ALS Advocacy

ALS Advocacy
Lou Gehrig's Disease - Motor Neuron Disease - Amyotrophic Lateral Sclerosis
Thought it had been cured by now? Still no known cause. Still no cure. Still quickly fatal. Still outrageous.

Thursday, March 17, 2016

This Was Simply Wrong On So Many Levels -- Neuraltus NP001



This is the story of a couple of my friends and an investigational drug for ALS -- Neuraltus' NP001.  It contains many pieces of ALS history that must not be forgotten.  And they must never happen again.

Introduction -- It Started in 2010
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I met Rob and Ben online as a result of their participation on some ALS message boards. They were both really smart gentlemen with ALS.  They were both scientists.  Rob was an accomplished statistician who had professionally worked for General Motors on predicting car parts failures.  He said it was excellent background for his second career in trying to outsmart ALS.  Ben was a medical physicist.  His expertise was in medical proton accelerators.  He said that he worked on equipment that took cancer patients within inches of their lives so that they could live.  He wanted the same right for himself.  Rob and Ben were also young fathers with lovely families.  We three all had dogs named Otis.  And so the story begins.  By time you finish reading this, you will know them, too.

It started in June of 2010.  People interested in ALS science kibitz on the forum at als.net.  The first inquiry about Neuraltus' NP001 came up.  Did anyone know anything about it?  The question was posed by Eric Valor, a young man with ALS and a gifted scientist. When he asks, people listen.  And he was an essential force throughout the NP001 saga that followed.  The images below are from conversations on the fora at als.net or patientslikeme.com.









The conversation began.

By August, Rob was really digging in.  He and the others on the forum do this with everything that comes up in the news or literature, trying to figure out what the stuff is. Rob found evidence that it was related to a compound already marketed in Europe for other indications - WF10.  It was some form of sodium chlorite.

The  Phase I trial was a safety/dosing trial on the surface, but there was a placebo arm.  Something else was going on.  Every ALS trial is an efficacy trial, regardless of what the phase says it is. Maybe that was it.  Or maybe they were looking for a biomarker.  You just don't think of placebos as being essential in a safety/dosing trial.

Rob scoured the literature. That Phase I trial went quickly.  By November they knew that NP001 was safe and a dose-dependent biomarker had been tracked.  Interesting.

By December, Rob had uncovered some patent applications.  The startling part was that as far back as 2005 the similar product, WF10, had been used in two people with ALS with good results.  Five years earlier there was a reason to think that this could do something.  Five years.  Nobody pursued this in five years.  That was another 600,000+ ALS deaths ago.  You can see Rob's comment below.








Chapter I -- The 2010 Symposium
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Every December there is a global ALS symposium that attracts around 800 researchers and healthcare professionals.  It has never encouraged people with ALS to attend, but that didn't stop Rob. It was in Orlando that year. He was interested in the science. Nothing would discourage him from attending.  The most hyped new drug for ALS to this point was dexpramipexole.  NP001 was still in the shadows.

Rob met researchers working on several clinical trial candidate drugs.  He came home with a particular interest in NP001.  It was based on data (albeit a very small sample) and science.  And he wanted to find out if his patent research was correct.












Chapter II -- The Phase II Trial Starts
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Keep in mind that dexpramipexole Phase II trial enrollment was being hyped by a lot of organizations.  NP001 was simply not on the radar.  Rob was concerned about the NP001 exclusion criteria that would keep him out of that trial.  He was quickly approaching 24 months post-onset, a traditional barrier to ALS trial participation.



NEALS (referenced in Rob's message above) is a large Clinical Research Organization (CRO) that is considered to be the leading such organization for ALS clinical trial design and administration.  Neuraltus was using a different CRO.







People online were starting to get interested in NP001, and a man with ALS made a telling comment on a forum.  There were no contingencies for access to NP001 after the trial or for those with ALS who did not qualify for the trial.







Yes, people with ALS can interact intelligently with scientists and business executives, yet they are never called to the table for input before things are designed. The importance of trial design will become even more apparent as you read on.  In the meantime, Rob kept working trying to get the inclusion criteria for the NP001 trial expanded.








Rob was placing the investment of himself in medical research with NP001.  He enrolled in the trial and didn't say too much publicly about his experience.









The schedule slippage began.  Take a look at the last paragraph.













