The Tone-Deaf Won't Defeat ALS

For decades some people with ALS and caregivers have worked hard to nudge and push the fight in new directions.  Organizations and the FDA often appear to be listening, but in reality, they have been tone-deaf to ideas that will require big changes.  They are confident to stay their course, and besides, the annoying people demanding change eventually fade away with this quickly fatal disease.

Yesterday I went through transcripts of the February, 25, 2013, FDA hearing on ALS.  What a complete disappointment that none of the stakeholders in that room delivered on any of the ideas that people with ALS and their caregivers presented there.  Nothing.  That's tone-deaf.  That's a waste of time, money, energy, and, yes, lives.

"Stay the course" is nuts.  The failed status quo must go.  The tone-deafness must end.

A group of thoughtful, unfunded, grassroots people with ALS and those who care about them have found their voice thanks to social media.  Below is an announcement that they issued for your consideration.  They deserve to be heard by people who can actually grasp what they are saying and who are capable of change.

Members of the  ALS patient community are pleased to announce the creation of a new organization, Hope NOW for ALS, (www.HopenowforALS.org )  The  mission of this grassroots organization, comprised of people with ALS (PALS) and their families and friends,  is “to expedite access to promising investigational drugs for the current generation of PALS through the FDA’s Accelerated Approval Program (AAP) and other pathways, and to speed up ALS drug development by promoting improved alternative and humane designs for clinical trials.”   Hope NOW for ALS is hosting the “ALS Rally for Faster Drug Approval” in Washington D.C. on May 11 and hundreds are expected to attend from across the country. www.meetup.com/ALS-Faster-Drug-approval/events/221529700/ 

ALS, also known as Lou Gehrig’s Disease, is a fatal disease for which there is currently no cure and no effective treatment to stop the progression.  The average life expectancy after diagnosis is two to five years.  Some live longer but about half will pass away in under three years.  The genesis for Hope NOW for ALS was a petition, www.change.org/ALSMedication, started in January calling for “accelerated approval” of a promising new ALS drug called GM604.  Through the campaign, many in the patient community became aware of the outdated and broken drug approval system based on the 1962   “gold standard” or double blind randomized controlled trial (RCT) protocol required for new drugs to be approved.  This 53-year-old protocol requires Phase I, II, III trials that take 10 to 15 years and require tens of millions of dollars.  Many promising drugs never make it to Phase III due to the prohibitive cost, or because they don’t meet stringent FDA criteria (P=.05) that often dismisses data even when they demonstrate a drug is effective on a subset of the population.  The current generation of people with ALS has almost no hope for survival unless treatments become available much faster through the Accelerated Approval Program (AAP) adopted in 1992 as a result of AIDS-HIV activism.  AAP was designed to speed up drug approvals for serious conditions that have an unmet medical need.  Still, not a single drug for ALS has moved through the AAP process.  Hope NOW for ALS intends to change that. 

Nick Grillo, Jehad Majed, Eric Valor, and Linda Clark

Email:  info@HopenowforALS.org

Did Anybody Ask Dr. Brantly

Are you worried about side effects from this experimental drug?

Are you worried that it might make you worse?

Do you want a chance at a placebo?

Are you concerned that another scientist might have an option that would be much smarter for your disease... after you are dead?

http://www.alsa.org/news/archive/letter-to-the-als-community.html

Time Out! It's Time To Listen To The Adults In The Room

OK, everyone, this is about much more than GM604.

Genervon and the FDA have been engaging in an interesting p.r. war, lobbing statements overhead while people with ALS and their caregivers are stuck in the trenches.

Genervon has been obvious (and, therefore, not very effective) in trying to make a very public appeal for FDA Accelerated Approval of GM604 for ALS.

The FDA has been very nuanced in making statements to cast aspersions on Genervon.  I'm pretty sure this recent public statement cost the American taxpayer a small fortune http://www.fda.gov/Drugs/DrugSafety/ucm443242.htm

And the media know an interesting story when they see one.

So who is using whom here?  I don't know.  I don't really care.

We need to take a time-out from this p.r. circus and listen to the adults in the room -- the people with ALS and their caregivers.

This is about much more than Genervon.  This is about a failed process for testing and approving therapies for ALS.

Fact:  A number of years ago an FDA representative explained to some ALS advocates that the FDA can't just do things.  They need to react to things that are brought to them, and, frankly, the FDA doesn't get much for ALS beyond a few traditional Phase 1,2,3 trials.

Fact:  Genervon took them something different -- a request to use the Accelerated Approval path that was established for the FDA some years ago.

Fact:  People with ALS and their caregivers have asked repeatedly for the chance to assume more risk in order to try investigational therapies and to advance the science more quickly.  The FDA and our ALS organizations have nodded but delivered nothing to let that happen.

Fact:  We don't know if GM604 will work, but its safety profile to-date does not put the fear-of-God in most people with ALS.

Fact:  Traditional Phase 2 trials are not big enough to be definitive.  They are not designed to look for efficacy, yet for a disease like ALS, every trial is being scrutinized for some sign of efficacy.

Fact:  Traditional Phase 3 trials are dreadfully expensive; therefore, "promising" drug candidates sit on shelves while people with ALS die.

We have a failed process.  It takes too damned long.

