Deupirfenidone may stabilize lung function in IPF: Long-term data
Developer making plans for Phase 3 trial following positive results
Long-term treatment with deupirfenidone (LYT-100) is generally well tolerated and may stabilize lung function in people with idiopathic pulmonary fibrosis (IPF), according to new clinical trial data announced by the therapy’s developer, Puretech Health.
Puretech has already met with the U.S. Food and Drug Administration to discuss the Phase 2b trial data, and the company is now making plans for a Phase 3 trial to further test deupirfenidone in IPF.
“If deupirfenidone performs in Phase 3 as it did in Phase 2b, physicians may finally be able to tell patients: ‘We can stabilize your lung function with manageable side effects over the long term.’” That’s a message people with IPF have been waiting a long time to hear,” Camilla Graham, MD, Puretech’s senior vice president of medical affairs, told Pulmonary Fibrosis News in a written interview.
Details about the Phase 3 plans are expected to be announced in the coming months.
“We believe deupirfenidone has the potential to become a new standard of care in IPF, and we are actively engaging with regulators to finalize the Phase 3 trial design and expect to share an update in the fourth quarter,” Sven Dethlefs, PhD, CEO of Celea Therapeutics, the Puretech spinoff created to advance deupirfenidone, said in a company press release.
Deupirfenidone is a modified version of Esbriet’s active ingredient
IPF is a chronic disorder marked by scarring in the lungs, which makes it harder for the lungs to take in oxygen and results in symptoms like coughing and shortness of breath. Esbriet (pirfenidone) is an approved oral IPF therapy that’s been proven to reduce fibrosis (scarring) and preserve lung function, but tolerability issues have limited the ability to use higher doses that might improve patient outcomes. Deupirfenidone is a modified version of Esbriet’s active ingredient designed to overcome these limitations.
According to Graham, having a therapy that can deliver meaningful efficacy without major tolerability problems could lead to more IPF patients receiving treatment.
“In the U.S., only about one quarter of IPF patients ever start on standard-of-care antifibrotics, largely because of the prevailing sentiment that their modest efficacy isn’t worth their side effects and tolerability challenges,” Graham. “With a substantial increase in efficacy without sacrificing tolerability, the shared [decision-making] around initiation of antifibrotic treatment may shift to more people starting treatment.”
The Phase 2b ELEVATE IPF clinical trial (NCT05321420) enrolled more than 200 people with IPF. For the first six months of the study, some participants were randomly assigned to take deupirfenidone at one of two doses, while others were assigned to take either Esbriet or a placebo. Graham noted that this Phase 2b study is “the first industry-sponsored trial to include an approved antifibrotic agent as an active comparator.”
The study’s main goal was to assess the impact of treatment on forced vital capacity (FVC), a standard measure of lung function that assesses how much air, in mL, a person can blow out after a deep breath.
Having 12-month data inspires ‘greater confidence’ in findings
Results showed that, after about six months, the average FVC decline in patients given the higher dose of deupirfenidone (825 mg three times a day) was 21.5 mL. According to Puretech, this is within the typical range for lung function decline in healthy elderly adults. By contrast, FVC declined by 51.6 mL and 112.5 mL in patients given Esbriet and the placebo, respectively.
“What was most striking about the ELEVATE IPF trial was the efficacy of deupirfenidone as measured by FVC. … Instead of losing hundreds of millilitres of lung function per year, patients may stabilize the rate of decline to that of a healthy older adult,” Graham said, noting that deupirfenidone’s efficacy was “approximately 50% greater than that of [Esbriet], based on their respective reductions in lung function decline versus placebo.”
According to Graham, a slower decline in lung function could allow patients to more easily engage in daily activities like walking to the mailbox or playing with grandchildren.
“By stabilizing lung function, deupirfenidone has the potential to support not only physical health, but also emotional well-being and quality of life,” Graham said.
After the initial six-month portion of the ELEVATE IPF study, most participants had the option to enter into an open-label extension where all are being given deupirfenidone and monitored for long-term outcomes. Data from patients given the placebo in the initial study showed mean FVC improved by 20 mL over six months of deupirfenidone treatment in the long-term extension. For patients who were originally given Esbriet but switched to deupirfenidone in the extension, the mean FVC decline was 23.1 mL over six months on deupirfenidone.
Based on the data, deupirfenidone may offer enhanced efficacy without sacrificing tolerability. If these results are replicated in Phase 3, deupirfenidone could meaningfully change the way IPF is treated.
Patients who were on deupirfenidone in the original trial and continued the therapy in the extension continued to experience stabilization in lung function decline, Graham noted. She added that having 12-month data contrasts with the typical 12-week duration of Phase 2 trials of IPF, giving “greater confidence” in the findings.
“Taken together, the data from the blinded Part A of the ELEVATE Phase 2b trial, as well as the open-label extension …, highlight the reproducibility of the data and the durability of the treatment effect. This gives us strong confidence in the robustness of the findings and the potential for success in Phase 3,” Graham said. That Phase 3 trial will assess the “holistic impact of deupirfenidone,” she added.
Safety data from the Phase 2 study and extension have overall been positive; Graham noted that no treatment-related deaths were reported. In the first part of the study, rates of most digestive side effects were lower with deupirfenidone than Esbriet.
“Based on the data, deupirfenidone may offer enhanced efficacy without sacrificing tolerability,” Graham said. “If these results are replicated in Phase 3, deupirfenidone could meaningfully change the way IPF is treated.”
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