CURRENT SERIES:
Understanding the Subpopulations of Pulmonary Hypertension

The Evolving Treatment Landscape of PH and PAH

Looking toward the future management of PH and PAH, experts review investigational strategies.


Looking toward the future management of PH and PAH, experts review investigational strategies.

Transcript
Derek van Amerongen, MD, MS, FACOG: In terms of the therapy pipeline, there are certainly huge numbers of drugs in development across so many conditions, including PAH [pulmonary arterial hypertension] and PH [pulmonary hypertension]. We have pharmacists at Humana Inc whose job it is to monitor the pipeline and track this over 12 to 24 months in advance. We all get monthly updates on that, but ultimately as a medical director and as someone who’s involved with the P&T [pharmacy and therapeutics] committee, when a drug gets on my radar, it’s usually within 3 to 4 months before launch.

At that time, we begin preparing our draft policies. We begin preparing to understand the impact of that drug on the current treatment paradigm and how it’s going to fit in along with the other drugs that are currently being used. All that preparation leading up to the discussion once the drug is approved then comes very shortly thereafter to P&T. The challenge with the pipeline of course is that there are so many drugs in development that never make it to that point. At the same time, we realize that as drugs get closer to launch, it is really important to make sure that we’re beginning to engage in discussions with manufacturers and—if appropriate and helpful—with clinicians at the national level and in the community, to understand the import of what this new drug is potentially bringing to the table.

Hilary M. DuBrock, MD: For connective tissue disease [CTD]–associated pulmonary arterial hypertension, I’m specifically looking forward to different types of approaches to medical therapy that include immunomodulators such as rituximab and tocilizumab, as well as medications that affect the immune system, because that plays an important role in connective tissue disease–associated PAH. Additionally, I think medications that target right ventricular function are important in patients with connective tissue disease–associated PAH, since RV [right ventricle] function is an important prognostic variable in those individuals.

For portopulmonary hypertension, there are recent data that suggest that BNP9 and BNP10 play an important role in disease pathogenesis. Certainly, targeting or augmenting these pathways may be important in treating portopulmonary hypertension and highlights the fact that a personalized approach to treating different types of pulmonary hypertension is needed. For chronic thromboembolic pulmonary hypertension [CTEPH], our treatments are fairly effective. I would like more information on best approaches in terms of managing combination therapy and when to pursue procedures such as balloon pulmonary angioplasty in patients with CTEPH.

Charles D. Burger, MD: Depending on how one counts the FDA-approved drugs in the United States for group 1 pulmonary arterial hypertension, it’s certainly in the range of about a dozen medications. However, though there are about a dozen medications, all of them are in 1 of 3 pathways: the endothelin pathway, nitric oxide pathway, and prostaglandin pathway. We need new pathways. I think we’ve maximized options in the 3 areas I’ve mentioned, but I’d really like to add a fourth pathway and fifth pathway on the presumption that if you can come at this from multiple angles or with multiple targets, the benefit will be shown in reversal of the disease, improved symptoms, and better functional status.

There are several pathways that are under investigation. One active phase I study is looking at an inhaled agent that would inhibit platelet-derived growth factor in the tyrosine kinase inhibition pathway. That has, based on the science, a reasonable chance of being effective in pulmonary hypertension. I think further investigation and the discovery of pharmaceuticals, interventional agents, and different pathways could be combined to our existing FDA-approved medications to be tolerable and safe and enhance outcomes in terms of improvement of the pulmonary hypertension by objective measures and reduction in symptoms. This would keep people at work or in school, keep them out of the hospital, keep them functional, and keep them alive to see their kids graduate from high school and college. To do the same for their grandkids would be more than exciting. That would be what I would look forward to regarding advances in the field. There’s lots of work being done. Excitement of course needs to be translated into reality, so it will require scientific study to prove tolerability and benefit. But I remain very hopeful.
 
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