Skip to main content
Premium Trial:

Request an Annual Quote

RNAi Field Sees Failures of Key Candidates


Despite the promise of RNAi as a therapeutic, the road from the clinic to the marketplace for drugs based on the gene-silencing technology has proven to be a bumpy one with the failure of some of the field's earliest candidates.

Among the most notable is Opko Health's bevasiranib, an siRNA-based treatment for wet age-related macular degeneration that was the first drug of its kind to enter human testing and the first to reach the final phase of clinical development.

Bevasiranib was originally developed by Acuity Pharmaceuticals. But in early 2007, Acuity was acquired by a publicly traded shell company that later became the ophthalmics firm Opko.

An unmodified siRNA targeting vascular endothelial growth factor, the drug, formerly known as Cand5, showed potential early on. However, questions about bevasiranib's efficacy began coming to the surface, culminating with the 2008 publication of data in Nature showing that the drug's anti-angiogenic effect was the result of toll-like receptor 3 activation rather than an RNAi effect.

About a year later, Opko announced that it had halted a phase III study of bevasiranib after preliminary data indicated that the drug was "unlikely" to meet its primary endpoint. While the company did not expressly say that it was stopping development of the AMD therapy, it has not made any mention of bevasiranib since and all references to the drug have disappeared from Opko's corporate website.

Suffering a similar fate as bevasiranib is AGN-745, a chemically modified, VEGF receptor-1 targeting siRNA that had been under phase II development for AMD.

Developed by Sirna Therapeutics as Sirna-027, the drug was licensed to Allergan in 2005 while still in phase I testing. Like bevasiranib, it was designed to be injected directly into the eye and inhibit abnormal blood vessel growth.

But in the same 2008 paper that examined bevasiranib's immunostimulatory properties, AGN-745 was also found to trigger TLR3 and not work via RNAi.

— Doug Macron

RNAi Notes

Exiqon announced a new grant initiative, called the Exiqon Grant Program, to fund North American researchers who focus on microRNA-related projects. The company has set aside $25,000 for this program.

German regulators approved Silence Therapeutics' application to begin a phase I study of its siRNA-based cancer drug Atu027 that targets PKN-3, a protein kinase linked to tumor growth
and metastases.

SanoGene, an RNAi therapeutics startup, has initiated studies to support an investigational new drug application for its lead drug candidate, SG-1311, for glioblastoma multiforme.

MDRNA announced it is now in compliance with the Nasdaq Stock Market's $1 minimum bid requirement for being listed on the exchange.


$31 million
Amount Opko Health has raised through private stock placements with seven investment groups

Funded Grants

$48,773/FY 2009
Screening for drug targets in a Drosophila model of muscle degeneration
Grantee: Edward Kwame Owusu-Ansah, Harvard Medical School
Began: Apr. 1, 2009; Ends: Mar. 31, 2011

With this grant, Owusu-Ansah will study the molecular mechanisms of muscle degeneration in Drosophila, develop an assay for muscle degeneration, and identify drug targets. In particular, he will use publicly available RNAi transgenic lines to perform a genome-wide in vivo screen to identify relevant genes and pathways.

$525,000/FY 2009
Regulation of CD45 alternative splicing by HNRPLL
Grantee: Anjana Rao, Immune Disease Institute
Began: Dec. 24, 2008; Ends: Nov. 30, 2013

Following up on her previous studies on HNRPLL, which regulates alternative splicing in T cells, Rao plans to define the mechanism of action of HNRPLL. She will use RNAi-based screens to identify signaling pathways and transcription factors modulating CD45 splicing, and will study the role of HNRPLL in vivo. According to the abstract, this will "increase our general understanding of how signaling pathways regulate mRNA splicing."

The Scan

Harvard Team Report One-Time Base Editing Treatment for Motor Neuron Disease in Mice

A base-editing approach restored SMN levels and improved motor function in a mouse model of spinal muscular atrophy, a new Science paper reports.

International Team Examines History of North American Horses

Genetic and other analyses presented in Science find that horses spread to the northern Rockies and Great Plains by the first half of the 17th century.

New Study Examines Genetic Dominance Within UK Biobank

Researchers analyze instances of genetic dominance within UK Biobank data, as they report in Science.

Cell Signaling Pathway Identified as Metastasis Suppressor

A new study in Nature homes in on the STING pathway as a suppressor of metastasis in a mouse model of lung cancer.