Viralytics' anticancer virus aces checkpoint inhibitor combo trials

Viralytics just reported impressive data for its virus-based cancer therapy that could bring commercial partners out of the woodwork, say analysts.

The Australian biotech's lead oncolytic virus drug Cavatek achieved a 100% disease control rate in melanoma patients when combined with Merck & Co.'s PD-1 inhibitor Keytruda (pembrolizumab) in a Phase Ib trial, providing further evidence for the value of combining these two types of cancer immunotherapy.

Direct injection of the genetically modified virus into the tumor at the same time as starting Keytruda therapy reduced the size of tumors in seven out of 10 patients in the study, and stabilized disease in the remaining three, with few side effects.

Meanwhile, a second trial of Cavatek plus Bristol-Myers Squibb's PD-1 inhibitor Opdivo (nivolumab) revealed a 50% response rate in the first 18 patients treated in a 26-patient trial in advanced melanoma, which according to analyst Dennis Hulme at Edison is an "impressive response rate in a heavily pre-treated population."

Hulme notes that both results are promising, given that Keytruda and Opdivo achieved response rates of 33% and 11% respectively when used as single agents in advanced melanoma, while Cavatek on its own worked in just over one-fourth (28%) of patients.

"The encouraging results are a good sign for the ongoing trials of Cavatak and are likely to be of great interest to potential partners," he writes in a research note

Checkpoint inhibitors have dramatically improved prospects for patients with a number of cancers, but nevertheless response rates tend to be relatively low when used on their own. For this reason the emphasis is on developing them in combination, and Edison believes oncolytic viruses could be particularly potent partners.

This type of therapy can "prime" or initiate the immune response, which can then be strengthened by combination with checkpoint inhibitor therapy, which "loosens the host 'immunological handbrake,'" they note.

There has already been an uptick in interest among big pharma companies in oncolytic virus therapies since Amgen bagged approval for the first drug in this class—Imlygic (talimogene laherparepvec, or T-Vec) for melanoma—in 2015.

In the last few months Boehringer Ingelheim signed a €210 million option deal to buy Austria's ViraTherapeutics, whose lead candidate VSV-GP is in preclinical development, once Phase I trials are complete. 

Meanwhile, Bristol-Myers Squibb has partnered with PsiOxus to run trials of its oncolytic virotherapy enadenotucirev in combination with Opdivo, while Merck has a similar agreement in place to test Keytruda alongside Oncolytics Biotech's Reolysin (pelareorep) in a Phase Ib study.

And in July, Celgene took part in a $57 million fundraising by startup Oncorus, which has an oncolytic virus candidate for brain cancer in preclinical development.

"These deals reflect the belief that oncolytic viruses may provide a complementary mechanism to address tumours that are resistant to [checkpoint inhibitor] therapy," says Hulme, who predicts that Viralytics will sign a partnering deal for Cavatak or outlicense the drug in 2017.