By Fineline Cube Eli Lilly and Company (NYSE: LLY) announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to sofetabart mipitecan (LY4170156), a folate receptor alpha (FRα) antibody‑drug conjugate (ADC), for platinum‑resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients previously treated with bevacizumab and mirvetuximab soravtansine.
Regulatory Milestone
| Item | Detail |
|---|---|
| Company | Eli Lilly and Company (NYSE: LLY) |
| Drug | Sofetabart mipitecan (LY4170156) |
| Designation | Breakthrough Therapy Designation (BTD) |
| Agency | U.S. FDA |
| Indication | Platinum‑resistant ovarian/fallopian tube/primary peritoneal cancer (post‑bevacizumab + mirvetuximab) |
| Mechanism | FRα ADC with proprietary linker + exatecan payload |
| Basis | Phase 1 responses at all dose levels and FRα expression levels, including post‑mirvetuximab progression |
| Safety Profile | Low ILD, peripheral neuropathy, alopecia; no ocular toxicity |
| Next Steps | Phase 3 FRAmework‑01 study (NCT07213804) – monotherapy in PROC, combo with bevacizumab in PSOC |
Drug Profile & Differentiation
- Mechanism: FRα‑targeting ADC delivering exatecan payload, a topoisomerase I inhibitor with high potency
- Proprietary Linker: Designed for stable circulation and controlled tumor release, minimizing off‑target toxicity
- Key Advantage: Demonstrates activity across all FRα expression levels, including low‑expressors, and post‑mirvetuximab patients, suggesting non‑cross‑resistance
- Safety: Favorable tolerability with low rates of ILD (<2%), peripheral neuropathy (<5%), alopecia (<3%), and no ocular toxicity – a key differentiator vs. mirvetuximab
Clinical Evidence & Development Path
| Study | Design | Key Findings |
|---|---|---|
| Phase 1 | Dose‑escalation/expansion | Responses at all dose levels; activity in low FRα and post‑mirvetuximab patients |
| Phase 3 (FRAmework‑01) | Monotherapy (PROC) + combo with bevacizumab (PSOC) | Initiated 2026; primary endpoints: PFS, ORR |
| Primary Endpoint | PFS by RECIST 1.1 (PROC), OS (exploratory) | – |
- Phase 3 Launch: NCT07213804 initiated in Q1 2026, targeting enrollment completion by Q4 2027
Market Opportunity & Competitive Landscape
| Parameter | Platinum‑Resistant Ovarian Cancer (PROC) | Global Ovarian Cancer Market |
|---|---|---|
| Annual Incidence (2026E) | 45,000 (US) | 300,000 |
| FRα‑Positive (≥1%) | 35‑40% of cases | – |
| Post‑Mirvetuximab Eligible | 60% of FRα‑positive PROC | – |
| Current Standard | Chemo (liposomal doxorubicin), PARP inhibitors (limited) | – |
| Annual Cost (Est.) | $180,000‑220,000 | – |
| Sofetabart Peak Share (2032E) | 25% | 8% |
| Peak Revenue (2032E) | $180 million (PROC) | $420 million (global ovarian) |
Key Competitors:
- Mirvetuximab soravtansine (Elahere, ImmunoGen/AbbVie) – First‑in‑class FRα ADC, approved for FRα‑high PROC; limited activity post‑progression
- PARP inhibitors (olaparib, niraparib) – Maintenance therapy, not for platinum‑resistant disease
- Chemotherapy – Standard of care, poor outcomes (ORR < 15%)
- Sofetabart – Potential best‑in‑class with broader FRα coverage and superior safety profile
Strategic Positioning
- Manufacturing: Lilly’s Indianapolis biologics facility (capacity 20,000 L) will produce sofetabart; FDA inspection completed 2025
- Commercial Readiness: 800‑person US oncology sales force already detailing Verzenio and Retevmo; cross‑detailing capability for sofetabart upon approval
- Global Expansion: Lilly plans EU MAA filing in 2027 and Japan filing in 2028, leveraging Phase 3 data
- Next‑Generation Pipeline: Success validates exatecan payload platform for other ADC targets (e.g., HER3, B7‑H4)
Forward‑Looking Statements
This brief contains forward‑looking statements regarding Phase 3 trial outcomes, regulatory approvals, and commercial forecasts for sofetabart mipitecan. Actual results may differ due to competitive responses, clinical trial risks, and market access dynamics.-Fineline Info & Tech