Cytokinetics Part 2

Thank you to everyone who responded either publicly or privately about my letter to Cytokinetics. I want to share with you the following correspondence, because I do believe that people who are working toward new drug therapies for ALS have the best intentions at heart. This letter is from Dr. Jeremy Shefner, the person to whom I sent the original letter describing my experience with tirasemtiv. He also forwarded my letter on to Cytokinetics so that higher ups in the company including the president were aware of its existence. Late yesterday, I received a letter from the Medical Director and Senior Vice President of the company. I will not reprint that letter here, for I have not received permission to do so, but his concern was very similar to Dr. Shefner’s. Below is his letter with my reply.

Dear Dr. Kramer:

Thank you for your extremely thoughtful letter.  I have passed it on to Cytokinetics, and I am sure you will hear from them as well.  As I do not make decisions regarding access to drug outside of the trial, I will defer to them on that issue.  However, I did want to respond with respect to some of your other points.  First, I do truly appreciate the effort that ALS patients expend on participation in clinical trials.  From conversations with people I care for,  I know that, while everyone hopes for personal benefit in any trial, the main motivations are much more altruistic, and involve hopes for better treatment in the future even if they personally may not be directly impacted. 

The commitment of ALS patients to improving future care helps me maintain my own enthusiasm and commitment toward an effort that, in the last 20 years, has seen more than a fair share of disappointment.

I was also very interested in your comments regarding your perceived areas of improvement on drug, and the question of whether the evaluations in the trial will capture these events.  I guess the only real answer is that we will see.  Improvements in sleep should be associated with changes in respiratory function, and neck control hopefully associated with changes in strength of other muscles that we are measuring.  However, your observations highlight a major problem in ALS trial design, which is that patients present with different constellations of disability, and uniform assessments are likely to miss some areas affected.  As you point out, the evaluations that occur in this study are already extensive and potentially fatiguing; its hard to imagine a trial where even more measures were employed.

The issue of open access to drug for patients who successfully complete a trial is complex.  One sobering fact is that, in the last 20 years, patients in placebo groups of ALS trials have fared better than those in the active treatment groups, primarily due to unanticipated adverse events from the experimental agent.  While the early small studies of Tirasemtiv are encouraging, they are by no means definitive, and prolonged open label treatment prior to the analysis of Benefit ALS carries risks as well as potential benefits.  This drug is different than others tested previously in that, if effective, Tirasemtiv is more likely to produce a symptomatic improvement than agents targeting disease progression.  However, I have talked with patients from many previous studies who are absolutely convinced that an agent which has been shown ineffective in general was working on them.

I am extremely enthusiastic about the potential of Tirasemtiv to improve function in patients with ALS, and committed to see the development process move as quickly as possible so that all ALS patients have access to the drug if it proves to be effective.

I know that Cytokinetics shares this commitment.

Best regards,

Jeremy Shefner

And here is my reply:

Dear Dr. Shefner,
Thank you for replying so quickly to my letter. I sent it to you, because you are the principal investigator  for the tirasemtiv  study, and I thought you might  find the observations from one of the participants in the study  to be of interest. I also sent it to you with the idea that any form of communication concerning the difficulties you so rightly point out in measuring response  in persons with ALS might advance the conversation toward more creative and robust methodologies while still controlling for multiple variables. The fact that you would write such a thoughtful and well considered response is indicative of your own care, and I truly appreciate it.

As you probably saw, I carbon copied a number of politicians and persons with some influence in the ALS research community. This was not done to put you or Cytokinetics on the hot seat, but to acknowledge the complexity of ALS drug trials. There are so many players and so many priorities that must be met in order for a drug to actually be brought to market that the possibility of more responsive testing can be difficult to comprehend. My own work as an educational leader  has showed me that until we put all of the facts and all of the feelings, at least as much as possible, onto the table, with all of the players present – government, industry, researchers, advocacy organizations, study participants – we really have only an incomplete picture of the complexity, and therefore less possibility of constructing more  responsive and creative methods to account for the complexity.

