Holding Hope Hostage

 Hope. 

It's so important to families dealing with ALS.  It's what keeps many of them going.  You hope for a better day tomorrow.  You hope for an effective treatment.  You hope for a miracle.  Hope is more precious to you than almost anything.  You look for it everywhere.  

Today, thousands of families dealing with ALS have found hope in an investigational therapy called NurOwn being developed by Brainstorm Cell Therapeutics, Inc.  It is the beam of light they have sought every day they deal with the stinking ALS.

Brainstorm completed a Phase III trial over three years ago.  If failed to meet its endpoints.  It failed royally.  Unfortunately many ALS trials do.

NurOwn represents a huge amount of hope because many of us have seen people who were in the trial actually feel improvement.  That is literally miraculous in ALS.  Unfortunately every time we go back and look at that summary report from the trial, the trial failed.  But hope in ALS Land isn't easily smothered when something good has happened to someone.  That hope is precious to thousands.

Through social media and a lot of hype,  the hope has grown and reached thousands more people.  And then thousands more.  

But every time we go back to that report, the trial was a failure. 

Brainstorm didn't step up and run another trial on those it suspects are the responders.  Instead it decided to rearrange the data from the trial and convince us that they have the hope that every person with ALS seeks.  If you remove the people that NurOwn didn't work for, it works!  That's not great science, but it sure stokes the hope business.

And there have been all kinds of excuses for not doing another trial or providing expanded access to their unapproved therapy.  People don't want to challenge those excuses.  They don't want to mess with the holder of their hope.

For the last three months, since I made a comment quoted in a national publication that I suspected that the reason for never telling their trial participants (from a trial that ended in 2020 and has added no new data since) if they got placebo or treatment might have something to do with some of the public miracle cases having received placebo, my online life has become nothing short of a nightmare.  Clearly many think I deserve it because I'm being critical of their ray of hope.  

No, I'm being critical of a company that is holding their hope hostage.

I've learned a lot about adult cyber bullies.  I've learned even more about parents and grandparents who teach the kids to be kind and then say some terrible things about another person online.  They see me as stealing their hope -- a hope that they feel is so close to delivering them their miracle.

In reality, there is much that Brainstorm could have been doing to deliver some of the fruits of that hope  sooner and to offer some scientific proof to back up the miracles.  They have instead decided to hold hope hostage for one and only one ransom -- FDA approval to sell NurOwn to people with ALS at a price of their choosing.

Today, September 27, there is an FDA Advisory Committee meeting to help the FDA make its decision.  

Two days ago we first saw the documents related to that meeting.  The FDA briefing document was stunning.  It took me  hours to wade through the problems they found in Brainstorm's data, and perhaps of even more concern, the problems in their manufacturing processes.  The normally noisy online ALS world supporting NurOwn was quiet.  Journalists were busy pumping out coverage of a remarkable document.  I suspected that the NurOwn supporters were reading and stunned, too.  Silly me.

Yesterday we saw organizations completely ignoring the FDA briefing document and doubling-down on supporting approval.  Didn't they even read what the FDA had found?  Perhaps they don't want to be the ones to suggest we refuse to pay the ransom of approval of a product that represents precious hope but does not represent good science yet.

An online mob thinks I am trying to steal their hope. Brainstorm says the only way to get the hostage hope out of that room is FDA approval.

Today we will see people critical of anyone (including the FDA) who wont capitulate to the company that holds their hope hostage.  The facts won't matter

I wish that more people would actually read the reports and think for themselves.

A company is holding their hope hostage rather than having used the last three years to find the scientific truth.

All with ALS deserve better than hope that isn't moored in truth.

People With ALS Deserve Access AND Proof of Efficacy

Dear Advisory Committee Advisors, FDA Staff, and, yes, Brainstorm Cell Therapeutics Management,

As you know from hundreds of other comments, ALS is an awful disease. It's just awful. We lived the nightmare with Mom in 1997. It's not substantially better today.  People with ALS deserve more options than the few they have.

They deserve access to investigational therapies. People with ALS should not have to wait years (literally lifetimes) for successful clinical trials and FDA approvals before they can try experimental treatments that have been proven safe.

Many have recently been convinced that the answer to access is to simply change the adjective from "investigational" therapy to "approved" therapy and let the company sell the therapy as if it had met the evidentiary standards for an approval.  I respectfully disagree.  Companies should provide access, and they have Expanded Access tools that the FDA provides until they establish efficacy.

We run Phase 3 trials for a reason.  If we are not going to believe them, then let's not waste the tremendous amount of time and money and human commitment spent on them. 

The NurOwn (debamestrocel) trial took three years, and it seems the company has then spent the next three years telling us not to pay attention to the trial. Six years. They could have run another Phase 3 trial in the last three years that might have focused on one of their suspected responder groups. Had they done so, we wouldn't be in the pickle that we are all in today.

If the FDA finds that the existing evidence supports approval, fine.

But if we're lowering the bar for Phase 3 evidence so far that we're completely ignoring the facts from that trial, then I think we're taking the idea of regulatory flexibility past its elastic limit. Springs that have been stretched too far don't just bounce right back.

We can't afford to make FDA approvals a charade when it comes to efficacy. 

Access and evidence are both critical, and I appreciate that we have a regulatory system that can and should support both. 

Thank you for listening.

