Final PRAISE Trial Data Supports Pamrevlumab’s Efficacy, Safety for IPF

Final data from the PRAISE trial support the efficacy and safety of pamrevlumab, an investigational therapy for the treatment of idiopathic pulmonary fibrosis (IPF) being developed by FibroGen.

Data showed that into-the-vein (intravenous) infusions of pamrevlumab reduced the decline in respiratory function by 60.3%. It also cut to one third, over one year, the proportion of patients with disease worsening.

The trial results were detailed in “Pamrevlumab, an anti-connective tissue growth factor therapy, for idiopathic pulmonary fibrosis (PRAISE): a phase 2, randomised, double-blind, placebo-controlled trial,” a study published in the journal The Lancet Respiratory Medicine.

Pamrevlumab, also known as FG-3019, is a fully human, lab-made antibody that blocks connective tissue growth factor, or CTGF — a secreted protein that has a central role in the process of fibrosis.

The medication binds to CTGF, keeping it from binding to cytokines — signaling molecules that transmit immune signals from one cell to another — and preventing inflammation. As a result, pamrevlumab is thought to work as an anti-fibrotic treatment that directly tackles the underlying mechanism of IPF.

PRAISE (NCT01890265) was a Phase 2, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of pamrevlumab in people with IPF. The study was run across multiple countries, including Australia, Bulgaria, Canada, India, New Zealand, South Africa, and the U.S.

Between 2013 and 2017, a total 103 patients with IPF, ages 40 to 80, were randomly assigned to receive either intravenous infusions of pamrevlumab 30 mg/kg (50 patients), or infusions of placebo (53 patients). The infusions were given every three weeks over 48 weeks, or for approximately 11 months; there were a total of 16 infusions.

Only patients with a percentage of predicted forced vital capacity (FVC) — a measure of lung function — of 55% or greater were enrolled in the study.

Trial results showed that pamrevlumab reduced the decline in lung function, the primary efficacy outcome measure. Patients receiving pamrevlumab experienced a less sharp worsening in predicted FVC compared with the placebo group — a mean change of less 2.9% versus less 7.2% in the placebo group.

This translated into a 60.3% relative reduction in predicted FVC decline in participants treated with pamrevlumab at week 48.

The treatment also was associated with a halt in disease progression. At week 48, 10% of the participants in the pamrevlumab group and 31.4% in the placebo group had experienced disease progression, defined as a decline in percentage of predicted FVC of 10% or more, or death.

Other positive findings were seen for secondary efficacy outcomes, including lung function. For the first time, positive findings also were seen in quality of life, and chest imaging through a quantitative high-resolution computed tomography (HRCT).

Regarding safety, pamrevlumab was found to be well-tolerated, with a safety profile similar to the placebo. Treatment-emergent serious adverse events were observed in 24% of participants on pamrevlumab, and 15% of those in the placebo group. Three patients on pamrevlumab and seven on placebo discontinued the treatment.

Among the three (6%) deaths in the pamrevlumab group, and six (11%) in the placebo group, none was associated with treatment.

Overall, “pamrevlumab attenuated progression of idiopathic pulmonary fibrosis, and was well tolerated,” the researchers said.

“Pamrevlumab shows promise as a novel, safe, and effective treatment for idiopathic pulmonary fibrosis,” they said.

These results match the prior preliminary findings of PRAISE, and data from another Phase 2 trial called Gorina (NCT01262001).

“IPF is a difficult-to-treat condition with a poor prognosis for patients and a great need for innovation and new medicines. I am excited by the promise of a therapy that differs from current therapies in directly targeting the underlying fibrotic mechanism of this disease, as measured by quantitative assessment,” Luca Richeldi, MD, PhD, lead author of the study, said in a press release.

“As seen in the positive data reported from the PRAISE Phase 2 clinical study, pamrevlumab truly has a unique mechanism that may offer clinicians and their patients a safe and beneficial approach to addressing the progression of IPF and improving quality of life,” said Richeldi, who heads the division of pulmonary medicine at Catholic University of the Sacred Heart in Rome.

Pamrevlumab was granted fast track designation by the U.S. Food and Drug Administration last year. FibroGen recently launched a larger, Phase 3 clinical trial, called ZEPHYRUS (NCT03955146), to evaluate pamrevlumab’s benefits over a 52-week period. That trial is currently enrolling. For more information on contacts and locations, please visit the official site here.

“With strong Phase 2 results showing significant improvement in the primary efficacy endpoint of FVC change from baseline, and reduction in disease progression, we are committed to advancing this program, consistent with the vision of our late CEO, Tom Neff, whose goal in founding FibroGen was to treat fibrotic disease,” said Elias Kouchakji, MD, FibroGen’s senior vice president, clinical development, drug safety, and pharmacovigilance.