As you also can tell, I only know enough about research design to be a little dangerous. Most of my own research has been qualitative in nature, a methodology that is not understood in the hard sciences but might have much to offer in humanizing and accounting for the complexities presented by a disease such as ALS. I do not know how much time I have (most of us don’t), but I do know that helping the science to become more responsive, better able to account for the multiple presentations that my disease offers, is one of my final priorities. Thus, I would offer that if there is anything that you think I might do to advance such a dialogue, if there is anything that I might do that could help you in your role as an ALS researcher, please do not hesitate to ask. It would be a privilege.

Finally, I have a request. As you may or may not recognize, I have been blogging my experiences with ALS for over a year and a half. My blog, the Dis Ease Diary is not followed by thousands, but it does reach out to several hundreds. As you may have guessed, my blog entry for this week was my letter to you. Your kind and considered response would be most welcome on the blog, and I would ask if you might grant permission for me to share it along with this email back to you. As you can imagine, the responses have ranged from sadness to realism to a sense of wanting to do something. My greatest hesitation in writing my letter in the first place was that some would see it as demonizing the research and the methods. Nothing could be further from the truth.

Dr. Shefner, your response was most welcome, and I do have great hopes for this particular trial. Thank you for taking away a little bit of the isolation of ALS. I wish you only the best.

Bruce H. Kramer, PhD and person with ALS

I am waiting to see what happens next, but at least a dialogue is now opened. I don’t believe that this is all about profit, nor do I believe that we have arrived at the best system.  But I do know that it is the system that we have, and to change it fully would be like turning the Empire State building in the middle of the ocean, if you will pardon the mixed metaphor.

Thank you again for your support and loving expressions. It’s been a remarkable two days.

9 thoughts on “Cytokinetics Part 2

  1. Bruce, your talents, brilliant mind and caring soul inspire. I hope that you are able to impact “the system” and move ALS research forward. It’s way past time for ALS and other neuromuscular and neurological diseases (e.g., Alzheimer’s) to move to the front lines in research and developments of treatments and cures. I also hope you get back the med that helped your sleep and neck strength. Best of luck. Sandy

  2. Dr Bruce, You are such a “warrior” for the good of all, and at the top of my prayer journal entries. May you feel the presence of God in your pain and suffering, an odd sort of paradox!

  3. Bruce, Your teaching skills remain intact.
    Many of us are listening and learning. I hope the medical research people do as well. I continue to hold you and your family in my heart and prayers

  4. Bruce and Ev, you continue to encourage and inspire. Power to the PALS and those who love them.
    Love and Peace
    Brian Boysen

  5. Thank you for posting this personal story. I’m the oldest daughter of 3 to a 66 yr old Dad who was diagnosed last fall with Progresive Bulbar ALS. He has deteriorated rapidly. Down to less than 30% vital lung capacity, can no longer speak and has extremely difficulty breathing as this disease has settled in his respiratory system (less than 1% happens this way). He’s a stubborn, Hungarian immigrant who only retired 2 yrs ago t

    • Sorry, this ended before I was finished. He retired 2 yrs ago to take care of my mom who has severe Alzehimers at the age of 68. He is desperate and so am I to find a cure for him. I attended ALS advocacy event in DC and I can’t help think that his work of being a welder and being exposed to fumes is the reason he had ALS since genetically he was ruled out. Can you direct me to see if this is a possible treatment for him? I think it is.. But need some direction. He tried Rilutek and within 2 days his tongue swelled, he couldn’t swall

      • Again- cut off.. He couldn’t swallow and almost choked again. No one has ever heard of this reaction and I find this puzzling.. His doctors are amazing, but not as willing to take the risks my dad and I are willing to do, please help us fight this disease with every fiber we have.. Graciously- Elsa

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