📚 Part of the OBX-319 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.

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Module 1 (KR) — Administrative & Label (OBX-319)

Document ID: M1-KR
Version: 1.0
Change History: 1.0 — Initial issue.
Standard(s): MFDS

Korea (MFDS) Administrative & Label — OBX-319

This module provides the Korea (MFDS) regional administrative content and the Korean product information (허가사항 / 첨부문서) for OBX-319, drafted to the MFDS labelling format and kept in strict consistency with the pivotal clinical data set out in Module 5 and the integrated summaries in Module 2.

OBX-319 is a humanized IgG1 bispecific monoclonal antibody that simultaneously engages CD19 and CD20 on the B-cell surface, producing broad, near-complete peripheral B-cell depletion across the pre-B through memory-B and plasmablast compartments implicated in Systemic Lupus Erythematosus (SLE). The dual-target design is intended to deplete cells that escape single-target agents (for example, CD20-negative plasmablasts and early CD19-positive precursors). The active substance is expressed in a Chinese hamster ovary (CHO) cell line and is formulated as a sterile solution for subcutaneous (SC) injection. The applicant/sponsor of record is Virtual Biopharma Inc.

The regional dossier follows the ICH-harmonised CTD structure. The molecule is a biotechnology-derived therapeutic protein; accordingly, the quality, nonclinical and clinical packages are developed under the applicable ICH guidance — ICH Q5A(R2) (viral safety), ICH Q5C (biological product stability), ICH Q6B (specifications for biotechnological products) and ICH S6(R1) (preclinical safety of biotechnology-derived pharmaceuticals) — and the manufacture is conducted under KGMP with reliance, where appropriate, on the global marketing dossier submitted as a Biologics License Application under 21 CFR 601. The Korean product information, container-closure labelling, and administrative particulars in this module are derived from, and reconciled against, that common technical dossier.

Product particulars. Active ingredient: OBX-319 (anti-CD19 × anti-CD20 humanized IgG1 bispecific antibody). Dosage form: solution for subcutaneous injection. The finished product is stored refrigerated at 2–8 °C, protected from light, and must not be frozen or shaken; it is administered without dilution using the presented device/vial. Full composition (active substance, buffer, stabiliser, surfactant and excipient functions) is stated in the Korean labelling consistent with Module 3.

Indications

OBX-319 is indicated for Systemic Lupus Erythematosus (moderate-to-severe active).

The indication targets adults with moderate-to-severe active SLE who are receiving background standard-of-care therapy and who have residual disease activity, typically with serological activity (elevated anti-dsDNA and/or low complement) and clinically meaningful organ-domain involvement. The wording, target population, and positioning relative to background therapy are aligned with the enrolled population of the pivotal study OBX319-301 (baseline SLEDAI-2K approximately 11), in which OBX-319 was added to, rather than replacing, standard-of-care immunosuppressive and/or antimalarial and corticosteroid regimens. The indication statement is to be finalised in the Korean labelling in line with the confirmed efficacy population and MFDS review.

Clinical efficacy (OBX319-301)

Efficacy was established in OBX319-301, a Phase 3, randomized, double-blind, placebo-controlled study that enrolled adults with moderate-to-severe active SLE on background standard-of-care. A total of 480 subjects were randomized 1:1:1 to OBX-319 High dose (162), OBX-319 Low dose (158) or placebo (160) and treated for 52 weeks. Baseline disease activity was well matched across arms (mean SLEDAI-2K approximately 11), consistent with a moderate-to-severe active population. The primary efficacy endpoint was the proportion of subjects achieving an SLE Responder Index-4 (SRI-4) / low disease activity (SLEDAI-2K ≤ 4) response at Week 52; the principal continuous secondary endpoint was the least-squares (LS) mean change from baseline in SLEDAI-2K at Week 52.

The LS-mean change analysis was performed on the randomized population, and the binary responder analysis on the pre-specified primary efficacy (responder) population; the differing analysis-population sizes are reflected in the two tables below. All numbers are as reported in the statistical analysis of OBX319-301.

