Dr. Sabrina Paganoni, MD, PhD, at Mass. General Hospital and Spaulding Rehabilitation Hospital, talks about treatment for ALS disease.
Interview conducted by Ivanhoe Broadcast News in October 2022.
Can you give me a little background on ALS?
PAGANONI: ALS is an awful disease where patients progressively lose the ability to move and the disease affects every part of the body. Essentially every muscle becomes weak over time. People will lose the ability to speak, to swallow, to walk, to use their hands, and ultimately they die because it’s hard for them to breathe on their own, so respiratory function is affected as well.
How much time do patients have from first onset usually until it progresses to the point where there’s no return?
PAGANONI: On average, it takes about three to four years after the first symptoms. It’s really sad that when we see people in the clinic because it takes time to diagnose them. On average after we first diagnose them and tell them that they have ALS, they live about two years.
When does this often strike? Is this an elderly population or these people in the primes of their lives?
PAGANONI: Many people with ALS develop the disease in the prime of their life. Although the disease can really strike at any age. We have had people as young as 20 and people as old as 80 or older. It’s a disease that can affect anyone at any time.
Is there a cure?
PAGANONI: There is no cure. There’s no way to stop or reverse the disease. We have had two drugs approved by the FDA until recently with the approval of a new drug. Those drugs only have a modest effect on disease outcomes.
Can you talk about the drug you were investigating on?
PAGANONI: The new drug is called AMX0035. It is a combination of two different drugs. The drug works by attacking two different parts of the cell. The idea was that by combining two drugs instead of using just one, we could have a more robust effect on the disease because the disease is caused by multiple mechanisms, multiple things that go wrong in the cell. W wanted to tackle two at the same time to be more effective. And can I keep going and then you cut, right? So specifically, the drug attacks- targets two different components of the cell. It works on trying to restore mitochondrial function and mitochondria are the powerhouse of the cell. Also it works on something called ER stress, which is basically a mechanism to clear toxic debris from the cells. These are two common mechanisms that are thought to be implicated in all forms of ALS. So they’re broadly relevant for the ALS population. What we did was to test the drug in people with ALS. We did so in the CENTAUR trial. The CENTAUR trial was a trial that we designed and led from Mass General in collaboration with Amylyx Pharmaceuticals. It was really a great partnership within the ALS community because we leveraged the input from many colleagues, scientists, and importantly the patient population who provided great input into trial design and conduct. It was really wonderful trial to be involved with. The trial showed that when people were given AMX0035, they were able to retain their physical functions for longer. Things that we do every day and take for granted, like talking, swallowing, or walking stairs. People who took the drug did better on those functions for longer compared to people who received placebo. Then we also gave everyone who participated in the trial the opportunity to take drug long term. We monitored their survival long-term and saw that the people who started receiving AMX0035 earlier lived longer, on average five months longer than people who started the drug later. This was important because we saw that during the trial, people who were on the drug retained their physical functions for longer and then they also lived longer, long term. Both aspects are really important for people with ALS.
For patients who are working towards milestones, what is the impact is for them?
PAGANONI: What people tell us over and over is that they really value any additional time that they have to spend with their families.For many people, this is connected to some important family or personal milestones. For example, people want to see their kids graduate from school or they want to see their first child get married. Five or six months could be the difference between making it to the event or not.
What’s the implication of the impact of having something now as opposed to two years ago?
PAGANONI: This drug is similar to the other ones in terms of efficacy. The important thing is that now we’re combining them for added value. Before the approval of this new drug, we only had two other drugs that were available for patients. It did help to some extent, but obviously, we needed more. With this drug, we saw benefits in terms of retention of function and independence and longer survival, which were seen on top of standard of care. Here the idea is to use a cocktail approach so that we have multiple drugs that we can give to the same patient to give them their best shot.
Was this a powder or a liquid? Can you tell me how it was administered?
PAGANONI: This new drug comes as a powder. It’s mixed with water and becomes a drink. It can be given easily to people with ALS. They can either drink it by mouth or if they have a feeding tube, they can also take it by feeding tube. It can be used throughout the course of the disease.
Why is that important rather than upheld to swallow?
PAGANONI: People with ALS oftentimes lose the ability to swallow. Oftentimes they will need to have a feeding tube inserted to continue to get nutrition. This drug is particularly easy to administer both by mouth and by feeding tube. If people lose the ability to swallow, they can continue to receive it.
If people who haad the drug seem to do better, how much earlier was it, first onset of symptoms?
PAGANONI: In the trial, we assigned people randomly to either active drug or placebo for six months. The people who received active drug did better in terms of being more independent and have better function over those six months compared to the people who received placebo. Then we give we gave everyone the possibility of continuing in the trial and be monitored long-term to monitor their survival. The people who started on AMX0035 six months earlier than people who started on placebo lived about five months earlier on average. Starting the drug earlier seem to be predictive of better outcomes.
What do you and your colleagues ultimately want to do next?
PAGANONI: ALS is such a complex disease and it’s caused by many different things that go wrong in the nerve cells. We need to continue to find new targets, so that we can continue to add new medications to try to slow down the disease from different angles. That’s exactly what we’re doing now. Now we have a cocktail of drugs that we can give to our patients. We want to be as aggressive as possible and start drugs as early as possible, so that they can continue to remain independent and be more functional, live longer. We are also doing a lot of research. Right now there’s a lot of research into new medications. We are testing more medications than ever and we have a number of clinical trials. I think the most important message for people with ALS and their families is that there is hope. There is a lot of hope in research. We are testing more drugs than ever. This is the right time to get involved. We research in clinical trials. With that on top of standard of care, we can also test and hopefully offer new medications that we’re developing right now.
When was the FDA approval?
PAGANONI: FDA approval was September 29th. The drug was approved a couple of weeks ago and now we are starting to prescribe it, and obviously it’s going to be a process for people to receive it.
What is the market name?
PAGANONI: It’s called Relyvrio.
Is there anything else I didn’t ask you that you want people to know?
PAGANONI: The concept of hope and the concept of research is important.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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