The realignment of the company’s research priorities follows a meeting held with the U.S. Food and Drug Administration (FDA) in January 2018. Prometic will test its oral anti-fibrotic candidate PBI-4050 in an “all comers” study in mild-to moderate IPF patients, eligible regardless of whether they are taking the standard-of-care medication Ofev (nintedanib, Boehringer Ingelheim). Patients taking Esbriet (pirfenidone, Genentech) will be excluded, however, as previous studies reported a drug-drug interaction between PBI-4050 Esbriet.
The Phase 3 trial will assess the efficacy of PBI-4050 both as a stand-alone treatment and as an add-on to Ofev, and will integrate a dataset supporting a simple, all-inclusive indication for IPF treatment. The multi-center study will be conducted at sites across the U.S., Canada, Australia, the U.K., and Europe. Prometic anticipates starting patient enrollment in mid-2018.
“Idiopathic pulmonary fibrosis (IPF) is now priority No.1 for PBI-4050” Pierre Laurin, president and CEO of Prometic, said in a press release.
“IPF remains to this day a significant unmet medical need affecting hundreds of thousands of patients … The clinical efficacy demonstrated so far in multiple phase 2 clinical trials combined with an impressive safety and tolerability profile gives us great confidence in PBI-4050’s ability to efficiently address fibrotic diseases,” Laurin added.
A Phase 2 study (NCT02538536) in 40 IPF patients reported a stabilization in lung function among those given PBI-4050 as a stand-alone therapy or in combination with Ofev after 12 weeks of treatment, while a significant further decline was seen in those taking PBI-4050 plus Esbriet.
As part of its clinical realignment, Prometic terminated clinical trials of PBI-4050 in cystic fibrosis-related diabetes and is evaluating other programs underway. The company is also analyzing the development of PBI-4050 analogs (similar compounds), which demonstrated similar effects or even outperformed PBI-4050 in preclinical studies. These analogs could enable targeting other fibrotic-related indications, the company said.
Prometic also hopes to bring Ryplazim (plasminogen) to the market to treat as a treatment of congenital plasminogen deficiency. It is awaiting the review of its Biologic License Application submitted to the U.S. Food and Drug Administration (FDA).
Patients with IPF may also benefit from Ryplazim, Prometic states. The body converts plasminogen to the enzyme plasmin, which is key in wound healing and could work to reduce IPF flares. The company plans to test Ryplazim in IPF patients in upcoming clinical trials. The treatment candidate recently received orphan drug status by the FDA, a designation for medications that intend to treat disorders affecting fewer than 200,000 patients in the U.S
In addition, Prometic is developing PBI-4050 as a treatment for Alström syndrome, a rare, genetic, multi-organ disease. Current data from prolonged treatment with PBI-4050 in a Phase 2 trial (NCT02739217) in the U.K. supports the treatment candidate’s use as a stand-alone medication in this patient population. The company plans to meet with regulatory agencies in the U.S. and Europe regarding this program.
“Safety and efficacy data collected and demonstrated to date in such a challenging patient population will also contribute to the clinical design and potential treatment for future clinical development initiatives of the Corporation with respect to indications such as heart, kidney & liver fibrosis,” Laurin said.