While you read, enjoy this picture of my lungs.

Yesterday, UNC School of Medicine published a research article in Science Translation Medicine saying that they found evidence that Vertex Pharmaceuticals experimental potentiator drug—the one that is supposed to move the defective CFTR protein—is destabilizing the CFTR protein after the corrector drug fixes it.

Now, this wasn’t observed in patients, but in “…cultured CF epithelial cells in an environment that mimicked a human lung”, but it’s the first evidence we’ve seen that the combination therapy for Delta F508 patients might not be everything Wall Street wants it to be. The press release goes on to say that perhaps “the destabilizing effects of VX-770 on the corrected CFTR protein might be less robust in the human body than were the effects seen in lab tests using human lung cells” and lead researcher Martina Gentzsch, PhD notes in the press release that

…the drugs may produce beneficial effects by mechanisms unrelated to correcting the mutant CFTR protein. For example, Gentzsch’s team found that VX-770 can decrease the function of a sodium channel in CF epithelial cells and other cells. Researchers also have found that VX-770 has antibacterial properties.

Aside from all the talk about destablilization, I think it’s interesting that the words Vertex and Kalydeco don’t show up anywhere in the press release. Perhaps that’s not so strange—this is honestly only the second research related press release I’ve ever read, the first being the actual Vertex release—but given the adverse reaction I had to the Vertex spin machine back in June (when their intial results were announced), it’s something I immediately noticed.

I posted how I felt about the study before the results came out because—in the interest of science—I wanted to catalog my initial reaction. For those who don’t feel like reading the other piece my reaction boiled down to “Nice try, but we’re not quite there. Also, I can’t stop shitting.”

Roughly two weeks later, I saw that Vertex stock went up 40%, which meant two things: the study results were out and I was violently wrong about them.

The first article I read about the results was this one from Forbes:  This section caught my attention:

Some important caveats on the data: Vertex did the analysis itself, and even lead investigator Ramsey hasn’t had a chance to look at it deeply, as she will before it is published. The company shared the data with me ahead of its release this morning on the condition that I only talk to Vertex executives, Ramsey, and a representative of the Cystic Fibrosis Foundation , which funded the drugs development. I think the data are strongly positive, but I haven’t had a chance to show the results to outside experts as I usually would.

Hmm.

Reading the actual press release, I at least learned why I didn’t feel like the pills worked: very few people did. From the press release:

Statistically significant changes were not consistently observed for patient-reported respiratory symptoms as reported in the CF questionnaire-revised (CFQ-R).

That means that the increase in lung capacity of 2.6-4% is not easily observable by patients in their everyday lives.

What I have observed is that it’s really fucking weird when a bunch of people get really excited that they might be able to sell you a drug for six figures a year. I felt like there was more commentary on the stock price than the actual results. The question wasn’t so much “Will it actually help the 22,000 people with the Delta F508 mutation?” as “How much will those 22,000 people pay for it?”

It has made me very, very angry.

Mind you, I’m not anti-capitalism. I’m sure my attitude would have been much different if this had been a functional cure (my favorite deleted joke from the Can’t Eat, Can’t Breathe book: “There are some exciting new drugs being developed for CF. No one seems to want to use the “c-word”, but they also don’t want to say “cure.”) It just felt wrong to me, like everyone was cheering a single as if it were a home run or praising the Emperor’s new clothes even though his “suit” is clearly just a Crown Royal bag cinched around his dangly bits. So, I wrote about it.

It quickly became clear that my tone was wrong. This was still the honeymoon period and I was showing up with too many sour grapes, too much anger, like I was over compensating for everyone else’s excitement. Like my mother used to say “Don’t piss in a river and expect to change the current. All you’re doing is making yourself feel better.” (My mother never actually said that, but I like the sound of it).

I never posted that piece, but I’d like to share some of it with you now:

This data assumes that the effect of all treatment is cumulative. I’m not saying it’s not; I’m saying we can’t assume it is. For instance, my morning routine consists of Pro Air, Pulmozyme, Hypertonic Saline and 30 minutes of Vesting. A 2-4% increase in lung function is not enough to stop all of that. However, my lung function was never measured after I did all that. That’s good: we know that these pills cause an increase in baseline lung function. But does my morning routine build on top of that? Does changing the makeup of my mucus change the way Pulmozyme—a drug that thins mucus—affects it? What about the hypertonic saline? These are things that should be tested before we throw a parade.

I also object to—though I am not surprised by–some of the soft language in the press release. I understand that side effects are now “adverse events,” but dyspnea? I had to look that one up. It means shortness of breath. 55 (15%) patients in the once daily 600 mg Lumacaftor group and 48 (13%) in the every 12 hour 400mg Lumacaftor group experienced dyspnea. 40 patients (11%) in the 600 mg group experienced “respiration abnormal” while 32 patients (8.7%) in the 400 mg group experienced it. How much overlap is there between these two groups? Are these the same patients?

I really wanted to have a conversation about the actual benefits of these pills, but I was too emotional. I probably felt a little left out since my pet problem–the fact that these pills appear to be running a train on my digestive system—doesn’t show up anywhere in the press release. I hope these new findings open up the conversation and aren’t just immediately dismissed. Even though the increase in testosterone from taking the pills has made my face look like I was it with a burrito supreme, I’m still on them. I just want some hard data to show it’s worth the six figures they want for them.