Targeting Chronic Cough in Covid-19 Pandemic Times

Consider a person who has been diagnosed with idiopathic pulmonary fibrosis, a terminal disease that scars their lungs and causes them to cough incessantly. Now consider what that can be like in the midst of the COVID-19 pandemic.

They can’t breath well and are easily fatigued. When performing everyday activities, it can often feel like they are breathing through a straw. If they wear a mask, it can be worse. Already socially isolated because people don’t understand their disease, they now get nasty looks when they cough in public. A difficult life before the pandemic is made significantly worse, leading to anxiety, embarrassment, and stigmatization.

William Gerhart, CEO of Respivant Sciences, is hoping the company’s experimental inhaled anti-inflammatory that targets that chronic cough will ease their burden.

Pulmonary fibrosis (PF) is comprised of more than 200 different, individual lung diseases. It can be caused by certain drugs, by radiation, a reaction to airborne substances, an underlying autoimmune or connective tissue disease, or it can be idiopathic, meaning of unknown cause. Sometimes pulmonary fibrosis can result in only mild symptoms and doesn’t progress. But for the most part the fibrosis will progress creating a life-threatening situation.

About 200,000 Americans are afflicted with pulmonary fibrosis, with idiopathic pulmonary fibrosis (IPF) accounting for about half of those cases. IPF has the worst prognosis with a life expectancy of three to five years after diagnosis. That is worse than for any cancer except for pancreatic and lung cancers. An estimated 30,000 to 40,000 Americans die from IPF every year.

Coughing is a common symptom, and it can range from being mild and treatable with over-the-counter cough medicines, to severe and persistent, and unresponsive to any therapy.

“Your life revolves around avoiding triggers of that cough,” says Gerhart. “Patients say, ‘If I wasn’t coughing all the time, I wouldn’t know I was sick.’ It’s a very significant problem.”

Respivant was launched two years ago by Roivant Sciences to develop an inhaled anti-inflammatory product developed by Gerhart’s previous company Patara Pharma.

Gerhart has a lot of experience in the area, having previously helped to develop an inhaled antibiotic, now marketed for cystic fibrosis, and an inhaled bronchodilator, now marketed for COPD. Patara had developed a proprietary inhaled formulation of an anti-inflammatory with mast cell stabilizing and pleiotropic immune modulating activity that could potentially treat multiple diseases. Patara conducted several studies to optimize the formulation and demonstrate its efficacy, including a phase 2a study to treat the persistent cough in pulmonary fibrosis.

Based on the positive results from that study, Roivant reached out to Patara about setting up a “Vant”, or subsidiary, to develop the product, dubbed RVT-1601. Based on Roivant’s commitment and the opportunity to build a new respiratory focused company, Patara sold the drug candidate and its three co-founders joined Respivant.  They started a large phase 2b dose ranging study to evaluate RVT-1601 for treating persistent cough in patients who have idiopathic pulmonary fibrosis.

Then the COVID-19 pandemic got in the way, challenging clinical operations. Respivant had been on track to completely enroll the study mid summer 2020, but had to pause recruitment of new patients in March. With the uncertainty around when it could resume enrollment, Gerhart says they decided to terminate enrollment and analyze the data from the patients already enrolled.

“Of the 180 patients targeted, we enrolled about 100 patients,” Gerhart said. “We had our last patient, last visit, at the beginning of July, and we are now in the process of closing out that database, scrubbing it down, and we’ll be able to get the results by the end of the third quarter.”

Although disappointed, Gerhart feels that if the drug has a robust treatment effect, they will see it in the smaller patient group, and hopefully those results will enable Respivant to move RVT-1601 into phase 3, and eventually to approval and the market.

One thing Gerhart doesn’t have to worry about right now is raising money, as he says Roivant has a strong balance sheet that provides for flexibility. Respivant is fully focused on developing RVT-1601 as a treatment for idiopathic pulmonary fibrosis and potentially other indications.

“Pulmonary fibrosis is made worse by chronic inflammation, and there is a lot of data that shows that chronic inflammation is also contributing to the progression of fibrosis,” said Gerhart. “We are evaluating the potential for the drug to slow down progression of generalized disease in the study that we just recently completed. In addition to the cough endpoints, we will be looking at the disease modifying endpoints of changes in pulmonary function, disease related quality of life scores, and six-minute walk test.”

The impact of the pandemic on the patients who are constantly coughing drives Gerhart. “In addition to the physical impact of their underlying disease, they have the emotional impact of this condition that can lead to embarrassment and stigmatization, anxiety,” he says. “The pandemic has magnified the intensity of their issues because people are hypersensitive about coughing being a threat.”

There is also the fear that even with a vaccine, awareness of the role cough plays in the spread of respiratory disease will remain etched in people’s minds for a long time.