Sillajen explains Pexa-Vec trial failure – it was the rescue meds

South Korean biotech Sillajen was hit hard last week when its oncolytic virus therapy Pexa-Vec failed a phase 3 trial, but the company reckons it doesn’t spell the end of the programme.

The oncolytic virus therapy – also being developed by French biotech Transgene – failed to show any additional benefit when added to treatment with Bayer/Amgen’s targeted therapy Nexavar (sorafenib) in patients with liver cancer, and was halted for futility.

Shares in both companies plummeted after the decision was announced, but Sillajen has now told the Korea Biomedical Review that the problem lies in rescue medicines used in the study for patients who were failing treatment.

An oncolytic virus is a genetically engineered or naturally occurring virus that can selectively replicate and kill cancer cells without harming healthy tissues. In contrast to gene therapy, where a virus is used as a carrier for transgene delivery, oncolytic virus therapy uses the virus itself as a cancer cell-killing weapon, as well as a vehicle to express drugs.

Pexa-Vec (pexastimogene devacirepvec) is a modified vaccinia virus that has been engineered to express immune-boosting cytokine GM-CSF.

The PHOCUS trial of Pexa-Vec was terminated on the advice of its independent data monitoring committee after an interim analysis suggested it was unlikely to show an increase in overall survival when given ahead of Nexavar for hepatocellular carcinoma (HCC), the most common form of liver cancer.

Sillajen has told the KBR however that 63 out of 203 patients on the Pexa-Vec/Nexavar regimen received rescue or salvage therapies, compared to 76 out of 190 in the control arm, and it believes that skewed the results. Five anti-cancer drugs were deployed for salvage in non-responding patients.

The list including Bristol-Myers Squibb’s cancer immunotherapy Opdivo (nivolumab), Eli Lilly’s Cyramza (ramucirumab), Eisai’s Lenvima (lenvatinib), Bayer’s Stivarga (regorafenib) and Exelixis’ Cabometyx (cabozantinib), all of which are indicated for HCC treatment.

Of these, Opdivo, Cyramza and Lenvima were administered at around the same frequency across the treatment and control groups, but there was markedly higher use of Stivarga and Cabometyx in the latter, according to Sillajen.

The company’s chief medical officer Kwon Hyuk-chan said that because of the disparity “we do not believe that Pexa-Vec is not effective,” according to KBR.

Shares in Sillajen lost a third of their value when the PHOCUS decision was first announced, reflecting the fact that the oncolytic virus accounts for all but one preclinical programme in its pipeline. Transgene – which has a number of other candidates in the clinic – fell 13%.

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