Arm	N	LS-mean Δ SLEDAI-2K @ Wk 52 (points)	Diff vs placebo (95% CI)	p
OBX-319 High	162	-6.37	-2.91 (-3.12, -2.69)	0.0000
OBX-319 Low	158	-5.62	-2.17 (-2.38, -1.95)	0.0000
Placebo	160	-3.46	— (reference)	—

Responder analysis — Low disease activity (SLEDAI-2K <= 4)

Arm	N	Responders, n/N	Rate	Risk diff vs placebo (95% CI, %)	p
OBX-319 High	145	76/145	52.4%	46.4% (37.4, 55.4)	0.0000
OBX-319 Low	145	49/145	33.8%	27.8% (19.2, 36.4)	0.0000
Placebo	150	9/150	6.0%	— (reference)	—

Both OBX-319 dose regimens met the primary endpoint with statistical separation from placebo. At Week 52 the low-disease-activity (SLEDAI-2K ≤ 4) response rate was 52.4% (76/145) on the High dose and 33.8% (49/145) on the Low dose, versus 6.0% (9/150) on placebo, corresponding to placebo-adjusted risk differences of 46.4% and 27.8%, respectively. The continuous endpoint was concordant: the LS-mean reduction in SLEDAI-2K was -6.37 (High) and -5.62 (Low) versus -3.46 on placebo, giving placebo-adjusted differences of -2.91 and -2.17. A dose-ordered effect (High > Low > placebo) was observed on both the responder and continuous endpoints, supporting an internally consistent exposure–response relationship.

Pharmacodynamics and mechanistic support. The clinical effect was accompanied by the expected on-target pharmacodynamics. Both active arms produced near-complete depletion of circulating CD19+ B cells (approximately 210 → 7 cells/µL), whereas B-cell counts were essentially unchanged on placebo. Depletion was mirrored by falling anti-dsDNA autoantibody titres and by normalisation of complement C3/C4 in responders, providing serological corroboration of the B-cell-directed mechanism and reinforcing the plausibility and durability of the clinical benefit. These pharmacodynamic changes are consistent with the dual anti-CD19/anti-CD20 mechanism and the target-mediated disposition of the antibody, and they are used to support dose selection and the benefit interpretation in the Korean labelling.

Dosage and administration

OBX-319 is administered by subcutaneous injection. Two dose regimens (a higher and a lower regimen, corresponding to the High and Low arms of OBX319-301) were characterised for efficacy, pharmacodynamics and safety; the recommended regimen and dosing interval stated in the Korean labelling correspond to the confirmed benefit–risk of the pivotal study. Treatment is initiated and supervised by a physician experienced in the management of SLE and in the use of B-cell-depleting biologics. Because injection/administration reactions are anticipated for this modality, initial doses are given under conditions where reactions can be managed, and appropriate observation and supportive measures are available. Prior to initiation, patients should complete age-appropriate immunisations, and screening for chronic/latent infection (including hepatitis B) should be performed as described under Warnings and Precautions.

Contraindications

OBX-319 is contraindicated in patients with known severe hypersensitivity to OBX-319 or to any excipient of the product, and in patients with active, clinically significant infection until the infection is controlled. Live or live-attenuated vaccines are not to be co-administered during periods of B-cell depletion.

Warnings and precautions

• Serious and opportunistic infections. Profound B-cell depletion is associated with an increased risk of serious and opportunistic infections. Patients should be evaluated for active and latent infection before initiation, monitored during therapy, and treated promptly for infection; dosing should be withheld during serious infection.
• Hepatitis B virus reactivation. As with other B-cell-depleting therapies, screen for HBV (HBsAg and anti-HBc) before initiation and manage carriers per specialist guidance because of the risk of reactivation.
• Hypogammaglobulinaemia. Prolonged B-cell depletion can lead to reduced serum immunoglobulins. Immunoglobulin levels should be assessed at baseline and periodically, particularly in patients with recurrent or severe infections; immunoglobulin replacement may be considered.
• Injection/administration and hypersensitivity reactions. Injection-site and systemic administration reactions may occur; observe patients appropriately and manage reactions with standard supportive care.
• Immunogenicity. Anti-drug antibodies (ADA) may develop and can, in principle, affect exposure, pharmacodynamics, efficacy, or hypersensitivity risk. Immunogenicity is monitored in the clinical programme and characterised in the Korean labelling.
• Immunisation. Administer all required vaccinations before starting therapy where feasible; avoid live/live-attenuated vaccines during B-cell depletion. The immune response to vaccines may be blunted during depletion.
• Progressive multifocal leukoencephalopathy (class consideration). Remain alert to new neurological signs or symptoms consistent with PML, a recognised class consideration for B-cell-depleting agents.

