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, July 30, 2015

Of the PALS, By the PALS, For the PALS



It's happening thanks to some formidable people with ALS and caregivers.  They aren't waiting for a system that doesn't understand urgency.

Here is a posting from a gentleman with ALS on the forum (it requires registration to view) at
Rich Casey, the CEO of Neuraltus, mentioned that ALSA is considering funding an Expanded Access (Compassionate Use) program for NP001, in addition to its $1.5M grant for a new clinical trial. As you know, Phase II clinical trial of NP001 yielded promising results in 2012, though falling short of its effectiveness goals. However, post hoc analysis identified "responder" biomarkers. Neuraltus has been trying to secure more clinical-trial funding ever since. Now ALSA expressed interest in underwriting a Compassionate Use program for NP001, along with the trial. Neuraltus believes there is an immense interest in the ALS community for this idea, but would like to have concrete evidence. Having a ready list of potential participants would help this cause, demonstrating the unmet need to ALSA as the sponsor. If you are interested, send a letter to Neuraltus requesting compassionate use access to NP001. This would strengthen Neuraltus's hand in dealing with the FDA as well as ALSA. We also should emphasize that the drug should not be withdrawn from those it helps, to prevent " crashes", like those experienced by Persevering and others during the wash-out period of the 2012 trial.

To: Rich Casey
Below is a  bare-bones sample letter to sign and send, but it would be good include your personal information and why you need NP001. 
Thank you. 

Dear Mr. Rich Casey,
As a person with ALS I want to join the Compassionate Use program for NP001. I am aware that the upcoming clinical trial would have only a limited enrollment. A large Expanded Access arm would benefit ALS research and help PALS. It is also important that long-term access to the drug should be ensured for those participants that benefit from it. Sincerely,
Xxxxxxxx Yyyyyyyyyyy

There are a number of threads on the forum at that discuss NP001.  I urge any PALS, CALS interested to read them.  It definitely did something in some PALS in the Phase 2 trial.  Some also crashed terribly when the drug was taken away.

Here is an article from the WSJ regarding one of the PALS who was in the last Phase 2 trial in 2012:

And finally, here is a powerful letter that one of the Phase 2 volunteers just wrote to Mr. Casey:

Dear Mr. Rich Casey,
As a person with ALS I want to join the Compassionate Use program for NP001. I was in the NP001 Phase II trial and received the high dose. NP001 stopped my ALS dead in it's tracks during the time I was on it. I know first hand that NP001 is a safe and effective treatment for ALS patients. I am aware that the upcoming clinical trial would have only a limited enrollment. A large Expanded Access arm would benefit ALS research and help PALS. It is also important that long-term access to the drug should be ensured for those participants that benefit from it. Thank you for the opportunity to provide NP001 to the broader ALS community, I know it will save many lives.
Kindest regards,
Certainly an expanded access program isn't ideal, but it is something.  This potential therapy for some PALS (elevated IL-18 was cited as being characteristic in responders) has sat on the shelf for almost three years while the drug developer has not been able to raise the capital needed for a Phase 3 trial.  The system is broken.  Why scientists have not been more curious about what was happening with this drug is beyond me.

People with ALS and their caregivers are taking matters into their own hands and trying to open up some options.  They are demanding and getting attention.

I encourage all PALS, CALS who are at all interested in trying to email Mr. Casey now at .  

Thursday, July 23, 2015

Urgency: People with ALS and the FDA

People with ALS and their caregivers understand urgency.

People who work for a large government agency simply don't.

It's time for the former to change the latter.

The people with ALS and caregivers at have issued an update and a call to action.  It is long but well worth reading below.  It will enlighten some and it will make us all think.  These are grassroots people with the ultimate skin in the game. They have studied.  They are thoughtful.  They are leading.  They have made tangible, reasonable proposals to the FDA.  They will also listen to you if you have different or better ideas.

Then please act.  A few messages to FDA officials won't make a difference.  A few hundred might.  A few thousand will.  Please contribute your thoughts directly to FDA employees who work in a bureaucracy that simply does not grasp urgency.

Then please ask others to act.  This is how we all can make a tangible difference.

Thank you.  It's urgent. The FDA needs to know that we're not going away.


