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Problem with Clinical Materials Forces Benitec To Delay Filing IND for HIV/AIDS Therapy

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Benitec has delayed the filing of an investigational new drug application for its RNAi-based HIV/AIDS therapy after the company discovered "one aberrant result in the release tests of the clinical materials," the firm said this week.

Benitec had been planning to begin a phase I trial of the therapy — the most advanced in its development pipeline — in the first half of this year. However, this timeline has been pushed back indefinitely, Benitec CEO Sara Cunningham told RNAi News.

Cunningham added that the problem, which was recently discovered, is not related to the activity of the drug. Benitec is not able to provide a new timeline for the regulatory filing, she said.

The HIV/AIDS treatment, being developed in collaboration with the City of Hope, involves using granulocyte colony stimulating factor to mobilize stem cells in AIDS lymphoma patients.

Once the stem cells begin circulating peripherally, they can be collected, isolated, and genetically modified with a lentiviral vector containing three therapeutic genes: DNA that encodes for shRNAs targeting the tat-rev exon, a ribozyme that cleaves the mRNA for CCR5, and a nucleolar-localizing TAR decoy.


"Is it an artifact of how
we were doing the assay? Is it only within that one sub-lot? Was it the CD34 cells? There are a lot questions that we still
have to answer."


The patients undergo full chemoablation, which kills both the regenerative cells of the bone marrow and lymphoma cells, and then the stem cells are infused back into their bloodstreams so that they can migrate to, and engraft in, the marrow.

According to Cunningham, the problem "came up in the release testing of the lentiviral prep. In the laboratory preps of the lentiviral vector carrying the [drug's] three components, we had always correlated titer on an indicator cell line, HT-1080, and CD34-positive cells, which are the cells that we'll actually transduce in the trial," she said.

"We had always had very good correlation between those two titers," Cunningham said. "The virus was produced in 11 sub-lots [at the City of Hope's Center for Biomedicine and Genetics], and in one of the sub-lots that were tested we didn't get as tight a correlation between the titer on HT-1080s and CD34s.

"Is it an artifact of how we were doing the assay? Is it only within that one sub-lot? Was it the CD34 cells? There are a lot questions that we still have to answer," she said. "Until we understand whether this result is just completely artifactual and aberrant, we're just not comfortable filing the IND."

— Doug Macron ([email protected])

This week, Benitec announced that it has delayed the filing of an investigational new drug application for its HIV/AIDS therapy after running into problems with clinical materials (see related story, this issue). The news marks the latest setback for a company that has struggled in recent years with patent lawsuits, licensing disputes, a cash crunch, and a management shake-up.

Below is a timeline of Benitec's history as an RNAi drugs developer, as reported by RNAi News.


click for larger view

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