At the beginning of the month, the FDA approved Orkambi, Vertex's second drug that treats the underlying cause of cystic fibrosis. Unlike Kalydeco, which treats about 5% of the CF population, Orkambi (which is a combination of Kalydeco—ivacaftor—with another ingredient, lumacaftor) could eventually treat 50-60% of CF patients worldwide, which is pretty huge. I have several friends who have already received Orkambi and started taking it. While it's not as universally helpful as Kalydeco and there are some patients who don't see much difference in their health except for becoming more stable, it's still really thrilling to watch it starting to roll out.
Long before Orkambi hit the market, I started getting e-mails from women and occasionally men who were hoping that Orkambi (previously called VX770/809) would help them but wondering about its safety profile in pregnancy. I totally get this, since one of my big concerns before and after Kalydeco was released was how it would effect a fetus, since I had been trying to get pregnant for about a year and a half when I started taking Kalydeco. For a long time I didn't have anything to say to these curious people, because Vertex didn't release any of its data from rodent studies of pregnancy and lactation until Orkambi was FDA approved. Now, however, they have, and since I'm getting this question even more I figured I would make a handy dandy blog post that shared all of the information I've been able to find.
A quick recap: Why I stayed on Kalydeco (and why I can't tell you if you should stay on Orkambi!) while pregnant
(For a more complete picture, read this blog post)
Let me start this post with a big fat disclaimer: I am not on Orkambi, I have never been on Orkambi, and I can't tell you if you should try to get pregnant on it or not.
There are so many factors that go into making huge decisions like these, and the clinical safety data is only one small part of the puzzle. I've heard from women who have decided to stay off Orkambi until they get pregnant and then start it, which is great. Had I been less fertility-challenged than I was, I might have done the same thing with Kalydeco when it was first released. However—and this is a key part of my story—I'd already been trying to conceive for a year and a half when Kalydeco became available, and at that point I was nearly menopausal at twenty-three because my hormone levels were dangerously low due to the stress CF put on my body. I considered it dang good if I had four menstrual cycles a year, which is a condition under which it's next to impossible to get pregnant.
The way things were going, we were staring down the barrel of a long-term infertility problem, and my doctor and I both felt like waiting to start Kalydeco until after I gave birth was unwise because that could potentially be a very long time down the road. Also, although my lung function was high, I had had a very rough and unstable couple of years in which I was hospitalized regularly and spent most of my time feeling very sick. Had my lung function been more stable or my overall health been better, I might have decided to wait.
So I think it's important to remember, if you're in the position of trying to decide whether to roll the dice with a brand-new drug and pregnancy, that there are a lot of factors going into it and that you have to ultimately do what you feel most comfortable with. What I chose to do was not necessarily what my doctor was most comfortable with (see my original blog post, linked above), but it was what my husband and I felt was right after much soul-searching, prayer, and research.
Orkambi's safety data, and why those myths you've heard aren't true
And now to the good stuff: How safe IS Orkambi in pregnancy?
While the VX770/809 trial was happening, there were years' worth of rumors about how unsafe the combination was going to be for pregnancy. The study required two forms of birth control, and had very strict rules about being disqualified from the study if you discovered you were pregnant anyway. Because of this, a lot of people started hypothesizing that 770/809 was extremely dangerous to a fetus and already known to cause birth defects. This always seemed very fishy to me, but at that time Vertex had not released any of the data from its rodent studies, and so I couldn't ever completely dismantle the rumor mill.
However, there are two things it's really important to understand about Orkambi: First, that every drug trial will require birth control. (And if they don't, they're not very ethical, or it's a drug that's been on the market for a long time and is just being used in a new way.) This is for two reasons—because it's highly unethical to try an untested drug on a pregnant human, and because many medications can interfere with hormonal birth control and no researcher wants people accidentally getting pregnant during her study because it turned out that the new drug interacted with a patient's birth control pill. I was offered the chance to be in the original studies for Kalydeco, and the requirements were exactly the same. Two forms of birth control. Immediate disqualification if you were found to be pregnant.
The second thing that's important to understand is something I already said above, but I'll say it again: None of the data from the rodent studies of pregnancy and lactation had been released for Orkambi until it was FDA approved. Therefore, all the rumors that Orkambi caused terrible birth defects were just speculation.
Now that the data has been released, it's very easy to find: It is in every package insert in every box of Orkambi, and also available online here. And guess what? Just like Kalydeco, Orkambi has been given a Category B rating by the FDA, which means it's unlikely to cause harm. Although it hasn't been tested on humans (because, again, that's highly unethical), none of the rodent studies (during which rats and rabbits were given many times the human doses of both lumacaftor and ivacaftor) turned up any birth defects or other issues with the pregnancy, although both drugs cross the placenta and are excreted in breastmilk.
My own experience with Kalydeco is that some doctors are very trusting of the Category B rating, and others (like my own doctor at the time) don't feel like it means much at all without the human data to back it up. However, to put it into perspective, most CF drugs are actually rated Category C (a slightly higher risk of adverse events in pregnancy), including things like pancreatic enzymes. My point there is not that Orkambi is necessarily safer than enzymes, but that almost no CF drug is without some degree of risk in pregnancy.
So what should you do?
Only you, your doctor, and your partner can make that call.
Were I in the same position I was in before starting Kalydeco—infertile, unstable, and frequently ill—I would probably choose to start Orkambi and stay on it during my pregnancy. Personally, I would probably not choose to start Orkambi and then stop it later if I found out I was pregnant; although I did consider doing this with Kalydeco when it was a brand-new drug and not much was known about it, I've since heard several stories of people who stopped Kalydeco for one reason or another, ended up getting really sick, and never were able to get back to the health they'd experienced before once they resumed their Kalydeco. It's a phenomenon my previous doctor noted too—he went so far as to say that he felt like even one missed dose of Kalydeco can have serious adverse effects. I don't know if Orkambi will be the same, but it's similar enough that I personally would probably not risk it, because the beginning of pregnancy is a time when you want your health to be at its peak, not taking a huge hit.
And, before I go, one last thought: I've had several women tell me that it's so much scarier to think of taking Orkambi in pregnancy than Kalydeco, because there are so many anecdotal stories of Kalydeco being safe in pregnancy now. And that's totally true. But it wasn't that way for me, or for the other women who got pregnant on Kalydeco immediately after it was released. There were about 4 of us who all got pregnant very close to each other in the three or four months after Kalydeco hit the market, and with one exception, none of us even found each other until after our babies were born. At the time that I got pregnant with Kate we though I might be the only person in the world who had ever gotten pregnant on Kalydeco. (A few weeks later we learned that there was another woman a few months ahead of me, and after Kate was born I connected with a few more who had gotten pregnant very close to the time that I did.) Kalydeco itself was a totally new quantity in the world of medicine as a whole; nothing like it had ever existed before and nobody had any idea how it might affect a fetus.
So I most certainly do understand how terrifying it is to think about yourself and your baby being medical pioneers in this way. And, as I said before, I really can't speak to what anyone should or shouldn't do, because every situation is shaded in its own unique and specific ways. Still, I hope that this information can help a few ladies out there to have safe, confident pregnancies. CF mamas are some of the bravest, toughest warriors I've ever met!