Please read and share this important update! 
Hope Now for ALS update: Summary of July 6th call 
Dear Hope Now for ALS (HNFA) supporters, 
We apologize for the delayed update. We have been trying to schedule the next meeting so we could report that in this update. After our July 6 meeting, we submitted a detailed proposal to the FDA and requested a timely response, but it appears the FDA is stalling. They suddenly want to invite other “stakeholders” to our meeting. We believe this is a tactic to bring people and organizations into the discussion that will defend the status quo and to convert the role of actual PALS and CALS into a minority voice. With much regret, we need to report that after three meetings we see little evidence that the FDA is willing to be flexible with respect to clinical study designs and data analysis approaches that could accelerate the development and delivery of safe and effective medicines for ALS. WE WILL NOT ACCEPT THIS! 
Please write the FDA today and copy members of Congress and the media expressing your outrage that ALS is still not being treated with urgency. Demand that the FDA respond immediately to Hope Now for ALS (HNFA) in a substantive and meaningful way as they promised they would. State that you regard Hope Now for ALS as your representative for this process and that you expect the FDA to continue timely, direct discussions with HNFA on expedited and modernized development and approval pathways for ALS treatments – a 21st Century Approval Process! 
Please email Dr. Woodcock at the and copy the people below and your representatives and media contactsdruginfo@fda.hhs.govrichard.mosc 
Summary of the July 6th conference call 
Our third meeting with Janet Woodcock and her staff focused on finding common ground; specifically, balancing the need for faster, less costly, more conclusive trials and the FDA’s desire to keep ineffective treatments off the market. We were able to agree on FVC (change) as a primary endpoint, and ALSFRS (change) as a secondary endpoint. The ensuing discussion focused on topics fundamental to designing quick confirmatory studies that could lead to approvals for drugs/treatments that have demonstrated safety and preliminary evidence of efficacy in Phase 1 or 2 trials. Two principal topics that emerged from this discussion were (1) use of a patient-specific ALS progression predictive algorithm to construct a virtual and homogeneous placebo trial arm designed to reduce statistical noise in trials caused by the heterogeneity of ALS; and (2) understanding where and how the FDA can show some flexibility in the use of its statistical significance standard based on calculation of a p value as the standard for establishing “efficacy.” Achieving a p-value of < 0.05 in a trial where measuring a modest improvement in ALS progression is the primary endpoint necessarily increases trial size to substantiate positive outcome, adding time, cost and other complications that function as disincentives for companies to pursue approval of new medicines for ALS. However, by incorporating progression prediction models and patient-specific data, a 21st century approach to trial design, we would be more likely accurately measure the effect of the drug, improving the chances for recognizing of success when it occurs. We also advocated for the collection of secondary data in trials especially investigational biomarkers, and stratification of patients to better discern evidence of “efficacy” and to identify subsets of patients who benefit from a drug when efficacy is not seen in a majority of the patients. Unfortunately, as with our previous in-person meeting and our prior teleconference with FDA, we did not receive clear, actionable responses from FDA, and on some critical points of discussion, we encountered firm resistance to any form of new thinking in how drugs for ALS are developed and approved. 
Detailed Notes of the July 6th Conference Call 
On June 6, 2015, Hope Now for ALS held its third meeting with the FDA to discuss creation of an expedited development and approval pathway for new ALS treatments. We opened the meeting with some sad news, informing the FDA that a member of our leadership team, Dr. David Huntley (husband of Linda Clark – also on our leadership team) lost his battle with ALS on July 4th. We informed the FDA of his passing at Linda’s request to remind everyone that making and delivering progress for ALS is a matter of extreme urgency. FDA responded with an expression of sorrow and a statement that they understand and share the urgency felt by the patient community. 
Bob Hebron led the meeting for Hope Now for ALS (HNFA). The primary participants for FDA were Drs. Janet Woodcock and Ronald Farkas, although most of the FDA participants from the prior call also attended. 
HNFA introduced the concept of using a predictive algorithm to select patients for a study, and then to serve as a second control arm alongside an actual control arm with the objective of reducing the statistical noise caused variability in the rates and characteristics of progression among PALS. The predictive algorithm approach was then discussed in some detail, including input from experts developing a predictive algorithm for ALS using existing patient data. It was explained that the algorithm accurately predicts decline in ALSFRS and can be adapted to predict other measurement endpoints, such as FVC.HNFA then proposed that a clinical study designed to test for a slowing of progression could be conducted by using the predictive algorithm to select fast-progressing patients (termed “enrichment” by FDA) that could fill the study with “like” patients in terms of rate of progression. A positive effect on fast progressors might be seen more quickly (statistically), and in a smaller study population, than trying to discern the same effect in a population of mixed rate progressors. FDA indicated that enriching the study with fast progressors might be acceptable to them, and they expressed an openness to using the predictive algorithm for that purpose; however, they noted that if the study were populated only with fast progressors, the results might not be as generalizable to the larger ALS population as it would be if the study were run in a broader population of PALS (i.e., fast and slower progressing PALS).  
HNFA then proposed that the study could perhaps be stratified (meaning looking at subgroups within the population) to learn more from the study, and to try to further reduce the statistical noise generated by the variability in the progression rates and types of motor functions lost as the disease progresses, seen at the individual patient level. FDA responded that attempting to stratify a study prospectively would complicate study design, lengthen the time needed for enrollment and cause the study to have to be larger (i.e., FDA would be looking for a much larger, longer study with each subgroup large enough to have adequate statistical power if the sponsor intended to draw conclusions regarding drug effect based on any subgroup analysis). FDA then said that retrospective analysis could be conducted on the study results to try to understand what happened, but the implication was that retrospective analysis would likely not support an approval. 
HNFA then made the point that the patient community is looking for an agreement with FDA on smaller, smarter studies to keep the cost down and speed up the entire process. 
FDA’s response was entirely statistics-based and summarized below:• A study can be small if there is a huge treatment effect• A small study risks statistically missing a small treatment effect• FDA reported that some Breakthrough drugs approved based on early data didn’t show a large treatment effect in later confirmatory studies.• FDA advised that once an expected treatment effect is estimated (e.g., how much more slowly a drug might cause ALS to progress in the study population), cut it in half and design the study to be large enough to detect the smaller treatment effect to a level of statistical significance.FDA did not directly respond to our statement regarding an agreement on smaller, smarter studies. 
