By Fineline Cube Changchun High & New Technology Industries (Group) Inc. (SHE: 000661) announced that China’s National Medical Products Administration (NMPA) has approved a clinical study for GenSci145, a mutation‑selective PI3Kα inhibitor, in patients with locally advanced or metastatic solid tumors harboring PIK3CA mutations, addressing the toxicity limitations of earlier‑generation PI3K inhibitors.
Regulatory Milestone
| Item | Detail |
|---|---|
| Company | Changchun High & New Technology Industries (Group) Inc. (SHE: 000661) |
| Drug | GenSci145 (mutation‑selective PI3Kα inhibitor) |
| Application | Clinical Trial Approval (CTA) |
| Agency | NMPA (China) |
| Indication | Locally advanced or metastatic solid tumors with PIK3CA mutations |
| Study Phase | Phase I/II |
| Approval Date | 16 Jan 2026 |
| Key Differentiator | Selective for mutant PI3Kα; avoids wild‑type inhibition‑related toxicities |
Drug Profile & Mechanism of Action
- Target: PI3Kα (phosphatidylinositol 3‑kinase alpha) – key driver of tumor cell growth and anti‑apoptotic signaling in PIK3CA‑mutated cancers
- Selectivity: Specifically inhibits PIK3CA hotspot mutations (e.g., H1047R, E545K) while sparing wild‑type PI3Kα, minimizing off‑target metabolic effects
- Clinical Advantage:
- Avoids hyperglycemia: Unlike non‑selective PI3Kα inhibitors (e.g., alpelisib), GenSci145 does not inhibit wild‑type PI3Kα in normal tissues
- Blood‑brain barrier penetration: Demonstrates good CNS penetration, offering potential for brain metastases
- Improved tolerability: Preclinical data show no traditional side effects (hyperglycemia, rash, diarrhea) associated with first‑gen PI3K inhibitors
Preclinical Evidence
| Parameter | GenSci145 | Earlier‑Gen PI3Kα Inhibitors (e.g., Alpelisib) |
|---|---|---|
| PIK3CA Mutant Selectivity | High (hotspot mutations) | Low (wild‑type + mutant) |
| Wild‑Type PI3Kα Inhibition | Minimal | Significant |
| Hyperglycemia Risk | None observed | High (dose‑limiting) |
| Rash/Diarrhea | Absent | Common (Grade ≥ 3: 20‑30%) |
| BBB Penetration | Good | Poor |
| Anti‑Tumor Activity | Potent in PIK3CA‑mutant models | Moderate, limited by toxicity |
Market Opportunity & Competitive Landscape
| Parameter | China | Global |
|---|---|---|
| PIK3CA‑Mutated Solid Tumors | 280,000 | 1.1 million |
| Breast Cancer (PIK3CA‑mutant) | 95,000 | 420,000 |
| Current Standard | Alpelisib + fulvestrant (limited by hyperglycemia) | |
| GenSci145 Addressable Market | 85,000 | 380,000 |
| Market Value (2030E) | ¥6.5 billion | $4.2 billion |
| Peak Market Share | 12 % | 5 % |
| Peak Revenue (2032E) | ¥780 million | $210 million |
Key Competitors:
- Alpelisib (Piqray, Novartis) – First‑gen PI3Kα inhibitor approved for HR+/HER2‑ breast cancer; limited by metabolic toxicities
- Inavolisib (GDC‑0077, Roche) – Selective PI3Kα inhibitor in Phase III; no BBB penetration data
- LOXO‑783 (Lilly) – PI3Kα H1047R‑selective inhibitor in Phase I/II
- GenSci145 – First NMPA‑approved Chinese mutation‑selective PI3Kα inhibitor with BBB penetration and clean safety profile
Strategic Positioning
- Manufacturing: Changchun High‑Tech’s Changchun biologics facility (capacity 8,000 L) will produce clinical supply; GMP certification for small molecule completed in 2025
- Clinical Development: Phase I/II study initiation planned for Q2 2026, focusing on PIK3CA‑mutant breast cancer and endometrial cancer; US IND filing targeted for H2 2026
- Combination Strategy: Planned studies with endocrine therapy (fulvestrant) and CDK4/6 inhibitors to overcome resistance
- Commercial Reach: Existing oncology sales force (1,200 reps) covering tier‑2/3 hospitals can support launch upon approval
Forward‑Looking Statements
This brief contains forward‑looking statements regarding clinical development timelines, regulatory pathways, and commercial projections for GenSci145. Actual results may differ due to clinical trial outcomes, competitive dynamics, and market access challenges.-Fineline Info & Tech