Rob didn't say much at all publicly, but he told me that he was noticing things.  He was still driving and one day realized that he was able to work some controls in the car that he had not been able to work before.  ALS trials always try to determine if people are getting worse less quickly than they were before.  Rob was actually seeing improvements. He didn't want to say much but was tracking data religiously and taking videos of what was happening.


Ben had indicated that he was going to join the dexpramipexole trial. It seemed most promising to him.  After some correspondence with Rob, he decided to try the NP001 trial even though it was less convenient for him.  The two scientists wanted to be human lab rats with something that  perhaps was actually doing something.  It may not have been a long-term solution, but it was doing something.


Ben enrolled and started NP001 infusions on June 20, 2011.  And his tagline reflected his belief that the data must be captured publicly if the science is to advance.











The trial was designed to require 21 weeks of infusions with a placebo, a low dose, or a high dose.  Each participant would then be monitored every four weeks during a washout period to watch the activity of a proposed biomarker.  No drug would be available during that washout period, and there would also be further monitoring through about 9 months with a final interview at 49 weeks.




Chapter III -- Fill the Trial!
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Ben was on a mission as you see below.  Both Ben and Rob believed that if there were participants who were actually improving that the Data Safety Monitoring Board (DSMB) for the trial would step in and not withhold product from those who were experiencing improvements.  Surely.










As the realization that the trial design wasn't ready for patients experiencing good things was sinking in, Rob asked people to reach out to Neuraltus.


Ben loved coffee.  The ALS had made it impossible for him to drink it without choking.  He emailed me that he inadvertently had taken a cup of coffee at one of his infusion appointments in Lexington and suddenly realized that he had finished a cup of coffee.  Something was going on.






















Rob expressed frustration at NP001 not being on organizations' promoted trials lists.  





They started speculating on possibilities for approval, yet they knew that the only thing they could control was filling that trial quickly.














The reality of the trial design was sinking in.  The biomarker was going to be tracked come hell or high water, regardless of what that meant for the people in the trial.  Read Rob's last sentence below.












And Ben questions whether we have developed an obsession with biomarkers and have lost sight of ethical ways to find them.










And Rob agrees.


And the statistician Rob pleas with researchers to look at what is going on here.  It's different.






Ben continued to fill seats in the trial.  He traveled from Indiana to Lexington for his infusions.  He searched for ALSA support group meetings in Lexington and showed up one night.  The people there were not aware that in their own backyard there was a trial seeking volunteers.  That's a telling indictment of the effectiveness of organizations at getting information to patients regarding clinical research.  If they wonder why people don't enroll in trials, they should look in the mirror.  Ben and Rob filled a trial in record time through their own efforts.







And Rob was giving interested people information that they were not getting from the trial sites. 






And their efforts continued.  And ALS organizations should have been embarrassed.




Both Ben and Rob were keeping meticulous records in their profiles at PatientsLikeMe.com.  They were encouraging all in the trial to post their data, too.





And some things are just not captured by ALSFRS-R.






And they continued to recruit relentlessly.








There was still a confidence that the DSMB could and would see that some patients were getting actual improvements and would act.
\

The term "Accelerated Approval" enters the conversation.








Chapter IV -- The Horrible Premonition Sets In
__________

The reality of an inflexible system is starting to set in to Rob who is approaching the end of his time on NP001.  The DSMB won't learn about their improvements.  There will be no decisions to modify the plan.  And there is a long period staring at him when he will no access to the drug so that a biomarker can be tracked.




They are capturing and watching data.  Statistician Rob has figured out some subgroups (high side effects, low side effects, no side effects), and responders seem to be in the high side effects group.  Rob's words below are a terrible portent of what is to come -- "This has me really concerned for what will happen at the end of the trial. I am convinced that I wlll again decline, just like those of the patent..."















Ben comments on the trial design and his pessimism about what will happen next is setting in, too.











Ben will fulfill his commitment to the trial, but he is planning ahead.  And his words in his last paragraph below about his work and cancer patients should stick with us all.






And Ben continued to monitor his grip strength, an outcome that this trial did not measure.  And he was clearly measuring improvement.













And see Ben's words below. Surely the world would watch in horror as those in the study begin to decline again. Surely.


And Rob speculates and says that Neuraltus must lead.  Surely they will. Surely.









