Reolysin

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REOLYSIN® (pelareorep; Wild-Type Reovirus; Serotype 3 Dearing; Oncolytics Biotech Inc.), is a proprietary isolate of the unmodified human reovirus (reovirus) being developed as a first-in-class systemically administered immuno-oncology viral agent for the treatment of solid tumors and hematological malignancies. REOLYSIN is classified as an oncolytic virus, a virus that preferentially lyses cancer cells. Based on both single-arm and randomized phase 2 clinical studies, REOLYSIN also promotes an inflamed tumor phenotype through innate and adaptive immune responses. Clinical trials have demonstrated that REOLYSIN may have activity across a variety of cancer types (including breast, colorectal and pancreatic, as well as multiple myeloma) when administered alone and in combination with other cancer therapies.

In April 2015, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to REOLYSIN for malignant glioma. In May 2017, the FDA granted Fast Track Designation for REOLYSIN in metastatic breast cancer.

Oncolytics Biotech Inc. (Oncolytics) has more than 415 patents for REOLYSIN issued globally, including more than 60 in the U.S. and 20 in Canada, as well as numerous patents pending worldwide.

Video Reolysin

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.

In both single-arm and randomized phase 2 clinical studies, REOLYSIN, in combination with various chemotherapeutic agents, has shown a trend to improve overall survival (OS) in certain indications and patient populations, while having a limited impact on objective response rate (ORR) or progression-free survival (PFS), a therapeutic profile consistent with those observed with approved immunotherapies. Based on these observations, Oncolytics believes REOLYSIN has multiple components to its mechanism of action (MOA):

• Direct tumor lysis - selective viral replication in permissive cancer cells leading to tumor cell lysis;
• Innate immune response - viral replication resulting in a cascade of chemokines/cytokines causing natural killer (NK) cells to recognize and attack cancer cells; and
• Adaptive immune response - antigen presenting cells (APCs) display tumor-associated antigens (TAA) and viral-associated antigens (VAA) to educate T-cells to recognize and destroy cancer cells.

Maps Reolysin

Clinical trials

REOLYSIN has been evaluated in numerous clinical trials in variety of cancers, including pancreatic, breast, head and neck, prostate, lung, colorectal, bladder and ovarian cancers.

REOLYSIN's clinical development plan is based on drug combinations that can potentially boost each response of REOLYSIN's mechanism of action, with three development pathways: 1) chemo combinations (direct cell lysis) 2) immunotherapy combinations (adaptive immune response) and; 3) combination with (immunomodulators) IMiDs / targeted therapy (innate immune response).

As part of REOLYSIN's registration pathway, Oncolytics, in partnership with the Canadian Cancer Trials Group (CCTG) (formerly the National Cancer Institute of Canada Clinical Trials Group), is conducting a phase 2 clinical trial in metastatic breast cancer patients receiving standard weekly paclitaxel therapy. In March 2017, the company announced positive overall survival data from the open-label, randomized study where, in the intention-to-treat patient population, there was a statistically significant improvement in median overall survival from 10.4 months on the control arm to 17.4 months on the test arm. In May 2017, Oncolytics announced that the FDA granted Fast Track designation for REOLYSIN for the treatment of metastatic breast cancer, and in September 2017, the company announced a successful End-of-Phase 2 meeting with the FDA.

Oncolytics is conducting its first study of REOLYSIN in combination with a checkpoint inhibitors in an open-label phase 1b trial. The trial will assess the safety and dose-limiting toxicity of REOLYSIN in combination with pembrolizumab (KEYTRUDA®) and chemotherapy in patients with advanced or metastatic pancreatic adenocarcinoma who have failed, or did not tolerate, first line treatment.

In March 16, 2017 Oncolytics announced that cancer charity Myeloma UK launched MUK eleven, a phase 1b trial studying REOLYSIN in combination with Celgene Corporation's immunomodulatory drugs (IMiDs), Imnovid® (pomalidomide) or Revlimid® (lenalidomide), as a rescue treatment in relapsing myeloma patients. The first patient was treated in September 2017.

Oncolytics is conducting two phase 2 clinical trials studying REOLYSIN in pancreatic cancer: in collaboration with the University of Texas, Oncolytics is studying REOLYSIN in combination with gemcitabine (Gemzar®) in patients with advanced pancreatic cancer, and in collaboration with the NCI, Oncolytics is studying REOLYSIN in combination with carboplatin and paclitaxel as a first line treatment of patients with recurrent or metastatic pancreatic cancer.

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See also

• Virotherapy
• Oncolytic virus

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References

src: www.dovepress.com

External links

• oncolyticsbiotech.com

Source of article : Wikipedia