Seth Hall, MBA, RRT - phaware® interview 520

Seth Hall, MBA, RRT, takes listeners on a journey through the past, present, and future of inhaled therapies. Discover how these treatments have evolved, the life-changing benefits they offer, and the revolutionary technologies that could redefine outcomes for PAH and PH-ILD patients.

This Special Edition episode is sponsored by Liquidia.

My name is Seth Hall. I started my career as a critical care respiratory therapist in Washington D.C. Over the years, I traveled around the country working at various academic centers; Duke and Stanford and Columbia, and several others. I was just like a sponge. That experience just allowed me to keep learning, growing, and luckily, I was able to surround myself with some really great mentors. I landed in respiratory and took care of a lot of patients with pulmonary hypertension in my past, throughout my years working clinically.

I'm actually from a very small coal mining community in West Virginia. Some of my current research I do independently from work also revolves around addressing barriers and access to care with patients with cardiopulmonary illnesses, specifically in rural communities. I'm very passionate about advocating for patients with cardiopulmonary diseases and illnesses, and very lucky and fortunate to have been involved in the care of PH patients in my past.

Currently I work as a medical science liaison or MSL at Liquidia, and we strive to bridge the gap between that clinical research and finding solutions to unmet needs for patients. We really help bridge that gap of clinical research and the scientific discussion and exchange.

With my respiratory background, something I've always been interested in is just the evolution of inhaled therapies and how we've got to where we are now with managing some of these complex respiratory diseases. Last year, we published a piece in Respiratory Therapy: A Journal of Pulmonary Technique where we talked about just that. We looked at the historicity benefits, future potential options for inhaled therapies, and we really focused on emerging technologies. We wanted to really focus on how targeted drug delivery could potentially transform care for millions of patients.

Looking back, it actually goes back pretty far. Almost 4,000 years, actually. Some early medical practices that emerged in India over 2000 BC, where they looked at inhaled therapies for opening up the lungs and what we refer to as bronchodilatory properties. Then, around 1500 BCE, Egyptians were looking at inhaling vapors and other plant medicinal purposes for other respiratory relief. Even when you look back at ancient Greeks under Hippocrates, they developed one of the earliest actually medical devices, and that was simply just a pot with a reed and you inhaled medicines. These vapors were therapies for patients. Then, these practices, which we see all over the world, were found in Central and South America and Africa. They were the early foundation for what we're doing today in the development of modern inhalation therapy. This evolution of inhaled therapies, it really just reflects the ongoing innovation to provide more solutions for people around us.

To fast-forward, we now have nebulizers. These emerged around the 19th century. These delivered medicine via an aerosol. Think of a liquid droplet. It can be very effective, but sometimes can be quite cumbersome, with parts and pieces due to the size and assembly. You can imagine being a patient and trying to travel with this. If you have an active lifestyle, it might not be practical for daily use.

Then, fast-forward a little bit more looking into around the 1950s, metered-dose inhalers came around or MDIs. These were a good alternative to nebulizers, however, they really require precise coordination. What I mean by that is essentially the patients have to actuate the drug and then time it with their inhalation or with breathing in. You can imagine how for some patients this could be a challenge.

Now we have dry powder inhalers or DPIs, which emerged around the 1990s, that really addressed some of those limitations that we spoke to with earlier devices. They're simple to use, they're portable, but they're actually breath-actuated. In order to disperse the medication and get them where they needed to go, the patient just takes in a deep breath. This really helped out with usability and patients adhering to medicine, because we know if we make it easier for patients to take their medicine, they're more likely to be compliant with their treatments.

Direct lung delivery has proven itself to be the cornerstone for effective treatment, especially for respiratory diseases. By giving the medication directly to the lungs, we are bypassing potential systemic side effects. The intended site of action is in the lungs, that's where we're delivering the medicine. Whereas, if you're getting medicine via orally or IV administration, you're now exposing other parts of the body to that medication, as well. Essentially, the localized drug delivery can help enable lower therapeutic dosing. You can use less drug. It provides a very rapid onset, you're going to where the drug needs to be. This targeted delivery for symptoms and all different types of diseases, you might have bronchoconstriction or vasoconstriction, inflammation. Essentially, you're just targeting exactly where the drug needs to go.