[Explanation – not from the FDA. What FDA actually said here is that they expect any entity trying to develop a new drug for ALS to do conduct the same large, time-consuming. randomized controlled studies today that the agency would have required 10, 20 or even 30 years ago. The FDA’s response is rooted in its long-standing its adherence to a purely statistical approach to designing studies and evaluating study results, and is based on the results of at least one, and preferably two, randomized controlled studies producing positive results at a measure of statistical significance, called a p-value, of 0.05 or less. Setting the p-value requirement at 0.05 or less means (in simplified terms) that the chance the results seen in the study happened because of chance (and not because of the drug) is 5 percent or less. FDA was explaining that an acceptable p-value can result from a large treatment effect in a small population of patients; however, to detect a small slowing of progression to a level of statistical significance acceptable to the FDA (p = 0.05 or less), a much larger, longer, more expensive study would need to be run. This convention, which has been relied on by FDA for decades as its standard for approving new drugs (since the 1960s), creates a reality in which getting a modestly effective drug approved by FDA takes much longer, costs much more and is much more uncertain for sponsors, than getting a highly effective drug approved. Given the current state of the medical science for ALS, all the drugs currently in the pipeline appear to have the potential for causing modest positive effects on disease progression and symptoms; thus, the FDA’s position on study size and statistical significance creates a financial and technical barrier to sponsors who might otherwise be interested in trying to navigate the agency’s development and approval process if a more creative and financially-feasible pathway was available. It also creates an obvious problem for the current and future generations of PALS and CALS who are faced with a drug development and approval process that makes approval of a new drug in a timeframe meaningful to them, all but impossible. HNFA is attempting to negotiate a more reasonable and productive development and approval path for ALS treatments with the FDA. So far, it appears that FDA has no interest in joining us in thinking outside the traditional statistical box.] 
HNFA raised the concept of using the predictive algorithm to analyze the study results as a second control arm (run alongside an actual control arm with patients receiving a placebo) that might be a better way to control a study because of the algorithm’s potential to reduce statistical noise associated with variability among patients and the accuracy/precision noise known to be associated with measures like the ALSFRS and FVC. FDA replied that they would not object to looking at its use as a control arm, and that the usefulness of the algorithm could be evaluated by comparing the control outcomes predicted by the algorithm with the outcomes from the actual control arm. FDA described use of the algorithm for this purpose as exploratory, and appeared to be disinclined to rely on anything learned from its use to interpret the study results. 
HNFA then asked: What is different about the input we are receiving from FDA today from what we would have heard 5, 10, 15 or even 20 years ago? FDA responded that the difference is they are talking to us about it – something they would not have done in the past. FDA did not offer any other explanation of differences between the advice they are offering us now versus what they would have advised in the past. HNFA then proposed that the study should include a cross-over provision (to the active drug) for patients randomized to the placebo control group, if after an appropriate period of following the patients in their respective groups (treatment and control), the drug appeared to be having a positive effect for some patients. FDA responded that they thought we were talking about a delayed start trial where some patients would start on a placebo, then be switched to the active drug. We responded that we were actually proposing a more traditional randomization to treatment or placebo at the start, with cross-over at the end of the monitoring period, and that if some of the patients who crossed over to the active drug then responded to treatment (for example by seeing their progression slowed), those responses should be considered favorable and could be compared to the predicted rate of progression using the algorithm. FDA did not provide a clear response to this concept but seemed to be discouraging it, and we raised the question regarding why FDA had never developed a way to consider patient responses observed after cross-over from the control to the treatment group as evidence supporting efficacy of the drug being tested? FDA responded that they were talking about these kinds of concepts at a high level but had not begun applying them at the study design and review level. 
HNFA expressed its growing frustration that we do not seem to be getting clear and actionable responses from FDA. In response FDA asked that we submit a list of things the FDA had expressed “openness” about so they could confirm or clarify their position.FDA reiterated its concerns about trying to use biomarkers as supporting evidence in an ALS study, stating that they had been burned by biomarkers too many times. (We did not pursue this discussion further since based on previous discussions, use of biomarkers at this time appears to be off the table with FDA. It seems they have no objection to collecting biomarker data – but they are not open to using them for purposes of regulatory decision-making regarding an ALS treatment.) 
On endpoints, FDA stated that they think there is significant variability in ALSFRS and FVC measurements, and stated that if FVC is selected as the primary endpoint, it would not be evaluated in a vacuum. They would be looking for concordance in other measures (e.g., they would want to see ALSFRS and other patient outcome measures generally go in a positive direction if FVC outcomes were statistically positive). 
During the meeting, HNFA expressed the following to FDA and FDA provided the following responses:• We have made clear to FDA the ALS community’s perception of risks versus benefits, and that the community considers the risks of the disease to substantially outweigh the risks of investigational treatments that, based on early data, indicate they may provide some benefit.FDA responded that they understand that the ALS community supports approval of treatments with adverse side effects if the drugs also provide some benefit.• HNFA clarified that the community extends their position on risk to FDA being open to approving drugs in an expedited manner based on limited data, and then relying on post-approval studies and registries to learn more, faster about the safety and efficacy of the treatment and how to optimize its use, even if granting the early approval might result in some treatments ultimately being found less safe or effective than originally thought, requiring re-labeling or even withdrawal from the market. Presently, PALS have almost nothing available to them and the pipeline is thin in part because of the high regulatory hurdles for ALS treatments; problems that can only be addressed through a stream-lined and expedited development and approval path. A specific recommendation that was made during the meeting was that FDA should be more flexible with its statistical significance standard (p = 0.05) for diseases like ALS with an extreme unmet medical need, which would allow for smaller, faster studies that, if positive at a lower level of statistical significance, could lead to a conditional approval (which is what accelerated approval already is), supported in the post-approval space by continued study.FDA responded in a noticeably rigid manner that it must meet its statutory standard in the Food Drug and Cosmetic Act (FDCA), and that if the ALS community wanted the standard changed, they should pursue that with Congress.[Explanation – not from FDA . The standard for approval in the FDCA is generally worded and allows broad discretion to FDA in deciding what the standard for approval should be for any drug intended to treat any disease. Congress has directed FDA to be more flexible when setting the standards for new medicines intended to treat serious and life-threatening diseases with unmet needs. ALS is among the most serious of all known diseases, and is almost universally fatal within 2 to 5 years) In our case, FDA has firmly indicated that they do not intend to be flexible.]HNFA responded that FDA has broad discretion in interpreting and applying the approval standards in the FDCA, and that Congress had already instructed them to use that discretion for new medicines intended to treat diseases like ALS.HNFA explained to FDA that our goal is to complete these discussions regarding a streamlined development and approval path for ALS drugs in a few additional weeks, then move to the next stage of proposing the pathway to sponsors for comment and potential use in starting registration clinical studies within the next few months, with the goal of completing the data collection portion of those studies by the end of this year, and that we expected FDA to partner with us in achieving this goal.In follow up communications between HNFA and FDA since the July 6th meeting, HNFA has opted to submit a conceptual study design to FDA, and FDA agreed to provide feedback within approximately one week. The conceptual study design was provided to FDA and we expected a response this week. Instead, we received an e-mail from FDA stating that they would “…like to broaden the participants so more members of the ALS community can participate and provide input.” This decision by FDA, which was made unilaterally without consultation with HNFA, appears to mean that they do not intend to respond to our proposal in a timely manner. It also means that the pace of discussions with FDA regarding the modernization and acceleration of new drug development programs for ALS will be substantially slowed, and will lose focus as “stakeholders” with goals that differ significantly from the urgent needs of PALS and CALS are selected by FDA and brought into the process.

