Peringatan Keamanan

Toxicity information regarding nadofaragene firadenovec is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as disseminated adenovirus infection.L44381 Symptomatic and supportive measures are recommended. The carcinogenic, mutagenic and fertility effects of nadofaragene firadenovec have not been evaluated.L44381 Cynomolgus monkeys given 2.5 x 1011 or 1.25 x 1013 viral particles of nadofaragene firadenovec 90 days apart (1 x 1011 or 5x1011 viral particles/mL) experienced inflammation, urothelial hyperplasia, cytoplasmic vacuolation, and focal/multifocal ulceration in the urinary bladder and irritation in the ureter and urethra at necropsy 7 days after the first and second doses. These findings were resolved following the 57-day recovery period after the second administration. At this point, a limited number of monkeys had minimal fibrosis in the lamina propria of the bladder.L44381

Nadofaragene firadenovec

DB17381

biotech approved investigational

Deskripsi

Nadofaragene firadenovec (nadofaragene firadenovec-vncg) is a recombinant non-replicating adenovirus serotype 5 vector containing a transgene encoding human interferon alfa-2b (IFN?2b).L44381 It was approved by the FDA on December 2022 for the treatment of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is the first gene therapy approved by the FDA for the treatment of bladder cancer.L44381,L44431

BCG-unresponsive NMIBC has a high recurrence and is notably difficult to treat. Most patients with this condition undergo radical cystectomy since other non-surgical treatments are far less effective. The use of nadofaragene firadenovec provides a therapeutic alternative to patients seeking non-surgical alternatives for the treatment of BCG-unresponsive NMIBC.A255111 Nadofaragene firadenovec is formulated with an excipient (Syn-3) that facilitates gene transfer across the urothelium and promotes the transduction of IFN?2b. The localized expression of this gene induces anti-tumor effects.A255106,L44381 Nadofaragene firadenovec also has a manageable adverse event profile. Compared to pembrolizumab, a smaller proportion of patients experienced grade 3-4 adverse events (4% vs 12.7%).A255111

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) -
Volume Distribusi -
Klirens (Clearance) -

Absorpsi

The biodistribution of nadofaragene firadenovec was evaluated in two clinical studies. One of the patients given a second dose of nadofaragene firadenovec at 3 x 1011 vp/mL (2.25 x 1013 vp) had measurable vector DNA in blood. The rest of the patients did not have measurable vector DNA in blood one hour after nadofaragene firadenovec administration. In a phase 1 study, one out of 4 patients given 3 x 1011 vp/mL (2.25 x 1013 vp) of nadofaragene firadenovec had detectable levels of vector DNA at Day 14. In a phase 2 study, 16 out of 19 patients had detectable levels of vector DNA at Day 12.L44381

Metabolisme

As a gene therapy medicinal product, nadofaragene firadenovec is expected to be metabolized by nucleases throughout the body.

Rute Eliminasi

Nadofaragene firadenovec can be detected in urine. The frequency of detection of urine samples positive for vector-derived DNA and persistence of vector-derived DNA is correlated with the dose level.L44381

Interaksi Obat

0 Data
Tidak ada data.

Referensi & Sumber

Artikel (PubMed)
  • PMID: 33253641
    Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM, Bivalacqua TJ, Montgomery JS, Lerner SP, Busby JE, Poch M, Crispen PL, Steinberg GD, Schuckman AK, Downs TM, Svatek RS, Mashni J Jr, Lane BR, Guzzo TJ, Bratslavsky G, Karsh LI, Woods ME, Brown G, Canter D, Luchey A, Lotan Y, Krupski T, Inman BA, Williams MB, Cookson MS, Keegan KA, Andriole GL Jr, Sankin AI, Boyd A, O'Donnell MA, Sawutz D, Philipson R, Coll R, Narayan VM, Treasure FP, Yla-Herttuala S, Parker NR, Dinney CPN: Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021 Jan;22(1):107-117. doi: 10.1016/S1470-2045(20)30540-4. Epub 2020 Nov 27.
  • PMID: 33253640
    Kulkarni GS: Nadofaragene firadenovec: a new gold standard for BCG-unresponsive bladder cancer? Lancet Oncol. 2021 Jan;22(1):8-9. doi: 10.1016/S1470-2045(20)30586-6. Epub 2020 Nov 27.
  • PMID: 35847448
    Mokkapati S, Narayan VM, Manyam GC, Lim AH, Duplisea JJ, Kokorovic A, Miest TS, Mitra AP, Plote D, Anand SS, Metcalfe MJ, Dunner K Jr, Johnson BA, Czerniak BA, Nieminen T, Heikura T, Yla-Herttuala S, Parker NR, Schluns KS, McConkey DJ, Dinney CP: Lentiviral interferon: A novel method for gene therapy in bladder cancer. Mol Ther Oncolytics. 2022 Jun 10;26:141-157. doi: 10.1016/j.omto.2022.06.005. eCollection 2022 Sep 15.
  • PMID: 35158964
    Deininger S, Torzsok P, Mitterberger M, Pallauf M, Oswald D, Deininger C, Lusuardi L: From Interferon to Checkpoint Inhibition Therapy-A Systematic Review of New Immune-Modulating Agents in Bacillus Calmette-Guerin (BCG) Refractory Non-Muscle-Invasive Bladder Cancer (NMIBC). Cancers (Basel). 2022 Jan 29;14(3):694. doi: 10.3390/cancers14030694.

Contoh Produk & Brand

Produk: 1 • International brands: 1
Produk
  • Adstiladrin
    Suspension • 300000000000 {VP}/1mL • Intravesical • US • Approved
International Brands
  • Adstiladrin — Ferring Pharmaceuticals

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