Time's A Wasting

The ALS clock is running. 

In the next few weeks, the FDA will make a decision regarding approval of NurOwn for ALS.

Either way, another trial will be needed, so let's get moving.

If NurOwn is approved

Another trial will still be needed to confirm efficacy.

It is unlikely that payers will step up to pay for the therapy, so the confirmatory trial will be one path to affordable access (albeit with potential placebo exposure) for those who cannot self-pay. For those who can self-pay or raise funds or get insurance coverage, they will be able to purchase commercial access to the therapy.

If NurOwn is not approved

Another trial will be needed to produce efficacy data.

The trial will provide access (albeit with potential placebo exposure again) to those who can get in, and an Expanded Access Program (EAP) can provide broad access for those who cannot get into the trial.

"We can't afford it" need not be a Brainstorm excuse.

There are public funds available to help them via Act for ALS.

And Brainstorm can use the cost-recovery option allowed for EAP in order to remain whole while offering Expanded Access.  People with ALS would still have to pay, but it would be cost only,  without any profits that they would be responsible for with an approved product. 

All roads lead to another clinical trial. Let's get going.

We can't afford another three years of rearranging  existing data.  We have seen anecdotal evidence of efficacy that makes it unconscionable to horse around any longer.  

Let's get on with it and run the trial and provide access to people with ALS who want access. Now.

"Never Wrestle With A Pig"

At the risk of giving some recent nonsense any more oxygen, I think it's important to document a few things.

I try to live by the "never wrestle with a pig because you both get dirty and the pig likes it" rule.

For years we in ALS Land have disagreed about things.  That's fine because we've not exactly been successful at delivering therapies and great care for people with ALS.  We certainly need to challenge the status quo and each other.

We also need to be realistic that there are well-intentioned people who want to help.  They don't have time to dig into the weeds and often they are just looking for talking points that they trust and that make sense to them.

There are others who like to get into the weeds and discussion of public policy and regulatory science. The More Than Our Stories (MTOS) was a conference designed for them.

A few days before MTOS in February, I was contacted by a New Yorker writer who was working on a possible story and asked if he could attend.  We had room and plenty of food, so we welcomed him. 

In the following months many of us were interviewed by that writer. I had no idea what directions the story might take (or if it might be published at all). but I found him to ask interesting questions and to absorb a lot about ALS.

The long story was published a couple of weeks ago.

https://www.newyorker.com/magazine/2023/06/26/relyvrio-als-fda-approval

Within hours, nasty personal emails hit my inbox.  Mind you. it takes a long time to read this article and it took several readings for me to catch the many sides to issues that were covered. Some folks were clearly Evelyn Wood graduates or did not read the story all that carefully, and they took offense at one of my comments related to NurOwn. The emails were personal attacks. They had similar structures and there were even some remarkably coincidental, vile attacks on my religion.

I have a corollary to the pig-wrestling rule that is seldom needed. Once someone sends me an offensive email, anything further from that email address goes straight to spam.  That should have been the end of the story, but it wasn't.

There were many things in that New Yorker piece that could have upset people a lot more than the few NurOwn comments. but there's nothing quite like the flame-fanning capabilities of some who are singularly fixated on NurOwn approval with no room for discussion.  God help you if you challenge data or the company's tactics that have put people with ALS and the company itself in a difficult situation.  No discussion.  No questions.  If you ask questions, the social media tools are pulled out to block you and silence you.  And if you have a decent following of your own, more menacing personal attacks follow.

People who actually know me know that I work hard and read a lot and try to push the fight against ALS in some new directions. I try to ask good questions and the answers aren't always black and white. I'm not one to be a sheep and I do get into the weeds to try to understand things and find creative change.  I respect science and scientists and regulators.  And I will not be bullied into silence.

“When people show you who they are, believe them the first time."  Thank you, Maya Angelou.

We Have A Santa Claus Problem

 We have a Santa Claus problem.

NIH

We read of an NIH that has expertise and exerts leadership in other areas such as cancer or infectious diseases.

NIH is in the midst of doing a strategic plan for ALS, and so far in the drafts, we have seen a punch list of 15 priorities.  There is a little something for everyone in ALS research. In the plan, NIH (specifically NINDS) will give grants and our researchers will have resources to move their work ahead.  It's like Santa Claus, and who doesn't love Santa!  But Santa doesn't provide a grand vision of where we're going or accountability for how we're getting there.  Santa has something for everyone in the form of fixed grants.  Santa is not providing leadership or expertise for ALS.  This is a problem, but who is going to talk about it because who doesn't love Santa?

CDC ATSDR

For over a decade we have watched a CDC ATSDR Registry disappoint when it comes to deliverables on the incidence and prevalence of ALS in the US.

Somewhere along the way, a generously funded Registry project started giving grants to researchers for epidemiological work related to ALS.  It was like Santa funding important work that seldom if ever was directly related to the basic disappointing Registry work.  But who doesn't love Santa?  ALS researchers loved the CDC ATSDR Registry, not because it was fulfilling its core mission, but rather because it was a source of valuable grants every year.  Who is going to criticize the Registry work because who doesn't love Santa?

We have a Santa Claus problem, and until we admit it and make government agencies be accountable for leadership and results rather than just doling out grants, we will continue to be stuck with a big red bag full of fragmented, expensive research projects.  

But who doesn't love Santa?