Monday, July 20, 2015

"The Single Largest Research Project Ever Created"

Those are the words of the ALS Association regarding the CDC's ATSDR ALS Registry.  We believe in its largeness in terms of expenditure.  There are some serious questions about the largeness of the results.

This week the Registry's annual meeting is being held in Atlanta.

This twitter exchange is telling --

And finally after various advocates pressed the issue, the CDC reneged and the meeting will be webcast --

Starting Wednesday, July 22, 8:30 am EDT

I hope that people will listen in. And I hope that we never again have to ask to have any Registry meeting webcast.   There is a lot that needs to be discussed and understood, and sunshine only helps.

I hope that the following questions will be among those answered:

- As you introduce people at the meeting, will you please ask for any business relationships that the participants have with one another?  And who nominated each to participate in the meeting?  And who is paying each's expenses?

- What is the project total expenditure to-date?

- When will we have some completeness studies of the national Registry versus metro studies so that we get some insight in how many people with ALS are being missed by the national algorithm?  The "we don't know what we don't know" problem concerns many of us.

- Two years ago it was pointed out at the annual meeting that HMO data were missing from the Medicare files.  Are those the Medicare "Advantage" plans?  Do we have any reason to believe that PALS use those less than the proportions noted in this Kaiser article?  Is this a significant problem whose backbone is the idea that a very high percentage of PALS will be in government files?

- MDA indicated in the last meeting that they have around 13,000 PALS in their database.  Does that not cause concerns that an organization that sponsors only a portion of clinics has so many PALS compared with the first Registry report and compared with the annual self-enrollments?

- Last year an annual meeting participant wisely pointed out that you can't manage what you don't measure.  Surely ALSA and MDA are able to tell us how many new PALS entered their clinic systems in the past year.  How does that compare with the new self-enrollments in the Registry?

- Have ALSA and MDA ever simply sent out an email survey blast to all their PALS -- Did you self-enroll in the Registry?  If not, why not?

- Have you measured how many PALS actually enrolled in the clinical trials for which they were notified via a Registry email? The importance of this was broached in the last meetings discussion and I hope has been measured since.

- In an OMB filing, the "annual cost to the government" for the ALS Registry was given as $1,100,000 annually.  Why does that differ so from the $10 million that we request every year?

- Could we get a ballpark breakdown of the annual budget by these categories, please?

- There was a public comments period for a new outbound telephone plan within the Registry project to move non-clinic neurologists' behavior to increase self-enrollment.  What data show that telemarketing like this will change neurologists' behavior?

- Is the premise in the telemarketing plan that non-clinic neurologists are a significant factor in low PALS self-enrollment not at odds with the special status that ALSA and MDA have been given in this project because of their clinic systems?

- Would you discuss Stephen Finger's article on Registry completeness and the first prevalence report, please?

- Would you discuss Stephen Finger's comment related to the recent survival data publication from the Registry, please?

- Would you discuss why Stephen Finger was not invited to participate in the annual Registry meeting, please?

- This observation was first brought up by a PALS at the advocacy conference in May, I believe.  Metro studies are done in areas with much larger minority populations than the general U.S. population, yet Metro studies are showing more ALS than the general U.S. population.  Does that not refute the conclusions of the first national Registry report that ALS is more common in white males?

- Why are we not getting a second annual report?

- The recently published report from the biorepository study group had some votes regarding the future of this part of the Registry.  The report said that ATSDR and McKing employees were not allowed to vote. Could we find out who the 12 voters were, please?

- Could any of the collected tissue samples potentially be used to develop iPS models?

- A recently published article associated formaldehyde exposure with ALS, and funeral directors were spotlighted as being at possible risk.  When something like this is published, how long does it take for ATSDR to review the Registry self-enrollment data to see if the Registry occupational data support or refute a theory?

- If an ALS researcher requests information from the self-enrollment portal, how will those data be released?  Will any of those data be released that have not yet been matched with the government files that are several years behind?

We have advocated hard and at our own expense to get this project more than enough taxpayer dollars to fill its mission and we look forward to the discussions on Wednesday and Thursday.

Monday, July 6, 2015

Before You Put Anything Else On Your Plate...

Mom would tell you to finish your peas.

We see the buildup to a concerted effort to try a redux of the fundraising part of the ALS Ice Bucket Challenge.

I hope that every organization that tries to do this will first give us a clear accounting of what it did with its windfall funds from last year -- simply an orderly list of the checks that have cleared and what they were spent on, and what, if anything, is left in the bank.  We don't need a foggy infographic with fine print (but perhaps there will be a line item of dollars spent on those).

Do you still have peas on the plate in front of you right now?

Sometimes the fight against ALS just needs a dose of motherly common sense.


Thursday, July 2, 2015

Some Days You Just Don't Want To Enter That Maze Ever Again

Yesterday was one.

It's easy to be lured into that maze entrance with announcements and press releases and "promising" approaches.  Been there. Done that.  We always seem to get lost inside.

The Big Biomarker Trial Announcement
Boy, did that ever sound good.  Three million dollars.  Two trials. "Promising" biomarkers.  Walk right into that maze and see what a wonderful destination we find.  Whoa.  Wait a minute.  I really don't want to enter that maze if it ends up anything like our last Phase 2 trial of NP001. 
My understanding is that the $3 million in grants announced yesterday were specifically for professional CRO services from NEALS for Phase 2 trials.  That's certainly not chopped liver, but it's not flexible like cash.  Do those kinds of grants mean that investigators and drug developers and organizations will not be tempted to challenge the old Phase 2 model? 
And now we come to NP001 itself.  We already learned from Dr. McGrath's comments at the big ALS symposium in December that high LPS PALS were the responders in the old Phase 2 trial in 2011.  And we also know from experiences of PALS in that trial that some PALS experienced improvements and then had terrible crashes during the washout period where the LPS biomarker was tracked.  And no NP001 was made available to any of those trial volunteers after that. 
Will this trial be designed more humanely? 
And what will we have at the end of another long Phase 2 trial?  More certainty on biomarkers but still nothing accessible for PALS?  Will Neuraltus still be passing the tin cup to investors to come up with the $30-$35 million dollars they say they need for a Phase 3 trial? 
Urgency, anyone? 
Or are we just expected to enter the maze again and see where it takes us? 
And if anyone is worried about the dangers of GM604 if granted FDA Accelerated Approval, we can let them talk to the widows and orphans of the brave NP001 trial volunteers about safety and risk and the old approval process. 

