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.

I am a patient or relative

Summary

Argeon is a recombinant mammalian arginase fused to an albumin-binding domain, administered every 14 days 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); Argeon 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, or the referring physician's own institution where national law permits named-patient use of an unlicensed medicine; ARGEA supplies the enzyme, protocol and monitoring support. 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)	Argeon
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; 14-day dosing (our laboratory data)
Clinical status	Phase III (ATOMIC-Meso, positive); regulatory submission announced 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)

Argeon+ (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 Argeon, 7 doses on 31 Mar, 9 Apr, 16 Apr, 25 Apr, 7 May, 21 May, 6 Jun 2025. No adverse events reported.

CEA (ref. < 5 ng/mL): elevated 21 Feb → within range 14 MayCA 15-3 (ref. < 31.3 U/mL): within range 14 MayDay 37 after first dose; possible effect from 7 May

CLL, stage A, male, 48

No hospital intervention. Argeon, 5 doses on 10, 17, 24, 31 May and 6 Jun 2025. No adverse events reported.

Lymphocytes: 51.1 → 40.0 × 10⁹/L in 27 daysΔ −11.1 × 10⁹/L (−21.72 %)Reference 1.5 to 4.0 × 10⁹/L, not reached

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.

CEA lung: 12 → 10.8 → 3.8 ng/mL (4 months)CEA breast: 10.4 → 8.6 → 3.7 ng/mL (1 month)

Monitoring protocol

Parameter	Baseline	q14d visit	q4w	Wk 8/16/24
Plasma arginine (trough)	✓	✓ (+ day 2–5 after dose 1)		✓
CBC, liver panel, creatinine/eGFR	✓	✓		✓
Ammonia	✓	if indicated
Tumour markers (entity-specific)	✓		✓	✓
Imaging, RECIST 1.1	✓ (≤ 4 wk)			✓
ECOG, vitals, AE review	✓	✓		✓
CTC count (optional)	✓			✓

BaselineHistology with ASS1 and OTC IHC where tissue available; plasma arginine; tumour markers appropriate to entity; CBC, liver panel, creatinine/eGFR, ammonia; imaging (CT/MRI/PET) within 4 weeks; ECOG.

DosingEvery 14 days (q14d): 12 doses over 24 weeks, 4 per 8-week block. Observation after dose, extended at doses 1 to 3.

Plasma arginineDay 2 to 5 after first dose, then at every visit (trough, before dosing). Target < 10 µmol/L. Rising level under dosing → check adherence, then anti-drug antibodies.

Safety labsCBC, liver panel, creatinine at every visit (q14d); ammonia if clinically indicated; blood pressure at every visit.

ResponseTumour markers every 4 weeks; imaging at weeks 8, 16, 24 (RECIST 1.1 where applicable); CTC count optional.

Stopping rulesProgressive disease at any review; grade 3 or higher toxicity attributable to the enzyme; persistent loss of arginine suppression; patient withdrawal.

ExclusionsPregnancy or lactation; urea-cycle disorder; Child-Pugh C; eGFR < 30; uncontrolled infection; ECOG 4.

Referral

1 · ContactUse the enquiry form and state that you are a physician. You receive a clinical summary and a direct line to the treating physicians within five working days.

2 · RecordsThrough a secure channel: reports, histology (slide or block for ASS1/OTC IHC), recent labs, latest imaging, current medication.

3 · ReviewWritten eligibility outcome to you and the patient. Your combination plan, if any, is discussed before disclosure.

4 · During treatmentResults after every block or on request. Standard therapies remain yours to prescribe and bill.

5 · SummaryFull written summary at end of treatment with every value measured.

Laboratory documentation on Argeon (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.