Sandeep Sahay, MD - phaware® interview 462

Apr 2, 2024

Dr. Sandeep Sahay, a pulmonologist at Houston Methodist Hospital, discusses the concept of disease modification in the treatment of pulmonary hypertension (PH). He explains how traditional PH therapies focus on vasodilation, reducing pressure in the pulmonary artery by dilating blood vessels. However, newer therapies, such as sotatercept, work in different ways to reduce smooth muscle proliferation and thickness of the artery walls. Dr. Sahay suggests that if a drug is labeled as disease-modifying, it may be used in combination with existing PH medications from the beginning of treatment. However, he notes that further research, regulatory approval, and payer considerations are necessary for this to happen. @MethodistHosp @SandeepSahayMD

Hi, I am Sandeep Sahay. I'm a pulmonologist. I'm at Houston Methodist Hospital, Houston, Texas. I've been involved with pulmonary hypertension patients and the PH Center at our place for the last 10 years. Clinically, I see patients with PH, or chronic thromboembolic pulmonary hypertension (CTEPH), or different types of pulmonary hypertension. I'm actively involved in research. We do a lot of clinical trials with the disease state. And also, our own academic stuff with grants and coming up with more thought-provoking ideas in this disease state, so that we can help our patients. 

In the last three decades, we have made a lot of progress in this particular disease state. I would like to thanks to all my colleagues, and researchers, and my friends, mentors for the last two to three decades who invested their whole lives and careers into this disease state and made tremendous progress. But still there’s a lot more work to do. We are here to further the science and advance in this disease state.

On that note, the new thing, which is sort of I can say talk of the town is about disease modification. Many may wonder what this really means, and why we are even talking about it, and what's so new. I think this all started with us looking beyond our traditional PH therapies, which were generally considered as vasodilators. When I say that term in simple words, it means that we tend to reduce the pressure in the pulmonary artery by dilating the blood vessel. So most of our current therapies sort of classify into that category.

But now with newer therapies, specifically sotatercept, which I think many patients are excited about. I would say clinicians, researchers, physicians, we are all excited about this therapy. This is not in a way our traditional PH therapy. When I say that term, what I really mean is that it doesn't work the way our traditional drugs work. It doesn't dilate the pulmonary artery, which we historically understand with our currently approved therapies.

This drug kind of works in a different mechanism. When we look at that mechanism, the way it works, I'm going to be putting it in a very simplistic way that it just sort of tries to reduce that smooth muscle proliferation. Or, I should say that in PH, the thickness of the artery. It tries to reduce that by different mechanisms. I'm not going into detail scientifically that what it does, but it tries to restore the cellular level dysfunction in the endothelial cells, and then reduces the thickness of the vessel wall, so that it increases the size of your pulmonary artery. Now, since this drug works in a little different mechanism, we started thinking that, how do we describe how this drug works? When we started thinking about that, one of the things that naturally came to our mind was, should we call this drug as disease-modifying agent?

Now, what that really means is that by definition, which could modify the course of the disease. When we use this term as physicians and researchers, we generally tend to refer it in a positive connotation. It means we believe that the drugs which can affect the pathophysiology or the underlying process of the disease in a positive way, it means improving the disease. However, it's a generic English term disease-modification. Last week, I got surprised when one of the patients, actually, heard this term, she actually was thinking this can mean anything. Actually, she was right. Because disease-modification, could mean positive or could mean negative. But in the scientific world, in our research world, when we started using this term, we thought of it only in the positive way. We didn't really think in the negative way, because we were talking about the treatment agent.

This term actually comes from other disease states like rheumatological conditions. For example, rheumatoid arthritis, where you may have drugs to relieve the joint pain like your regular pain medications. But at the same time, there may be drugs which will work on the underlying mechanism, what causes rheumatoid arthritis and tries to prevent further damage to your joints. So, I'm just trying to make it a little different.

I'm going to take one example in the PH world also, when someone has pulmonary hypertension and is symptomatic, more short of breath. You start noticing that you develop fluid swelling, or leg fluid retention, or leg swelling, or fluid retention on your body. Then, you take a water pill. Those water pills can get your fluid off, can make you feel better, but they do not do anything to your pulmonary hypertension. But then your doctors will, after the water pill, they will say, "Okay. Well, you need to take PH medications also," which are whatever… you know all those names.

So then, you are started on those PH medications, in addition to the water pill. So try to understand the water pill doesn't really do anything. It doesn't change anything about your pulmonary artery pressure or the mechanism by which you develop that disease. But then your PH medications, on the other hand, I’ll take an example of those infusion pumps or those prostacyclin drugs. They definitely do help to relieve the pressure on your right side of the heart by dilating the pulmonary artery. So, that basically changes something about your pulmonary hypertension, which you do not see with the water pill. So, this is how the distinction is.

To further advance our understanding in these PH medications, we have this newer drug, sotatercept. In the future, you will see many more such drugs will come out. There is a lot of exciting work being done currently. So, all these different drugs, which are going to come out, they affect your disease process itself. That's why they're called disease-modification. Now, this term is generally used by the regulatory bodies, like FDA or maybe the European drug approving agencies. It's not something which we commonly use in our day-to-day practice when we are talking to patients.

The relevance of using this drug could be if, let's say, hypothetically speaking a drug gets a label from a regulatory authority that this drug is disease-modifying. Then, there may be a possibility that this drug may get inducted into the treatment algorithms along with your currently existing medication. There may be a possibility. And again, this will need a lot of research, regulatory body approval, and then with payers, etc. We're not going into all that. But in very simplistic way, what I'm trying to explain, if a drug becomes disease-modifying labeled along with the other properties, you could use that drug from the very beginning in addition to your other PH medications. There is a possibility. Maybe we will be using it this way. I don't know right now, because we don't have the drug available right now. We are waiting for FDA's call how and what all the recommendations when the drug gets approved.

This is why this whole new terminology is being discussed. To be honest, it's a good thing to do. It's a good scientific exercise. We all are learning through this process. So, I believe that yes, we should be discussing this, because that's how we advance new ideas come. That will be very helpful for everyone, for the scientific community, for our patients, and for everyone around us. So, I tried to explain this in a very simplistic way. I hope this is helpful for our patients and their care providers. But again right now, there is no gold standard way for us to define this term. It's a work in progress. So with that, I would like to end. If you have any questions, please reach out to us at www.phaware.global.  

I am Dr. Sandeep Sahay, and I'm aware that my patients are rare.

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