Andrii Yalanskyi
This is my first Travere Therapeutics (NASDAQ:TVTX) article. In this article I discuss its prospects following its restructuring announced in its 12/2023 press release.
Sparsentum’s initial approval was based on surrogate pathway of proteinuria reduction.
On 03/21/2022 Travere announced its NDA for accelerated approval of sparsentan for the treatment of IgA nephropathy (IgAN). On 05/16/2022 the FDA accepted the NDA for filing setting a PDUFA date of 11/17/2022. The FDA extended the PDUFA date by three months for it to review Travere’s required update to its proposed Risk Evaluation Mitigation Strategy [REMS].
Finally on 02/17/2023 the FDA granted accelerated approval to FILSPARI (sparsentan) to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression. Accelerated approval sounds wonderful in that it allows marketing of the approved product; however it comes with a catch.
I have set out the FILSPARI’s catch in italics from its approval announcement below:
This indication is granted under accelerated approval based on reduction in proteinuria. It has not been established whether FILSPARI slows kidney function decline in patients with IgAN. The continued approval of FILSPARI may be contingent upon confirmation of a clinical benefit in the ongoing Phase 3 PROTECT Study, which is designed to demonstrate whether FILSPARI slows kidney function decline. …
The FDA characterizes the accelerated approval pathway as complicated and nuanced. It allows the FDA to approve a drug based on surrogate endpoints without direct proof of its clinical effectiveness in combatting its targeted disease. The FDA granted accelerated approval for FILSPARI upon Travere’s showing that it:
- was safe, and
- reduced proteinuria.
Accelerated approval should not be thought of as a lesser form of approval; it is conditioned upon subsequent validation of the drug’s approval in a confirmatory study. The rational for accelerated approval is that a surrogate endpoint is thought to predict clinical benefit. In the case of FILSPARI reduction of proteinuria is thought to slow kidney function decline.
Disappointing data from Travere’s pivotal PROTECT trial set the stage for trouble.
Travere initiated its PROTECT trial, NCT03762850, in 12/2018. Its brief summary described it as a trial to:
…determine the long-term (approximately 2 years) nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with immunoglobulin A nephropathy (IgAN).
Its detailed description goes on to note its open-label extension period of up to 156 weeks, for a total duration of up to 270 weeks. The trial’s so-called actual primary completion date was 08/2023 with its study completion date not expected until 07/2026.
Travere’s latest 10-K (p. 8) explains that its initial accelerated approval was the result of data from its ongoing PROTECT trial showing clinically meaningful and statistically significant improvements in proteinuria. As noted above its approval was subject to potential reversal should it be unable to show FILSPARI’s actual clinical benefit.
On 09/21/2023 Travere’s stock dropped ~40% from its 09/20/2023 closing price of $12.88 to close on 09/21/2023 at $7.64. The falloff followed its 09/21/2023 press release titled:
Travere Therapeutics Announces Confirmatory Data from the Phase 3 PROTECT Study of FILSPARI® Demonstrating Long-Term Kidney Function Preservation in IgA Nephropathy; Narrowly Missing eGFR Total Slope Endpoint versus Active Control, Irbesartan
Travere clearly wanted to put its best foot forward emphasizing that it only “narrowly” missed. Judging by its emphatic share decline on huge volume the market was viewing a miss as good as a mile in this situation. After dropping to an intraday low of $5.25 on 11/09/2023, shares have been recovering a bit with its latest closing as I write on 01/27/2023 at $8.60.
Beyond its study travails, Travere also faces significant competitive issues
IgAN has attracted strong competitive interest over the years. One of my favorites Omeros (OMER) has long boasted IgAN as one of its late stage candidates for its Narsoplimab. In 10/2023 Omeros decided to drop this indication from its pipeline.
In its latest 10-K (pps. 12-13) Travere sets out a daunting list of both large and small pharmas that have programs addressing IgAN in various stages of development. In 12/2021 the FDA granted Swedish drugmaker Calliditas Therapeutics’ (CALT) Tarpeyo (budesonide) accelerated approval to treat IgAN, based on the surrogate marker of proteinuria.
In 12/2023 the FDA granted Tarpeyo full approval to treat IgAN. For Q3, 2023 Calliditas reported SEK 283.6 million in Tarpeyo net sales (~$30 million) compared to SEK 123.4 million for Q3, 2022.
As for Travere’s Q3, 2023 revenues during its Q3, 2023 earnings call (the “Call“), CFO Cline advised that it scored net product sales of $33.9 million; of that amount, Thiola and Thiola EC contributed $25.9 million leaving a paltry $8 million as FILSPARI’s quarterly take, far less than that for Tarpeyo.
Travere’s ambitious plans for 2024 include a reorganization to conserve cash for ongoing FILSPARI launch
Travere has issued two recent important press releases:
- 12/04/2023 release titled “Travere Completes Successful pre-NDA Meeting for FILSPARI in IgAN; Provides Regulatory Updates for both IgAN and FSGS” and
- 01/08/2024 release titled “Travere Therapeutics Provides Corporate Update and 2024 Outlook”.
Its December release covered the following key points following its FDA meeting it plans to:
- submit a supplemental New Drug Application (sNDA) in the first quarter of 2024 for conversion of the existing U.S. accelerated approval of FILSPARI to full approval;
- re-engage with the FDA following FDA’s advice that Travere’s Phase 3 DUPLEX Study results alone were insufficient to support an sNDA submission for an focal segmental glomerulosclerosis [FSGS] indication for sparsentan, leaving FSGS with no clear forward regulatory path;
- implement a strategic reorganization in Q4 2023 to focus near-term resources on the ongoing FILSPARI launch in IgAN and the advancement of pegtibatinase in classical homocystinuria (HCU).
The reorganization which will include an indeterminate number of layoffs will open Travere’s cash runway into 2028.
Its January press release highlighted its increased Q4, 2023 FILSPARI revenues of $15 million. It also confirmed plans to submit an sNDA to FDA in Q1 2024 for conversion of the existing U.S. accelerated approval of FILSPARI in IgAN to full approval.
It also advised that a CHMP opinion on potential approval of sparsentan for the treatment of IgAN in Europe was expected in Q1 2024. Lastly it pointed to its 12/2023, initiation of a pivotal Phase 3 Study (HARMONY) to support the potential approval of pegtibatinase for the treatment of classical HCU.
Conclusion
There is a lot to unpack when considering an investment in Travere. I look at it from a simplified point of view. Its near term fortunes depend on how its planned FILSPARI sNDA fares with the FDA. Assuming it succeeds there, over a more intermediate period its FILSPARI launch metrics will take center stage as it jousts with Tarpeyo over IgAN revenues.
I intend to watch the situation; as I write on 01/28/2024 I am holding back. I rate Travere a “Hold”.