The ALS Registry Annual Meeting
And we had an opportunity to step into yet another maze yesterday afternoon.  Per @CDCEnvironment the ALS Registry Annual Meeting will not be webcast this year because of budget limitations.  That's certainly a huge step backwards in transparency in a project that people care about.  It's also not fair to those who advocate for tens of millions of dollars for that project.  We step into another maze when we have to wait for a written report on the meeting that is published far after the fact.  We get lost when we don't see the interaction and questions and answers and project leadership dynamically. 
And we also learned yesterday from @CDCEnvironment that the annual report of Registry results that we was promised every year after the initial report last summer will be delayed.  "The 2nd & 3rd report (i.e. 2012-2013) will be combined into 1 report. Therefore, it will be released in early 2016."  Oh, it's like we just took a bad turn in the maze again. 

The shortest distance between two points isn't in a maze.   Transparency and challenges to the status quo are healthy, and you just get lost when you walk right into that adjective-laden door.

Friday, June 26, 2015

Well Done, Good and Faithful Servant

Every now and then I can just hear God's words as one of our beloved friends with ALS arrives at the pearly gates.

Chuck Hummer fought the good fight.  He lasted a long time with ALS with help from his beloved bride and family.  ALS finally won yesterday.  It always does.  But Chuck made a huge difference in lives.  ALS couldn't steal the good that he did.

Almost a decade ago the ALS Association started something called their Virtual Advocacy Community.  Chuck Hummer entered our lives.

Log in and look for OldChuck.  When I first visited that site, I seriously thought that OldChuck was ALSA's shill for their advocacy efforts. He explained and motivated. He wrote beautifully.  He treated people kindly. He was smart. He was the virtual mayor of the VAC and made it a great place for people interested in advocacy.

OC, as I called him, knew a lot.  He had a career in government work and knew the drill (and tricks) for getting funds in DC.  He had started a not-for-profit centered around his beloved Panama Canal, and he knew a lot about not-for-profit management.  And most important of all, he had been an AIDS activist with his son.  He saw that movement finally succeed, but it was too late for his dear son.  He knew much of what it would take for the fight against ALS to succeed.

So we had an awesome little VAC with quite the mayor.  ALSA had a gift.

Eventually he started challenging the status quo of 2006.  He asked questions about the return-on-investment for the big advocacy conference that ALSA held in Washington.  He pressed for bigger requests for funding.  He demanded better inter organizational coordination.  And he knew the rights of people who required accessible rooms at an ALSA-sponsored gathering.  He was pushing and pressing to improve the fight.  It was energizing.  Unfortunately ALSA never engaged in the energized VAC.

He was soon kicked out of the VAC.  Somebody at ALSA pulled out the rule book and managed to silence him.

OC felt so strongly about the cause and advocacy that he managed to sneak back into the VAC by setting up an identity with a grandchild's name.  The Washington Wizards (as he brilliantly called them after his first ejection) soon caught on and booted him again.

OC was my hero.

He was opinionated, but you didn't have to agree with him to be his friend.  ALSA missed out on a great force that could have made the fight so much better.

He was a pioneer in online peer support.  Google for gamboachuck or oldchuck or oldchuckles or grumpyals and you'll see a gentleman who was a godsend of support to hundreds of people with ALS and caregivers.

He blogged and he commented and participated in all kinds of online media.  He was kind and helpful to so many.  And could he ever write.

This morning I saw on Facebook how many people who benefited from his love and mentorship are grieving today.

You were a good egg, OC, and a Double Domer to boot.

How I miss you already.


Monday, June 15, 2015

If You Want To Get Something Done...

... give it to a busy person.  That's what my grandmother always said.  She sure got it right.

In the past couple of months, we have seen a remarkable grassroots group of people with ALS and caregivers get traction with the FDA. They are thoughtful. They embrace discourse. They question.  They do their homework.  They study.  They won't back down.  And yes, they are busy.  They are beyond busy because they are in the throes of dealing with ALS.

They have another meeting with the FDA this week.  Below I paste some information that they shared on their Hope Now for ALS Facebook page and their page.

Please follow them, read the material carefully, and act. Sure it's long and you're busy, but you and I aren't that busy.  Thank you for your consideration.  These amazing people with ALS and caregivers about getting things done. They understand urgency. They stare it in the face every day.

It's about time.


