Rodolfo Estrada, MD - phaware® interview 523

Dr. Rodolfo Estrada, is a seasoned pulmonologists currently at UT Health San Antonio with significant experience in the management of patients with different forms of pulmonary hypertension. In this episode, Dr. Estrada will discuss the technology and clinical development behind YUTREPIA™ (treprostinil) inhalation powder and why it might be a good option for some PAH and PH-ILD patients.

This Special Edition episode is sponsored by Liquidia.

Please see the Important Safety Information following this podcast. The Prescribing Information and Instructions for Use for YUTREPIA (treprostinil) inhalation powder are available at YUTREPIA.com. 

YUTREPIA is approved for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) and pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve the ability to exercise.

Steve Van Wormer:
Hi, welcome to I'm Aware That I'm Rare: the phaware podcast. I'm your host, Steve Van Wormer. Today we are here with Dr. Rodolfo Estrada from UT Health in San Antonio, Texas. He’s here to tell us about some exciting happenings that are taking place in the world of pulmonary hypertension and a new therapy that's been brought to market. Dr. Estrada, welcome.

Rodolfo Estrada, MD:
Thank you so much for having me. It's really great to be here. As you mentioned, I'm Rodolfo Estrada. I'm a pulmonologist at UT Health San Antonio, and there I lead the pulmonary hypertension program. My focus is now on caring for patients with pulmonary arterial hypertension or PAH and advancing research in this area.

Steve Van Wormer:
Dr. Estrada, it's a very interesting time in the world of pulmonary hypertension. There's a lot of moving parts, a lot of changes taking place in the community. I'd like you to share a little about where we are today.

Rodolfo Estrada, MD:
You're absolutely right. Even if we’ve made all this progress in PAH, PAH is still serious, and it's a progressive disease that can take a big toll, not only on the patients, but also on caregivers and families. We improved a lot in diagnosing it earlier and managing risk more precisely.

We have more treatments available now more than ever, but we still are faced with big challenges. Diagnosis often comes up late, and many patients can’t tolerate the medication or don't have access to advanced therapies when they need them the most.

For example, data from the REVEAL registry showed that only about a third of patients had received any form of prostacyclin, and half of those who died had never been started on IV therapy. And we get it. These medications really aren't easy. The side effects can be tough, and depending on how they're given, especially with IV or sub-Q options, there's a real risk of infection or complications from the delivery method.

That's why inhaled prostacyclins have become an important alternative. Delivering the medications straight into the lungs helps reduce the side effects that you might get when the drug circulates around the body. But even with inhaled options, there are some hurdles, like needing frequent doses, challenges with breathing patterns, and a ceiling effect, at times, of how much you can increase the dose.

Now here's where things get exciting. A new inhaled prostacyclin called YUTREPIA was recently approved. It's a dry powder inhaler that delivers medications using a special technology that’s called PRINT® that makes uniform particles just one micron in size. These particles travel deep into the lungs where they are needed the most. The medication comes in capsules you load into the device, and then you puncture the capsule and take two breaths four times a day. This device requires low effort from the patient, it seems to be well tolerated and easy to use, and hopefully this will help with the adherence of these patients.

Steve Van Wormer:
It's always an exciting time when there's a new tool in the toolbox for doctors and healthcare providers to offer patients. Can you tell us a little bit about your experience with this clinical trial and the patients that you saw that really led to this approval.

Rodolfo Estrada, MD:
Sure, happy to. In the Phase 1 study of YUTREPIA, they found that 79.5 micrograms of YUTREPIA gave similar systemic exposure to about nine breaths of nebulized treprostinil. Where in another analysis showed that patients had a greater survival and longer time before starting parenteral therapy when they were on doses greater than this threshold of 79.5 mcg four times a day. 

Then, there was a study called INSPIRE, which was a Phase 3 open-label, multicenter trial that included about 121 patients. These patients were either started on YUTREPIA or they transitioned from nebulized treprostinil. The main goal was to see if the medication was safe and tolerable, and it was.  

The study included patients with PAH and WHO Functional Class II and III. Everyone had to be able to walk at least 150 meters and have a good lung function. Most patients were on background therapies, and patients had been diagnosed with PAH for about seven years on average for those who transitioned, and about four years for the ones who were newly started. Those transitioning, had to be on stable nebulized treprostinil for at least three months. 

They also used an explanatory analysis to look at things like six-minute walk distance and patient-reported outcomes. On average, patients who were new to prostacyclin showed improvement, especially as doses increased, and those who transitioned didn't lose ground in their exercise capacity.

Notably, a hundred percent of the patients who transitioned from nebulized treprostinil say they preferred to stay on YUTREPIA after a few months of trying it.

Steve Van Wormer:
Can you walk us through a little about how the medication was being used in the INSPIRE study or tell us what kind of doses was the study aiming to achieve?

Rodolfo Estrada, MD:
The way the trial was done is patients were started on 26.5 micrograms four times a day, with weekly increases up to a maximum of 212 micrograms four times a day. By two months, 78% of the transition group and 71% of the treatment-naive group were above the key threshold of 79.5 micrograms four times a day.

At one year, 40% reached a dose equal or greater to 132.5 micrograms or what's the equivalent of about 15 breaths of nebulized treprostinil. In the open label extension, about one third of patients reached a dose equal or greater than 159 micrograms, which is about 18 breaths of nebulized treprostinil. Even at two years, there were patients who reached up to 238 micrograms, which is around 27 breaths of nebulized treprostinil.

