Thursday, October 11, 2012


It is hard to believe that so much activity and information can possibly be packed into a single day...This morning Brock and I kicked off the NACFC with a breakfast meeting with Dr. Beall.  I get incredibly nervous when I know I will be meeting with Bob, but after that first hug and bout of tears, it only takes minutes before his demeanor puts me at ease.  We took the opportunity to share all the details of our Kalydeco experience with him and gave him the book we made filled with the "true Kalydeco stories" from other patients.  Hearing those success stories is extremely rewarding for Bob and if you contributed to the book, Thank you.  He truly loved it.  I feel like a big hog, because all the "thanks" has been given to me, even though all I did was assemble the stories.  When I get back home, I will post some pics of the final product.  It was such a privilege to put together so many beautiful stories. 

* The most exciting and fantastic news that I have to report from today is the positive buzz regarding the VX-809/VX-770 combo!   Tweaking dosages of both compounds has enabled them to reach the statistically significant improvements they were looking for.  They were able to rescue approximately 30% CFTR function, which is sort of the magic number to see big clinical improvements ((Kalydeco rescues approximately 50%, for perspective).  HELL YA!!  I'm super encouraged that this combination will be progressing to phase 3 trials, and could be coming along sooner rather than later.  Even if it isn't the "magic bullet" that Kalydeco is for gating mutations, this combo could go a long way toward improving/stabilizing lung function and increasing quality of life. Isn't that what it is all about? 

* The recently listed trial on taking place in Denver for heterozygotes IS the individualized "trial of 1" or "trial in a box" design that Peter Mueller of Vertex proposed earlier this year!  It is a small initial trial, but this is really exciting news for heterozygotes, patients with rare CF mutations, or anyone who wants to see individualized genetic modifier treatments reach patients FASTER.  This will enable patients with any suspected surface CFTR activity to trial Kalydeco and decide whether the therapy should be continued based on their own body's response.  Again, HELL YA!!  

* The overall feel I got today regarding Ataluren, is that this drug hasn't lived up to expectations.  There was some discussion about the possibility of combining a drug to increase translational read-through of the CFTR protein (like Ataluren), with a potentiator like Kalydeco to boost results... But, it was mentioned several times that they already have discovered compounds that work BETTER than Ataluren ever did at improving protein read-through.  The biggest problem with Ataluren is that it binds to the same site on the cell's ribosome as some inhaled antibiotics like Tobi and other aminoglycosides.  Basically, Tobi and Ataluren need to work on exactly the same spot in the cell...if Tobi is there, Ataluren can't bind and do its job.  Inhaling Tobi almost completely nullifies the therapeutic effect. Damn.  The Ataluren presentation was very vague and I still don't have any answers about what their steps are moving forward (I even mustered the balls to stand up to the mic and ask the presenter a question about their plans for further trials or to combine with another compound and wasn't given a conclusive answer.).   Again, I'm not certain about the future of Ataluren, but my overall feeling is pretty negative about this drug reaching the market to treat Class 1 mutations on its own.  The primary trial endpoints were not met, and the antibiotic interaction problem may be too large to overcome.  Again, the information given was quite vague, and I just want to reiterate that this blog is my interpretation of what was presented.  It was never directly stated that Ataluren won't move forward.  In their words, "we are working with regulatory bodies in the U.S. and Europe to determine the best path forward."  What does THAT mean?? 

* Lastly, I want to mention that the first Plenary session today was amazing.  There was a SHORT celebration of the success of Kalydeco, followed by details of their plans to move forward to treat the rest of the CF pop.  They are impatient and understand the urgency to keep progressing.  They now understand, in dizzying detail, the dysfunction of F508 and have a road map for correcting it.  As mentioned earlier, there is positive buzz about the VX-809/VX-770 combo, but the "second generation" of combos already being tested in the lab have the potential to rescue 70-80% CFTR function--far exceeding the effect of Kalydeco for gating mutations.  To achieve these results, the second generation drugs must address the multiple dysfunctions that this mutation presents: 1) folding, 2) stabilization, and 3) gating.  I said it last year and I'll say it again: THEY HAVE IT FIGURED OUT.  IT IS A MATTER OF TIME AND MONEY.  I'm more optimistic than ever after a full day of lecture.  I have so much more to say, but it is after midnight and I have another full day tomorrow.  I plan to write summaries of the individual talks I attended today, which focused mainly on F508 correction and early CF lung disease.  Brock and I also attended a fancy dinner this evening, where my Kalydeco tattoo was finally uncovered to be appreciated and photographed by many : )  The speakers at this dinner gave moving presentations that didn't leave a dry eye in the house.  I am experiencing emotional overload.  I may have finally exhausted myself to the point of sleep.


  1. I knew you couldn't go to bed without an update! Thanks for taking time to share so much. You must be exhausted--both mentally and physically! I listened to the Vertex conference call today and it was very informative. Had much of the same info you mentioned above about the Vertex trial data and the future drugs in the pipeline. While I'm excited, the combo timeline for heteros always leaves me a little sad. I hope the label for the 809/770 combo will be broad enough to include heteros so they can at least try it and see if it works like Kalydeco does for Savannah. Also, would love to see them open up the trials for 661/770 combo for 12 yrs old and up like they did the trials of 1 in Denver. Could you ask if you get the ear of someone from Vertex?

    Can't wait to see pics. Have fun!

  2. Nice Job. Really. Nice analysis.
    about the recent "trial in a box". I'm happy that it's the same trial Peter mueller anticipated on March, but why is enrollment just for 21 patients? And investigators are recruiting in the "Devnver" area at the moment, why not expanding in the whole USA or even in Europe (in a vision of expanding label to Europe then).
    Thanks for your "mission"

  3. Well done Rebecca! And thank you for reporting from the front line. It is great to see there is an effective treatment out there for the rest of the CF population. I cant wait until CF is not something considered a life sentence.
    I am so pleased Bob liked the book. I feel so incredibly lucky that my daughter could be part of something he had been instrumental in creating…I just wish it was not SO expensive.
    I look forward to hearing your updates from the rest of the conference.
    Karen xx

  4. Rebecca- Can't begin to thank you enough for bringing this information back to the rest of us who can't be there to witness it, but are waiting with bated breath (literally and figuratively) to hear the news.

    I was thrilled to hear about the success of 809/770 yesterday, but as someone with 2 copies of W1282X and advanced disease, I can't help but feel left out of the excitement and hope. It is the best time in the world to have CF because control is really in sight -- unless you have a stop mutation. It's a hard place to be.

    Regardless, thank you for your interest and attempts to probe about Ataluren. The vagueness is frustrating. I'd rather know the truth, no matter how bleak it is, than continue to hold out unsubstantiated hope for its future (in combo with a potentiator).

    I'm looking forward to the rest of your summaries. Thanks so much again! Emily

  5. Excellent information, Rebecca!! Thank you!!

  6. So wonderful to meet you last night! Sorry I didn't have much time to talk but glad I got to find your blog this morning. Have a great time learning more today :)

  7. Rebecca you are nothing short of amazing!!! Thank you so very much for sharing with us, I know you have to be so exhausted!! I will have to find a way to see the internet this weekend!! I worry like Teresa that they will leave the label closed to only Homozygotes so no one can at least try it until the Hetero comes out. Also that is amazing about all of the new things yet to come!!!

  8. Rebecca, WOW! thanks for sharing this. That last point made me gasp out loud. 70-80%??? That is incredible! I am so excited for the future of CF care! And I'd love to see pictures of the book!