Polio-Rhinovirus Conjugate Receives Breakthrough Therapy Designation for Glioblastoma

May 20, 2016

The US Food and Drug Administration granted the “breakthrough therapy” designation to a recombination poliovirus/rhinovirus conjugate known as PVS-RIPO, for treatment of recurrent glioblastoma multiforme.

The US Food and Drug Administration (FDA) granted the “breakthrough therapy” designation to a recombination poliovirus/rhinovirus conjugate known as PVS-RIPO, for treatment of recurrent glioblastoma multiforme (GBM).

A group led by Darell D. Bigner, MD, PhD, of Duke University in Durham, North Carolina, developed the therapy. PVS-RIPO involves a live attenuated oral serotype 1 poliovirus vaccine modified to contain portions of human rhinovirus type 2. The resultant recombinant virus recognizes nectin-like molecule-5 (Necl5), a tumor antigen found in the cells of many malignancies.

The breakthrough designation allows for expedited development and review of the drug; the FDA uses it for therapies that treat life-threatening illnesses and that may represent a drastic improvement over existing therapies.

PVS-RIPO has a two-pronged mechanism of action: it can kill tumor cells through binding to Necl5, and it also produces an inflammatory reaction. In an interview with the ASCO Post in 2015, Bigner said that “secondary immune response is the most important part of the antitumor killing mechanism.”

Development of PVS-RIPO is still in its early stages, though initial results have been promising. A phase I trial was presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. That trial included 24 patients with recurrent GBM; as of the 2015 ASCO meeting, 12 of 24 patients had died, and 3 patients survived for long periods (22, 34, and 35 months).

In a press release regarding the breakthrough designation announcement, Duke University noted that of 23 patients enrolled at what was determined to be the optimal dose level, 15 are currently still alive. Three other patients, treated with different doses in early stages of the phase I trial, are still alive now more than 36 months from the start of treatment. The median survival for GBM in general is under 15 months.

Among the first 20 patients treated, some of the common adverse events included grade 3 pyramidal tract syndrome in 5 patients, seizures of grades 1 to 3 in 11 patients, headache, and others. There was one grade 4 intracranial hemorrhage at the time of catheter removal.

The phase I trial continues to recruit patients with GBM, with a total planned enrollment of 65 patients. The researchers also hope to begin recruiting this year for a trial of PVS-RIPO in children with brain tumors, and will also explore its effects in other solid tumors.