Idiopathic pulmonary fibrosis (IPF) is a rare, progressive, and ultimately fatal lung disease. Characterized by irreversible scarring of lung tissue, IPF leaves patients struggling to breathe and steadily robs them of quality of life.
The current standard-of-care antifibrotics, pirfenidone and nintedanib, represented milestones when first approved more than a decade ago. However, uptake remains strikingly low in the US, with only about one-quarter of patients with IPF ever receiving an antifibrotic. The result is a community where, despite available drugs, most patients remain untreated or under-treated.
In this context, deupirfenidone (LYT-100), a deuterated form of pirfenidone, may offer enhanced efficacy while maintaining tolerability. Celea Therapeutics, which was founded by PureTech Health, is responsible for the development of this therapy.
At the 2025 European Respiratory Society (ERS) Congress, PureTech presented new results from the Phase IIb ELEVATE IPF trial and its open-label extension, demonstrating encouraging stabilization of lung function.
To understand the implications of these findings, Drug and Device World spoke with Camilla Graham, MD, MPH, Senior Vice President of Medical Affairs at PureTech Health. A practicing physician at Beth Israel Deaconess Medical Center and faculty member at Harvard Medical School, Dr. Graham has spent her career balancing clinical practice and drug development. In this wide-ranging discussion, she reflects on the current treatment landscape, the barriers to antifibrotic use, what the new Phase IIb data reveal, and why she believes deupirfenidone could represent a turning point for people living with IPF.
A Landscape of Unmet Needs
Dr. Graham began by painting a stark picture of today’s IPF treatment paradigm. Despite the severity of the disease, uptake of available antifibrotics remains poor.
“Only about a quarter of people with IPF in the United States had ever been exposed to an antifibrotic,” she noted. “Compare that to cancer, where you would rarely see patients not even attempting treatment despite high mortality. Something isn’t working here.”
She stated that the main contributor is not the financial barriers, which do have some influence, but the limited efficacy of currently available medications, especially when accounting for the side effects. This unfavorable efficacy/tolerability balance creates the need for physicians to manage side effects, which is more easily accomplished at specialized centers such as academic ILD (interstitial lung disease) clinics.
“At ILD centers, 70 to 80% of patients may start therapy. They have nurses who can manage side effects, pharmacists to navigate prior authorization, and the infrastructure to support patients,” she explained. “But in community settings, physicians already overwhelmed with COPD (chronic obstructive pulmonary disease) and asthma patients often lack those supports. When side effects arise, the path of least resistance is to stop treatment.”
The result, she said, is a sense of futility. “Doctors know these drugs work—they slow progression and improve survival. But they don’t stabilize lung function, and patients often feel worse from side effects. Leading to many physicians and patients asking, ‘Is it worth it?’”
Efficacy vs. Tolerability
A critical question for drug developers is whether patients would prioritize tolerability or efficacy if forced to choose. PureTech sought to answer that by surveying patients with hypothetical drug profiles.
“Sixty-nine percent said they would choose higher efficacy even if tolerability was worse,” Dr. Graham emphasized. “They understood that efficacy could translate into more time—seeing grandchildren, attending graduations, doing what matters most. A smaller group, about 31%, prioritized minimizing side effects. But almost everyone said they would proactively ask their doctor about a better option if it were available.”
This insight frames PureTech’s approach to deupirfenidone: a therapy that could meaningfully stabilize lung function without worsening tolerability.
Phase IIb ELEVATE Data
The randomized, placebo- and active-controlled Phase IIb ELEVATE IPF trial was designed to rigorously test deupirfenidone at two doses: 550 mg and 825 mg, each given three times daily.
At 26 weeks, deupirfenidone 825 mg TID significantly slowed lung function decline compared to placebo. Patients lost just -21.5 mL of forced vital capacity (FVC), versus -51.6 mL with pirfenidone and -112.5 mL with placebo—a 91 mL improvement over placebo.
“This was profound,” Dr. Graham recalled. “Instead of hundreds of milliliters lost per year, patients on 825 mg showed a rate of decline approaching that of healthy older adults.”
