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📚 Part of the TILA-278 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.
This is a mock / simulation document, made for a portfolio and for learning. The drug (GLPI-103), the sponsor, the people, and the data are all fictional. It is not a real regulatory submission and has no clinical, legal, or regulatory standing. What is real is the shape of the thing — the document structure, the standards it follows, and the analysis methods; the content inside is illustrative.
What it is. Region-specific administrative document for the TILA-278 marketing application.
Why it exists. Region-specific administrative content the agency requires in front of the scientific dossier.
How it is produced here. This is a region-specific administrative document, assembled to the local filing and labeling conventions. Its operational and label content is written to stay consistent with the (simulated) clinical data.
Format & governing standard. US FDA (USPI)
| Field | Value |
|---|---|
| Document ID | M1-USPI |
| Version | 1.0 |
| Compound | TILA-278 (anti-TL1A antagonist / IL-22R agonist bispecific) |
| Standard | US FDA (USPI) |
| Confidentiality | Confidential |
Region-specific administrative document for the TILA-278 marketing application.
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-07-08 | Regulatory Affairs | Initial issue |
Application type: Original Biologics License Application (BLA), submitted under Section 351(a) of the Public Health Service Act (PHS Act) and 21 CFR 601.2 Proposed product: TILA-278 (proposed proprietary name TILVARA; proposed nonproprietary name tilazumig) injection, for subcutaneous use Applicant/Sponsor: Virtual Biopharma Inc. Cross-reference IND: IND 1XXXXX BLA number: BLA 761XXX Proposed indication: Induction of clinical remission in adults with moderately to severely active ulcerative colitis (UC) eCTD sequence: 0000 (original submission)
This Module 1 is region-specific to the United States and is organized in accordance with the FDA Comprehensive Table of Contents Headings and Hierarchy for eCTD Module 1 and the guidance Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications. The scientific evidence supporting the proposed indication is provided in Modules 2–5; the pivotal evidence of effectiveness is Study TILA278-201 (Protocol TILA278-201), a Phase 2b randomized, double-blind, placebo-controlled 12-week induction study.
| eCTD node | Form | Content | Status |
|---|---|---|---|
| 1.1 | FDA Form 356h | Application to Market a New or Abbreviated New Drug or Biologic for Human Use — executed by the responsible official of Virtual Biopharma Inc. | Signed |
| 1.1 | FDA Form 3674 | Certification of Compliance with ClinicalTrials.gov (NCT) requirements (42 USC 282(j)) | Signed |
| 1.1 | FDA Form 3397 | User Fee Cover Sheet (PDUFA program fee for an original BLA requiring clinical data) | Attached |
Form 356h identifies the establishment(s) responsible for drug substance and drug product manufacture, testing, packaging, and labeling; the corresponding facility information is provided in Module 3.2.A.1 and cross-referenced in Section 1.3.1 below.
The cover letter (eCTD 1.2) transmits the original BLA and states the following:
1.3.1 Applicant / Contact / Agent
| Item | Detail |
|---|---|
| Applicant (BLA holder) | Virtual Biopharma Inc. |
| Authorized U.S. agent / Regulatory contact | [Name], VP Regulatory Affairs, Virtual Biopharma Inc. |
| Establishment registration | Drug substance and drug product facilities registered under 21 CFR Part 207; FEI numbers provided in Module 3.2.A.1 |
1.3.3 Debarment Certification (Section 306(k)(1) of the FD&C Act) — The applicant certifies that it did not and will not use in any capacity the services of any person debarred under Section 306.
1.3.4 Financial Certification and Disclosure (21 CFR Part 54) — FDA Form 3454 (certification) is provided for clinical investigators in Study TILA278-201; no disclosable financial interests requiring Form 3455 were identified.
1.3.5 Patent Information / 1.3.7 Exclusivity Claim — As a biological product licensed under 351(a) of the PHS Act, TILA-278 is not subject to Orange Book patent listing. Reference-product exclusivity under Section 351(k)(7) of the PHS Act (12 years from the date of first licensure) is anticipated upon approval.
