Novel Agents for IPF Management

Steven D. Nathan, MD, FCCP: Pirfenidone and nintedanib have been around for 7 years. What’s going to come down the pike next? I mentioned inhaled treprostinil is approved to treat complicating PH [pulmonary hypertension] being studied as a potential antifibrotic. There are many other drugs in various stages of development.

Drug development takes awhile, and inhaled treprostinil is in phase 3. There’s the drug that was owned by Promedior and is now owned by Roche, PRM-151. That’s being studied in a phase 3 clinical trial by Roche. There was the Galapagos study [ISABELA phase 3 trial], which got halted earlier this year for some reason. Data still have to be presented, but that was halted early so it’s not going to bear out as a therapy. There’s FibroGen’s anticonnective tissue growth factor infusion that’s being studied in a phase 3 trial as well.

It takes awhile for these drugs to go through phase 3, for the data to be scrubbed and analyzed, for patients to be followed, to go before the FDA. If any of the 3 agents I just mentioned that are on phase 3 do bear fruit and are shown to work in IPF, then it’s probably a minimum of another 2 years to maybe 4 years before 1 of them becomes available for clinical practice.

Many other drugs in phase 2 are even further behind. Many who will go on to phase 3 will depend on the phase 2 results, obviously. The next wave after these 3 that I mentioned is probably 7 to 10 years down the road. At this point, therefore, we have pirfenidone, nintedanib, and inhaled treprostinil that we can give our patients who have IPF [idiopathic pulmonary fibrosis]. We have to be patient, and our patients have to be willing to get enrolled and recruited into clinical trials. That’s important in our global management of these patients: the opportunity of being enrolled in a clinical trial because the availability of pirfenidone, nintedanib, and inhaled treprostinil is only through the good graces of the patients previously who were willing to participate in randomized controlled, placebo-controlled clinical trials.

Fernando J. Martinez, MD, MS: There’s a tremendous push. It’s amazing to see how much advance is taking place in IPF over the last decade. It’s unbelievable. We have 2 agents that work, and dozens of clinical trials are ongoing with agents that span the spectrum of how the lung is injured and how it responds to that injury. Several drugs are in advanced-stage development, in phase 3, the traditional large, blinded, placebo-controlled trials.

There’s a drug being tested that specifically targets a very downstream pathway in the fibrotic pathway, which is pamrevlumab. It’s had impressive phase 2 results. It’s in a phase 3 program now. We’re all excited about how that looks. There’s a drug called ataxin-2 that targets a particular inflammatory process that’s been associated with progressive fibrosis, also with very impressive phase 2 data and in a phase 3 program. I’m 1 of the co–PIs [principal Investigators] of that study, so I’m biased. That study is now global and enrolling patients.

There was a recent study of inhaled treprostinil, which was more targeted to the pulmonary hypertension complication of ILD [interstitial lung disease]. But it suggested that it may improve lung function, so that’s being tested. There are 27 or 28 earlier-stage phase 2 studies that are ongoing. It’s dramatic how much advance we’ve made. The discussions that we have with patients at our center [Weill Cornell Medicine] are about not only the antifibrotics but the 5 or 6 active clinical trials that are present at any given time.

My suspicion is that within the next 2 or 3 years, the situation will be much more hopeful with combinations of these agents targeted to a specific patient. The overall approach and prognosis of patients is going to be markedly improved, and it’s not going to be 20 years. It’s going to be within the next few years. I am absolutely convinced that’s going to be the case.

Steven D. Nathan, MD, FCCP: Stem cells have been looked at for IPF, mostly just feasibility and tolerability. I know stem cells sounds sexy for everything, but we don’t have efficacy data yet. There’s some promise to using stem cells, but I cannot endorse this in any way, shape, or form outside a clinical trial until we have the appropriate clinical trials to show that this is a strategy that works.

Transcript Edited for Clarity