What Will it Take to Solve the Devastating Riddle of Idiopathic Pulmonary Fibrosis?

In September 2022, journalist and critic Robert Woodward published a compelling editorial decrying both the lack of awareness and lack of effective treatments for idiopathic pulmonary fibrosis (IPF), a disease he’d never heard of before his own diagnosis. Less than a year later, Woodward became another casualty of this brutal, progressive lung disease and the absence of effective treatments for it.

Among those IPF patients who receive existing FDA-approved treatments, the average life expectancy following diagnosis is estimated to be between three to four years. Up to 80 percent of IPF patients die within five years of diagnosis. “Almost as shocking as the rapid progression of the disease is its obscurity,” Woodward said, concluding that, “The powerful tools of the medical-industrial complex can’t be trained on solving the riddle of IPF until more people learn that it exists.”

Pulmonary Fibrosis Awareness Month starts in five days, offering an ideal opportunity to honor Woodward – and the millions of others who have died of and are living with IPF -- by supporting his dual call to action: (1) raise awareness of IPF, and (2) help solve its cruel riddle. At Endeavor BioMedicines, we are doing both.

Since I founded Endeavor five years ago, I have become acutely aware of IPF and its devastating impact. Approximately 3 million people worldwide are living with IPF, and the disease has a worse prognosis than several cancers, including colorectal, bladder and breast cancers. Currently approved therapies incrementally slow the rate of IPF progression, but do not stop or reverse the disease, and they have tolerability issues that limit their long-term use in most patients.

That’s the terrible news. The good news? I think we now have a much better idea of how to solve the IPF riddle:

• Target the cause of the disease: In cancer, tremendous advances have been made over the past two decades by attacking the cellular causes of the disease. This approach has not historically been pursued in IPF, and we believe it is the missing piece to improving clinical outcomes. While the exact cause of IPF is unknown, we now know that the biological process ongoing when the patient presents at the pulmonologists’ office or hospital looks very much like abnormal wound healing and scarring. This pathological scarring is what causes the lungs to become thick and stiff and eventually kills patients. We are targeting the cellular driver of this biological process with ENV-101, our investigational Hedgehog signaling pathway inhibitor, and believe blocking it may be the missing piece to yield better clinical outcomes.
• Be flexible: We need a regulatory and clinical environment that is keen to get more effective drugs to patients who need them quickly. Currently approved therapies – which offer only incremental benefit – required multiple one-year studies with nearly 1,000 patients to show significant and potentially clinically meaningful benefit. If a drug currently in development shows clinically meaningful and statistically significant benefits faster and with fewer patients, then we should not delay getting that therapy to dying patients for the sake of doing what’s been done before.
• Stop the negative cycle: When available therapies are considered ineffective and/or toxic, patients tend to be underdiagnosed. Once they are diagnosed, treatment is often initiated too late in the disease process. All of this contributes to suffering and mortality. Using the example of cancer again, we’ve seen that when very effective cancer drugs, such as Gleevec, were introduced into poorly served patient populations, patients were diagnosed sooner and, as a result, lived longer. Our hope is that, as the biopharma industry develops more effective therapies, this domino effect will happen in IPF as well.

Over the next few weeks, our team at Endeavor BioMedicines will support patient advocacy organizations around the world in their incredible efforts to raise awareness about IPF, improve diagnosis, and generate research funding during Pulmonary Fibrosis Awareness Month. We will also continue our quest to solve the IPF treatment riddle by prioritizing clinical development of ENV-101. Recent data from a Phase 2a randomized, controlled trial of this promising agent showed that it was well-tolerated and effectively inhibited what we believe to be the cellular cause of IPF. In the trial, IPF patients treated with ENV-101 experienced improved lung function and a reversal of key measures of lung fibrosis, demonstrated by statistically significant and clinically meaningful improvement in lung function continuously over three months.

Two years ago, Robert Woodward observed that, “The discouraging lack of progress in finding a cure for [IPF] may explain the relative silence about [it].” Who’s with me? Let’s start making tremendous noise? and tremendous progress to cure this disease. September is only five days away – it’s the ideal time.

To see the many ways you can support people living with IPF – including how to get involved in Pulmonary Fibrosis Awareness Month – visit Action for Pulmonary Fibrosis (United Kingdom), the Canadian Pulmonary Fibrosis Foundation, ?Lung Foundation Australia, PF Warriors, or the Pulmonary Fibrosis Foundation (United States).