In the Journals

Pamrevlumab may be safe, effective in IPF

In a phase 2 trial, pamrevlumab, a fully recombinant human monoclonal antibody against connective tissue growth factor, appeared to reduce the decline in lung function among patients with idiopathic pulmonary fibrosis.

Specifically, patients randomly assigned IV pamrevlumab (FibroGen) had a lower decline in percentage of predicted FVC — the primary efficacy endpoint — than those assigned placebo (–2.9% vs. –7.2%; P = .033), corresponding to a 60.3% relative reduction in the pamrevlumab group after 48 weeks of treatment. The change in absolute FVC measurement in volume from baseline to 48 weeks was also lower among patients taking pamrevlumab vs. placebo (–0.1 L vs. –0.3 L; P = .025), with a relative difference of 57.9%.

Furthermore, fewer patients assigned pamrevlumab, as compared with placebo, experienced disease progression, defined as a decline in percentage of predicted FVC of 10% or more or death, at 48 weeks (10% vs. 31.4%; P = .013).

Luca Richeldi, MD, from A. Gemelli University Hospital IRCCS and the Catholic University of the Sacred Heart in Rome, and colleagues conducted the phase 2, randomized, double-blind, placebo-controlled trial at 39 medical centers in seven countries from 2013 to 2017. They recruited patients aged 40 to 80 years with IPF and percentage of predicted FVC of 55% or greater and assigned them to IV infusion of pamrevlumab 30 mg/kg (n = 50) or placebo (n = 53) every 3 weeks for 48 weeks. The researchers excluded two patients from the intention-to-treat population due to enrollment error.

Safety, quality o f life

In addition to a reduced decline in lung function, pamrevlumab was associated with lower quantitative lung fibrosis high-resolution CT scores when compared with placebo at both 24 weeks (24.8 mL vs. 86.4 mL; P = .009) and 48 weeks (75.4 mL vs. 151.5 mL; P = .038). Results also showed a correlation between change from baseline in percentage of predicted FVC and change in quantitative lung fibrosis score at 24 and 48 weeks.

In terms of quality of life, St. George’s Respiratory Questionnaire scores decreased from baseline to 48 weeks in the pamrevlumab group and increased in the placebo group; however, the difference did not reach statistical significance (–2.8 vs. 2.5; absolute between-group difference, –5.4). Nevertheless, changes in the University of California, San Diego, Shortness of Breath Questionnaire after treatment were “significant and encouraging,” according to the researchers.

The safety profile of pamrevlumab appeared comparable to placebo, with treatment-emergent serious adverse events occurring in 24% of the pamrevlumab group and 15% of the placebo group. Three deaths occurred in the pamrevlumab group and six in the placebo group, although none were deemed related to treatment.

‘Encouraging’ results

These data, the researchers noted, suggest that pamrevlumab “has the potential to be an important therapeutic option for patients with IPF” and will be examined further in the ongoing phase 3, randomized, placebo-controlled ZEPHYRUS trial.

In an accompanying editorial, Athol U. Wells, MD, PhD, from Royal Brompton Hospital in London, noted that the efficacy data for pamrevlumab in patients with IPF are impressive, but the safety data are particularly interesting.

“The fact that side effects were similar in the active treatment placebo groups is a departure from earlier trials of antifibrotic drugs,” he wrote. “It might be possible, for the first time, to show a clear improvement in quality of life with active treatment in IPF in the phase 3 pamrevlumab trial.”

Looking ahead, it may be worth evaluating whether pamrevlumab can be added to antifibrotic agents to further improve outcomes, according to Wells. However, physicians and researchers will have to wait on results from ZEPHYRUS.

“In conclusion, it is difficult to imagine a more encouraging phase 2 trial of a novel drug for IPF. Only time will tell whether the results of the study prove too good to be true, or whether pamrevlumab can meet our expectations in the phase 3 trial and beyond,” Wells wrote. – by Melissa Foster

References:

Richeldi L, et al. Lancet Respir Med. 2019;doi:10.1016/S2213-2600(19)30262-0.

Wells AU. Lancet Respir Med. 2019;doi:10.1016/S2213-2600(19)30339-X.

Disclosure s: This study was funded by FibroGen. Richeldi reports he has received grants from Boehringer Ingelheim and Roche and personal fees from Asahi Kasei, Biogen, Boehringer Ingelheim, Celgene, FibroGen, Nitto, Pliant Therapeutics, Promedior, Prometic, Respivant, Roche, Sanofi-Aventis, Toray, Veracyte and Zambon. Please see the study for all other authors’ relevant financial disclosures. Wells reports he has received personal fees from Boehringer Ingelheim, Blade and Roche.