Rob speaks to what we already knew about the lessons from the old data on WF10.  Is Neuraltus going to withhold drug to watch a biomarker crash while the trial participants crash?  Why is this trial designed this way?





Neuraltus knows the patients are going to crash.  Why are they doing this?









And Rob notices that the patient advocacy organizations are conveniently failing to pay attention to their plight.











We hear more from Rob on his condition and the trial's endpoint selection.


















And again, Rob speaks to what is within the control of Neuraltus. Surely they will act. Surely.




















Chapter V -- Neuraltus and Others Fiddle, Patients Burn
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Clearly the search for the worshipped biomarker is at odds with urgency and humane treatment of participants with this trial design.













Rob and Ben finished their commitments to the trial.  They endured the washout period and crashed, each losing the gains and wondering where they ended up relative to where they would have been without the trial.  Neither posted much about how poorly they were doing without the NP001 while their data were monitored, but their emails reflected their frustrations and disappointment, not only with Neuraltus, but also with organizations that they thought would advocate on their behalf.


Both tried some do-it-yourself  NP001 options after that washout period.  Ben was featured in the Wall Street Journal for his efforts.  Both men tracked their data religiously at PatientsLikeMe so that others might learn.

They weren't the only ones who wished the trial had been designed differently.  I met a grandmother at the ALSA Advocacy Conference that year.  She had terrible bulbar symptons.  She said that she had been in the trial and had done so well, and since the washout period when they were observing her without NP001, she had just gotten so much worse.  And there were others on the message boards who felt the same way.

Below is Rob's ALS Functional Rating Scale R (ALSFRS R) chart from PatientsLikeMe.  ALSFRS R is a summary measure that misses many details.  You can see the uptick during the period when he was on NP001.  There was an immediate and steep decline while Neuraltus watched his data decline relative to their biomarkers.


And below is Rob's weight chart. 


Here is Ben's ALSFRS-R chart.  ALSFRS-R wasn't granular enough to pick up many of his gains



And Ben, too, had the precipitous weight loss.




They did not have easy deaths.

Rob died on September 10, 2012.
ROBERT WAYNE TISON
ARDEN - Robert Wayne Tison, 42, passed away peacefully on September 10, 2012 in his home in Arden, after a brave battle with Lou Gehrig's disease (ALS). He was a loving and devoted husband to his wife of 17 years, Kelly and beloved father to Tyler (15) and Sydne (12) and his best buddy Otis.
He is survived by his wife, Kelly Renea Tison and two children, Tyler and Sydne; his parents, Barbara and Darryl Tison; a brother, Lynn Tison (Lisa) and a sister, Cassie Jerore (Duane) of Michigan; in-laws, Grandpa George Thatcher, Rich and Sue Thatcher of Asheville, sister-in-law, Amy Herren of Asheville, and many nieces and nephews who loved him very much (Matthew, Megan, Michael, Mitchell, Madison, Taylor, Luke, Cody and Jordan).
Rob grew up in Commerce Township, Michigan and was a 1988 graduate of Walled Lake Central High School and 1993 graduate of General Motors Institute. He has worked as a mechanical engineer for Rockwell, Con-Met (Oregon), American Axle, Cane Creek Cycling, Borg Warner Cooling and Turbo systems. He was a licensed Realtor, and most recently a project manager for Glennwood Custom Builders.
He was an avid outdoorsman and loved cycling, running, hiking, geocaching, kayaking and camping. After being diagnosed with ALS on March 8, 2010 he focused his skills on finding a cure for ALS. He was a patient representative for the CDC National ALS Registry, ambassador for the Northeastern ALS Consortium, and advocated on Capitol Hill three times for money to fund ALS research. He received many awards for his advocacy, including the ALS Association 2012 Rasmussen Advocate of the Year award.
He could be found regularly on PatientsLikeMe.com giving advice and input with graphs to back up his analysis. A Facebook Page was created in honor of his advocacy for ALS (Persevering - You are a game changer).
A gathering for the Celebration of Life service will be at Zephyr Hills Baptist Church, 283 Shelburne Road, Asheville, NC 28806 at 10:30 AM Wednesday, September 12, 2012 with the service starting at 11:00. The family graciously asks that in lieu of flowers, memorial donations be made in Rob's memory to the college fund savings account for Tyler and Sydne Tison at any local First Citizens Bank.



