Rolling the Dice

About a year ago the FDA approved a drug for people with Cystic Fibrosis harboring two copies of the F508del gene mutation called Orkambi. It’s not like many other medicines. It’s in a special class of medicines called gene modifiers. True to the name its job is to manipulate a defective gene. Welcome to the 21st century – we’re not just treating symptoms anymore, we’ve begun treating diseases at the genetic level.

Since my husband is a carrier of the double delta F508, we followed the drug’s development very closely for a few years. We read the outcomes of the two 24-week trials. We asked his specialists about it. When it was approved we read the blogs and message boards where CFers posted their experiences. But instead of jump on board we sat on the sidelines and watched the parade go by.

We waited for a few reasons. One reason was we felt there wasn’t enough research. Less than 800 people participated in both of the trials that lasted less than a year. There is still no research on what this drug might do after two years, five years, ten years, etc. The only other gene modifier that preceded it’s release (Kalydeco which targeted a different gene mutation in CFers) only preceded Orkambi by a few years. Frankly we really don’t know that much about the effects of manipulating someone’s DNA yet.

Another reason we waited was because the benefits weren’t that promising. Of the small pool of people they researched for Orkambi, some saw about a 3% increase in lung function. Compare this to Kalydeco where the average was 12%. It also seems less safe. Kaydeco is approved for ages 2 and up, Orkambi is not for anyone under 12. Perhaps not surprisingly there was a camp that asked the researchers to go back to the drawing board until they had something better.

The cost didn’t go unnoticed either. Orkambi packs a price tag of overĀ  $250,000 a year. The initial stories were copays of a few hundred dollars a month IF your insurance would cover it. Last night Orkambi was highlighted on the Nightly Business Report because NICE (the UKs government healthcare) – not wanting to set a precedent for backing a medicine that would cost an estimated $100 million annually – denied it. Vertex, the company that developed Orkambi, cites seventeen years of research as justification in the cost. The landscape is still shifting. The specialists tell us the copays now are between $10-$20 for each prescription.

But the final and most compelling reason we hadn’t jumped on the bandwagon yet was the effect the drug has on the body of a CFer. Orkambi is not a cure, nor does it claim to be. It also doesn’t guarantee an improvement of any sort. The best they can tell us is he might see as much as a 3% improvement in lung function and potentially fewer exacerbations.

What we have seen across the various media reviews is Cfers coining the term “hell week” for the initial phase while the body adjusts to the new medicine. They warn the first part – that can last a month or more – is like the worst flu you’ve ever experienced. Many have given up and stopped Orkambi before their “hell week” ended. It must be bad. CFers are not a troupe of pansies.

What began to change our minds now that the drug has been out a year was our last visit to the adult CF clinic. The doctors had changed their tune. An attitude of “it costs too much and doesn’t do enough for all it puts you through” had become “you are a great candidate for Orkambi and it’s a fantastic drug.” Either Big Pharmaceutical got to them or enough patients made it through hell week and saw enough of a change it became worth it to pitch it to other patients.

For the past week we have talked every night. We’ve talked about the good and the bad. The potential and the unknown. The risk and the reward. I am one of those people that won’t take a Tylenol without very good cause and he was participating in drug trials as a kid. We are a good blend of overcautious and experimental.

The trouble with treating CF is they are still discovering things about it. There is still so much they don’t know. For the majority of his life, the medicines he has taken have been giant question marks. Taking a new medicine and not knowing what will come of it is old hat to him. All of the talking and reading and researching and asking has led us to a place where he wants to try Orkambi. It feels like a real life version of the game ‘Would You Rather…?’

He has convinced me all that we don’t know about it might be good. If a defective gene is the problem, what if making that gene behave appropriately for a year, two years, ten years, twenty years reaps results we can’t even imagine? What if each of the effected organs begin functioning better after a period of exposing them to a physical environment with less mucus blocking important passageways? He ultimately convinced me that “what if…” doesn’t have to be a bad thing. It could actually be a very good thing.

So we are rolling the dice. The prescription has been requested and we are waiting for a call from a specialty pharmacy. He tells me he will stick it out for six weeks and hope hell week ends before the six weeks is up. I have arranged a private meeting with my boss to prepare for potential “I need to leave work right now” moments. All of the ducks are lining up for us to step into 21st century medicine.