The FDA has agreed to engage with us on behalf of the PALS community to discuss a path toward getting ALS treatments/drugs into the Accelerated Approval Program. This will require a series of discussions covering a number of discrete topics (surrogate endpoints and relevance of biomarker data, design of a validation process to determine accelerated approval efficacy where evidence of efficacy and safety coming out of a Phase 2 trial exists, etc.) with the goal of defining a method for validating efficacy for drugs/treatments where safety has already been demonstrated. We look forward to engaging with the FDA and taking concrete steps in getting this done. We recognize the urgency that this process has for the existing generation of PALS and will always make that our foremost consideration in moving forward in this process. Our next meeting with FDA is scheduled for June 17th and according to the list of FDA attendees provided by the agency in their invitation, the meeting will include most of the key agency personnel needed to make material progress toward establishing an expedited development and approval pathway for new ALS medicines. According to FDA, the following agency staff will be attending the meeting:
Dr. Janet Woodcock, Director of the Center for Drug Evaluation and Research (CDER)Dr. Richard Moscicki, Deputy CDER Director for Science OperationsDr. John Jenkins, Director of the Office of New Drugs, CDERDr. Billy Dunn, Director of the Division of Neurology Products, CDERDr. Ronald Farkas, Division of Neurology Drug Products, CDERDr. Nicholas Kozauer, Division of Neurology Drug Products, CDER
The objectives of HopeNOWforALS are described below:
• Clearly communicate our sense of urgency regarding the need for rapid development of the expedited pathway,• Establish a framework for achieving Objective No. 1 with weekly meetings over the next 4 to 6 weeks,• Reiterate the ALS patient community position on how FDA should evaluate the potential for drug-related risks versus the potential for benefit in the context of the risks posed by the disease,• Hear FDA’s thoughts and proposals for an expedited pathway and express our own,• Attempt to reach agreement on the major elements of an expedited development and approval pathway for new ALS medicines, including evidentiary requirements that would be considered adequate to support agency acceptance and review of an application for Accelerated Approval before the end of this year.• Set action items for FDA and HopeNOWforALS, • Schedule the next meeting.
Our objectives for this initial meeting are ambitious, and may exceed the FDA’s customary pace of discussions regarding drug development programs; consequently, we are communicating our expectations for the meeting to FDA in advance in hopes that they will come prepared to negotiate a set of initial agreements in good faith, and with a shared sense of urgency. We will know more about our goals for the next meeting after our upcoming meeting on the 17th. 
Because the details of an expedited drug development and approval pathway must also be agreed to by the drug sponsor(s) who will navigate the pathway, it is our intent to bring sponsors who are interested in using an expedited pathway into the process quickly, potentially as early as the third meeting. We anticipate that this involvement will include Genervon in pursuit of an Accelerated Approval for GM604, and we are hopeful that others will elect to collaborate in this process as it moves forward.
We need your help leading up to our June 17th meeting. Please contact the FDA (see below) and your contacts on the Hill. Urge them to ensure that FDA enters this process with a shared sense of urgency and a willingness to fully consider and factor into its regulatory policy and decision-making, the perspectives of the ALS patient community regarding the dire need for a process that allows all PALS the opportunity to access promising new medicines for ALS at the earliest possible point in the learning process, and to participate in the completion of that learning process in a post approval environment, as intended by Congress in FDASIA, enacted in 2012. Please make the critically important point that FDA’s current, inflexible, years-long process for bringing new ALS drugs to the point of approval is failing to meet the dire unmet medical needs of PALS, and needs to be remade into a process where FDA views the patient community as full and equal partners in the making of medical progress against ALS.
In Food and Drug Administration Safety and Innovation Act (FDASIA) Congress expressed: 
SENSE OF CONGRESS.—It is the sense of Congress that the Food and Drug Administration should apply the accelerated approval and fast track provisions set forth in section 506 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356), as amended by this section, to help expedite the development and availability to patients of treatments for serious or life threatening diseases or conditions while maintaining safety and effectiveness standards for such treatments.
Congress went on to describe the evidence that could support an Accelerated Approval: 
‘‘(B) EVIDENCE.—The evidence to support that an endpoint is reasonably likely to predict clinical benefit under subparagraph (A) may include epidemiological, pathophysiological, therapeutic, pharmacologic, or other evidence developed using biomarkers, for example, or other scientific methods or tools.”
The intent of these provisions was to direct FDA to use its Accelerated Approval authority for disease like ALS, and to make exceedingly clear that the agency did not need to wait for evidence from multiple phases of long, expensive, randomized controlled clinical trials before granting Accelerated Approval. 
We are standing on solid legislative ground with this effort, but to date, FDA has not shown a willingness to use its Accelerated Approval authority as intended by Congress for new drugs intended to treat neurological diseases like ALS. Please weigh in and strongly urge FDA to work with us in good faith, and in accordance with Congressional intent, to bring new medical options to ALS patients as rapidly and flexibly as possible.
We will provide an update after the meeting. 
We're in this together,Jehad Majed (, Matthew Bellina, Nick Grillo (, and the Torrino Family
Please email the Dr. Woodcock at the FDA:janet.woodcock@fda.hhs.govand copy these people:druginfo@fda.hhs.govrichard.mosc
Start with any opening you choose but please include any of the following that you feel represents your voice:
It is my understanding that you will be meeting with members from HopeNOWforALS on June 17th to discuss a pathway forward for the evaluation of investigational treatments for ALS. I recognize that the FDA -- and particularly the Division of Neurology Products -- has been unwilling to implement the Accelerated Approval Program in the manner intended by Congress and so expressed in the FDASIA of 2012. I am also aware that the ALS patient community has not been given the chance to participate in discussions regarding risk vs. benefit and that those discussions have either been non-existent or differed to large "advocacy organizations" that I feel do not represent my best interests.Over the past 6 months, the ALS patient community has been fighting for Accelerated Approval of Genervon's GM604 and I understand the FDA has denied Genervon's request to discuss this further. As a member of the grassroots movement working to get safe investigational treatments to market, I expect that you will work closely with HopeNOWforALS and make a change from the status quo -- and make that change very soon!
The FDA’s current, inflexible, years-long process for bringing new ALS drugs to market is failing to meet the needs of PALS and needs to be remade into a process where FDA views the patient community as full and equal partners.
Please do not patronize the patient community with information about the Expanded Access Program (Compassionate Use). This program is unable to meet the needs of and entire population of patients with no treatment options. Accelerated Approval was designed for this purpose.
By the FDA’s own admission, "It can take too long for an investigational treatment to definitively demonstrate a clinical benefit and then go through the process of securing FDA approval." On the website, the FDA claims that the 1992 Accelerated Approval Program is a way to speed new drugs to market that treat serious diseases and fill an unmet medical need. If this program isn’t meant to address ALS, then I want to know what are your definitions of “serious” and “unmet medical need"?
Know that I will continue fighting with my last ounce of energy and last breath to help the ALS Community see viable treatment options.

Sunday, May 31, 2015

We Need A Webinar - The Business 101 of Clinical Trials

It's confusing.  It's a business.  We all need to be better consumers.  I think we have a big information gap that is just crying to be filled.

Clinical trials are critical to finally finding a treatment for ALS.  We all know that they are expensive, but how expensive are they?  And who pays whom to do what?  And how does the whole business process work?

