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(1/6) $TVTX THREAD - Why I believe sparsentan will be approved for FSGS indication ahead of Monday’s PDUFA
First of all, I think that the FDA’s decision to extend review of the FSGS application by 3 months can ultimately be viewed as a positive. If it was as obvious CRL like some are claiming, why wouldn’t the FDA have just issued it in January? The review extension & request for additional information suggests a willingness to work with $TVTX towards an ultimate approval. Historically, >85% of applications that have approval decisions get pushed out 3 months, ultimately get approved by the FDA.
We know that in October 2024, the PARASOL working group (which is comprised of academics, the FDA, & clinicians) examined datasets from 25+ studies & >1,600 FSGS patients and determined that eGFR (which was the primary endpoint in the failed Ph3 DUPLEX trial) is not a feasible outcome measure for FSGS trials.
If we look at the context clues since then, multiple developments have occurred that bode positively for $TVTX ‘s FSGS application:
(1) Last year the FDA cancelled the previously assigned Advisory Committee panel that was scheduled ahead of the original decision date.
(2) At the Annual Rare & Genetic Renal Diseases Conference last year, Dr. Aliza Thompson (Director of the Division of Cardiology & Nephrology at FDA) expressed that there is a continued push for the FDA to utilize surrogate endpoints to accelerate drug development in kidney diseases where there is a significant unmet medical need. This is the exact case for FSGS, which has no approved treatment options. The PARASOL workshop concluded with unanimous agreement by the group on the value of proteinuria as an approvable endpoint.
Despite the eGFR improvement primary endpoint failure in Ph3, Filspari DID show benefit across multiple other kidney function measurements, including proteinuria, which was also reported in their previous studies.
All of this suggests there is significant support (from Dr. Thompson on down) for Filspari to get approved for use in FSGS based on the impact the drug showed on proteinuria in the DUET and DUPLEX studies. Again, the fact that they didn’t simply issue a CRL in January also supports this notion and implies a strong willingness to work with $TVTX toward an approval.
First of all, I think that the FDA’s decision to extend review of the FSGS application by 3 months can ultimately be viewed as a positive. If it was as obvious CRL like some are claiming, why wouldn’t the FDA have just issued it in January? The review extension & request for additional information suggests a willingness to work with $TVTX towards an ultimate approval. Historically, >85% of applications that have approval decisions get pushed out 3 months, ultimately get approved by the FDA.
We know that in October 2024, the PARASOL working group (which is comprised of academics, the FDA, & clinicians) examined datasets from 25+ studies & >1,600 FSGS patients and determined that eGFR (which was the primary endpoint in the failed Ph3 DUPLEX trial) is not a feasible outcome measure for FSGS trials.
If we look at the context clues since then, multiple developments have occurred that bode positively for $TVTX ‘s FSGS application:
(1) Last year the FDA cancelled the previously assigned Advisory Committee panel that was scheduled ahead of the original decision date.
(2) At the Annual Rare & Genetic Renal Diseases Conference last year, Dr. Aliza Thompson (Director of the Division of Cardiology & Nephrology at FDA) expressed that there is a continued push for the FDA to utilize surrogate endpoints to accelerate drug development in kidney diseases where there is a significant unmet medical need. This is the exact case for FSGS, which has no approved treatment options. The PARASOL workshop concluded with unanimous agreement by the group on the value of proteinuria as an approvable endpoint.
Despite the eGFR improvement primary endpoint failure in Ph3, Filspari DID show benefit across multiple other kidney function measurements, including proteinuria, which was also reported in their previous studies.
All of this suggests there is significant support (from Dr. Thompson on down) for Filspari to get approved for use in FSGS based on the impact the drug showed on proteinuria in the DUET and DUPLEX studies. Again, the fact that they didn’t simply issue a CRL in January also supports this notion and implies a strong willingness to work with $TVTX toward an approval.
