Module 2.7.3 — Summary of Clinical Efficacy
| Field | Value |
|---|---|
| Document ID | M273 |
| Version | 2.0 (full) |
| Compound | GLPI-103 (GLP-1/APJ dual agonist) |
| Standard | ICH M4E(R2) §2.7.3 |
| Confidentiality | Confidential |
Synthesizes efficacy across the program (Phase 2 GLPI103-201; pivotal Phase 3 GLPI103-301). Pivotal figures trace to
outputs/and are reconciled (reconcile_csr.py, 23/23). See ISE-301.
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-29 | Clinical | Initial |
| 2.0 | 2026-06-29 | Clinical / Biostat | Full — all primary & secondary endpoints, subgroups, dose–response |
1. Background & Studies Contributing
| Study | Phase | N | Design | Role |
|---|---|---|---|---|
| GLPI103-201 | 2 | 240 | dose-finding | dose–response/PoC [MOCK] |
| GLPI103-301 | 3 | 900 | DB, double-dummy, active-controlled | confirmatory |
2. Study Populations & Analysis Sets
Pivotal FAS N=900 (IV 300, Oral 301, Semaglutide 299); Korean adults with T2DM inadequately controlled on metformin; balanced baseline (mean age ~59–60; HbA1c 7.9–8.0%; BMI ~28–29; FPG ~12.2–12.5 mmol/L; disease duration ~10.6–12.2 yr) (CSR-301 §11.2).
3. Primary Endpoint — HbA1c CFB at Week 52 (ANCOVA, FAS)
| Arm | LS-mean CFB (%) | 95% CI |
|---|---|---|
| GLPI-103 IV | −2.57 | −2.67, −2.47 |
| GLPI-103 Oral | −2.23 | −2.33, −2.13 |
| Semaglutide Oral | −1.89 | −1.99, −1.79 |
Superiority vs semaglutide: IV −0.68% (95% CI −0.81, −0.55; p<0.001); Oral −0.34% (95% CI −0.49, −0.23; p<0.001). The fixed-sequence hierarchy was satisfied (all 8 steps rejected; SAP-301 §7.3; outputs/stats/multiplicity_results.csv).
4. Longitudinal Effect (MMRM)
Progressive reduction with maintained between-arm separation through Week 52 (LS means IV −2.66, Oral −2.33, Semaglutide −1.97); onset evident by Week 4 (CSR-301 §11.4; Figure 2). The MMRM (mmrm package, unstructured covariance, Kenward-Roger DF) accommodates the 9.3% discontinuation under MAR.
5. Key Secondary & Other Endpoints (Week 52)
| Endpoint | IV | Oral | Sema |
|---|---|---|---|
| Body-weight CFB (kg) | −14.5 | −10.3 | −7.6 |
| ≥10% weight loss, % | 100.0 | 83.0 | 44.2 |
| HbA1c <7.0%, % (completers) | 94.1 | 94.6 | 86.2 |
| FPG CFB (mmol/L) | −4.7 | −4.3 | −3.5 |
| SBP CFB (mmHg) | ~0 | −0.8 | ~0 |
GLPI-103 produced substantially greater weight reduction and higher responder rates than semaglutide. NT-proBNP/hsCRP were pre-specified but [MOCK — not in dataset].
6. Subgroups & Consistency
Treatment benefit was consistent across baseline HbA1c (<8.5/≥8.5), BMI (<30/≥30), age (<65/≥65), and sex (CSR-301 §11.6; Figure 3), and directionally consistent with the Phase 2 dose–response.
7. Conclusions on Efficacy
GLPI-103 (IV and Oral) is superior to oral semaglutide on glycaemic control and weight, with high responder rates and consistent subgroup effects — supporting the dual GLP-1/APJ mechanism and the primary efficacy claim (TPP-001).