Shares in 4SC AG surged more than 38 percent Thursday on news that its histone deacetylase (HDAC) inhibitor resminostat hit the primary endpoint of a Phase II trial in advanced hepatocellular carcinoma (HCC).

According to preliminary data, evaluable patients (n = 15), whose tumors had already progressed after receiving Nexavar (sorafenib) as first-line therapy, attained median progression-free survival (PFS) of 4.6 months (140 days) after 12 weeks on a resminostat-sorafenib combination regimen.

Those who received resminostat alone (n = 9) attained median PFS of 1.4 months (42 days) at the same timepoint.

Two-thirds (10/15) of patients in the combination arm remained free of disease progression after 12 weeks, as did one-third (3/9) of those in the control arm.

The primary endpoint of the open-label study was a PFS rate of 20 percent after 12 weeks or six cycles of therapy.

The result, despite the small numbers, is clinically meaningful, 4SC CEO Ulrich Dauer told BioWorld Today. "We believe that it's at least as exciting as [it is] from a share price point of view," he said.

The Martinsried, Germany-based company now will begin drawing up plans for a pivotal Phase III trial.

"Currently, we do not see the necessity for a further interim study before we would enter a pivotal trial in second-line treatment," he said. The company is making preparations for drawing up a protocol and seeking scientific meetings with regulators on either side of the Atlantic.

"If they go as planned, we may be able to initiate a trial toward the end of the year or the beginning of next year," Dauer said. However, the company is unlikely to initiate such a study without a deal, and talks with prospective partners are under way.

The data provided additional clinical support for the hypothesis that resminostat acts by overcoming an epigenetic drug tolerance mechanism associated with HDAC activity and resensitizing tumor cells to first-line therapy.

The open-label study enrolled 38 patients whose tumors had progressed following first-line treatment with Nexavar, the multikinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor and Raf kinases, which is marketed by Leverkusen, Germany-based Bayer Healthcare AG and Onyx Pharmaceuticals Inc., of South San Francisco.

Twenty-six were assigned to the combination arm and 12 to the monotherapy arm.

Seven patients in the combination arm and another two in the control arm dropped out before evaluation was possible, but 4SC said "early withdrawal because of side effects was a rare occurrence and only partly attributable to the study medication."

Overall survival is a secondary endpoint, but it will take some time before those data become available, Dauer said. As several patients remain on therapy – one remains free of disease progression after around 18 months – the survival effect seen so far could change in the final analysis.

"It could improve; it could be a little less," Dauer said.

The final data will be apparent shortly. "With the combination arm, we will be able to have all patients staged at 12 weeks probably by February this year, and in the monotherapy arm a little bit later," he said. But the overall result will remain unchanged.

Resminostat is already the subject of a deal with Tokyo-based Yakult Honsha Co. Ltd., which licensed Japanese rights to all oncology indications for $6 million up front and another $127 million in potential milestones.

The drug also has met the primary efficacy endpoint in a Phase II trial in Hodgkin lymphoma, an indication with a smaller patient population than advanced HCC. A Phase I/II trial in colorectal cancer patients carrying a KRAS mutation is ongoing.

In HCC, "there's actually not that much up ahead of us," Dauer said. New York-based Bristol-Myers Squibb Co. recently reported that its kinase inhibitor brivanib, which acts on vascular endothelial growth factor receptor and fibroblast growth factor receptors, failed to reach the primary endpoint of improving overall survival in a Phase III trial in HCC patients who had progressed following Nexavar therapy.

A head-to-head study of brivanib vs. sorafenib as first-line therapy is ongoing. Abbott, of Abbott Park, Ill., also is conducting a head-to-head study of its kinase inhibitor linifanib (ABT-869) against sorafenib in patients with advanced HCC.

Shares in 4SC (FRANKFURT:VSC) closed at €2.05 (US$2.65) Thursday, up €0.57 from the previous day, having reached €2.446 during earlier trading.