Thoughts on $TVTX tomorrow?

# Clinical Context and Trial Data FSGS is a rare kidney disease with **zero FDA-approved pharmacological treatments**. The current standard of care is limited to off-label immunosuppressants, dialysis, or transplant. # The DUPLEX Phase 3 Trial Results The FDA’s decision rests on the DUPLEX study, which yielded mixed results: * **Primary Endpoint (Failed):** The drug failed to show a statistically significant difference in **eGFR slope** (a measure of long-term kidney function) over 108 weeks. * **Secondary Endpoint (Success):** The drug achieved a significant reduction in **proteinuria** (protein in urine), which is a key biomarker for kidney stress. # Bull Case 1. **The PARASOL Consensus:** The FDA co-authored the PARASOL scientific paper, which identifies proteinuria reduction as a valid surrogate endpoint for FSGS. Bulls argue this provides the regulatory framework to approve Filspari despite the failed eGFR endpoint. 2. **Accelerated Approval Framework:** Under Subpart H, the FDA can approve drugs for serious conditions with no current treatments if they are "reasonably likely to predict clinical benefit." The lack of alternatives for FSGS patients may lower the bar for approval. 3. **Established Safety Profile:** Filspari has an existing safety record through its IgAN indication. Recently, the FDA relaxed the Risk Evaluation and Mitigation Strategy (REMS) requirements, signaling high confidence in the drug’s safety. 4. **Absence of Advisory Committee (AdCom):** The FDA waived the AdCom meeting. Proponents suggest this indicates a straightforward approval, as the agency may not feel the need for external validation on a well-understood molecule. # Bear Case 1. **Partial vs. Complete Remission:** While the PARASOL consensus supports proteinuria, it specifically emphasizes **Complete Remission**. Travere’s data largely relies on **Partial Remission** (FPRE). Critics argue the FDA may deem partial reduction insufficient for a formal label expansion. 2. **Prior Regulatory Guidance:** In a December 2023 Type C meeting, the FDA explicitly stated that the DUPLEX results, as presented then, were **not sufficient** for a supplemental NDA. Without new data, a reversal is statistically unlikely. 3. **Failure of Functional Endpoints:** The FDA traditionally prioritizes functional outcomes (eGFR) over biomarkers. Approving a drug that failed its primary functional endpoint could set a difficult regulatory precedent. 4. **AdCom Waiver Ambiguity:** A waived AdCom is not always bullish; it can also signal a "straightforward rejection" if the agency believes the clinical failure is too significant to warrant discussion. I am bullish and avg price of $35. Sorry if i made any mistakes, first time posting, mods lmk if this needs to be moved or something. ily all GL