Ben died on August 15, 2013.
Ben Harris, 46
JAN. 2, 1967 — AUG. 15, 2013
BLOOMINGTON — Ben William Harris, 46, passed away peacefully at his home in Bloomington on Thursday, August 15. Ben was born on January 2, 1967, in Menomonee Falls, Wisconsin, to William and Claire Harris.
Ben attended high school at Northfield Mount Hermon boarding school and received his BS in physics from Columbia University. He went on to receive Masters degrees in both philosophy and physics from the University of California, Riverside, and subsequently worked as a dosimetrist and later calibration physicist at Loma Linda University Medical Center. He was granted certification by the American Board of Radiology in 2005. He continued to work with protons when he moved to Bloomington, Indiana, where he was employed as Director of Medical Physics by ProCure Treatment Centers.
Since first learning of his ALS in January 2011, Ben showed incredible courage and indomitable will to make a difference in the face of something that most of us would have succumb to just out of hopelessness. He has shown us again, it’s not when you go, it’s how you go. Ben is survived by his wife, Rebecca; son, Rawden; parents, William and Claire; siblings, Michael, Daniel, Kathy, Amy and Jason; as well as four nieces and seven nephews. Ben was a gentle soul, a devoted husband and father, and a brother without peer.
A memorial service will be at the Unitarian Universalist Church in Bloomington at 3 p.m. on Sunday, August 18. Friends are welcome to visit with the family in their home after 5 p.m. In lieu of flowers, donations may be made to American Funds for an account set up in the name of his son, Rawden.



Chapter VI -- So What?
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This isn't meant to be about a particular drug.  This is about real people and a process that failed them.  This is about two beloved husbands and fathers who volunteered to advance the science who were stuck with a clinical trial design that was inhumane.  This is about all those who weren't paying attention.

This must never happen again. 

Every time we hear about the important search for biomarkers, we should ask whether that will be allowed to impede an efficacy trial.

Every time a drug developer proposes a Phase II trial on the cheap (and, yes, I realize that they are all expensive), we should ask whether it should wait until they can afford to treat the volunteers humanely.

Every time a person with ALS is handed informed-consent documents, he or she should ask, "What will happen to me if this stuff actually does something good?"

We must learn from all that we lost in these two fine people.

Dad always told us that there is a right way and a wrong way to do everything.  This was so terribly wrong.











Wednesday, March 2, 2016

I Am No Longer Speechless

I was speechless when I saw the memo below last night.  I am no longer speechless.

Didn't any of the many powerful addressees say, "This is a horrible response to a serious problem and proposal?"

__________

https://www.change.org/p/tell-als-association-improve-home-care-for-als-patients/u/15675167

Barbara Newhouse's memo to ALSA
staff

Catherine Scott
Murrieta, CA
Mar 1, 2016 — Below you will find the content of a memorandum Barbara Newhouse sent to her staff prior to responding to my first letter. In it, she once again demonstrates a blatant indifference to the urgent home care issues facing ALS patients and their families today. Talking points, concern for stakeholders and a dismissal of the petition’s social media presence…How does that help us? We simply cannot tolerate the leader of the nation’s largest ALS advocacy organization not putting our needs first on her list of priorities.

******* Beginning of Memorandum *******
MEMORANDUM
The ALS Association
DATE February 24, 2016
TO National Board of Trustees - Chairman’s Council - Board of Representatives - Chapter Executives - National Office Staff
FROM Barb Newhouse, President and CEO
SUBJECT Change.org Home Healthcare Petition

Many of you may have seen the petition on Change.org that is directed at me and The ALS Association, challenging us to improve home health care for patients. I am including some talking points in this memo should you receive any questions from concerned stakeholders. I am also including my personal email response to Catherine Scott, who started the petition, who is a person living with ALS.

We are not seeing a lot of traction on social media with this particular petition but do feel it is important for The Association to respond. Therefore, we will likely be posting a note in the comments section of the petition to communicate with those individuals who feel passionate about this issue.

If you have any questions, please contact Brian Frederick, Chief of Staff, bfrederick@alsa-national.org.

