PureTech's Deupirfenidone Shows Promise in Extended IPF Trial, Challenging Recent Boehringer Ingelheim Results

PureTech Health has reported encouraging long-term data for its idiopathic pulmonary fibrosis (IPF) candidate deupirfenidone, potentially raising the bar for treatment expectations in this challenging disease area. The results, presented at the American Thoracic Society International Conference in San Francisco, come just a day after Boehringer Ingelheim shared data from its own IPF candidate, nerandomilast, setting the stage for an intriguing competition in the field.

Extended Efficacy Data Bolsters Deupirfenidone's Potential

PureTech's latest results from an open-label extension study of deupirfenidone demonstrate sustained efficacy over 52 weeks of treatment. In a cohort of 101 patients who received the drug for at least 52 weeks, the decline in forced vital capacity (FVC) – a key measure of lung function – was limited to -32.8 mL. This figure falls within the expected range of -30 mL to -50 mL for natural lung function decline in older, healthy individuals.

These findings build upon earlier positive data from the phase 2b Elevate study, which showed an FVC decline of just -21.5 mL after 26 weeks of treatment with deupirfenidone at a dose of 825 mg. The sustained effect over a longer period without compromising tolerability is particularly noteworthy, as it suggests a potential breakthrough in IPF treatment.

Dr. Toby Maher, the trial's lead investigator and a professor of medicine at USC, emphasized the significance of these results: "The ability for a monotherapy to reduce lung function decline close to a level seen in healthy older adults and to sustain that effect over time without compromising tolerability, is not something we have seen with currently available therapies. Deupirfenidone has the potential to raise the bar for what patients and physicians can expect from IPF treatment."

Deupirfenidone: A Deuterated Approach to IPF Treatment

Deupirfenidone is a deuterated version of Roche's established IPF drug Esbriet (pirfenidone), which maintained blockbuster status from 2018 to 2022 before losing patent protection. The deuteration process, which replaces hydrogen atoms with a heavier hydrogen isotope, aims to enhance the pharmacokinetic properties of existing drugs, potentially improving both efficacy and safety.

Preliminary pharmacokinetic data from the trial revealed that deupirfenidone at 825 mg resulted in approximately 50% higher drug exposure compared to 801 mg of pirfenidone. Importantly, this increased exposure did not lead to additional tolerability issues, suggesting that the deuterated structure may overcome dose-limiting adverse events associated with pirfenidone.

Competitive Landscape: Deupirfenidone vs. Nerandomilast

The timing of PureTech's announcement is particularly interesting, coming just after Boehringer Ingelheim's presentation of phase 3 results for its IPF candidate nerandomilast. While Boehringer's drug showed some promise, with patients on a high dose experiencing a mean FVC change of -114.7 mL at 52 weeks compared to -183.5 mL for placebo, analysts at Leerink Partners described the effect as "incrementally better" than the blockbuster drug Ofev, but still "disease-slowing rather than disease-halting."

In contrast, PureTech's deupirfenidone appears to be pushing the boundaries of what's possible in IPF treatment, with its ability to limit lung function decline to levels close to those seen in healthy older adults. This stark difference in outcomes sets the stage for an intensifying race in the IPF treatment landscape.

As PureTech prepares to meet with the FDA by the end of the third quarter and initiate a phase 3 trial of deupirfenidone before year-end, the pharmaceutical industry will be watching closely to see if this deuterated compound can indeed redefine expectations for IPF treatment efficacy and tolerability.