4SC shelves U.S. Nexavar combo trial after Asian PhII misses primary endpoint

(By Ed Uthman from Houston, TX, USA (Hepatocellular carcinoma) [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons)

4SC (FRA:VSC) has reported lackluster data from a Phase II trial of its liver cancer asset resminostat. The trial, which was run by 4SC’s Japanese partner Yakult Honsha, failed to detect an improvement in time to disease progression in the resminostat arm, prompting both companies to rethink plans to advance the drug.

Yakult gave resminostat in combination with Bayer’s (FRA:BAYN) Nexavar as a first-line treatment to people with hepatocellular cancer (HCC). Another cohort of the 170-person trial received just Nexavar. The expectation was that the presence of resminostat, an oral histone deacetylase inhibitor, would delay disease progression in the experimental treatment arm. However, Yakult ultimately failed to identify a statistically significant difference between the two arms in time to disease progression.

In a statement to reveal the news, 4SC flagged up the performance of patients with high-expression levels of ZFP64 as a reason not to write the program off just yet. High levels of ZFP64, also known as zinc finger protein 64 homolog, reportedly appear to correlate with longer time to expression in the resminostat arm than the control cohort. Yakult is now digging through the data in search of reasons to salvage the program.

The success, or otherwise, of this data dive will go some way toward shaping the future of resminostat, which 4SC had planned to move into clinical trials in the U.S. later this year. The FDA signed off on an IND earlier this year for a clinical trial of resminostat in combination with Nexavar, the active ingredient in which is sorafenib. Now, 4SC is unlikely to design a trial targeting all liver cancer patients, what it calls an “all-comers” study.

“For all-comers, we are not very likely to initiate a trial of the resminostat-sorafenib combination in HCC in the U.S.,” Wolfgang Güssgen, head of corporate communications and investor relations at 4SC, told FierceBiotech. “However, with the detailed results analysis from Yakult still outstanding, once these results are available we may consider to run additional HCC trials in subgroups in the U.S. and/or elsewhere.”

Yakult’s reading of the data will also influence how much money 4SC earns from its licensing deal with the company. 4SC handed over the Japanese rights to Yakult in 2011 in return for €6 million upfront ($6.7 million), up to €127 million in milestones and a shot at double-digit royalties. With Yakult seeing the Phase II data as a death knell to its ambition to bring resminostat to market as a broad treatment for liver cancer, the fate of these milestones is tied to its faith in the ZFP64 data.

Shares in 4SC fell by more than 20% following the release of top-line data from the Yakult study, but regained some of the lost ground days later when the company entered into a seperate China development pact worth up to €76 million.

- read the release
- and the China news

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