Adverse reactions

The safety profile in OBX319-301 was consistent with the pharmacological class and the subcutaneous route. The most relevant reactions expected and monitored are infections (including serious/opportunistic infections), injection-site and administration reactions, hypersensitivity, and laboratory findings of reduced immunoglobulins/hypogammaglobulinaemia associated with sustained B-cell depletion. Category frequencies and preferred-term tabulations from the pooled safety population are presented in the Korean labelling in the standard MFDS format, consistent with Module 2.7.4.

Use in specific populations

• Pregnancy. OBX-319 is a humanized IgG1 antibody; IgG is actively transported across the placenta, particularly in the second and third trimesters, and may cause transient B-cell depletion in the fetus/neonate. Use during pregnancy only if the potential benefit justifies the potential risk; avoid administration of live vaccines to infants with in-utero exposure until B-cell recovery is confirmed.
• Lactation. It is not known whether OBX-319 is excreted in human milk; a decision to breastfeed or treat should weigh the benefit of breastfeeding and the clinical need for therapy.
• Paediatric use. Safety and efficacy in paediatric patients have not been established.
• Geriatric use / renal and hepatic impairment. As a monoclonal antibody cleared by target-mediated disposition and catabolic pathways rather than renal or hepatic metabolism, no specific dose adjustment is anticipated for renal or hepatic impairment; use in elderly patients follows the general precautions for infection risk.

Nonclinical and clinical pharmacology (regulatory basis)

The nonclinical programme was designed under ICH S6(R1) for a biotechnology-derived antibody. The cynomolgus monkey was the sole pharmacologically relevant toxicology species, as the human CD19/CD20 target epitopes are not cross-reactive in rodents; toxicology, safety pharmacology and toxicokinetic assessments were therefore conducted in the non-human primate. Pharmacokinetics are nonlinear and target-mediated (TMDD), reflecting binding to and clearance via CD19/CD20-bearing B cells, with dose-dependent disposition consistent with the observed depletion pharmacodynamics. Immunogenicity (ADA) was assessed as a standard element of the antibody programme. Consistent with ICH S6(R1) and the general expectations for monoclonal antibodies, genotoxicity, carcinogenicity, and dedicated cardiac safety-pharmacology studies (hERG assay and thorough-QT study) were not conducted, as such studies are not warranted for a large-molecule antibody that does not distribute intracellularly or interact with cardiac ion channels. The regulatory basis and study-waiver rationale are documented in Module 2.4/2.6.

Quality and manufacturing (administrative summary)

The active substance is a humanized IgG1 anti-CD19 × anti-CD20 bispecific antibody produced by CHO cell culture and purified by a platform downstream process comprising Protein A affinity capture followed by polishing chromatography, with orthogonal viral clearance steps. Viral safety is established per ICH Q5A(R2); the stability programme follows ICH Q5C; and the specification (identity, quantity, potency by target-binding/B-cell-depletion bioassay, and control of product-related variants and impurities including aggregates and charge variants) follows ICH Q6B. Manufacture, testing and release comply with KGMP, and the container-closure system and finished-product controls support the labelled 2–8 °C storage conditions.

Pharmacovigilance and risk management

The Korea Risk Management Plan aligns with the global RMP. Important identified risks are serious and opportunistic infections and hypogammaglobulinaemia associated with B-cell depletion. Important potential risks include immunogenicity/ADA with potential effects on efficacy or hypersensitivity, and malignancy as a class consideration. Missing information includes use in pregnancy and lactation and long-term safety. Routine pharmacovigilance is complemented by risk-minimisation measures reflected in the Korean labelling (screening for infection and HBV before initiation, immunoglobulin monitoring, vaccination guidance, and management of administration reactions).

Administrative particulars

Applicant: Virtual Biopharma Inc. Product type: biotechnology-derived (recombinant) therapeutic monoclonal antibody for subcutaneous administration. The Korean application is supported by the common technical dossier underlying the global Biologics License Application filed under 21 CFR 601, and by the ICH-aligned quality, nonclinical and clinical modules (ICH Q5A(R2), Q5C, Q6B and S6(R1)). This Module 1 administrative and label content is maintained in synchrony with the source dossier; any change to the indication, dosing, warnings, or product particulars will be reflected here and versioned in the Change History above.