Clinical information for referring physicians
Mechanism, comparative pharmacology, raw observational data, the monitoring protocol and how referral works. Written for oncologists, internists and general practitioners considering the programme for a patient.
Healthcare professionals
The following content contains raw patient data and comparative pharmacological information not written for a lay audience.
Summary
NGA-8000 is a recombinant mammalian arginase fused to an albumin-binding domain, administered weekly to deplete plasma arginine below 10 µmol/L in patients whose tumours lack ASS1 or OTC. It is unlicensed and available only as physician-led individual treatment. The principle has Phase III support (pegargiminase, ATOMIC-Meso); NGA-8000 has been administered to more than 100 patients; structured, uncontrolled observations with laboratory follow-up exist for five. Treatment sites: partner clinics in Georgia, the United Arab Emirates and Hong Kong. Intended use: ASS1- or OTC-deficient solid tumours and selected leukaemias, as monotherapy where standard options are exhausted or as a sensitiser alongside low-dose chemotherapy, checkpoint inhibition, targeted therapy or radiotherapy.
Comparative pharmacology
| ADI-PEG 20 (pegargiminase) | AEB1102 (pegzilarginase) | NGA-8000 | |
|---|---|---|---|
| Origin | recombinant bacterial protein (Mycoplasma) | recombinant human arginase 1, PEGylated | recombinant mammalian arginase, albumin-binding domain |
| Reaction | arginine → citrulline | arginine → ornithine | arginine → ornithine |
| Sensitive tumours | ASS1-negative | ASS1- or OTC-negative | ASS1- or OTC-negative |
| Immunogenicity | high; anti-drug antibodies after ~8 weeks, loss of effect | low | low (our laboratory data, not independently verified) |
| Half-life | short | short to intermediate | extended by albumin binding; weekly dosing (our laboratory data) |
| Clinical status | Phase III (ATOMIC-Meso, positive); BLA submitted 2023 | EU approval in ARG1 deficiency 2023; oncology Phase I/II | preclinical; individual cases; no approval |
| Combinations studied | cisplatin, pemetrexed, docetaxel, temozolomide, azacitidine, venetoclax | chemotherapy, anti-PD-1 | cisplatin, gemcitabine, trastuzumab, anti-PD-1/PD-L1, radiotherapy (planned) |
NGA-8000+ (asparaginase/glutaminase variant with albumin-binding domain) exists for ALL and lymphoblastic lymphoma and is not covered on this site.
Signalling and cell death
Arginine depletion inactivates Rheb and thereby mTORC1, with downstream inhibition of S6K, dephosphorylation of 4E-BP1, reduced translation initiation and ribosome biogenesis. AMPK is activated and autophagy induced. Under prolonged arginine starvation, prostate (CWR22Rv1) and gastric (MKN-45) carcinoma cell lines showed depolarisation of mitochondrial membrane potential, ROS increase in cytosolic and mitochondrial fractions, nuclear DNA leakage and chromatin autophagy with consecutive cell death (prostate: 0 to 120 h; gastric: rising Annexin V positivity 24 to 72 h).
Resistance: re-expression of ASS1, among others via c-Myc-mediated promoter demethylation, typically after weeks to months. Combinations with chemotherapy or checkpoint inhibition target the window before resistance forms. Rising plasma arginine under continued dosing indicates anti-drug antibodies rather than tumour resistance and is the first parameter to check.
Raw observational data
Uncontrolled observations from our programme, not evidence of efficacy. Partly concurrent with standard therapy; effects cannot be attributed.
TNBC, stage IV, female, 50
Chemotherapy at a university hospital, concurrent NGA-8000, 7 doses on 31 Mar, 9 Apr, 16 Apr, 25 Apr, 7 May, 21 May, 6 Jun 2025. No adverse events reported.
CLL, stage A, male, 48
No hospital intervention. NGA-8000, 5 doses on 10, 17, 24, 31 May and 6 Jun 2025. No adverse events reported.
Further cases, 2024
Lung cancer stage IV with bone metastases; colorectal cancer stage III; breast cancer recurrence stage IV. CEA decline documented over 1 to 4 months.
Monitoring protocol
Referral
Laboratory documentation on NGA-8000 (preclinical data, characterisation, production) is available on request.
References
- Delage B. et al. Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer 2010;126:2762–2772.
- Szlosarek P.W. et al. Pegargiminase plus first-line chemotherapy in patients with nonepithelioid pleural mesothelioma: the ATOMIC-Meso randomized clinical trial. JAMA Oncol 2024;10:475–483.
- Changou C.A. et al. Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy. PNAS 2014;111:14147–14152.
- Cheng P.N.-M. et al. Mono-PEGylated thermostable Bacillus caldovelox arginase mutant (BCA-M-PEG20) induces apoptosis, autophagy, cell cycle arrest and growth inhibition in gastric cancer cells. 2022.
- Zhang Y. et al. Pegylated arginine deiminase drives arginine turnover and systemic autophagy to dictate energy metabolism. Cell Rep Med 2022;3:100498.
- Tsai H.J. et al. A phase II study of arginine deiminase (ADI-PEG 20) in relapsed/refractory or poor-risk acute myeloid leukemia patients. Sci Rep 2017;7:11253.
- Zou S. et al. Arginine metabolism and deprivation in cancer therapy. Biomed Pharmacother 2019;118:109210.
- Dillon B.J. et al. Incidence and distribution of argininosuccinate synthetase deficiency in human cancers. Cancer 2004;100:826–833.
- European Medicines Agency. Loargys (pegzilarginase), EPAR, 2023.