Merck KGaA and its avelumab partner Pfizer have agreed to test the cancer immunotherapy alongside an oncolytic virus therapy developed by US biotech Vyriad.
Rochester, Minnesota-based Vyriad – which spun out of the Mayo Clinic – will contribute its lead drug candidate Voyager-V1 to a trial in which it will be paired with PD-L1 inhibitor avelumab as a combination therapy for solid tumours.
The rationale behind the trial is that Voyager-V1 – a vesicular stomatitis virus (VSV) genetically engineered to express an imaging agent (sodium iodine symporter or NIS) and human interferon beta – causes an inflammatory reaction in the tumours, while avelumab take the brake off a T-cell mediated immune response in a double-whammy against the cancer, according to Vyriad’s chief executive Stephen Russell.
Oncolytic viruses are engineered to selectively replicate within and destroy cancer cells while simultaneously augmenting anti-tumour immunity, and are generally injected directly into tumour sites. Voyager-V1 is no exception, although Vyriad is also investigating intravenous administration of the therapy in a phase I trial.
The first and so far only therapy of this type to reach the market is Amgen’s melanoma therapy Imlygic (talimogene laherparepvec or T-Vec, approved by the FDA in 2015, although sales have been small – partly because of the impressive efficacy seen with checkpoint inhibitor drugs in this indication which are also easier to administer.
There’s a lot of activity going on in R&D however, with a dozen or more oncolytic viruses in clinical development, and developers have become acquisition targets for big pharma companies. In May, Johnson & Johnson paid $140m upfront for BeneVir in a deal that could see its value head north of $1bn, while other deals have been done by AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and Pfizer, amongst others.
Meanwhile, for Merck and Pfizer the deal adds another combination to the clinical programme for avelumab, which was the fourth drug in the PD-1/PD-L1 inhibitor category to reach the market after Bristol-Myers Squibb’s Opdivo (nivolumab), Merck & Co’s Keytruda (pembrolizumab) and Roche’s Tecentriq (atezolizumab).
The drug – sold as Bavencio – has been approved for skin cancer Merkel cell carcinoma and bladder cancer, but in February failed a trial as a second-line therapy for non-small cell lung cancer and also had a knockback in third-line stomach cancer last year.
“A primary focus of our clinical development program for avelumab is to evaluate the role and potential of immunotherapy combination regimens, in an effort to support patients with challenging cancers,” said Chris Boshoff, Pfizer’s head of immuno-oncology, early development and translational oncology.
“We look forward to working with Vyriad to explore this novel combination for patients with solid tumours.”