If we understand the roles and the business and responsibilities and compensation better, every patient, caregiver, donor, and advocate will better understand how and why things are done.  And with that, we'll all be able to set more realistic, responsible expectations for change.

Some things that I would love to understand better --

  • Who gets paid to design clinical trials?  How do they go about it?  How does a budget play into trial design?
  • Who draws up all of the consent forms for a trial?
  • Are clinical trial sites usually paid per patient?  Are they still paid when patients drop out?
  • Why can patient travel reimbursements vary from site to site for the same trial?
  • Who is paid to be the keeper of the data?
  • Who is paid to be the analyzer of the data?
  • What is a CRO?  
  • Do for-profit CROs differ from not-for-profit CROs in what they do or how much they charge?
  • Are investigators paid individually or are their institutions paid to conduct trials?
  • Is any drug developer willing to share with us how much an actual ALS clinical trial cost both in internal expenses and in contracted services?
  • Do charitable donations play a role in clinical trials for drug candidates that are owned by private companies?
  • Do you have to pay fees to the FDA if you are conducting a clinical trial?

I obviously have  lot to learn.  Many of us do.  I hope someone will be able and willing to educate us so that we can be better informed.  Clinical trials and drug approvals are a hot topic right now, and some basic business information will certainly raise the quality-bar in the discussions.

Thanks to whomever will help teach us the Business 101 of Clinical Trials.

Monday, May 25, 2015

Meet Two Jimmy Clarks

Meet Jimmy Clark

Yesterday at the Indy 500 they celebrated the 50th anniversary of Jimmy Clark's victory with a pre-race lap of his beautiful winning car.  Jimmy Clark was special.  We called him "The Flying Scotsman." He wasn't flashy.  He was just fast. He looked more like an accountant than a race car driver, but he could drive. He used new technology to chase his dreams of winning.  He assumed risk with eyes wide open and he achieved great success in all kinds of racing.  We applauded his many victories and mourned when we lost this great talent and gentleman in a racing accident in 1968.

Meet Jimmy Clark

In March at the first Rally for Faster Drug Approval I met another Jimmy Clark.  He is special, too.  He is loved by his family and loves life.  He also has ALS.  That puts a bad wrench in things.  All he asks is that he be allowed to assume some risk with eyes wide open so that he might chase his dreams, too.  He wants to be allowed to take risks that are minuscule compared to those that are taken every weekend by those who participate in auto racing.  He wants to advance technology and science just as race car drivers are allowed to do.  He also wants to live for a family that is far more important than a race or a trophy.  This gentleman simply wants us to let him try an unproven, investigational drug with a good safety profile.

Why not, I ask.  Why not?  Where are our priorities?

Friday, May 22, 2015

Your Hands Aren't Really Clean

You don't want blood on your hands.  Nobody does.

If someone were to die because of an allowed, yet unproven ALS treatment, that would leave blood on the hands of the FDA.  Nobody at the FDA wants that.

IF someone were to die from untreated ALS, that's an act of God, right?  No blood ends up on anyone's hands, right?

Wrong!  It's on all of our hands.

Not acting doesn't wash our hands of responsibility to try to stop deaths from ALS.

Finding excuses and reasons to delay does not mean our hands are clean.

Regulators, scientists, advocates, physicians, and bloggers share a new permanent stain with every life lost to ALS.  Our hands are not cleaned by inaction.  You can't wash it off by letting ALS take its course.

Saturday, May 16, 2015

Just Read The Transcript

On February 25, 2013, dozens of people with ALS, caregivers, scientists, drug developers, ALS
organization employees, and clinicians made a trip (many at their own expense and with a great deal of difficulty) to testify to the FDA.

They gave a gold mine of ideas for speeding up drug development and approval.  It's a big gold mine because people testified all day in six-minute segments.

They talked about risk, biomarkers and endpoints, trial design, FDA processes, natural history, controls, and on and on.

Today we hear that the FDA guidance document that was indicated at that meeting is only now being started and that dozens of people with ALS, caregivers, scientists, drug developers, ALS organization employees, and clinicians will soon be convened to give their input.

Ok, everybody.  How about just reading the transcript from that FDA hearing?  You have the materials to start a draft FDA guidance document right under your noses.  Let's get moving.  Spending buckets of money on unnecessary meetings isn't a sign of an understanding of urgency.  Nearly 300,000 more people have died from ALS since that hearing.  Urgency?

You can watch.

You can read the whole thing.!documentDetail;D=FDA-2013-N-0035-0271

And you can read the FDA's summary and reaction.!documentDetail;D=FDA-2013-N-0035-0272

As an example, one of the ideas presented that day is that people with ALS have a right to know who is doing what during the clinical trial and FDA back-and-forth in the approval process.  Are we waiting for statisticians?  Are we waiting for an FDA decision?  Are we waiting for more data to be submitted?  What's going on?  Are we waiting for somebody on vacation?  Think about how much more clearly the Accelerated Approval application for GM604 might be perceived if we simply had this kind of transparency policy.  Any successful modern business has project teams that know what's going on in the scrum today, yet the veil of secrecy continues to obstruct the view of the most important people in the drug development and approval process -- those with ALS and their caregivers.

And there are hundreds of more examples of ideas that can have a direct impact on speeding up drug development and approval.

Just read the transcript.

Thursday, May 14, 2015

Some Stream-of-Consciousness Thoughts From #ALSAdvocacyDay2015

In no particular order, I reflect on my short trip to Washington, DC, this week.