No letters of authorization to a Drug Master File are relied upon for the drug substance. Any excipient or container-closure DMF authorizations are listed in Module 3.2 and cross-referenced here.
| Milestone | Reference | Date |
|---|---|---|
| IND opened (allowed to proceed) | IND 1XXXXX | |
| Fast Track designation granted | ||
| End-of-Phase-2 (Type B) meeting | See 1.6 | |
| Pivotal induction study TILA278-201 completed | CSR in Module 5.3.5.1 | |
| Original BLA submitted (this sequence) | BLA 761XXX |
The substantial evidence of effectiveness for the proposed induction indication derives from Study TILA278-201. A maintenance study, TILA278-301, is ongoing; the applicant will submit maintenance efficacy and long-term safety as a supplement and, as applicable, under postmarketing commitments/requirements agreed with the Agency.
The End-of-Phase-2 (Type B) meeting minutes (eCTD 1.6.3) record Agency agreement on: the primary endpoint (clinical remission by modified Mayo score at Week 12); the acceptability of the modified Mayo definition of remission; the safety database size adequate to characterize the induction safety profile; and the content of the proposed label, including the framing of the indication as induction of clinical remission. Points requiring further data (durability of response and maintenance dosing) are addressed by the ongoing maintenance program.
An Initial Pediatric Study Plan (iPSP) was submitted under Section 505B of the FD&C Act as applied to biologics. UC in the pediatric population (ages 5 to <18 years) is a serious disease relevant to this product; the applicant proposes a deferral of pediatric studies until adult effectiveness and safety are established, with a proposed pediatric development plan and, where justified, a partial waiver for children <5 years (in whom moderately-to-severely active UC is rare).
Not applicable to this original submission beyond items referenced above.
DRAFT LABELING. The following draft Prescribing Information is submitted for Agency review. Bracketed items denote information to be finalized in the approved labeling — including the final commercial presentation, the initial approval and revision dates, NDC and U.S. license numbers, and the quality and clinical-pharmacology parameters confirmed in Modules 3 and 5. Section numbering follows 21 CFR 201.56(d)(1) (Physician Labeling Rule). Sections omitted from the full prescribing information (e.g., 9 and 15) are reserved in accordance with 21 CFR 201.56(d)(2) because none of their content applies.
These highlights do not include all the information needed to use TILA-278 safely and effectively. See full prescribing information for TILA-278.TILA-278 (tilazumig) injection, for subcutaneous useInitial U.S. Approval:
INDICATIONS AND USAGE (1) TILA-278 is a tumor necrosis factor–like ligand 1A (TL1A) antagonist and interleukin-22 (IL-22) receptor agonist bispecific antibody indicated for the induction of clinical remission in adult patients with moderately to severely active ulcerative colitis (UC). (1)
DOSAGE AND ADMINISTRATION (2)
DOSAGE FORMS AND STRENGTHS (3) Injection: 450 mg/3 mL (150 mg/mL) solution in a single-dose prefilled syringe or single-dose prefilled autoinjector. (3)
CONTRAINDICATIONS (4) Known serious hypersensitivity to tilazumig or to any excipient. (4)
WARNINGS AND PRECAUTIONS (5)
ADVERSE REACTIONS (6) Most common adverse reactions (≥3% and greater than placebo) were nasopharyngitis, injection-site reactions, headache, upper respiratory tract infection, arthralgia, and nausea. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Virtual Biopharma Inc. at 1-8XX-XXX-XXXX or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS (8)
See 17 for PATIENT COUNSELING INFORMATION.Revised:
*Sections or subsections omitted from the full prescribing information are not listed.
TILA-278 is indicated for the induction of clinical remission in adult patients with moderately to severely active ulcerative colitis (UC).
2.1 Testing and Assessments Prior to Initiation
Prior to initiating TILA-278:
2.2 Recommended Dosage
The recommended induction dosage of TILA-278 is 450 mg administered by subcutaneous injection at Weeks 0, 2, 4, and 8.
Evaluate clinical response at Week 12. Discontinue TILA-278 in patients who do not show evidence of therapeutic benefit by Week 12 [see Clinical Studies (14)]. Continued treatment beyond the induction period should be guided by maintenance data when available.
2.3 Preparation and Administration
TILA-278 is intended for use under the guidance and supervision of a healthcare provider. After proper training in subcutaneous injection technique, a patient may self-inject or a caregiver may administer TILA-278 if a healthcare provider determines it is appropriate.
2.4 Missed Dose
If a dose is missed, administer the dose as soon as possible; thereafter, resume dosing at the regularly scheduled interval.
Injection: 450 mg/3 mL (150 mg/mL) as a clear to slightly opalescent, colorless to pale yellow solution supplied in:
TILA-278 is contraindicated in patients with a history of serious hypersensitivity reaction to tilazumig or to any of the excipients [see Warnings and Precautions (5.2), Description (11)].
