Peringatan Keamanan

Toxicity information regarding betibeglogene autotemcel is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as delayed platelet engraftment, neutrophil engraftment failure and insertional oncogenesis.^L42940 Symptomatic and supportive measures are recommended. No carcinogenicity studies have been performed with betibeglogene autotemcel, and its effects on fertility have not been evaluated. In a mouse model of ?-thalassemia, the intravenous administration of betibeglogene autotemcel did not show evidence of toxicity, genotoxicity, or oncogenesis.^L42940

Betibeglogene autotemcel

DB16900

biotech approved investigational

Deskripsi

Betibeglogene autotemcel is an autologous gene therapy that adds functional copies of the ?-globin gene (?^A-T87Q-globin) to hematopoietic stem cells in order to treat ?-thalassemia.^L42940 ?-thalassemia is a condition caused by mutations in the ?-globin gene (HBB) that leads to a significant decrease in the production of ?-globin. This affects hemoglobin levels, and in patients with severe forms of this disease, long-term red cell transfusions are required for survival and the prevention of serious complications.^A251770 Allogeneic hematopoietic-cell transplantation would be a therapeutic option in patients with ?-thalassemia; however, this process is reserved for young children with an HLA-identical sibling donor due to the risks of graft rejection, graft-versus-host disease, and other treatment-related toxic effects.^A251770

Patients treated with betibeglogene autotemcel are given an infusion of their own hematopoietic stem cells, previously enriched for CD34+ and transduced ex vivo with BB305 LVV, a self-inactivating lentiviral vector (LVV).^L42940 BB305 LVV encodes ?^A-T87Q-globin, compensating for the lack of ?-globin in these patients. The use of betibeglogene autotemcel is more effective in patients with ?-thalassemia with residual ?-globin synthesis (non-?⁰/?⁰ genotype) compared to those with no detectable ?-globin production (?⁰/?⁰).A251770,A251785 Betibeglogene autotemcel was approved by the FDA in August 2022 and is the first ex-vivo lentiviral vector gene therapy available in the U.S. for the treatment of people with ?-thalassemia.^L42960

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) -

Volume Distribusi The nature of betibeglogene autotemcel is such that conventional pharmacokinetic studies on distribution are not applicable.[L42940]

Klirens (Clearance) -

Absorpsi

The nature of betibeglogene autotemcel is such that conventional pharmacokinetic studies on absorption are not applicable.^L42940

Metabolisme

The nature of betibeglogene autotemcel is such that conventional pharmacokinetic studies on metabolism are not applicable.^L42940

Rute Eliminasi

The nature of betibeglogene autotemcel is such that conventional pharmacokinetic studies on elimination are not applicable.^L42940

Interaksi Obat

6 Data

Hydroxyurea	The therapeutic efficacy of Betibeglogene autotemcel can be decreased when used in combination with Hydroxyurea.
Elvitegravir	The therapeutic efficacy of Betibeglogene autotemcel can be decreased when used in combination with Elvitegravir.
Fostemsavir	The therapeutic efficacy of Betibeglogene autotemcel can be decreased when used in combination with Fostemsavir.
Ibalizumab	The therapeutic efficacy of Betibeglogene autotemcel can be decreased when used in combination with Ibalizumab.
Chromium picolinate	The risk or severity of adverse effects can be increased when Chromium picolinate is combined with Betibeglogene autotemcel.
Cefiderocol	The risk or severity of adverse effects can be increased when Cefiderocol is combined with Betibeglogene autotemcel.

Target Protein

Alpha globin

Referensi & Sumber

Synthesis reference: Bonner, M., et al. (2019). Vcn enhancer compositions and methods of using the same (U.S. Patent No. US 2019/0284533 A1). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/e2/ab/ac/4afae7ad9e148f/US20190284533A1.pdf

Artikel (PubMed)

PMID: 29669226
Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S, Magrin E, Schiller GJ, Payen E, Semeraro M, Moshous D, Lefrere F, Puy H, Bourget P, Magnani A, Caccavelli L, Diana JS, Suarez F, Monpoux F, Brousse V, Poirot C, Brouzes C, Meritet JF, Pondarre C, Beuzard Y, Chretien S, Lefebvre T, Teachey DT, Anurathapan U, Ho PJ, von Kalle C, Kletzel M, Vichinsky E, Soni S, Veres G, Negre O, Ross RW, Davidson D, Petrusich A, Sandler L, Asmal M, Hermine O, De Montalembert M, Hacein-Bey-Abina S, Blanche S, Leboulch P, Cavazzana M: Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia. N Engl J Med. 2018 Apr 19;378(16):1479-1493. doi: 10.1056/NEJMoa1705342.
PMID: 29807062
Sii-Felice K, Giorgi M, Leboulch P, Payen E: Hemoglobin disorders: lentiviral gene therapy in the starting blocks to enter clinical practice. Exp Hematol. 2018 Aug;64:12-32. doi: 10.1016/j.exphem.2018.05.004. Epub 2018 May 26.
PMID: 34891223
Locatelli F, Thompson AA, Kwiatkowski JL, Porter JB, Thrasher AJ, Hongeng S, Sauer MG, Thuret I, Lal A, Algeri M, Schneiderman J, Olson TS, Carpenter B, Amrolia PJ, Anurathapan U, Schambach A, Chabannon C, Schmidt M, Labik I, Elliot H, Guo R, Asmal M, Colvin RA, Walters MC: Betibeglogene Autotemcel Gene Therapy for Non-beta(0)/beta(0) Genotype beta-Thalassemia. N Engl J Med. 2022 Feb 3;386(5):415-427. doi: 10.1056/NEJMoa2113206. Epub 2021 Dec 11.
PMID: 33940155
Nualkaew T, Sii-Felice K, Giorgi M, McColl B, Gouzil J, Glaser A, Voon HPJ, Tee HY, Grigoriadis G, Svasti S, Fucharoen S, Hongeng S, Leboulch P, Payen E, Vadolas J: Coordinated beta-globin expression and alpha2-globin reduction in a multiplex lentiviral gene therapy vector for beta-thalassemia. Mol Ther. 2021 Sep 1;29(9):2841-2853. doi: 10.1016/j.ymthe.2021.04.037. Epub 2021 May 1.

Link

Contoh Produk & Brand

Produk: 2 • International brands: 1

Produk

Zynteglo

- • 10600000 cells/mL • Intravenous • EU
Zynteglo

Suspension • 20000000 1/1 • Intravenous • US • Approved

International Brands

Zynteglo — bluebird bio, Inc.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.