Long-term safety and efficacy of recombinant human pentraxin-2 in patients with idiopathic pulmonary fibrosis

Patients who completed the initial 28-week double-blind period (n=116) of the PRM-151-202 trial were eligible to participate in the open-label extension study (n=111). The 76-week results of this open-label extension study were published in the Lancet Respiratory Medicine during Prof. Ganesh Raghu’s (University of Washington, Seattle, USA) presentation. Long-term treatment with PRM-151 was well tolerated and the effects on percentage of predicted FVC and 6-min walking distance were persistent on continuation and positive in patients who crossed over from placebo [1, 2].

Recombinant human pentraxin-2 (PRM-151), also known as serum amyloid P, has been shown to reduce fibrosis in preclinical and early trial settings. Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with a median survival of 3-5 years after diagnosis. Currently available anti-fibrotic medical interventions retard but do not halt disease progression and the only curative therapy is lung transplant, an option not available for most patients. Pentraxin-2/PRM-151 is an agonist that acts as a macrophage polarisation factor to prevent and potentially reverse fibrosis.

Patients previously enrolled in the PRM-151 group of the PRM-151-202 trial were offered to continue their treatment after 28 weeks (n=74), and those previously in the placebo group could cross over to PRM-151 (n=37). Patients received PRM-151 in 28-week cycles with loading doses of 10 mg/kg by 60 min intravenous infusions on days 1, 3, and 5 in the first week of each cycle followed by one infusion of 10 mg/kg every 4 weeks. The long-term safety and tolerability of PRM-151 was the primary objective. All adverse events (AEs) up to week 76 were tabulated in all patients who received at least one dose of PRM-151.

Of 111 patients in the open-label extension study, 74 were from the original PRM-151 group and 37 from the original placebo group. Out of 111 patients, 84 (76%) received concomitant IPF therapy (pirfenidone n=55, or nintedanib n=29). AEs were consistent with clinical events observed in long-term IPF. Serious AEs were experienced by 31 (28%) patients, i.e. pneumonia (6/111 [5%]), IPF exacerbation (4/111 [4%]), IPF progression (4/111 [4%]), and chest pain (2/111 [2%]). Severe AEs were observed in 21 (19%) patients, of which IPF exacerbation and IPF progression each occurred in 2 (2%) patients. Two (2%) patients experienced life-threatening AEs (one had pneumonia and one had small-cell lung cancer). A persistent treatment effect was observed for PRM-151 in patients who continued treatment, with a decline in percentage of predicted FVC of -3.6% per year and in 6-min walking distance of -10.5 m per year at week 52. In patients who started PRM-151 during the open-label extension study only, an immediate effect was observed; their predicted FVC decline was ameliorated (from -8.7% per year in weeks 0-28 to -0.9% per year in weeks 28-52, P<0.0001) and 6-min walking distance prediction also stabilised (from -54.9 m per year to -3.5 m per year, P=0.0224). These findings warrant further study of PRM-151 in larger populations of patients with IPF.

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   1. Raghu G, et al. Long-Term Safety and Efficacy of Recombinant Human Pentraxin-2 in Patients with Idiopathic Pulmonary Fibrosis. A2636. ATS 2019, 17-22 May, Dallas, Texas, USA.
   2. Raghu G, et al. Lancet Respir Med 2019, 7(8):657-664.

 



Posted on 23 July 201917 May 2024