We have people with ALS and caregivers who are demanding that the word urgency finally be given some teeth in the fight against ALS.  They are the ones who need to be heard in this conversation.  They are smart.  They are thoughtful.  They are facing a fast and difficult path to death.  They understand good science.  They have eyes wide open about risk.  They know p.r. volleys when they see them, too.

Genervon has pushed the boundaries of the same old same old with their request for Accelerated Approval.  They have upset those who seem to believe that the existing Phase 1,2,3 trial model is the only way to do good science.

Listen to the adults in the room -- those with ALS and their caregivers.  They are smarter than any of the p.r. wonks realize.

You will have a chance to listen to some of them in person http://www.meetup.com/ALS-Faster-Drug-Approval/events/221529700/ .

They are the ones acting like adults here.  They need to be heard.  And this is about much more than GM604.

And The Problem Is... The Big "Therefore"

A public comments period is underway for another new component of the U.S. ALS Registry -- https://www.federalregister.gov/articles/2015/03/24/2015-06654/proposed-data-collection-submitted-for-public-comment-and-recommendations

Please read the proposal on increasing self-enrollment and comment before May 25.

Following are my comments:

"Therefore, efforts to increase Registry awareness among non-referral center neurology practices/neurologists is needed to increase self-enrollment of persons with ALS."

That's a pretty big "therefore."  They are jumping to a conclusion without data, and that's very wrong on a project that needs to be data-driven.

There is nothing in the MMWR report that addresses the completeness of the administrative databases or the self-enrollment portal.  We simply don't know now many noses were missed in their counting techniques.  We have no idea how incomplete their census of people with ALS was.

1. What basis in fact is there that the root cause of low self-enrollment is neurologists at non-referral centers?

ATSDR decided to give large, non-competitive contracts to the ALS Association (and subsequently to the MDA) for "education and outreach" for the ALS Registry.  I believe that the rationale for such no-bid contracts was that they had access to the vast majority of people with ALS in the US via their networks of ALS clinics and neurologists.  They had the captive audience to promote self-enrollment and they were being paid handsomely to deliver them to the self-enrollment portal.

How complete are the data in the MMWR report?  How many noses were not counted by either method used?  We must answer those questions before we fly off and try to solve a problem that we can't quantify.

It is clear from the MMWR report that ALSA and MDA were not able to deliver as many people with ALS through the self-enrollment portal as the administrative databases found.  Is that a problem with the size of the population of people with ALS in their clinic networks, or is it a problem with their education and outreach to motivate their own clinic neurologists and people with ALS to self-enroll?  It's time to do some measuring and to speak to data rather than to assume that the problem must be outside these contracts.

How many unique people with ALS were seen annually in ALSA and MDA clinics, starting with the MMWR report period?  That should be a first clue as to how incomplete the self-enrollment portal data were.  That is also a big clue as to the effectiveness of these no-bid contracts.  Without that introspection and some data, why would we assume that neurologists who are not involved in ALS clinics are "the problem."  

2. Even if the root cause of the low self-enrollment problem turned out to be non-clinic neurologists, what basis is there for the assumption that cold phone calls to neurologists' staffs will actually affect physician behavior to encourage people with ALS to self-enroll?  That seems to me to be an expensive, time-consuming project not based on any kind of behaviorial studies, and it certainly lacks measurable goals for outcomes. 

People with ALS, their caregivers, and American taxpayers need a more accountable, businesslike approach to a project that is important to the fight against ALS.  We need data-driven decisions and not a convenient "therefore" regarding the completeness and root problems of the ALS Registry.  

We're Ticked

The ALS ticking clock goes tickticktickticktick.  And then they're gone.

The clocks of those who are to deliver on behalf of those with ALS often go tick........tick................tick................................tick...............................................................tick.                                                          

The difference is palpable.

On February 25, 2013 (that's over two years or a quarter million ALS funerals ago), there was an FDA hearing on ALS.  The big ALS organizations were in the front row with bells on.  They had a lot to say.

ALSA Item

MDA Press Blurb

Joint ALSA MDA Statement

When you look at the joint ALSA MDA statement, an FDA guidance document for ALS is mentioned repeatedly.  Back at the time of the hearing, the first such document had just been issued for Alzheimer's Disease and it was felt to be a huge step forward in helping researchers design trials that would hit the marks that the FDA needs to do its job.  Having a similar document for ALS seemed to be a no-brainer for a disease needing faster trials and approvals.  The big ALS organizations talked of driving that effort.

Where is our document? It was not on the list of guidance documents that the FDA is scheduled to release anytime in 2015.  Tick.

DMD advocates submitted their draft last year.
DMD Draft FDA Guidance Document

Is it true that wagons are just starting to be circled for ALS organizational stakeholders to begin to talk about an ALS document?   Over two years later?  Tick.

At least the DMD folks blazed a nice trail to follow.

Need anyone wonder why people with ALS and caregivers are rallying in Washington again on May 11 to demand faster FDA paths to approval for possible ALS therapies?  They're ticked, and they live at a far different pace than bureaucracies.  I encourage you to stop by the rally and listen.  They are thoughtful and bright people, and, yes, they're ticked.  All of the talk of over two years ago has delivered nothing. And it seems like organizations are now convening to talk so they can talk about talking at ALS Advocacy Day in May.  We should all be alarmed.