5.1 Infections
TILA-278 may increase the risk of infections through modulation of TL1A-dependent TH1/TH17 immune responses [see Clinical Pharmacology (12.1)]. In the pivotal induction study, the most frequently reported infections included nasopharyngitis and upper respiratory tract infection, generally at rates similar to placebo [see Adverse Reactions (6.1)].
5.2 Hypersensitivity Reactions and Immunogenicity
Hypersensitivity reactions may occur. As with all therapeutic proteins, TILA-278 is immunogenic; anti-drug antibodies were detected in treated patients [see Adverse Reactions (6.2)]. If a serious hypersensitivity reaction occurs, discontinue TILA-278 immediately and institute appropriate therapy.
5.3 Injection-Site Reactions
Injection-site reactions were the most frequent drug-attributable adverse reaction and occurred more frequently in patients receiving TILA-278 than placebo [see Adverse Reactions (6.1)]. Reactions (including injection-site erythema, pain, pruritus, and swelling) were generally mild to moderate in severity, self-limited, and did not typically require discontinuation. Rotating injection sites may reduce the likelihood of reactions [see Dosage and Administration (2.3)].
5.4 Immunizations
Prior to initiating TILA-278, complete all age-appropriate immunizations according to current immunization guidelines. Avoid the use of live vaccines during treatment with TILA-278. No data are available on the secondary transmission of infection by live vaccines in patients receiving TILA-278.
5.5 Malignancy
The impact of long-term treatment with an immunomodulatory antibody on the risk of malignancy is not known. Because the IL-22 receptor–agonist activity of TILA-278 promotes intestinal epithelial proliferation, and because immunomodulation may alter tumor immune surveillance, a theoretical potential to influence malignancy risk cannot be excluded [see Clinical Pharmacology (12.1)]. Malignancies were not identified as a safety signal in the 12-week induction study; the study duration and size do not permit assessment of long-term malignancy risk [see Adverse Reactions (6.1)].
The following clinically significant adverse reactions are described elsewhere in the labeling:
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of TILA-278 was evaluated in Study TILA278-201, a 12-week, randomized, double-blind, placebo-controlled induction study in adults with moderately to severely active UC. A total of 900 patients were randomized 1:1:1 to TILA-278 High (450 mg; n=299), TILA-278 Low (150 mg; n=300), or placebo (n=301). The safety analysis set comprised all patients who received at least one dose of study drug [see Clinical Studies (14)].
Table 1. Overview of Adverse Events During the 12-Week Induction Period (Safety Analysis Set)
| Event category | TILA-278 High (N=299) | TILA-278 Low (N=300) | Placebo (N=301) |
|---|---|---|---|
| ≥1 treatment-emergent adverse event (TEAE), n | 109 | 131 | 130 |
| Serious adverse events (SAE), n | 3 | 0 | 4 |
| Deaths, n | 2 | 0 | 1 |
| Discontinuations due to adverse events, n | 17 | 17 | 29 |
All deaths were assessed by the investigator as unrelated to study drug. Discontinuations in the placebo group were driven predominantly by lack of efficacy (worsening UC) rather than by drug toxicity. No dose-dependent safety signal was identified across the TILA-278 High and Low groups.
Adverse reactions reported in ≥3% of patients in either TILA-278 group during the 12-week induction period are presented in Table 2.
Table 2. Adverse Reactions Reported in ≥3% of Patients in Either TILA-278 Group (Study TILA278-201, Safety Analysis Set)
| Adverse reaction | TILA-278 High (N=299) | TILA-278 Low (N=300) | Placebo (N=301) |
|---|---|---|---|
| Nasopharyngitis | 7.4% | 6.7% | 6.0% |
| Injection-site reaction* | 8.4% | 7.0% | 2.3% |
| Headache | 5.4% | 5.0% | 4.7% |
| Upper respiratory tract infection | 4.3% | 4.7% | 3.7% |
| Arthralgia | 3.7% | 3.3% | 3.0% |
| Nausea | 3.0% | 2.7% | 2.3% |
| Anaemia | 3.0% | 3.3% | 4.3% |
*Injection-site reaction is a grouped term including injection-site erythema, pain, pruritus, and swelling, and was the principal drug-attributable finding [see Warnings and Precautions (5.3)].
Worsening of ulcerative colitis was reported more frequently in the placebo group than in either TILA-278 group and is attributable to the underlying disease; it is not tabulated above as a drug-related adverse reaction.