Response to Catherine Scott:
Dear Catherine,
I’ve read through each and every comment in your letter and agree with you wholeheartedly that people living with ALS are suffering and families are struggling. These are the reasons I accepted my position with The Association – to help people living with ALS and their families.
Please know that we strongly support policies that expand the availability of long-term care services, including both skilled and non-skilled home health care services. We have a long history of fighting for people living with ALS on this issue. As you may know, we championed the Community Living Assistance Services and Support (CLASS) Act to create a federal program to provide long-term care insurance, including access to home health services. The legislation was enacted into law as part of the Affordable Care Act. Unfortunately, the program ultimately was repealed because it was not financially sustainable. We are continuing to fight for greater access to long-term care services.
Please also know that we are creating new home health care educational and training materials and improving our existing ones – a process we will finalize in the next couple of months. In doing so, we’re working with our Chapters, other organizations, and home health agencies and partners. The purpose of these materials is to provide training and educational resources that can supplement clinic visits, provide information to family/friend caregivers, educate on self-management practices, and aid in decision-making process for patients and caregivers.
Does more need to be done? Absolutely. We are in this together. The ALS Association will continue to actively distribute educational resources, offer care/respite programs via our chapter network, and
lead policy efforts that result in even greater access to home health services for people with this disease.
I would welcome the opportunity to discuss these issues with you in greater detail whenever is convenient. In the meantime, thank you for your comments and concerns. We are here fighting for you, Anthony, and everyone else living with ALS.
Barb

Talking Points:
-We understand that the needs of patients and families—who are living with ALS—are staggeringly great. Through our network of 39 chapters nationwide, The ALS Association is proud to support a variety
of programs that aim to help.
-In the next two months, The Association will be releasing a portfolio of home health care educational materials that address the multitude of questions facing people living with ALS, their families and caregivers.
-The Association whole heartedly understands the urgency around home health care and affordability when it comes to fighting ALS. We will continue to support initiatives that will ensure people get the highest quality care they need, when and where they need it.

Public Policy and Home Health
-The Association strongly supports advancing policies that expand the availability of long-term care services including both skilled and non-skilled home health care services. We have made progress on a number of fronts including:
Establishing a presumption of service connection for ALS at the Department of Veterans Affairs, which enables veterans with ALS to access long-term care services;
Enacting the Lifespan Respite Care Act and securing nearly $20 million for the program which provides grants to states to improve access to respite care;
Eliminating the 24 month Medicare waiting period for people disabled with ALS so that they can access Medicare without waiting for two years before becoming eligible. ALS is the only disease for which
Congress has eliminated the waiting period;
Extending the exceptions process that people with ALS can use to exceed spending and utilization caps on physical therapy, occupational therapy and speech-language pathology services;
Supported efforts to expand the availability of Medicaid so that more people can access long-term care services;
Worked to ensure people with ALS have access to Medicare’s hospice benefit, which can help provide home health care;
Advocated with the Social Security Administration to create a presumptive disability ruling, which enables people with ALS who are eligible for Medicaid to automatically begin to receive Supplemental
Security Income (SSI) payments even before their SSI application has been approved; and
Championed the Community Living Assistance Services and Support (CLASS) Act to create a federal program to provide long-term care insurance, including access to home health services. The legislation
was enacted into law as part of the Affordable Care Act. Unfortunately the program ultimately was repealed because it was not financially sustainable.
-This year, The Association is working with Members of Congress to waive the 5-month waiting period for Social Security Disability Insurance (SSDI) for people with ALS. This will allow people with ALS to immediately receive both SSDI payments and Medicare as soon as their claim for benefits is approved, which can be in as little as two weeks.
-The Association recognizes that while these policies have helped more people with ALS access vital care as quickly as possible, we still have much more work to do in order to ensure people have access to the full spectrum of care and support they need, including to home health care. We are committed to working with you, Members of Congress, regulatory agencies and others to advance this important
issue.

Care Services/Home Care Education Program
-Currently, The Association is collaborating with subject matter experts in order to develop a portfolio of home health care educational materials that address the multitude of questions facing people living with ALS, their families and caregivers.
-The purpose of these materials is to provide training and educational resources that can be distributed in order to supplement clinic visits, provide information to family/friend caregivers, educate on self-management practices, and aid in decision-making process for patients and caregivers.
-Resources will include manuals, brochures, informational one-pagers, videos and other materials and we expect them to be finalized within the next two months

******* End of Memorandum *******


PLEASE SIGN & SHARE THE PETITION:
https://www.change.org/p/tell-als-association-improve-home-care-for-als-patients