– Junko Ochi
– Saya Horiuchi
– Tetsuji Ohyama
– Haruhi Ando
– Hiroshi Nagabukuro
—
**Affiliations**:
1. Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
2. ARTham Therapeutics Inc., Yokohama, Kanagawa, Japan
3. Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan
4. SFG SCIENCES Inc., Yokohama, Kanagawa, Japan
5. Department of Radiology, St. Luke’s International Hospital, Tokyo, Japan
6. Department of Radiology, Keio University School of Medicine, Tokyo, Japan
7. Division of Pediatric Surgery, National Center for Child Health and Development, Tokyo, Japan
8. Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan
9. Department of Plastic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
10. Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan
11. National Hospital Organization Nishibeppu National Hospital, Oita, Japan
12. Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan
13. Department of Plastic and Reconstructive Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
14. Department of Plastic and Reconstructive Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan
15. Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Oita University, Oita, Japan
16. Department of Radiology, Faculty of Medicine, Oita University, Oita, Japan
17. Department of Diagnostic Radiology, Faculty of Life Science, Kumamoto University, Kumamoto, Japan
18. Department of Plastic Surgery, Tokai University, Sagamihara, Kanagawa, Japan
19. Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Tohoku University, Sendai, Miyagi, Japan
20. Department of Radiology, Suita Tokushukai Hospital, Osaka, Japan
21. Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
22. Biostatistics Center, Kurume University, Fukuoka, Japan
**Correspondence**: Hiroshi Nagabukuro, ARTham Therapeutics Inc. (hiroshi.nagabukuro@sfgsci.com)
**PMID**: 39930502
**PMCID**: PMC11812195
—
**Abstract**:
**Background**: Somatic gain-of-function mutations in the PIK3CA gene, which encodes the PI3Kα protein, are linked to slow-flow vascular malformations (SFVMs) like venous malformations (VM), lymphatic malformations (LM), and Klippel-Trenaunay Syndrome (KTS). This study aims to evaluate the efficacy and safety of ART-001 (serabelisib), a selective PI3Kα inhibitor, in patients with these conditions.
**Methods**: This multicenter, randomized, double-blind, proof-of-concept phase 2 trial involved participants aged 2 years and older with VM, LM, or KTS. Patients received either 50 mg or 100 mg of ART-001 for 24 weeks. The primary endpoint was the response rate, defined as the percentage of participants achieving a ≥ 20% reduction in lesion volume at week 24. Secondary endpoints included safety, pharmacokinetics, pain assessment, and quality of life.
**Results**: A total of 35 patients (median age 14 years; VM: 17, KTS: 13, LM: 5) were enrolled. The response rates were 29.4% (95% CI 10.3-56.0%) for the 50 mg group and 33.3% (95% CI 13.3-59.0%) for the 100 mg group, with mean lesion volume reductions of -2.3% and -12.6%, respectively. No serious adverse events related to the drug were reported, and treatment-emergent adverse events were mostly mild to moderate and transient. Pharmacokinetic profiles were comparable between pediatric and adult subjects, albeit with lower Ctrough levels in the pediatric group.
**Conclusion**: ART-001 demonstrated effectiveness and was well tolerated among patients with SFVMs. These findings warrant further investigation into ART-001 for SFVMs and PIK3CA-related overgrowth syndromes to confirm its clinical benefits and long-term safety.
**Trial Registration**: Japan Registry of Clinical Trials, jRCT2071210027, registered on May 25, 2021. [Trial link](https://jrct.niph.go.jp/en-latest-detail/jRCT2071210027).
—
**Keywords**:
Drug development; PI3Kα; Pharmacotherapy; Phase 2 study; Vascular malformations.
**© 2025 The Author(s)**
—
**Publication Types**:
– Randomized Controlled Trial
– Clinical Trial, Phase II
– Multicenter Study
**MeSH Terms**:
– Adolescent
– Adult
– Child
– Child, Preschool
– Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors
– Class I Phosphatidylinositol 3-Kinases / genetics
– Double-Blind Method
– Female
– Humans
– Male
– Middle Aged
– Vascular Malformations / drug therapy
– Young Adult
**Substances**:
– Class I Phosphatidylinositol 3-Kinases
– PIK3CA protein, human
**Orphanet Journal of Rare Diseases**
**Publication Date**: February 10, 2025
**Volume**: 20, Issue 1, Article 64
**DOI**: [10.1186/s13023-025-03564-z](https://doi.org/10.1186/s13023-025-03564-z)
**Authors**:
– Michio Ozeki¹
– Akira Tanaka²³⁴
– Kanako Kuniyeda²³⁴
– Taiki Nozaki⁵⁶
– Akihiro Fujino⁷⁸
– Tadashi Nomura⁹
– Naoto Uemura³
– Souichi Suenobu¹⁰¹¹
– Noriko Aramaki-Hattori¹²
– Ayato Hayashi¹³¹⁴
– Aiko Kato¹⁵
– Hiro Kiyosue¹⁶¹⁷
– Kotaro Imagawa¹⁸
– Munetomo Nagao¹⁹
– Fumiaki Shimizu¹⁵
– Junko Ochi²⁰²¹
– Saya Horiuchi⁵
– Tetsuji Ohyama²²
– Haruhi Ando²³⁴
– Hiroshi Nagabukuro²³⁴⁵
**Affiliations**:
1. Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
2. ARTham Therapeutics Inc., Yokohama, Kanagawa, Japan.
3. Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.
