Dec 29, 2020
Dr. Raymond Benza is the Director for the Division of
Cardiovascular Medicine at “THE” Ohio State University. He has been
in practice for more than 20 years. In this episode, Dr. Benza
GB002 Phase 2 Study and explains what differentiates
GB002 from other investigational drugs in
Raymond Benza, MD:
Well, good day, everyone. I hope everyone is staying safe in these crazy days. My name is Dr. Raymond Benza and I am currently the Director for the Division of Cardiovascular Medicine at “THE” Ohio State University. I am also a PH Clinician and Researcher. I've been working in the field of pulmonary hypertension for over 20 years and have been involved in the majority of the main clinical trials, exploring new therapeutics for the treatment of this very severe disease. I’ve treated many patients with this disease, personally. I've seen what patients have suffered through and really have come to be very close with this community and I'm very passionate about treating this disease process.
Over the last 20 years, we've seen a remarkable improvement in the way we manage patients with pulmonary arterial hypertension, so much so that we've actually tripled the life expectancy for patients with this deadly disease. Now, overall, that sounds like a good thing, but when you recognize that the majority of the patients who have this disease are young women, an extension of life from three years to nine years may not be enough. So we are all dedicated trying to find new therapies that really, really act at the heart of this disease in order to make a better impact on survival and to keep patients out of the hospital and make them feel better.
Unfortunately, the currently available therapies do not really address the proliferative process leading to pulmonary arterial hypertension. What I mean by proliferative is that this is a disease in which the cells of the blood vessels divide in an unchecked manner. These are the cells of the middle lining of the blood vessel called the media. By the expansion of this media, by these proliferating cells, the vessels become smaller and smaller such that blood cannot traverse the lung to get oxygen into them. This causes a series of problems, ultimately leading to heart failure and to patient demise or death. So our patients need better options. They need therapies that directly attack this proliferative process in order to reverse the course of the disease, improve their survival and their quality of life.
This is going to be one of the medications that we will be talking about today called GP002. Now I am a member of the steering committee and helped design the Phase 2 trial for this particular therapeutic in pulmonary arterial hypertension. I'm very familiar with the therapeutic and very excited about this. The main difference between available therapies for pulmonary hypertension and GB002, and what makes GB002 such an exciting clinical drug candidate, is that this is a new chemical identity that is developed specifically for the treatment of pulmonary arterial hypertension, that targets that underlying proliferative mechanism that we just spoke about. That really leads to the development of PAH and its ultimate progression.
Remember, the three pillars that drive pulmonary arterial hypertension are inflammation, fibrosis or scarring and proliferation. This is all occurring in the blood vessels or pulmonary arteries in the lungs. GB002 has demonstrated effects on several of these underlying mechanisms and pathways, suggesting that GB002 really has the potential to be disease modifying. Again, a drug that is doing much, much more than just dilating the blood vessels, but actually working on the mechanisms in the cells that cause these blood vessels to close down.
Interestingly in a healthy volunteer study, GB002 was shown to be very well tolerated with no significant adverse events that were observed. It is also being evaluated in patients with PAH in a Phase 1b trial. Now, this I believe will be completed by the end of December of this year. So we might have some really more exciting information to talk about, perhaps in a later podcast.
The other unique thing about GB002 is that it is delivered by a dry powder inhalation twice daily, and it can be self-administered by the patient. This delivery system, we'll talk about a little bit later, because it's pretty cool. I think most people will really like the way it works.
So where is GB002 now? Let's talk a little bit about the Phase 2 trial that I mentioned a little bit earlier. Again, I am part of the steering committee and helped design this Phase 2 study using GB002. This particular study, Phase 2, is also referred to as the Torrey Study. It's a randomized, double blind, placebo controlled, multi-center clinical trial, to evaluate the efficacy and safety of oral inhalation of GB002 for the treatment of WHO Group 1, pulmonary arterial hypertension.