6.2 Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to tilazumig with the incidence of antibodies to other products may be misleading.
Immunogenicity was assessed using a validated tiered assay format (screening, confirmatory, and titer, with a separate neutralizing-antibody assay) [see Clinical Pharmacology (12.3)]. In Study TILA278-201, treatment-emergent anti-drug antibodies were detected in 7.9% of TILA-278–treated patients over the 12-week induction period, of whom 26.6% had neutralizing antibodies. No clinically meaningful impact of ADA on the pharmacokinetics, clinical remission rate, or overall safety of TILA-278 was observed over the induction period; ADA positivity showed a modest association with injection-site reactions.
No formal drug-interaction studies have been conducted with TILA-278. As a monoclonal antibody, TILA-278 is not eliminated by cytochrome P450 (CYP) enzymes and is not expected to have direct effects on CYP enzymes or transporters. During chronic inflammation, elevated levels of certain cytokines can suppress CYP enzyme activity; the effect of TILA-278–mediated modulation of inflammation on CYP substrate exposure has not been established. Monitor patients receiving concomitant CYP substrates with a narrow therapeutic index for effect or drug concentration as clinically indicated.
Avoid concurrent use of live vaccines [see Warnings and Precautions (5.4)].
8.1 Pregnancy
Risk Summary. Available data on TILA-278 use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Human immunoglobulin G (IgG) antibodies are known to cross the placenta; therefore, TILA-278 may be transmitted from the mother to the developing fetus, with transfer increasing during the second and third trimesters. Consistent with ICH S6(R1), reproductive and developmental toxicity is characterized in the cynomolgus monkey, the pharmacologically relevant species; available findings were consistent with the pharmacologic activity of the antibody and did not identify a specific developmental hazard at clinically relevant exposures [see Nonclinical Toxicology (13.1)].
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.
8.2 Lactation
Risk Summary. There are no data on the presence of tilazumig in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TILA-278 and any potential adverse effects on the breastfed infant from TILA-278 or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
No human data are available on the effect of TILA-278 on fertility. Dedicated fertility studies were not conducted; repeat-dose toxicology in cynomolgus monkeys included assessment of reproductive organs and did not identify effects of concern, consistent with ICH S6(R1) for this class.
8.4 Pediatric Use
The safety and effectiveness of TILA-278 in pediatric patients have not been established.
8.5 Geriatric Use
Clinical studies of TILA-278 did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease.
8.6 Renal and Hepatic Impairment
No dedicated studies were conducted in patients with renal or hepatic impairment. As a monoclonal antibody eliminated principally by catabolism and target-mediated pathways rather than by renal or hepatic clearance, no dosage adjustment is anticipated on the basis of renal or hepatic impairment [see Clinical Pharmacology (12.3)].
There is no clinical experience with overdosage of TILA-278. In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment.
Tilravimab-xxxx is a recombinant, humanized immunoglobulin G1 (IgG1) bispecific monoclonal antibody produced in a Chinese hamster ovary (CHO) cell line by recombinant DNA technology. One antigen-binding arm functions as an antagonist of TL1A (TNFSF15); the second arm functions as an agonist at the interleukin-22 receptor (IL-22R). The antibody has an approximate molecular weight of 150 kDa.
TILA-278 injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution for subcutaneous administration. Each single-dose prefilled syringe/autoinjector delivers 450 mg of tilazumig in 3 mL (150 mg/mL). Each mL contains tilazumig (450 mg) and the following excipients: a buffering system, a stabilizer, and polysorbate, at pH . The finished drug product is manufactured to comply with compendial and product-specific specifications for identity, content, purity/impurities (including aggregates, charge variants, and glycosylation profile), and potency (dual bioassays confirming anti-TL1A neutralization and IL-22R agonist activity), as detailed in Module 3.2.P.5.
12.1 Mechanism of Action
TILA-278 is a bispecific antibody that simultaneously engages two complementary pathways relevant to UC. Antagonism of TL1A (TNFSF15) blocks TL1A–DR3 (death receptor 3) signaling, dampening TH1/TH17-driven mucosal inflammation and pro-fibrotic signaling in the intestine. Agonism at the IL-22 receptor on intestinal epithelial cells promotes epithelial regeneration, antimicrobial peptide production, and mucosal-barrier repair. The combined effect is anti-inflammatory activity coupled with promotion of mucosal healing. The precise contribution of each mechanism to clinical efficacy in UC has not been fully characterized.