In our center, we had a couple of patients in the trial who reached some of the highest doses, even in a woman in her 70s, which again, trial patients may not necessarily represent the real world. They tolerated it well and stayed at low risk longer really without needing additional therapy.

Steve Van Wormer:
So in these trials, what were some of the potential side-effects that patients experienced as they went through the trial?

Rodolfo Estrada, MD:
That’s a good question. The side effects were similar to other inhaled prostacyclins like cough, throat irritation, headaches and dizziness. These were mostly mild to moderate and tended to show up more in the treatment-naive group, as you would expect. Importantly though, at one year, no patient in the transition group had to stop the medication because of cough, and only 2 patients in the treatment-naive group had to. About 10% left the study due to side effects, but none of them were serious adverse events that were linked to the medication.

Steve Van Wormer:
So you had this successful trial and that’s led to a successful approval. Now that there's a new drug in your toolbox, what happens when a new therapy comes into play into the real world versus when it’s used in a trial group of patients?

Rodolfo Estrada, MD:
When we're doing trials, we're trying to answer a very specific question. And to be able to answer that specific question, we try to narrow the population that we can get the answer for. What happens in real world is that then the exposure of whatever intervention we did, medication or whatever else we would do, would be then offered to a broader range of profiles.

And then things that we may have not picked up on trials, then we pick it up in the real world, sometimes great, sometimes not as great. When you do a trial and it's a specific number of patients, usually a smaller number of patients than real world, as you get more exposure in the real world, we learn new things that we didn't know about it before.

Steve Van Wormer:
So what's great here in summary, doctor, is that we have a whole host of options for PAH patients, including YUTREPIA here, but also exciting for the PH-ILD population that has formerly only had one option. So, when a second option, a new option is laid out, how does that change the playing field for both of those subsets of patients?

Rodolfo Estrada, MD:
Yeah, it's a great point. We now have another inhaled option with YUTREPIA, which is now approved for not only PAH but also PH-ILD. It's a convenient dry powder inhaler that requires low effort from the patient, and it seems to be well tolerated and easy to use, which may help with the patient's adherence. From what we've seen, it offers a chance to deliver medication deep into the lungs, hit high doses, and potentially improve outcomes for patients who may not tolerate or access other forms of the medication.

Steve Van Wormer:
I really appreciate you being here today, doctor, to tell us about this exciting news for patients, exciting news for the healthcare providers like yourself, and thankfully to sponsors like Liquidia for the work they're doing to better the lives of patients with PAH and PH-ILD.

Rodolfo Estrada, MD:
Thank you for having me, Steve. It’s really been a pleasure talking to you about this today. And for the patients listening, while it is always exciting to have a new medication available in this space, it is very important that you discuss to the specific therapy plan that is best for your with your specific therapy providers and teams. My name is Rodolfo Estrada, and I'm aware that my patients are rare.

Please see the Important Safety Information in the show notes. The Prescribing Information and Instructions for Use for YUTREPIA are available at YUTREPIA.com. Learn more about the INSPIRE study.

Learn more about pulmonary hypertension trials at www.phaware.global/clinicaltrials. Engage for a cure: www.phaware.global/donate #phaware Share your story: [email protected] Like, Subscribe and Follow us: www.phawarepodcast.com. #phawareMD #PHILD @Liquidia_Corp @REstradaMD @UTHealthSA

IMPORTANT SAFETY INFORMATION
Before you take YUTREPIA, tell your healthcare provider about all of your medical conditions, including if you:

• Have low blood pressure
  
• Have or have had bleeding problems
  
• Have asthma or chronic obstructive pulmonary disease (COPD)
  
• Are pregnant or plan to become pregnant. It is not known if this product will harm your unborn baby
  
• Are breastfeeding or plan to breastfeed. It is not known if this product passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. YUTREPIA and other medicines may affect each other.

Especially tell your healthcare provider if you take:

• Medicines used to treat high blood pressure or heart disease
  
• Medicines that decrease blood clotting (anticoagulants)
  
• Water pills (diuretics)
  
• Gemfibrozil (Lopid®) or rifampin (Rimactane®, Rifadin®, Rifamate®, Rifater®)

What are the possible side effects of YUTREPIA?

This product can cause serious side effects, including:

• Low blood pressure (symptomatic hypotension). If you have low blood pressure, this product may lower your blood pressure more.
• Bleeding problems. This product may increase the risk of bleeding, especially in people who take blood thinners (anticoagulants).

The most common side effects of YUTREPIA are cough, headache, throat irritation and pain, nausea, reddening of the face and neck (flushing), fainting or loss of consciousness, dizziness, diarrhea, and shortness of breath. Like other inhaled prostaglandins, you may have trouble breathing after taking YUTREPIA because it may cause the muscles around your airway to tighten (bronchospasm). These are not all the possible side effects. Call your doctor for medical advice about side effects or if you have trouble breathing.

You may report side effects to the FDA at www.fda.gov/MedWatch or call 1–800-FDA-1088.

The risk information provided here is not comprehensive. To learn more about YUTREPIA, talk with your healthcare provider. Please see Full Prescribing Information for YUTREPIA and Instructions for Use. For additional information, call 1–888–393–5732.