Reolysin® (pelareorep; Wild-Type Reovirus; Serotype 3 Dearing; Oncolytics Biotech), is a proprietary formulation of the human reovirus (reovirus) being developed for the treatment of various cancers and cell proliferative disorders. Reolysin is classified as an oncolytic virus, a virus that preferentially lyses cancer cells. Clinical trials have demonstrated that Reolysin may have activity across a variety of cancer types when administered alone and in combination with other cancer therapies.
Contents
In April 2015, the US FDA granted Orphan Drug Designation to Reolysin for malignant glioma.
Completed trials
Reolysin has been evaluated in phase II clinical trials in head & neck, melanoma, pancreatic, lung, ovarian, and colorectal cancers. The trial drug has successfully completed a number of phase I and II clinical trials across a variety of cancer types.
Phase II
Reolysin was tested in combination with docetaxel for metastatic prostate cancer in a phase II trial. The study was completed in early 2016, but results have yet to be presented. Another phase II trial was completed in early 2016 combining reolysin with docetaxel or pemetrexed in patients with NSCLC. Results are still pending.
For treatment of metastatic melanoma, Reolysin was combined with paclitaxel and carboplatin in a phase II trial.
Phase III
A phase III trial of Reolysin in combination with paclitaxel and carboplatin for treatment of squamous cell carcinoma of the head and neck was completed in May 2014.
Ongoing trials
A number of clinical phase II and phase III trials are underway in a range of indications including squamous cell carcinoma of the lung, non-small cell lung cancer, pancreatic cancer, and ovarian cancer. The Company is also conducting a phase I trial in colorectal cancer.
A phase II trial of reolysin and paclitaxel combination therapy for metastatic breast cancer is taking place in Canada and expected to be completed in December 2016.
The Gynecologic Oncology Group (GOG), a US-based national non-profit organization, is conducting a phase II trial of paclitaxel with Reolysin in patients with persistent or recurrent, ovarian, fallopian tube or primary peritoneal cancer (GOG186H). This study has been approved and will be sponsored by the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the National Institutes of Health (NIH), under its Clinical Trials Agreement with Oncolytics.
Reolysin in combination with FOLFOX6 and bevacizumab is being evaluated in metastatic colorectal cancer (ClinicalTrials.gov Identifier: NCT01622543). The study started in August 2012 and enrolled 109 patients. As of January 2016 it is estimated to completed by March 2017 (with an estimated Primary Completion date in Sept 2016).
For patients with KRAS-mutant metastatic colorectal cancer, Oncyolytics is recruiting patients for phase I trial combining Reolysin with Irinotecan/Fluorouracil/Leucovorin (FOLFIRI).
Mechanism of action
Reovirus, an acronym for Respiratory Enteric Orphan virus, generally infects mammalian respiratory and bowel systems. Most people have been exposed to reovirus by adulthood; however, the infection does not typically produce symptoms.
Reovirus was noted to be a potential cancer therapeutic when early studies on reovirus suggested it reproduces well in certain cancer cell lines. It has since been shown to replicate specifically in cells that have an activated Ras (a cellular signaling pathway that is involved in cell growth and differentiation) with very little effect in cells that do not have active Ras pathways. Reovirus replicates in and eventually kills Ras-activated tumour cells, and as cell death occurs, progeny virus particles are then free to infect surrounding cancer cells. This cycle of infection, replication and cell death is believed to be repeated until all tumour cells carrying an activated Ras pathway are destroyed. Activating mutations of the Ras protein and upstream elements of the Ras protein may play a role in more than two thirds of all human cancers,including most metastatic disease, which suggests that Reolysin may be an effective therapeutic for many Ras-activated tumor types and potentially for some cell proliferative disorders.