The company is advancing product candidates through clinical studies. Promedior's current therapeutic programs are focused on rare fibrotic diseases, including myelofibrosis
and idiopathic pulmonary fibrosis
(IPF). The company is also interested in retinal fibrovascular diseases
such as age-related macular degeneration (AMD) and diabetic retinopathy (DR).
Promedior has designed its clinical development programs to demonstrate the ability of its therapeutics to benefit patients in specific diseases involving fibrosis.
A Phase 2 clinical study of PRM-151 in myelofibrosis patients is ongoing. Myelofibrosis (MF), a type of myeloproliferative neoplasm, is a serious, life-limiting cancer that is characterized by fibrosis of the bone marrow. Replacement of the bone marrow by scar tissue prevents the normal production of blood cells, leading to anemia, fatigue, and increased risk of bleeding and infection. Production of blood cells shifts to the spleen and liver (extramedullary hematopoiesis), which become enlarged, causing severe discomfort, inability to eat, and weakness. Symptomatic myelofibrosis affects approximately 18,000 patients in the US, with a median age at diagnosis of 60-65 years. The only potentially curative treatment is allogeneic bone marrow transplant, which results in reversal of fibrosis and all symptoms, but is a realistic option for only a small number of patients. Other currently available therapies address the symptoms, but do not appear to impact the underlying fibrosis. With its unique mechanism of action that offers the potential to prevent and reverse fibrosis, Promedior's PRM-151 has the potential to become a first-in-class disease-modifying treatment for this debilitating rare disease.
The ongoing Phase 2 clinical trial is a multi-center, two stage, adaptive design study to determine the efficacy and safety of PRM-151 as a single agent or added to a stable dose of ruxolitinib in patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (post-PV MF), or Post-Essential Thrombocythemia MF (post-ET MF). The primary endpoint is response rate according to the International Working Group–Myeloproliferative Neoplasms Research and Treatment (IWG–MRT) criteria, a comprehensive assessment tool designed by an international group of experts to objectively measure the effectiveness of treatments for MF1
In June, the preliminary Phase 2 data for PRM-151 were presented at two medical meetings for 27 patients with myelofibrosis, 18 of whom completed 24 weeks of therapy.
Idiopathic Pulmonary Fibrosis (IPF)
- In this study, PRM-151 demonstrated biologic activity with signs of improvement in hemoglobin, platelets, symptoms, and spleen on both weekly and monthly schedules.
- A decrease in bone marrow fibrosis by ≥ 1 grade was observed in 5 patients, with 2 of 3 patients confirmed 12 weeks later and 2 patients pending confirmatory biopsy.
- At study entry, most patients had progressed after ≥1 JAK inhibitor and/or were deriving no further benefit from a stable dose of ruxolitinib.
- PRM-151 was safe and well-tolerated alone and in combination with ruxolitinib, with no evidence of myelosuppression.
- More than half of the patients are continuing treatment beyond 24 weeks, which will provide information on the potential benefit of longer treatment duration.
- All treatment groups have met efficacy criteria for proceeding to Stage 2 of the Phase 2 study.
Promedior completed a Phase 1b clinical study of its lead product candidate, PRM-151, in IPF patients. IPF is a serious, life-limiting lung disease characterized by fibrosis and scarring of the lung tissue. Replacement of normal lung tissue by scar tissue results in restriction in the ability to fill the lungs with air and decreased transfer of oxygen from inhaled air into the bloodstream. This decreased oxygen transfer results in lower oxygen delivery to the brain and other organs, and produces symptoms of shortness of breath, particularly with exertion; chronic, dry, hacking cough; fatigue and weakness, chest discomfort, loss of appetite and rapid weight loss. While estimates vary, it is believed that IPF could affect approximately 130,000 patients in the US and approximately 76,000 patients in Europe. There is no curative therapy, and the only treatment that results in significant improvement is lung transplant.
- Promedior's clinical studies in IPF have investigated the safety and tolerability of PRM-151 and measured clinically relevant and exploratory endpoints. A Phase 1a clinical study in healthy subjects and IPF patients demonstrated that PRM-151 was well tolerated. A randomized, placebo-controlled Phase 1b multiple ascending dose study in IPF patients demonstrated that PRM-151 was generally safe and well‐tolerated and resulted in a mean improvement in Forced Vital Capacity (FVC) at 8 weeks after dosing for only two weeks, whereas patients receiving placebo had a decline in FVC. These data were presented at the American Thoracic Society Annual Meeting in May, 2013.
- Plans for a Phase 2 study in IPF are under way.
- Promedior has been granted Orphan Drug Designation for PRM-151 in IPF by the FDA in the United States and by the European Commission.
PRM-151 in Patients with IPF:
Relative change from Baseline on Day 57
in FVC % Predicted
Retinal Fibrovascular Diseases
FVC % predicted is a lung function test frequently used to assess efficacy of new drugs in IPF. In clinical trials in IPF, relative declines of ≥5% from baseline at 24 weeks correlate with decreased one year survival in IPF. In the Phase 1b study of PRM-151 in IPF, 6 out of 14 patients treated with PRM-151 experienced ≥5% increase from baseline at 8 weeks, and 2/14 PRM-151 patients and 2/6 placebo patients experienced ≥5% decrease from baseline at 8 weeks. Frequency of side effects was similar in PRM-151 and placebo treated patients, and there were no serious adverse reactions.
Promedior is developing PRM-167, the company's preclinical ocular product candidate, to assess its potential in age-related macular degeneration (AMD). PRM-167 is a variant of human Pentraxin-2 which is being developed specifically for intravitreal injection. Fibrosis—along with angiogenesis and inflammation—is a progressive pathological process that leads to vision loss and is associated with a number of retinal fibrovascular diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR). These diseases, which impact millions of people, are discussed further below.
Age-related macular degeneration (AMD)
is a degenerative disease of the central portion of the retina (the macula) that results primarily in loss of central vision. Patients with AMD experience gradual loss of vision in one or both eyes. According to the US National Institutes of Health National Eye Institute, it was estimated that there were 1.73 million Americans with AMD in 2010.
Diabetic retinopathy (DR)
is one of the most significant causes of visual loss worldwide, and is the principal cause of impaired vision in patients between 25 and 74 years of age. Diabetic retinopathy affects people with diabetes, and is most common in people whose blood sugar is not well-controlled. Vision loss due to diabetic retinopathy occurs through a variety of mechanisms, including retinal detachment, pre-retinal or vitreous hemorrhage, neovascular glaucoma, and macular edema. According to the US National Institutes of Health National Eye Institute, it was estimated that there were 7.68 million Americans affected by DR in 2010.