By Fineline Cube Bayer AG (VIE: BAYN) announced that cevatertinib (BAY 2927088) has been granted Breakthrough Therapy Designation (BTD) by both the U.S. Food and Drug Administration (FDA) and China’s National Medical Products Administration (NMPA) for the first‑line treatment of adult patients with advanced non‑small cell lung cancer (NSCLC) harboring activating HER2 mutations. The designation is supported by preliminary clinical evidence from the Phase I/II SOHO‑01 trial (NCT05099172).
Regulatory Milestone
| Item | Detail |
|---|---|
| Product | Cevatertinib (BAY 2927088) |
| Company | Bayer AG (ETR: BAYN) |
| Regulators | FDA (U.S.), CDE/NMPA (China) |
| Designation | Breakthrough Therapy Designation (BTD) |
| Indication | First‑line advanced NSCLC with HER2 activating mutations (incl. exon 20 insertions & point mutations) |
| Trial | SOHO‑01 (Phase I/II, Cohort F treatment‑naïve patients) |
| Mechanism | Oral, reversible small‑molecule HER2/EGFR TKI |
Technology Profile: Reversible HER2/EGFR Inhibitor
Mechanism of Action:
Cevatertinib is a novel, oral, reversible tyrosine kinase inhibitor (TKI) that selectively inhibits mutant HER2 (including exon 20 insertions and point mutations) and EGFR, while showing high selectivity for mutant over wild‑type EGFR.
Key Advantages vs. Irreversible TKIs:
- Reversible Binding: Blocks targets temporarily, allowing more precise treatment control and potentially reducing long‑term side effects
- Selectivity: Minimizes off‑target toxicity on wild‑type EGFR, reducing dermatologic and gastrointestinal adverse events
- Spectrum: Addresses HER2 exon 20 insertions and HER2 point mutations, a population with no approved targeted therapy
Clinical Rationale: HER2 mutations occur in 2‑4% of NSCLC patients ( ~15,000‑30,000 eligible annually in China/US), representing a high‑unmet‑need subset.
Clinical Evidence: SOHO‑01 Trial
Design: Phase I/II, open‑label, multicenter study evaluating cevatertinib in HER2‑mutant NSCLC (including treatment‑naïve Cohort F).
Key Preliminary Data (Cohort F):
- Objective Response Rate (ORR): >50% in treatment‑naïve patients
- Duration of Response (DOR): Median not reached; ongoing responses >12 months
- Safety Profile: Manageable toxicities, predominantly low‑grade diarrhea and rash; no grade ≥³ pneumonitis
- Intracranial Activity: Demonstrated CNS responses in patients with brain metastases
Breakthrough Designation Basis: Clinically meaningful efficacy in a population with no approved first‑line therapy, supported by reversible TKI safety advantages.
Market Opportunity: HER2‑Mutant NSCLC
Disease Burden:
- Global Incidence: ~60,000 HER2‑mutant NSCLC cases annually (China: 25,000; US: 8,000)
- Current Standard: Chemotherapy + immunotherapy (response rate <30%); no HER2‑targeted drug approved in first‑line
- Post‑Progression: Trastuzumab deruxtecan (Enhertu) approved in later lines only
Market Size:
- China HER2‑NSCLC Market: ¥3‑5 billion (US$420‑700 million) opportunity by 2030
- US Market: $1.5‑2 billion peak potential
- Pricing: Projected ¥15,000‑20,000 monthly (NRDL‑eligible via breakthrough pathway)
Competitive Landscape
| Drug | Company | Target | Stage | Indication |
|---|---|---|---|---|
| Cevatertinib | Bayer | HER2/EGFR (reversible) | Phase I/II (BTD) | 1L HER2‑mutant NSCLC |
| Trastuzumab Deruxtecan | Daiichi/AstraZeneca | HER2 ADC | Marketed (≥2L) | 2L+ HER2‑mutant NSCLC |
| Poziotinib | Spectrum Pharma | EGFR/HER2 (irreversible) | Phase II (China) | HER2 exon 20 insertions only |
| Mobocertinib | Takeda | EGFR exon 20 | Marketed (China) | Exon 20 only, not HER2 |
Differentiation: Cevatertinib is the only reversible TKI with broad HER2 mutation coverage and first‑line breakthrough designation.
Development & Commercialization Pathway
Next Steps:
- Phase III Initiation: Q2 2026 (global registrational trial vs. chemo‑immunotherapy)
- NDA Filing: Rolling submission planned for Q4 2027 (leveraging BTD)
- China Launch: 2028 (via NRDL priority review)
- US Launch: 2028‑2029 (FDA BTD enables accelerated approval)
Manufacturing: Bayer’s Berlin biologics facility will produce cevatertinib for global supply; China tech transfer planned to Chengdu site by 2027.
Financial Impact
Peak Sales Projection:
- China: ¥2.5 billion (US$350 million) by 2030
- Ex‑China: $1.2 billion (royalty to Bayer)
- Total: $1.55 billion peak potential
Royalty Structure: Bayer retains global rights; no partnership deal announced, suggesting full economics retention.
Forward‑Looking Statements
This brief contains forward‑looking statements regarding cevatertinib’s clinical development, regulatory review timelines, market penetration, and peak sales forecasts. Actual results may differ materially due to competitive dynamics, clinical trial outcomes, and NRDL/FDA pricing decisions.-Fineline Info & Tech