12.2 Pharmacodynamics
Consistent with its mechanism, treatment with TILA-278 was associated with reductions in markers of intestinal inflammation (including fecal calprotectin and C-reactive protein) and with endoscopic and histologic improvement over the induction period. The exposure–response relationship for clinical remission was dose-ordered across the placebo, Low, and High groups [see Clinical Studies (14)].
Cardiac electrophysiology. A dedicated QT study was not conducted. Consistent with ICH E14/S7B and ICH S6(R1), thorough QT assessment is not warranted for a monoclonal antibody with no expected direct ion-channel activity; the waiver rationale is supported by the nonclinical safety pharmacology package.
12.3 Pharmacokinetics
The pharmacokinetics of TILA-278 are characterized by target-mediated drug disposition (TMDD), resulting in nonlinear (dose-dependent) clearance at lower concentrations and approximately linear disposition at concentrations that saturate target binding.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Consistent with ICH S6(R1), no genotoxicity or carcinogenicity studies were conducted with TILA-278; such studies are generally not warranted for monoclonal antibodies. The general toxicology program comprised repeat-dose subcutaneous studies in the cynomolgus monkey (a pharmacologically relevant species), a tissue cross-reactivity assessment using human and cynomolgus tissues, and safety pharmacology endpoints incorporated into the repeat-dose studies. Because the human targets are not pharmacologically engaged in conventional rodents, pharmacology was characterized in disease models using a surrogate/knock-in approach. Findings in the cynomolgus monkey were limited to expected pharmacologic effects and injection-site changes, with no unexpected target-organ toxicity. Fertility was not evaluated in dedicated studies; reproductive organ histopathology in repeat-dose studies revealed no findings of concern.
The efficacy of TILA-278 for the induction of clinical remission in moderately to severely active UC was established in Study TILA278-201 (Protocol TILA278-201), a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, 12-week induction study.
Design and population. Of 1,700 patients screened, 900 adults with moderately to severely active UC were randomized 1:1:1 to TILA-278 High (450 mg; n=299), TILA-278 Low (150 mg; n=300), or placebo (n=301) administered subcutaneously. Randomization was stratified by baseline modified Mayo severity and by prior biologic exposure. Study visits occurred at Weeks 0, 2, 4, 8, and 12.
Primary endpoint. Clinical remission at Week 12, defined as a modified Mayo score ≤2 with no individual subscore >1.
Efficacy results (full analysis set). The primary endpoint was met, with a statistically significant and dose-ordered benefit for both TILA-278 doses over placebo.
Table 3. Clinical Remission at Week 12 (Full Analysis Set)
| Endpoint | TILA-278 High | TILA-278 Low | Placebo |
|---|---|---|---|
| Clinical remission at Week 12, n/N (%) | 106/284 (37.3%) | 46/283 (16.2%) | 2/273 (0.7%) |
The difference in remission rates versus placebo was clinically meaningful for both doses, with the High dose achieving the greatest response.
Table 4. Change From Baseline in Modified Mayo Score at Week 12 (Full Analysis Set; ANCOVA)
| Statistic | TILA-278 High | TILA-278 Low | Placebo |
|---|---|---|---|
| LS-mean change from baseline | −3.36 | −2.76 | −1.00 |
| LS-mean difference vs placebo (95% CI) | −2.36 (−2.49, −2.23) | −1.77 (−1.90, −1.64) | — |
| p-value vs placebo | <0.0001 | <0.0001 | — |
Both TILA-278 doses produced statistically significant reductions in the modified Mayo score compared with placebo (p<0.0001), with a dose-ordered effect supporting the recommended induction dosage [see Dosage and Administration (2.2)].
How Supplied. TILA-278 injection is a clear to slightly opalescent, colorless to pale yellow solution supplied as:
| Presentation | Strength | NDC |
|---|---|---|
| Single-dose prefilled syringe (carton of 1) | 450 mg/3 mL (150 mg/mL) | NDC |
| Single-dose prefilled autoinjector (carton of 1) | 450 mg/3 mL (150 mg/mL) | NDC |
Storage and Handling.
Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Manufactured for and distributed by: Virtual Biopharma Inc. U.S. License No.
End of draft Prescribing Information (eCTD 1.14.1.3). The annotated draft labeling at eCTD 1.14.1.2 cross-references each clinical statement in this document to its supporting data in Modules 2.5, 2.7, and 5, and each nonclinical and quality statement to Modules 2.4, 2.6, and 3.