In a phase 2 trial, pamrevlumab, a fully recombinant human monoclonal antibody against connective tissue growth factor, appeared to reduce the decline in lung function among patients with idiopathic pulmonary fibrosis.

Specifically, patients randomly assigned IV pamrevlumab (FibroGen) had a lower decline in percentage of predicted FVC — the primary efficacy endpoint — than those assigned placebo (–2.9% vs. –7.2%; P = .033), corresponding to a 60.3% relative reduction in the pamrevlumab group after 48 weeks of treatment. The change in absolute FVC measurement in volume from baseline to 48 weeks was also lower among patients taking pamrevlumab vs. placebo (–0.1 L vs. –0.3 L; P = .025), with a relative difference of 57.9%.

Furthermore, fewer patients assigned pamrevlumab, as compared with placebo, experienced disease progression, defined as a decline in percentage of predicted FVC of 10% or more or death, at 48 weeks (10% vs. 31.4%; P = .013).

Luca Richeldi, MD, from A. Gemelli University Hospital IRCCS and the Catholic University of the Sacred Heart in Rome, and colleagues conducted the phase 2, randomized, double-blind, placebo-controlled trial at 39 medical centers in seven countries from 2013 to 2017. They recruited patients aged 40 to 80 years with IPF and percentage of predicted FVC of 55% or greater and assigned them to IV infusion of pamrevlumab 30 mg/kg (n = 50) or placebo (n = 53) every 3 weeks for 48 weeks. The researchers excluded two patients from the intention-to-treat population due to enrollment error.

Safety, quality o f life

In addition to a reduced decline in lung function, pamrevlumab was associated with lower quantitative lung fibrosis high-resolution CT scores when compared with placebo at both 24 weeks (24.8 mL vs. 86.4 mL; P = .009) and 48 weeks (75.4 mL vs. 151.5 mL; P = .038). Results also showed a correlation between change from baseline in percentage of predicted FVC and change in quantitative lung fibrosis score at 24 and 48 weeks.

In terms of quality of life, St. George’s Respiratory Questionnaire scores decreased from baseline to 48 weeks in the pamrevlumab group and increased in the placebo group; however, the difference did not reach statistical significance (–2.8 vs. 2.5; absolute between-group difference, –5.4). Nevertheless, changes in the University of California, San Diego, Shortness of Breath Questionnaire after treatment were “significant and encouraging,” according to the researchers.

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The safety profile of pamrevlumab appeared comparable to placebo, with treatment-emergent serious adverse events occurring in 24% of the pamrevlumab group and 15% of the placebo group. Three deaths occurred in the pamrevlumab group and six in the placebo group, although none were deemed related to treatment.

‘Encouraging’ results

These data, the researchers noted, suggest that pamrevlumab “has the potential to be an important therapeutic option for patients with IPF” and will be examined further in the ongoing phase 3, randomized, placebo-controlled ZEPHYRUS trial.

In an accompanying editorial, Athol U. Wells, MD, PhD, from Royal Brompton Hospital in London, noted that the efficacy data for pamrevlumab in patients with IPF are impressive, but the safety data are particularly interesting.

“The fact that side effects were similar in the active treatment placebo groups is a departure from earlier trials of antifibrotic drugs,” he wrote. “It might be possible, for the first time, to show a clear improvement in quality of life with active treatment in IPF in the phase 3 pamrevlumab trial.”

Looking ahead, it may be worth evaluating whether pamrevlumab can be added to antifibrotic agents to further improve outcomes, according to Wells. However, physicians and researchers will have to wait on results from ZEPHYRUS.

“In conclusion, it is difficult to imagine a more encouraging phase 2 trial of a novel drug for IPF. Only time will tell whether the results of the study prove too good to be true, or whether pamrevlumab can meet our expectations in the phase 3 trial and beyond,” Wells wrote. – by Melissa Foster

References:

Richeldi L, et al. Lancet Respir Med. 2019;doi:10.1016/S2213-2600(19)30262-0.

Wells AU. Lancet Respir Med. 2019;doi:10.1016/S2213-2600(19)30339-X.

Disclosure s: This study was funded by FibroGen. Richeldi reports he has received grants from Boehringer Ingelheim and Roche and personal fees from Asahi Kasei, Biogen, Boehringer Ingelheim, Celgene, FibroGen, Nitto, Pliant Therapeutics, Promedior, Prometic, Respivant, Roche, Sanofi-Aventis, Toray, Veracyte and Zambon. Please see the study for all other authors’ relevant financial disclosures. Wells reports he has received personal fees from Boehringer Ingelheim, Blade and Roche.