Do RNAi Therapeutics have a Future?

Much is said about the unsustainable nature of the healthcare system particularly in the US, but also other developed countries. While a lot of the waste is due to expensive hospital stays, the practice of defensive medicines etc., the increasing costs of drugs is a factor nevertheless. Biologicals, therapeutics based on naturally occurring molecules and the bread and butter of the biotech industry, certainly contribute to that image. Although often an excellent treatment option, it is not uncommon to see annual drug costs in the range of $10,000-$100,000. It is therefore important to ask about the position of RNAi Therapeutics in this discussion.

Most RNAi Therapeutics would consist of the active siRNA (or DNA vector) and the delivery vehicle. While RNA synthesis is not dirt cheap at the moment, it is expected that as costs continue to come down they will eventually fall between the cost of small molecules and protein-based therapeutics on a logarithmic scale. Consequently, the comparison with more traditional biologics finds here in favour of RNAi Therapeutics. The unknown, however, is the delivery portion of the drug. Their cost can range from the insignificant, e.g. the conjugation of a simple cholesterol moiety to one end of the siRNA to conjugating the siRNA to a protein ligand recognising a cell-surface receptor. While both strategies are likely to be pursued by drug companies, I could imagine that if societal pressures demanded, a number of siRNA applications could be adjusted to cheaper delivery options.

The true cost of biologics and drugs in general, however, is not the cost of synthesising them, but their development. With the cost of developing a drug averaging more than 1 billion US dollars, drug companies have to charge a certain premium if they want to continue developing innovative and better drugs. Nevertheless, some politicians are busy promoting so called biogenerics which are supposedly equivalent to the original biologic, but can be sold for much cheaper because large-scale clinical trials and testing would not be needed for their approval. Personally, I find this view cynical, given that for a long time biotechnology as a business model was not profitable, and as the first success stories emerge, innovation is being put at risk for political gain. This is in addition to the fact that even scientifically biogenerics are not as trivial as is sometimes suggested. I digress…

Importantly, while RNAi as a lab technique is already helping to cut down development costs, by virtue of being able to select the best biological targets and the speed with which it is possible to identify an active siRNA for a given target RNAi Therapeutics should be cheaper to develop. Most of the $1 billion actually accounts for the many development candidates that never make it to the market, and by cutting down that number, drug costs have the potential to come down considerably. The speed of development that RNAi Therapeutics allow is demonstrated by the fact that only 5 ½ years after we even knew that RNAi works in humans, a few RNAi-based drugs are already in late phase I and II stages of clinical trials.

I also expect RNAi Therapeutics to fit in well as we move towards the increased adoption of evidence-based medicine where the benefit of a treatment has to be measurable. This is because the selection of the RNAi gene targets in the research phase will be based on measurable phenotypes that are then followed during the clinical trial stages. This should also help treatment outcomes, and this is where the real social and economic savings are to be found.