Drug Combination Slows Progression Of ALS And Could Mark 'New Era' In Treatment

Sep 2, 2020
Originally published on September 2, 2020 7:44 pm

A combination of two experimental drugs appears to slow the decline of patients with amyotrophic lateral sclerosis, an illness often known as ALS or Lou Gehrig's disease.

A six-month study of 137 patients with a fast-progressing form of the disease found that those who got daily doses of a two-drug combination called AMX0035 scored several points higher on a standard measure of function, a team reports in the Sept. 3 issue of The New England Journal of Medicine.

The difference was modest but meaningful to patients, said Dr. Sabrina Paganoni. She's the lead author and a researcher at the Sean Healey & AMG Center for ALS at Mass General and Harvard Medical School.

"They want to be able to continue to use their hands so they can cut their own food and type emails, or they want to be able to walk and climb stairs," Paganoni said. "And this is exactly what we measured in the trial."

The results are far from a cure. Even so, "I am convinced that we are at the beginning of a new era in ALS treatment discovery," Paganoni said.

"There's great hope for disease-modifying treatment," added Tania Gendron, who studies neurodegenerative diseases at the Mayo Clinic in Jacksonville and was not involved in the study. "In the next few years I think there are going to be some big discoveries."

ALS destroys the nerve cells that control muscle movement. Patients typically become disabled and die within five years of their diagnosis.

For decades, the only drug approved by the Food and Drug Administration for ALS was riluzole, which has been on the market since 1995 and has been shown to extend the lives of patients. Then in 2017, the FDA approved edaravone, which helps some patients retain function longer.

AMX0035 works by protecting nerve cells from two types of damage that are hallmarks of ALS. And in the study it produced a benefit, even though many of the patients were already taking riluzole and edaravone.

It appears that the new and old drugs all work in different ways to slow down the disease, Paganoni said. "We think ultimately we will need a combination of treatments to effectively fight ALS."

It's not clear yet whether AMX0035 extends life or maintains muscle strength. And ordinarily at least one larger study would be required before the FDA considered approving the drug.

But the ALS Association along with the advocacy group I AM ALS have joined forces to petition the FDA to make an exception.

"In ALS, a trial like this would probably take about three years," said Neil Thakur, chief mission officer of the ALS Association. "And so the question for the whole community is what do we gain for that three-year study?"

The ALS Association helped fund the research on AMX0035 and has a limited financial stake in its success. The group's main concern, though, is patients who won't live long enough to wait for another study, Thakur said.

"That's why we're thinking the best thing to do for the community is to make this drug available sooner and let everyone have it as a treatment option as soon as possible," he said.

AMX0035 has taken a highly unusual path toward approval.

It was developed by Amylyx, a tiny company founded by a couple of college students, Josh Cohen and Justin Klee, who are still in their 20s. The pair were working late one night in the company's Cambridge, Mass., office when they learned the results of the ALS study.

"When the statisticians called, you could hear their whole firm cheering in the background," Cohen said. "So we knew before they said the numbers that something good had happened."

But their elation was mixed with a sense of responsibility, Klee said.

"While these results are great, it's not a cure, and so we and others in the whole community need to keep pushing forward until we get cures," he said.

That's beginning to look more likely than it did even a few years ago, the Mayo Clinic's Gendron said.

One reason is that scientists are discovering new biological markers that appear in the blood or spinal fluid of ALS patients. These markers will allow earlier diagnosis when treatments are more likely to work, Gendron said. They will also help select which patients to give a particular drug and allow researchers to know whether the drug is reaching its intended target.

Another reason for optimism is the sheer amount of research going on.

"What makes this time so exciting is there are over 50 different clinical trials that are enrolling and recruiting ALS patients right now," said Kuldip Dave, the ALS Association's vice president of research. "And they're all going after different targets."

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MARY LOUISE KELLY, HOST:

Seattle's first Black female police chief will, within hours, be out of the job. Carmen Best announced her resignation in August just after Seattle's City Council announced cuts to the police department in the wake of protests, in part, aimed at police misconduct. Among other things, those cuts would eliminate the jobs of about a hundred officers, including, possibly, a young Black recruit who had emailed Chief Best this summer to share how ecstatic he was to work under her command.

(SOUNDBITE OF ARCHIVED RECORDING)

CARMEN BEST: His name is Marcus Jones, a great young man - tall, stout, wonderful African American man. And he is one of the people that will probably not keep a job here. And that, for me - I'm done, can't do it.

KELLY: Chief Best speaking there; and she joins us now from Seattle on her last day at the office.

Carmen Best, welcome back to ALL THINGS CONSIDERED.

BEST: Thank you for having me. I'm really glad to be here.

KELLY: I hear it's been quite a day so far, firefighters out lining the street. Tell me how it's unfolding.

