Personalized medicine starts with the genetic code

One of the most exciting drugs of 2012 was VX-770 or Kalydeco, as it is commercially known developed by Vertex Pharmaceuticals.  This drug was developed with strong support from the indomitable Cystic Fibrosis Foundation. In about 4-5% of cystic fibrosis patients, the G551D mutation, in the massive cystic fibrosis transmembrane conductance regulator gene (CFTR), leads to a protein that can reach the cell surface but not transport chloride ions. VX-770 can facilitate transport of chloride ions by the mutated protein. This drug follows at least one other that also targets genetic mutations, PTC124 or Atalurin from PTC therapeutics. Ataluren helps ribosomes read through premature stop codons to make full length protein, instead of truncated versions that accumulate and lead to several rare genetic disorders, including cystic fibrosis and muscular dystrophy. This is a water-shed moment in targeted gene therapy, and bypasses the messy business of actually correcting the genetic code or flooding the cell with the right copies of DNA.

Kalydeco was fast-track approved by the FDA, a first for these drugs. Though it can reach only about 4-5% of patients, it is remarkable that this drug (and others like it) actually address the underlying cause, and do not treat symptoms- in other words they seek to cure not just arrest the disease. For a disease like cystic fibrosis, where many mutations have been characterized in the CFTR gene, this could be the only viable treatment option. But it does come with a hefty price, costing upwards of $170,000- 240,000 per year for any patient. But, it clearly is the herald of a brave new world after many hiccups.

It answers some questions, while posing many more substantial ones. Eli Lily estimates the cost of developing a new drug and getting it to the market as 1-12 billion dollars. In the case of drugs such as Kalydeco, targeting a small group of patients, that cost is unevenly shifted to the patient’s pocket, giving us a drug which the wealthiest among us cannot afford for a lifetime. Though the development of the drug is conceptually and procedurally brilliant and rigorous, the price tag may make all that effort pointless. When extrapolated to a wide range of genetic disorders that are wide spread in the developing world, the cost factor takes a whole new dimension.  But still, it is a landmark achievement and its fast track approval, is a sure reason to celebrate. Let’s raise this one, to the genetic code and all its dark mysteries.