RNA interference ("RNAi"), a gene silencing technique with the potential to treat numerous diseases, has come a long way since Craig C. Mello and Andrew Fire won the Nobel Prize in Physiology or Medicine for their breakthrough RNAi research in 1998. A Challenging Beginning for an Exciting New Field in Science
Opko Health Inc. (NYSE: OPK) developed the first RNAi treatment to reach Phase III clinical trials with bevasiranib for the treatment of AMD - but terminated the trial in March of 2009 saying that it was unlikely to meet its primary end point. A mouse study published in Nature in 2008 suggested that bevasiranib actually worked by triggering an immune response in the eye that happened to curb blood vessel growth rather than selectively suppress VEGF gene expression.
Later, Allergan Inc.'s (NYSE: AGN
) AGN-745 treatment in the same area failed to meet a key efficacy end point in Phase II clinical trials and was ultimately sold to Merck & Co. (NYSE: MRK
) who has no plans for the drug. Many other large pharmaceutical companies, like Novartis AG (NYSE: NVS
) and Roche Holding Ltd. (OTC Markets: RHHBY
), have also pulled out of the RNAi space, either in their direct research interests or in their partnerships with other firms.
In the end, many specialty biotechnology firms and large pharmaceutical companies jumped into the RNAi space early on, but some key failures left many of them skittish. These companies largely decided to exit the space given these early failures, while others were forced back to the drawing board in order to determine the real problems facing the industry. But now, there’s new research and technology addressing these problems and driving a resurgence in RNAi. RNAi Delivery Remains The Key Hurdle
There's little question that the science behind RNAi therapeutics remains robust. Recently, neurologist Teresa Coelho of the Hostpital de Santo Antonio in Portugal and her colleagues developed an RNAi treatment for transthyretin amyloidosis patients that successfully cut transthyretin levels by 38% after just seven days, according to a report in the New England Journal of Medicine, demonstrating RNAi's abilities to target a robust protein decrease.
But, many biotechnology companies have struggled with delivery mechanisms that enable RNAi to effectively reach and silence the right genes. Companies like RXi Pharmaceuticals, Corp.(OTCQX: RXII
) - founded by RNAi Nobel Prize winner Craig C. Mello - have addressed these issues by carefully focusing on delivery. For instance, its sd-rxRNA[R] platform builds in drug-like properties to the RNAi compounds themselves in order to enhance delivery.
Other companies like Alnylam Pharmaceuticals Inc. (NASDAQ: ALNY) have developed delivery mechanisms of their own. For example, its GaINAc-siRNA conjugates utilize a much simpler technological approach for subcutaneous delivery with a wide therapeutic index. These different approaches have shown greater success in early clinical trials than the traditional lipid encapsulation that was used in the past to deliver RNAi throughout the body.
Investment Opportunities In The Space
There are several different public companies operating in the RNAi space, ranging from the large Alnylam Pharmaceuticals Inc. and ISIS Pharmaceuticals Inc. (NASDAQ: ISIS) to the smaller RXi Pharmaceuticals Inc. Investors deciding between these companies should carefully take a look at not only the clinical pipelines and progress, but also the delivery mechanisms that underlie the treatments.
On the large end, Alnylam's ALN-TTR aims to silence the TTR gene and treat TTR-mediated amyloidosis ("ATTR"). Affecting some 50,000 people worldwide, ATTR represents a major unmet medical need with significant morbidity and mortality. Phase II results in June showed a knockdown of TTR protein levels of up to 93% with a strong safety profile, while a Phase III pivotal trial is expected to start in FAP patients by the end of 2013 and is worth watching.
On the smaller end, RXi Pharmaceuticals' RXI-109 utilizes its sd-rxRNA[R] delivery technology to silence CTGF mFRNA to reduce dermal scarring. The company's second Phase I study showed that multiple injections were well tolerated and CTGF mRNA was reduced in a dose-dependent manner over a long period of time. While an FDA approval may be quite distant, the company could see a potential partner jump on board, if favorable results continue in the clinic.
In the end, investors have numerous opportunities in the RNAi space. Many compounds may have had trouble reaching commercial stage in the past, but the proven science and improving delivery mechanisms could increase the odds moving forward. As a result, investors may want to keep a close eye on both large and small companies in the space.
Sign Up to Receive Email Updates on RXi Pharmaceutical Inc.
About Emerging Growth LLC:
EGC is a marketing and consulting firm that specializes in creating ongoing communications strategies for public and private companies.
Disclosure:Except for the historical information presented herein, matters discussed in this release contain forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Emerging Growth LLC is not registered with any financial or securities regulatory authority, and does not provide nor claims to provide investment advice or recommendations to readers of this release. For making specific investment decisions, readers should seek their own advice. For full disclosure please visit: http://secfilings.com/Disclaimer.aspx
Leave a comment...