Facing the Future of PAH

Pale lips and blue-tinged fingers are a sign of cyanosis, a condition caused by a lack of sufficient oxygen in the blood, giving the skin a purple-blue tone. Cyanosis also inspired the periwinkle-colored ribbon selected for pulmonary hypertension (PH) awareness, recognized every November. 

For patients with PH, poor oxygenation means shortness of breath and an uphill battle for the energy needed for daily activities. Poor blood oxygenation means doing less of the things you love, with the ones you love. It means worry and pain and multiple medications, and it may mean a shorter life. 

A diagnosis of pulmonary arterial hypertension, or PAH, is often the first time patients are hearing of the disease; it can take 1.5-2 years for a proper diagnosis because symptoms start mildly and are nonspecific. Shortness of breath is mistaken for asthma or blamed on some other existing condition. Referral to a pulmonologist or cardiologist, along with the right tests, can bring answers, but finally having a diagnosis can bring its own concerns.

PAH causes a narrowing of the blood vessels in the lungs, resulting in increased resistance to blood flow. The heart, forced to work harder to meet this abnormal demand, over time weakens, leading to heart failure. In addition to disproportionally affecting women (65-80%), it often strikes in the prime of life, with the average age of those diagnosed now being in their 50’s. Despite therapies to manage symptoms, life expectancy is still poor, and quality of life deteriorates as fatigue makes simple tasks difficult.

One patient described the challenge of living with PAH: “We have children still at home. I want to be there for their tomorrow. I want to have the strength to make it to their sports game or to climb the steps at Back-to-School night to listen to the teachers talk.”

Unfortunately, the treatment options currently available are insufficient for many patients, with the most effective agents being invasive and sometimes painful. With these therapies, we still see patients doing only “okay” or even deteriorating while on treatment. It is not good enough. We need therapeutics that halt disease progression and put the brakes on the underlying cellular hyperproliferation causing the blockages that lead to PAH.  

I started working at Pfizer back in 1998, with drugs that had potent activity on the cardiovascular and pulmonary systems. Over time, my focus slowly shifted to apply those drugs into diseases like PAH. While I’ve had the opportunity to work on multiple drug development programs that ultimately led to the establishment of current PAH standard of care therapy, I still saw patients and physicians frustrated by the gap in treatment options for this life-threatening disease. I’ve stayed in the PAH space ever since in order to contribute to the development of better medications for the community. We’re now moving in a direction to realize new therapies that go beyond symptom management toward treatments that can halt or reverse disease progression.  

Oral imatinib is one of the drugs that showed dramatic efficacy on the condition in a Novartis clinical trial which was reported out in 2013. The results were quite exciting, but further development of the candidate was abandoned because of adverse side effects. 

Here at Aerovate, we’ve formulated imatinib into an investigational therapy called AV-101 so it can be inhaled and delivered directly to the tissues of the lungs, avoiding the high systemic exposure that produced such poor tolerability. We’re listening to the community to design a treatment that we already know has proven effective in improving PAH symptoms and is easy to use by people with PAH on their own, without pumps, in-office injections, surgeries, or the need for pain management. We’ve structured our Phase 2b/Phase 3 IMPAHCT clinical trial to be as efficient as possible so we can get a clear picture of the right dose and get AV-101 to market for patients as quickly as possible. With encouraging data from our Phase 1 safety trial, we’re excited to now be enrolling patients for IMPAHCT clinical trial.

Research in PAH is shifting towards next generation therapies that will truly change how PAH patients live and I’m honored to be a part of that discovery process. Our goal at Aerovate is to provide not just hope, but a meaningful solution to patients with PAH. This November, we honor all the patients and their loved ones who are living with PAH. We go to work every day to help people like them. I invite you to visit the Pulmonary Hypertension Association’s site with resources for patients, families, and physicians about medication, clinical trial options, and ways to support PH awareness.