DPIs have become a preferred choice for many respiratory diseases due to their portability, their ease of use, patient adherence, making it easier for patients to take their medicine. Unlike the metered-dose inhalers or the MDIs we just talked about, DPIs don't require that precise timing. They don't have a propellant. They don't require a spacer to take the medication. Then, their compact design makes it ideal for active patients on the go that are out and about with their families.

From a functional perspective, DPIs are breath-actuated. What that means is essentially it utilizes the energy of their own breath or their inhalation to overcome these cohesive forces that are holding the powder together. That helps to break up the particles. That process of breaking up the particles is referred to as de-agglomeration. So, the way that devices are engineered with DPIs, there's an internal resistance, and this resistance within the device provides a mechanical assistance with that de-agglomeration, and that helps with the distribution of the drug particles to the lungs.

Despite these advancements that we've had in respiratory treatments, inhaled drug deliveries still remains pretty poor. For instance, in the case of DPIs, what's currently available, patients with restrictive lung diseases might have a limited ability to use some of these higher resistance inhalers that the inhaler needs to break apart the medication. This essentially inhibits the complete particle de-agglomeration for the patients. Then, we know that when there's inadequate de-agglomeration that the dry powders are going to have more variability in their particle sizes. Some of these larger particle sizes tend to deposit more in the upper airway, which we refer to as the oropharynx, which can lead to patients having to cough.

Apart from increasing the potential upper airway irritation and the cough, you also have insufficient delivery of medication now to the lower airway where you want the drug to be. This could potentially result in increased systemic absorption and creating additional tolerability issues and challenges for patients trying to take their medicine.

So, a critical advancement would be if in the inhalation delivery space, we could make these particles uniform in their physical and chemical flow properties that might help resist this clumping together. Some of these advancements would really enable the use of lower resistance inhalers, because it wouldn't necessitate that you need to de-agglomerate with a high resistance. That means less effort that the patient requires for them to take their medication.

One novel formulation approach that has the potential to significantly advance the manufacturing of DPIs is something referred to as PRINT® Technology by Liquidia. PRINT®, which stands for particle replication and non-wetting templates, it actually originated in the electronics industry with microprocessors. Clinically, it's been studied though in vaccines and antivirals, ophthalmology, and even in topicals. Currently, it's of high interest in the inhaled therapy space. PRINT® Technology offers the unique ability to control for inhaled particle size and shape, giving a higher degree of confidence that the drug is reaching the targeted lung region where it needs to go.

It's essentially a mold technology. Think of ice cubes in an ice tray. They all look the same shape and size. That's what PRINT® does but on a micro level, with the actual formulation of these DPIs. The geometric precision and shape of these particles can potentially significantly enhance the aerosolization and potentially allowing these PRINT® formulations to be compatible with a diverse array of DPI devices, whether you have low or high resistance. Now, you can tailor the medicine specifically to the pathophysiology of whatever respiratory condition you're trying to treat. PRINT® Technology is designed to ensure that you have the homogeneity of the particle, concentration, and it's a critical factor in maintaining consistent dosing. We know that consistent dosing leads to therapeutic efficacy. This uniformity, it potentially mitigates the variability in drug delivery for patients.

As a respiratory therapist, I'm actually really excited. I think the evolution of device technology, along with advancements in drug formulations, holds great promise in improving pulmonary drug delivery. I mentioned formulation, so I'll just grow on that a little bit too. We have emerging liposomal formulations that are being studied right now in clinical trials that might also mark a significant milestone in this ongoing effort.

Liposomes are essentially nanoscale lipid vesicles that surround the medication or what we refer to as encapsulate. That's to help extend the release profile of the drug. It also can help enhance the stability, and now, you have a reduction in the dosing frequency required by the patient. These innovations could potentially provide sustained therapeutic benefits for a wide variety of respiratory illnesses, reducing the burden of the frequent dosing for the patients, and potentially improving patient adherence by making it easier on them.

All in all, the development of inhaled therapies really demonstrates our relentless pursuit, striving for more tolerable, patient-friendly just more options in the treatment of many conditions in the respiratory space. Innovations such as PRINT®  Technology and liposomal formulation really underscores the commitment to optimizing drug delivery for some of these really challenging conditions. As research continues and we have more data, the future of inhaled therapies holds immense potential to really address some of these unmet needs, and most importantly, improve the quality of life for patients all over the world.

My name is Seth Hall, and I'm aware that the patients we serve are rare.

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