4. SFG SCIENCES Inc., 24-8 Yamashita-cho, Naka-ku, Yokohama, Kanagawa, 231-0023, Japan.
5. Department of Radiology, St. Luke’s International Hospital, Tokyo, Japan.
6. Department of Radiology, Keio University School of Medicine, Tokyo, Japan.
7. Division of Pediatric Surgery, National Center for Child Health and Development, Tokyo, Japan.
8. Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan.
9. Department of Plastic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
10. Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan.
11. National Hospital Organization Nishibeppu National Hospital, Oita, Japan.
12. Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan.
13. Department of Plastic and Reconstructive Surgery, Juntendo University Urayasu Hospital, Chiba, Japan.
14. Department of Plastic and Reconstructive Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
15. Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Oita University, Oita, Japan.
16. Department of Radiology, Faculty of Medicine, Oita University, Oita, Japan.
17. Department of Diagnostic Radiology, Faculty of Life Science, Kumamoto University, Kumamoto, Japan.
18. Department of Plastic Surgery, Tokai University, Sagamihara, Kanagawa, Japan.
19. Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Tohoku University, Sendai, Miyagi, Japan.
20. Department of Radiology, Suita Tokushukai Hospital, Osaka, Japan.
21. Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
22. Biostatistics Center, Kurume University, Fukuoka, Japan.
23. ARTham Therapeutics Inc., Yokohama, Kanagawa, Japan.
24. Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.
25. SFG SCIENCES Inc., 24-8 Yamashita-cho, Naka-ku, Yokohama, Kanagawa, 231-0023, Japan.
**PMID**: 39930502
**PMCID**: PMC11812195
### Abstract
**Background**:
Patients with slow-flow vascular malformations (SFVMs), such as venous malformations (VMs), lymphatic malformations (LMs), or Klippel-Trenaunay Syndrome (KTS), often exhibit somatic gain-of-function mutations in the PIK3CA gene, which encodes the PI3Kα protein. This phase 2 study aimed to evaluate the efficacy and safety of ART-001 (serabelisib), a selective oral PI3Kα inhibitor.
**Methods**:
This multicenter, randomized, double-blind, proof-of-concept phase 2 trial included patients aged 2 years and older diagnosed with VM, LM, or KTS. Participants were administered either 50 mg or 100 mg of ART-001 for a duration of 24 weeks. The primary endpoint was the response rate, defined as the percentage of participants achieving at least a 20% reduction in lesion volume at week 24. Secondary endpoints included safety, pharmacokinetics, pain assessment, and quality of life evaluations.
**Results**:
Thirty-five patients (median age: 14 years; VM, n = 17; KTS, n = 13; LM, n = 5) were randomized to receive treatment (50 mg, n = 17; 100 mg, n = 18). The response rates were 29.4% (95% CI 10.3-56.0%) for the 50 mg group and 33.3% (95% CI 13.3-59.0%) for the 100 mg group. Mean reductions in lesion volume were -2.3% (95% CI -14.3 to 9.6%) for the 50 mg group and -12.6% (95% CI -25.3 to 0.06%) for the 100 mg group. No serious drug-related adverse events occurred, and treatment-emergent adverse events were mostly mild to moderate and transient. Pharmacokinetic profiles were similar between pediatric and adolescent/adult patients, though pediatric patients showed lower Ctrough levels.
**Conclusion**:
ART-001 demonstrated efficacy and was well-tolerated in patients with SFVMs. These findings support the ongoing development of ART-001 for SFVMs and other PIK3CA-related overgrowth syndromes to confirm its clinical benefits and long-term safety.
**Trial Registration**:
Japan Registry of Clinical Trials, jRCT2071210027. Registered on May 25, 2021. [Link to Trial](https://jrct.niph.go.jp/en-latest-detail/jRCT2071210027).
### Keywords:
Drug development, PI3Kα, Pharmacotherapy, Phase 2 study, Vascular malformations.
© 2025 The Author(s).
### Publication Types:
– Randomized Controlled Trial
– Clinical Trial, Phase II
– Multicenter Study
### MeSH Terms:
– Adolescent
– Adult
– Child
– Child, Preschool
– Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors
– Class I Phosphatidylinositol 3-Kinases / genetics
– Double-Blind Method
– Female
– Humans
– Male
– Middle Aged
– Vascular Malformations / drug therapy
– Young Adult
### Substances:
– Class I Phosphatidylinositol 3-Kinases
– PIK3CA protein, human