Now remember, Group 1, pulmonary hypertension is the type of pulmonary hypertension where the disease is intrinsic to the arteries of the lungs. It's not caused by some other secondary problem like heart failure or chronic lung diseases or blood clots in the blood vessels. It's actually an intrinsic problem of the blood vessels itself. This study will be enrolling around 80 patients with confirmed diagnosis of idiopathic pulmonary arterial hypertension, heritable pulmonary arterial hypertension, or pulmonary arterial hypertension related to connective tissue diseases. Now, the patients who enrolled in this study are functionally impaired. They know something is going on, but their symptoms can be minimal and really affects them only when they're really exerting themselves, or it can actually be affecting them so much that they have symptoms at rest. Particularly breathlessness. Now study sites are going to be located all over the United States, as well as in Canada and across the European Union.
Now, the good thing about this trial, is that unless a patient is on an inhaled prostacyclin like TYVASO or iloprost, the patients do not have to come off their currently approved PH therapies in order to participate. That's really great. Now the study duration will be 24 weeks in duration and here are some of the study requirements and visits for the patients. We're trying to keep it simple. In clinic visit spaces will be about 12 weeks apart. We wanted to make sure that we kept this simple because of the ongoing issues with the pandemic. There will be opportunity for a home health nurse for certain visits too. Again, to simplify things. There really are only two mandatory clinic visits at week 12 and 24. And again, this is an attempt for us to be COVID conscious in these days.
Now, let's talk a little bit about the administration because I mentioned earlier, this is really cool. The drug is going to be administered two times daily using a dry powder inhalation. Now, this dry powder inhalation is delivered by a very novel inhaler. I think the actual inhaler is the cool thing. It's very discreet and it can fit in the palm of your hand. It could fit in your pocket or in your purse. The size of the inhaler is similar to the bottle of hand sanitizer, which I hope you have all in your pockets right now. And smaller than the size of a computer mouse. If you just pick one of those up, you'll see what the inhaler sizes is like. So again, it's compact easy to use, and it has a well-established track record already. The FDA has approved this for other inhalational therapies.
Now the study objective, the primary one, is to determine the effect of GB002 on improving pulmonary hemodynamics. That means, the pressure in the lung or how well the heart circulates blood and subjects with WHO Group 1, pulmonary arterial hypertension. Which we explained early what that classification is, who are functional Class 2 or 3. Again, we explained the level of intensity of the disease a little bit earlier. Now the secondary objective is to determine the effective GB002 on improving exercise capacity in this population. And lastly, obviously, and very importantly, we want to evaluate the safety of GB002 in this population.
Now again, the specific pulmonary hemodynamic that we're interested in is the change in pulmonary vascular resistance using right-heart catheterization, which many of you are familiar and probably have had in the past from baseline to week 24. So two different heart catheterizations. Now, remember the resistance is the actual hemodynamic that reflects the degree of arterial remodeling in these blood vessels, in the lungs that we talked about earlier. Our secondary end point, which again is a measure of your exercise capacity as how far you can walk in the six minute walk tests between baseline and week 24. And again, everyone is very familiar and has probably been in these six minute walk tests in clinic, and we know how easy they are to do. Following the participation in the study, there will be an open label extension of the study that is also planned. So people can continue on this drug, which is very important, particularly if you have a really good benefit from the medication and we want to keep it going.
So to conclude, those interested in participating or potentially participating or learning more about the GB002 Phase 2 study, I encourage them to talk to their physicians and you can find out more details by using the following link on ClinicalTrials.gov and search for the Torrey Study or the GB002 Study. We will also have this cited at the end of this podcast today.
Remember GB002 targets a new pathway. It really acts on the cells that are in these blood vessels that's causing the disease. Given that PAH currently has no cure, it's important for patients to participate in clinical trials. This is how we push the needle forward, both by allowing researchers to study new pathways, like I just described, as well as helping them to discover and develop new and more effective treatments for this very deadly disease.
My name is Dr. Raymond Benza and I'm aware that I'm rare.
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