PBI-4050, Prometic Life Sciences’ treatment candidate, can prevent lung fibrosis progression in patients with idiopathic pulmonary fibrosis (IPF) when used alone or in combination with Ofev (nintedanib), Phase 2/3 trial data shows.
Data from the trial were the subject of an oral presentation at the American Thoracic Society (ATS) 2018 International Conference recently held in San Diego. The presentation was titled “Evaluation of the effect of PBI-4050 Alone or in Combination with Pirfenidone or Nintedanib on Blood Biomarkers Linked to the Fibrotic Process in IPF Patients.”
Results from an earlier, open-label Phase 2 trial (NCT02538536) showed that among 40 IPF patients, those given PBI-4050 alone or in combination with Ofev had stable lung function after 12 weeks. In contrast, a significant progressive decline in lung function was seen in those taking PBI-4050 plus Esbriet (pirfenidone).
Data from the current Phase 2/3 trial reveal that PBI-4050 can increase the levels of several biomarkers of anti-fibrotic activity. Upon completion of 12 weeks of treatment, patients had 35% more IL-9 and 14% more IL-7, which can directly prevent or regulate anti-fibrotic signals.
Also, the levels of MIP-1β were increased by 11% reflecting a change from a pro-fibrotic, pro-inflammatory environment toward a wound-healing state.
PBI-4050 alone was found to have no influence on the levels of CCL-18 — a recognized marker of disease severity known to be highly associated with disease progression. In contrast, PBI-4050 plus Ofev significantly decreased CCL-18 levels by 10%, suggesting that this combination may improve prognosis for IPF patients.
“Our evaluation of the effect of PBI-4050 on blood biomarkers linked to the fibrotic process in IPF patients has shown the positive impact the drug candidate has on antifibrotic pathways,” Lyne Gagnon, PhD, president of R&D preclinical at Prometic, said in a press release.
“These most recent data demonstrated that PBI-4050 was well-tolerated when given alone or in combination with nintedanib or pirfenidone, two marketed IPF treatments. In addition, PBI-4050 given alone, as well as in combination with nintedanib, showed promise in stopping the decline in lung function, something that current treatments have been unable to achieve,” Gagnon said.
Patients who responded to PBI-4050 were found to have higher serum plasminogen levels, suggesting that plasminogen may have an important role in IPF.
Supported by these findings, Prometic is currently developing Ryplazim (plasminogen), a plasma-derived product candidate, to manage acute exacerbation episodes in the lungs of IPF patients. Its most recent preclinical data was also presented at the ATS meeting in the poster, “Plasminogen Reduces Lung Fibrosis in the Bleomycin-Induced Lung Fibrosis Model.”
The study showed that under-the-skin injections of Ryplazim every three days significantly reduced collagen deposition in the inflamed areas of the lungs of mice with induced pulmonary fibrosis. In contrast, treatment with Esbriet or Ofev alone did not have a significant effect. Nevertheless, when these approved therapies were combined with Ryplazim, a significant reduction in the percentage of collagen was reported.
“The data presented at this year’s ATS conference further enhance our confidence that PBI-4050 and Ryplazim are well-positioned to treat the full spectrum of the IPF condition,” said Pierre Laurin, president and CEO of Prometic. “We look forward to continuing our clinical development of these two promising drug candidates to address the significant unmet needs of patients suffering from IPF.”
PBI-4050 has been granted orphan drug status, a designation that works to advance its development, as a potential IPF treatment by both the U.S. Food and Drug Administration and the European Medicines Agency.
Prometic is also exploring the potential of PBI-4050 to treat pulmonary arterial hypertension (PAH) by reducing associated fibrosis in the lungs and heart. Positive preclinical data on PBI-4050 in a rat model of PAH was also presented at the ATS 2018 meeting.