BEST: Well, the day has been absolutely awesome so far. Some of my original security detail took me to breakfast. And on the way back, in front of our headquarters building, right across the street from City Hall, the streets were lined with public safety people, all of our officers - many of our officers, I should say - and firefighters saluting me with their lights going. It was really touching and moving to see the whole thing.

KELLY: Yeah. I can imagine it must have felt great. But I do have to ask - you're leaving with so much stuff going on, in the middle of ongoing protests and in the middle of this whole national debate over police and how we should best police our cities. Do you have mixed feelings about walking away in such a crucial moment?

BEST: Of course I do. How could I not? We're in the middle of a social reckoning and a racial reckoning in the country with all of the demonstrations and the many conversations that we're having. We have to acknowledge that policing has a history that has, in many ways, been conducive to the racism that we're experiencing. But we also have to acknowledge that policing is working really hard to change that narrative. And we need to work with the public to figure out how we're going to do that. And we haven't always been on the right side of history, but I think that there's a real movement and a real energy to make sure that we are.

KELLY: There's no disputing there's a huge challenge ahead. I guess my question is, why not stay? Why not rise to the challenge? Why not lead this department you signed on to lead?

BEST: Well, I believe 100% that they were putting me in a position of destined to fail, cutting into a police department that already had low staffing numbers, was already struggling to keep up with the demand. And then not including the police chief - I've been here almost 30 years - in the conversation about what the future of policing will look like let me know very clearly it was going to be very difficult to move forward and make the changes needed to move the department in the right direction.

KELLY: You and I last spoke in July, and you were facing all kinds of criticism after protesters took over the whole neighborhood this summer and named it the CHOP. And you were very candid when I pushed you and said, was this a lawless, police-free zone? You said, yeah, order has broken down. How do you answer President Trump and his supporters when they say cities like Seattle, cities being run by Democrats - they are a mess and that only he can come in and fix things and restore order?

BEST: Yeah. Well, the thing is, you know, all those conversations are about politics, and I really want to be about policies. You know, I think it's important that we do recognize that we had - during that CHOP period, the Capital Hill Organized Protests, we did have an area that was lawless. And we did need to take, you know, some affirmative action to minimize that. And we still have people who are showing up. You know, many can be peaceful demonstrators. But we also have people that are showing up who are rioters, who are breaking property, who are assaulting people, who are trying to set the precinct on fire. And that is criminal activity, and we do need to address it. I'm not saying that that is a political partisan issue, but it is an issue of public safety.

KELLY: No. Regrets - what do you wish you'd done differently?

BEST: The only thing - I wouldn't necessarily say differently but we should have looked at it a little bit more before - when the demonstrations began and when these very violent groups embedded themselves amongst the peaceful protesters, we really didn't have a sufficient way to separate the two. And so we used chemical munitions. And that really caused some problems with people who were there peacefully.

KELLY: Chemical munitions meaning - what? - tear gas, in layman's terms.

BEST: Tear gas specifically - and so I'm still thinking that there's a way to have conversations about how we might be able to have a different or better tactic in reducing and minimizing the risk when we have a crowd like that. But, you know, that's something that I just think is going to evolve over time.

KELLY: Just to make this personal - and forgive me if it's uncomfortably so. But you're speaking to us as a Black woman and, of course, also as a police chief. Have you felt those two things being in conflict with each other this summer?

BEST: I actually haven't. And, you know - and I don't feel uncomfortable at all. I'm very proud to be an African American woman, and I'm also very proud of the time I've had as a police chief. You know, it's really interesting that people have this strange - they try to make it this strange dichotomy that somehow, you know, being African American means that you're anti-cop or being a cop means you're anti-African American. And neither of those things is true. I think that's a very false narrative. I can't - I have a family. I have 14 aunts and uncles - well, not now but originally - and, you know, a lot of cousins and a lot of family. And none of them wants to not be safe in their neighborhood. It's not that they don't want policing. They just want to make sure that when policing happens, it is fair and just. And that's what we're looking for. So I feel like I had a great role in trying to make sure that I was doing just that.

KELLY: I suppose I'm asking - as I was out covering some of the protests this summer in Atlanta, I watched as Black Lives Matter protesters were getting in the face of Black cops and saying, how could you? How could you be standing here stopping us from what we came to do tonight? And they weren't giving the same amount of grief to the white cops standing there. It was directed at the Black police officers. And I thought, I wonder what that feels like.

BEST: Yeah, that did happen. And that happened even here in Seattle because there are some who have taken that view that somehow being a part of the policing means that you are condoning or looking to subjugate African American people. But there's nothing that's farther from the truth. I believe wholeheartedly that the real way to make change is to get involved and to invest in what that change is going to be to make it a better future for our children and our next generation.

KELLY: Chief Best, many thanks, and best of luck to you.

BEST: All right. Thank you, Mary Louise. Take care.

KELLY: That is Carmen Best. She is, until the close of business today, the chief of police for Seattle.

(SOUNDBITE OF MUSIC) Transcript provided by NPR, Copyright NPR.