It is my expectation that in 15-20 years, every newborn and newly diagnosed cancer patient with good healthcare coverage will have their genomes sequenced. Personally, I cannot wait for consumer genomics companies like 23andMe to provide services that would allow me, a non-bioinformaticist, to readily analyze the sequences of friends and family. All this is made possible by the technical advances in bringing down the cost of sequencing so that for the price of a semi-luxurious holiday (~$4000) you can get your genome sequenced these days. Roche’s bid for the 800 pound gorilla of DNA sequencing, Illumina, illustrates that with its other molecular Dx costing not that much less, next-gen sequencing, especially that of whole genomes, has reached a stage where it has become relevant for diagnostic applications.
15-20 years is also about the time-frame when we should see a healthy flow of RNAi Therapeutics getting approved, many of those as personalized medicines, e.g. for the treatment of dominant-negative diseases such as TTR amyloidosis, Huntington’s Disease, or, of course, cancer. With many people knowing their genome sequence from birth, it will be possible to monitor and then start treating many of these gene carriers before they manifest symptoms and progress to more debilitating states. Others will benefit from an improved ability to correctly diagnose a disease in genetic terms, thus allowing the physician to prescribe the appropriate medicine. As a genetic medicine (aka gene therapy), RNAi Therapeutics is ideally suited to address many of these diseases. Sequencing technologies will also help unearth which gene targets such RNAi Therapeutics ought to go after and thus reduce target risk.
There is considerable discussion in biotech what would be the best business model for sequencing companies. The buzz around PacBio has fizzled a bit as there is a sense that their machines are too expensive and not best suited for the mainstream sequencing applications. Illumina meanwhile has a dual model: It caters to those that don’t want to mess with the sequencing themselves but would rather hand over the job to somebody with experience; it also does well in selling sequencing machines to those that prefer doing it themselves. This model, however, is agnostic to the type of sequence (human or not; whole genome or exome).
Complete Genomics, on the other hand, has specialized on just human whole genome sequencing. I like this model a lot from a commercial perspective as this is the area where the future diagnostic sequencing volume will be, and specialization not only allows the company to optimize its technology for this single application but also to put relatively more resources into developing the requisite, value-adding bioinformatic analysis tools. The company is struggling with convincing the market that the currently more widely used/pushed exome sequencing is not more than a blip in the history of sequencing, a history which will inevitably culminate in routine whole genome sequencing. Claiming that exomes, which cost almost as much as whole genomes to sequence, have staying power feels kind of like arguing that Alnylam has 'proprietary' SNALP technology, just because Alnylam has a larger advertising budget. Maybe not the best analogy, I admit, but if you are still reading this, then chances are that you don't mind and even agree with me.
Ultimately, what I find exciting and scary at the same time about this business model is that at one point a company like Complete Genomics will have assembled a treasure trove of sequence information. It will e.g. have a very good idea where to find the families with severe hypercholesterolemia, information that I imagine a Genzyme or healthcare insurance providers would love to know about.
Vertex Pharmaceuticals today received approval for a genetically personalized Cystic Fibrosis drug, Kalydeco (probably named by the same consultants that gave Kynamro its name), for which it has plans to charge around…three hundred thousand US dollars per annum (note: an earlier version mistakenly referred to Genzyme as the CF drug maker). It’s difficult for me to understand what a 10% improvement in lung function means to a CF patient (probably a lot), but even if it’s a great relieve who does not wonder whether such costs are sustainable: have 10-15 adults work for nothing else but to pay for the treatment of an unfortunate CF patient. I’m sure we’ll witness similar debates raging once the first RNAi Therapeutics get approved. Hopefully, a winning combination like RNAi and whole genome sequencing can contribute to keeping the financial cost of personalized medicines low by increasing drug development success rates through better targets and RNAi platform efficiencies and keeping waste to a minimum by only treating people genetically predicted to respond to the therapeutic.
Disclosure: I do not hold GNOM (Complete Genomics), and unless it drops by 30% for no good reason, do not have plans to buy over the next week.