FDA Grants Reolysin Orphan Drug Designation for Ovarian Cancer

Brad Thompson, PhD

The FDA has granted an orphan drug designation to Reolysin (wild-type reovirus) for the treatment of patients with ovarian cancer, according to the developer of the immunotherapy, Oncolytics Biotech, Inc.

“This is an important regulatory milestone for Oncolytics and will provide us with a number of benefits as we advance the development and commercialization process for Reolysin," Brad Thompson, PhD, president and chief executive officer at Oncolytics, said in a statement. "Ovarian cancer is a devastating disease that represents a significant unmet need, particularly for those patients diagnosed in later stages."

Reolysin is currently being studied in an ongoing randomized phase II trial (GOG186H) in combination with weekly paclitaxel versus weekly paclitaxel alone in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal cancer. The trial completed enrollment in September 2014.

The therapy is also being studied in a phase I/II clinical trial (OSU-07022) for patients with metastatic ovarian, peritoneal and fallopian tube cancers using intravenous (IV) and intraperitoneal (IP) administration of Reolysin. Early results from the trial provided the first evidence of viral targeting and replication in peritoneal and ovarian cancer cells.

The study look specifically at a Reolysin dose of 3x10¹⁰ TCID₅₀ by IV on days 1-5 and an IP dose on days 2 and 3. Tumor biopsy samples were examined by immunohistochemistry and displayed evidence of viral capsid protein in the tumor tissue. A comparison of tumor versus normal cells indicated that treatment was selective for tumor cells, with indications of reovirus replication within the tumor.

Reovirus, the main component of Reolysin, works by promoting an antiviral response within a cancer cell. By adulthood, most individuals have already been exposed to the virus, which is non-pathogenic and responses are typically asymptomatic.

However, unlike in normal cells, in cancer cells an aberrant antiviral response is elicited against the reovirus. This abnormality allows the reovirus to multiply to an extent that is potentially fatal to the cancer. Reolysin is based upon research into this mechanism conducted by the chief operating officer at Oncolytics, Matt Coffey, PhD.

"We are delighted to see that the research community has been embracing preclinical research utilizing reovirus," Coffey said when data from early studies were presented at the 2012 AACR Annual Meeting. "This research helps us to continue to refine our understanding of Reolysin's mechanism of action, its suitability for combination with other treatment modalities, and its potential for application to a growing range of potential cancer indications."

On February 9, 2015, Oncolytics also filed for an FDA orphan drug designation for Reolysin for the treatment of high-grade gliomas (HGG) in pediatric patients. Oncolytics has conducted three previous clinical studies in brain cancers including gliomas, and has found that Reolysin can infect a variety of brain tumors when delivered intravenously.

"Early clinical data suggesting that intravenously delivered Reolysin can cross the blood brain barrier and infect tumors opens up the possibility of treating a large patient group with unmet needs, specifically those with brain metastases associated with a number of cancer types,” said Thompson, in an April 2014 release.

Reolysin has also been studied in pancreatic cancer. A recent phase II study of Reolysin given in the first-line treatment of metastatic adenocarcinoma of the pancreas found that the virus did not improve outcomes in the overall population of the 73 patients in the study. Researchers are still looking at blood and tissue samples for a potential biomarker to better determine which patients could benefit from this therapy.

The FDA grants orphan drug designations to products that treat rare diseases, providing incentives to sponsors developing drugs or biologics. The program provides the sponsor certain benefits and incentives, including a period of marketing exclusivity if regulatory approval is ultimately received for the designated indication, potential tax credits for certain activities, eligibility for orphan drug grants, and the waiver of certain administrative fees.