Novel therapy for IPF shows sustained long-term benefits
Patients with idiopathic pulmonary fibrosis treated with a recombinant human pentraxin 2 protein exhibited sustained reductions in decline of FVC and 6-minute walking distance at 76 weeks, according to data presented at the American Thoracic Society International Conference and simultaneously published in The Lancet Respiratory Medicine.
The data come from a 76-week open-label extension study. The new results are consistent with those observed during the 28-week, double-blind period.
PRM-151 (Promedior) acts as a macrophage polarization factor to prevent and potentially reverse fibrosis, according to a company press release.
Results from the phase 2, double-blind, randomized controlled PRM-151-202 trial showed that treatment was associated with a decreased rate of decline in percentage of predicted FVC and stable 6-minute walking distance from baseline to week 28 compared with placebo.
Patients who completed the phase 2 portion of the study were then eligible to participate in the current open-label extension study that assessed the long-term safety and efficacy of PRM-151 at 76 weeks.
The extension study included 111 patients, of which 37 patients previously assigned placebo crossed over to the treatment arm. All patients received PRM-151 in 28-week cycles at a loading dose of 10 mg/kg PRM-151 for 60-minute infusions on days 1, 3 and 5 during week 1 of each cycle, followed by 10 mg/kg PRM-151 once every 4 weeks.
Eighty-four patients (76%) received concomitant IPF therapy with pirfenidone (n = 55; Esbriet, Genentech) or nintedanib (n = 29; Ofev, Boehringer Ingelheim).
At week 76, the observed mean changes in FVC were 191.7 mL in those who continued on PRM-151 vs. 213.1 mL in those who crossed over to the treatment arm.
The observed mean changes in 6-minute walking distance at week 76 were 5.9 m in those who continued on PRM-151 and 35.2 m in those who crossed over to the treatment arm, which corresponds to an overall benefit of 29.3 m with PRM-151.
The rates of treatment-related adverse events were consistent with long-term IPF sequelae.
“These findings support further study of PRM-151 in larger populations of patients with IPF,” Ganesh Raghu, MD, medical director of the Medicine Lung Transplant Program and director of the Interstitial Lung Disease/Sarcoid/Pulmonary Fibrosis Program at the University of Washington Medical Center, and colleagues wrote.
In an accompanying editorial, Demosthenes Bouros, MD, PhD, FERS, FCCP, FAPSR, head of the interstitial lung disease unit of the National and Kapodistrian University of Athens in Greece, and colleagues highlighted the need for continued data on this novel agent.
“The safety and efficacy signals emerging from the randomized controlled trial and the extension study ... justify the need for larger phase 3 trials with the hope of providing an add-on therapeutic option for patients with IPF that has sustainable efficacy and minimal side-effects even when administered concurrently with antifibrotic agents. Application of an oncological approach with personalized medicine strategies seems to be the only way forward,” Bouros and colleagues wrote. – by Jennifer Southall
Raghu G, et al. Advances in ILD Therapy. Presented at: American Thoracic Society International Conference; May 17-22, 2019; Dallas.
Disclosures: Raghu reports personal fees for consultation services from Boehringer Ingelheim, Fibrogen, Promedior, Revistan, Sanofi, Veracyte and Zambon; and consultation services to Avalyn, Bellorophon, Bridge Biotherapeutics, Blade Therapeutics, Bristol-Myers Squibb, Gilead Sciences, Nitto and Roche/Genentech. Please see the study for all other authors’ relevant financial disclosures. Bouros and colleagues report no relevant financial disclosures.