Open-label extension (OLE) findings from the global Phase IIb ELEVATE IPF trial build upon these initial 26-week data. Among 170 patients (over 90% of trial completers) who entered the open-label extension, those maintained on deupirfenidone 825 mg TID showed just -32.8 mL FVC decline over 52 weeks, mirroring the expected annual decline of healthy individuals.
“That was the moment of realization,” Dr. Graham said. “If replicated, this could mean transforming IPF from a rapidly progressive disease into one where patients age more like their peers.”
Switch Cohorts
The new data presented at ERS provided further compelling evidence from two additional patient cohorts. These were individuals who had experienced lung function decline while on either placebo or pirfenidone during the initial 26-week period and then switched to deupirfenidone for the OLE.
Patients switching from placebo to deupirfenidone 825 mg TID (n=17) saw a mean improvement in FVC of +20.0 mL after the switch, which was consistent with the 26-week data from the blinded portion of the trial. Meanwhile, those transitioning from pirfenidone to deupirfenidone 825 mg TID (n=16) experienced a mean change in FVC of -23.1 mL, which was an improved trajectory.
These “switch cohort” data are pivotal. “These cohorts confirmed what we’d already seen,” Dr. Graham explained. “Even after decline on placebo or pirfenidone, switching to deupirfenidone stabilized lung function. That reproducibility is critical for building confidence.”
Enhanced Safety Profile
A critical hurdle for any new IPF therapy, especially one demonstrating enhanced efficacy, is tolerability. Dr Graham noted that existing therapies can be notoriously difficult for patients to endure, which directly contributes to high discontinuation rates. Here, deupirfenidone’s profile appears promising.
The safety data from the OLE showed that deupirfenidone continued to be well-tolerated at both the 550 mg and 825 mg TID doses, with a safety profile consistent with the initial trial phase. As of 9 May 2025, data cut-off, common treatment-emergent adverse events for the 550 mg and 825 mg groups, respectively, included nausea (8.4% vs. 11.5%), dyspepsia (14.5% vs. 12.6%), and upper respiratory infections (16.9% vs. 17.2%).
This favourable tolerability profile is particularly significant given that pharmacokinetic data indicate the 825 mg dose of deupirfenidone provides approximately 50% higher drug exposure than standard pirfenidone. The fact that this substantial exposure boost translates into significantly improved efficacy without a corresponding dramatic increase in adverse events suggests a dissociation of efficacy from intolerability.
“Patients are willing to tolerate some side effects if efficacy is higher,” Dr. Graham said. “But with deupirfenidone, we may not even be asking them to make that trade-off.”
From Numbers to Lived Experience
While lung function measures like FVC are critical endpoints, Dr. Graham is passionate about connecting trial outcomes to real patient lives.
“One patient told his study coordinator how thrilled he was to play golf again,” she recalled. “That’s what matters—whether it’s golf, playing with grandchildren, or keeping a house clean. Clinical trials should capture those lived experiences.”
She envisions future trials including individualized patient-reported outcomes. “Imagine asking each patient what matters most to them, and tracking whether that function is preserved. That resonates far more than abstract numbers with people living with IPF and their care teams.”
PureTech is now in regulatory discussions to finalize Phase III trial design, with an update expected later in 2025. Key priorities will include survival, clinical worsening, hospitalizations, and patient-centered endpoints alongside FVC.
“There’s excitement not only about monotherapy but also the potential for combination therapy, as we’ve seen in pulmonary hypertension,” Dr. Graham said. “We want deupirfenidone to be a foundation drug—whether alone or in combinations.”
The broader field is also showing momentum. The decision from the US Food and Drug Administration (FDA) on Boehringer Ingelheim’s nerandomilast is expected by the end of the year. “Any new approval will energize the community—patients, physicians, advocacy groups,” she added. “After a decade of limited progress, IPF research finally feels dynamic.”
Dr. Graham remains cautiously optimistic for the future: “We have to prove the value of deupirfenidone in Phase III. But if the data hold, doctors may finally be able to tell patients: we can stabilize your lung function with manageable side effects. That’s a message this community has been waiting decades to hear.”
