N-of-1 studies make the most sense given the fact that there are 1900 mutations, the vast majority of these being extremely rare. To complicate matters even more, there is great variability between people who share the same mutation combination. Genetic modifiers and environment, not just mutations, play a part in how CF presents. This means that people with the same mutation(s) may respond very differently to these meds (this seems to be the case with those with ddf508 on the Orkambi trials). So far the number of mutations that Vertex has targeted, including VX-661-107 and VX-661-108 studies, is 157 (about 8% of mutations that have been identified). Granted, this 157 is a large percentage of the CF population since many of these 157 are among the most common mutations. But this doesn’t negate the fact that there are people out there, regardless of how rare their mutation is, that deserve a chance to try these potentially life-changing, life-saving medicines if there is reason to believe they may work for them This is especially the case for those with unstable and/or severe disease. They don’t have the time to wait. They should not be put at a disadvantage because of the rarity of their mutation. For some, this disadvantage may cost them their lives.
I don’t see the N-of-1 study design for individuals being adopted by Vertex anytime soon. So that leaves the options of getting in a study (which isn’t possible for many with rare mutations because their mutations aren’t included in study) and off-label use for those with mutations that have the potential to respond to Kalydeco or Orkambi based on in vitro studies and/or anecdotal evidence. Although this “anecdotal” evidence is actually much more than just patients accounts of their health status. There is scientific evidence involved-- just not part of an official study protocol. For the most part, I think people that have been given the chance to try off-label have had sweat chloride, PFT’s, Chest x-ray, weight checks, and symptom description documentation pre and post Kalydeco. They are officially documented in their personal health records. These results should be shared with other doctors somehow so that they can use this info. when making decisions on who to prescribe Kalydeco or Orcambi off-label. Information should also be shared with Vertex so that researchers can take results into consideration when designing future studies. Doctors need to publish their data in journals since insurance companies require journal articles when determining off-label use. Hopefully the CFF will recognize these needs and have a key role in encouraging all of this. They sold their royalties from Vertex. They no longer have a conflict of interest by promoting off-label use. Their interest should be to ensure that these drugs are accessible to those that will likely benefit from them.
Why am I so passionate about this? I had a lung function of 31% in November. I was not responding to IV antibiotics. Thankfully my doctor took the chance and prescribed Kalydeco off-label even though in-vitro results did not have promising results for my mutation (which is a residual function mutation). My lung function went up to 42% after being on Kalydeco for 5 days. I haven’t been on IV antibiotics since starting Kalydeco and my health has been much more stable than it was prior to Kalydeco. I have been granted the gift of years added to my life- all because my doctor had the chance to listen to other doctor’s accounts of off-label use at the CF conference last October. We need to get the word out there and expand off-label use. Please let me know if anyone has any ideas in helping to make this a reality.
