Tvardi Therapeutics’ stock crashes on Phase II IPF flop
Tvardi Therapeutics’ stock has crashed more than 80% after the company revealed that its idiopathic pulmonary fibrosis (IPF) candidate flunked in a Phase II trial. Tvardi will conduct additional analysis of TTI-101 to determine how to move the asset forward.
In the REVERT study (NCT05671835) TTI-101, both a STAT 1 and STAT 3 inhibitor, failed to show any significance over placebo in forced vital capacity (FVC) improvement from baseline, which is reported as 41% for the placebo, and 39% and 44% for the 400mg and 800mg arms, respectively.
FVC change from baseline overlapped between treatment arms, with large variability within each cohort. Notably, the placebo-treated patients’ FVC decline was lower than expected compared to historical controls.
Tvardi’s stock dropped by 85.66% after the data was reported on Monday, from a $43.26 close on 10 October to a $6.20 open on 13 October. The US-listed company now has a market cap of $62.74m.
The randomised, double-blind, placebo-controlled clinical trial evaluated TTI-101 alone or in combination with Ofev (nintedanib) in 88 patients with IPF. While the study was designed to assess safety and pharmacokinetics (PK), the company also wanted to evaluate efficacy-related exploratory outcomes related to lung function. After reviewing the preliminary safety data and exploratory efficacy results, including changes in Forced Vital Capacity (FVC), Tvardi concluded that the study did not meet its goals.
There is also cause for concern with safety as lower discontinuation was seen in the placebo group, at 10.3%, compared to treated arms, which were 56.7% and 62.1%, in the 400mg and 800mg cohorts, respectively. Discontinuation rates among the TTI-101 population were primarily driven by gastrointestinal adverse events, with higher rates of events and discontinuations among patients on concurrent Ofev.
CEO of Tvardi, Dr Imran Alibhai said: “In the aggregate, we did not observe a benefit of TTI-101 treatment in this IPF study. The limited data set, high variability within treatment arms, and unexpected performance of the placebo arm make it difficult to provide more definitive conclusions at this time. We are conducting additional analyses to further understand the results and inform our next steps.”
First IPF drug approved in a decade
On 7 October, Boehringer Ingelheim’s Jascayd (nerandomalist) became the first drug to be approved in IPF in the US in more than a decade. Until then, there were just two drugs used for IPF, Ofev and pirfenidone.
This marks what is likely to be a changing period of treatment, with many other drugs showing promise, GlobalData analysts say. This includes United Therapeutics’ Tyvaso and Celea Therapeutics’ deupirfenidone. GlobalData is the parent company of Clinical Trials Arena.