  • For the first time ever, I'm grateful for being held captive on a plane, waiting for a jetway.  My Senator across the aisle could not have been more gracious and concerned as we talked about ALS, drug approvals, and the FDA.  Thanks, USAirways.
  • The Rally for Faster Drug Approvals held by did not disappoint -- enlightening speeches, thoughtful PALS and CALS, good information on FDA and drug approvals.  It was hot, but the PALS, CALS there did not wilt.  And there were signs and cameras, and heads on the street turned.
  • A sign taught me that "We are the change that we have been waiting for." I love it.
  • The evil ALS continues to pick some remarkably talented individuals and families.
  • Double-blind, placebo-controlled trials don't need to be the "gold standard."  Shoot, the gold standard is no longer the "gold standard," a PhD economist with ALS explained.
  • You listen to the SGD, but you look at the PALS delivering a speech, and it's amazing.
  • Open and diverse discourse can teach us all new things, and God knows, we need new ideas.
  • The status quo is simply unacceptable.  Same old same old isn't good enough.
  • Denial of hugs is one of the big evils of ALS.
  • Bragging rights should not be an unspoken priority.
  • PALS, CALS are their stories and so much more. So much more.
  • The Abigail Alliance has a the most refreshing IRS Form 990 that I've ever read.
  • The ship's photographer can be annoying in a legislative meeting.
  • Advocacy is year-round work.  Many of us take that seriously. All the more reason to give advocates a heads-up when a HR number is changed and prior co-sponsors need to re-up on the new HR. 
  • Legislators are very frustrated with the FDA, too.
  • I love Hoosiers.
  • Dormant Therapies provision is important in 21st Century Cures, but there is a lot more than needs to be in there that will have a direct impact on getting therapies to PALS faster.  Is anyone looking out for PALS?  Really looking out?
  • We all don't have to agree.
  • What do those ALSA people who randomly morph into your legislative meetings really do?
  • Money doesn't buy a great advocacy experience.
  • A chance encounter with your other gracious Senator on Pennsylvania Avenue can cap off a good day of advocacy.  I'll always remember talking about 21st Century Cures with him directly across the street from where I held a sign at the Rally for Faster Drug Approvals a day earlier.
  • My favorite hashtag for the fight against ALS is #notquietly . 

Monday, May 11, 2015

We Need To Put The Sign Back Where It Belongs


A year ago we talked to legislators about some Medicare rules being implemented that were a crazy trip back to 1980.  They were denying people with ALS access to modern, economical technology related to speech generating devices.  When we talked to legislators and staff members, they were 100 percent in agreement that the rules were antiquated and wrong.

That was a full year ago.  There has been lots of talk and there have been band-aids, but we learned that we need a law.  The buck can't stop where it belongs for Medicare recipients unless we make a law.  Today people with ALS are denied or lose the very devices that let them be productive and engaged parents, citizens, and patients.

Enter a small charity that couldn't let those people with ALS lose the purpose, productivity, and joy
that the simple ability to communicate provides.  They let the buck stop with them because the need is vital.  In fact, they have spent over $1.4 million bucks in the last few months supplying enabled devices to people with ALS that Medicare should have been providing.  Perhaps the fact that this organization is led by a young man with ALS who uses this very technology is the reason he decided to help in a substantive way... rather than pass the buck.

Charitable contributions should not be expected to cover for a broken government rule.  Government should not be allowed to pass the buck.

But we need a law. Now.

Please write your Member of Congress. Today.  Demand quick support of the Steve Gleason Act.  Here is information and a convenient tool to submit your thoughts --

In an ultimate twist of irony, President Johnson signed Medicare and CMS into existence at the Truman Library in 1965.  They should have paid more attention to the sign while they were there.

Sunday, May 10, 2015

Before We Ask For Another $10,000,000.00 For The ALS Registry - Question 2

Which is it, $1.1 million or $10 million?

In the 2013 OMB filing for this project, we see the following:
(And a hat tip to the ALS advocate who sent that document to me yesterday.)

14.  Annualized Cost to the Government
Data analysis by ATSDR may result in action taken by the Division of Toxicology and Human Health Studies in response to the required CDC mandate in maintaining preventive health activities and surveillance systems.  The action taken will vary, depending on the analysis.
 The total cost to the federal government for the collection of this information for the three year ongoing project is $3,300,000 as itemized below. Annual ATSDR personnel costs $420,000 Additional expenses will be incurred by ATSDR in order to operate a successful surveillance program/registry.  Four staff will contribute to this program: a Senior Scientist (25% contribution=$75,000), and a program analyst (100% contribution = $100,000)  A contractor will be used to maintain the web portal for case registration and participation in surveys in addition to providing public user support 40 hours per week ($500,000).  Lesser expenses may include computer resources, telephone calls, and recruitment materials (approximately $5,000).
 The estimated annual cost to the government is $1,100,000.

So we're confused.  We ask for another $10 million every year.  Why?

The ALS Registry budgeting process has always been a bit of a mystery.  Last year we learned at the ALSA Advocacy Conference that the original $10 million number was a number that the legislative sponsor thought could be raised. It was not built up from a businesslike budget.  We also got our first glimpse into annual expenditures with some very broad percentage breakouts at that conference --

It would be respectful of those with ALS and caregivers who are going to legislators to ask for another $10 million to know more clearly how that much money would be spent by project component.:

And yes, it continues to be a concern that the advocacy organization that sets the public policy priority that champions $10 million for the Registry has itself been a large, paid contractor on the project.

Why are we asking for $10 million for a $1.1 million project?  More does not mean better.

Thursday, May 7, 2015

Before We Ask For Another $10,000,000.00 For The ALS Registry - Question 1

Next week ALS advocates will be sent to Capitol Hill to ask for another $10 million for another very generous ALS Registry budget.

We have questions.

A PALS described a problem with the first Registry report issued last July --

Q1:  Have any of the local studies that were funded as part of the Registry project shed any light on this significant concern on how large the big "unknown" patient population is?  Are we able to extrapolate how many PALS are likely not found via the Registry's database mining and the online enrollment portal?

Friday, May 1, 2015

These Seats Have An Obstructed View

It's just wrong.  You can't follow a game when you can't see who has the ball.  You can't figure out when to cheer or boo.  It's incredible that in this age of the taxpayer-financed sports palace that fans can be stuck with expensive seats with obstructed views.

Such is also the case with our view of the back-and-forth between Genervon and the FDA.  Who has the ball?

Are we waiting for the FDA to give Genervon something?

Are we waiting for Genervon to give the FDA something?

All we know is that the most important people in the stadium, those with ALS and their caregivers, can see time ticking off on the clock, but they can't even figure out who has the ball.  They have been assigned seats with a conveniently obstructed view.

It's just wrong.