Promedior Received Breakthrough Therapy Designation from FDA for PRM-151 in Idiopathic Pulmonary Fibrosis
LEXINGTON, Mass., March 26, 2019 /PRNewswire/ -- Promedior, Inc., a clinical stage biotechnology company developing novel therapeutics for the treatment of fibrosis, today announced that PRM-151, a novel investigational anti-fibrotic immunomodulator, has been granted Breakthrough Therapy designation (BTD) by the U.S. Food and Drug Administration (FDA) for Idiopathic Pulmonary Fibrosis (IPF). Promedior recently announced that it had reached an agreement with the FDA on the design of a Phase 3 registrational study for PRM-151 in IPF using forced vital capacity (FVC) as a primary endpoint and six-minute walk distance (6MWD) as a key secondary endpoint.
BTD is designed to expedite the development and regulatory review of drugs intended to address a significant unmet need in serious or life-threatening conditions. To qualify for the designation, preliminary clinical evidence must demonstrate that the candidate offers the potential for substantial improvement over existing therapies. BTD offers a sponsor more intensive guidance from the FDA, access to a scientific liaison to help accelerate review time, and eligibility for Accelerated Approval and Priority Review designations. BTD for PRM-151 is the first such designation granted in IPF since 2014 and highlights the potential to offer substantial improvement for IPF patients over the currently approved therapies.
"BTD underscores the disease-modifying potential of PRM-151 in IPF, a serious, life-limiting lung disease for which despite existing therapies, patient prognosis remains poor with a median survival of 3-5 years," said Jason Lettmann, Chief Executive Officer of Promedior. "Our pivotal program in IPF is designed to show outcomes that could provide meaningful benefit to patients and differentiation in the market over the standard of care. Outside of IPF, PRM-151 can address additional fibrotic diseases, and the team remains committed to evaluating strategic opportunities for advancing this promising candidate in other respiratory, oncology, hepatology, and nephrology indications."
The FDA's decision was informed in part by a Phase 2, randomized, double-blind, trial designed to evaluate the safety and efficacy of PRM-151, a recombinant form of human pentraxin-2 protein, versus placebo in 117 patients with IPF. 79% of the patients received standard of care treatment of either pirfenidone or nintedanib. Efficacy was evaluated at 28 weeks, among other measures, through pulmonary function tests including FVC, and six-minute walk distance (6MWD) as was published in JAMA in May 20, 2018.1 The patients who were treated with PRM-151 every four weeks exhibited a change in FVC percentage of predicted value of −2.5% compared with −4.8% with placebo – a statistically significant difference (p=.001) that indicates a reduction in decline of lung function. Change in six-minute walk distance was −0.5 meters among patients treated with PRM-151 compared with −31.8 meters for those with placebo (p < .001) – a clinically meaningful difference as a loss of >25 meters in 6MWD over 24 weeks is independently associated with 1-year all-cause mortality in IPF2. The nearly stable 6MWD result in the PRM-151 group is both unprecedented and suggests a potential benefit in overall functional capacity in patients with IPF. The short monthly infusion of PRM-151 was also well tolerated by the patients and study medication compliance was 97%.
About Idiopathic Pulmonary Fibrosis
IPF is a serious, life-limiting lung disease characterized by fibrosis and scarring of lung tissue with a median survival of 3-5 years after diagnosis. Replacement of normal lung tissue by fibrosis results in restriction in the ability to fill the lungs with air and decreased transfer of oxygen from inhaled air into the bloodstream resulting in lower oxygen delivery to the brain and other organs. Patients with IPF most often suffer from progressive shortness of breath, particularly with exertion; chronic cough; fatigue and weakness, and chest discomfort. Currently available approved drugs slow down but do not halt disease progression and the only curative therapy is lung transplant, an option merely available for a small group of patients. While estimates vary, it is believed that IPF could affect approximately 130,000 patients in the US and approximately 76,000 patients in Europe.
PRM-151, Promedior's lead product candidate, is a recombinant form of the endogenous human innate immunity protein pentraxin-2 (PTX-2), which is specifically active at the site of tissue damage. PRM-151 is an agonist that acts as a macrophage polarization factor to prevent and potentially reverse fibrosis. PRM-151 has shown broad anti-fibrotic activity in multiple preclinical models of fibrotic disease, including pulmonary fibrosis, myelofibrosis2, acute and chronic nephropathy, liver fibrosis, and age-related macular degeneration. In addition to the randomized Phase 2 study in IPF, Phase 1a and 1b clinical studies in healthy subjects and IPF patients have demonstrated that PRM-151 was well-tolerated. Additionally, the Phase 1b study in patients with IPF showed encouraging results in exploratory efficacy endpoints4.
Promedior is a clinical stage biotechnology company pioneering the development of targeted therapeutics to treat diseases involving fibrosis. Fibrosis is a harmful process that occurs in many diseases, when normal healthy tissue is replaced with excessive scar tissue, compromising function and ultimately leading to organ failure. Promedior's proprietary platform is based upon pentraxin-2, an endogenous human protein that is specifically active at the site of tissue damage, preventing and potentially reversing fibrosis.
Promedior has successfully advanced its lead therapeutic candidate in human clinical trials and is initially focused on rare fibrotic diseases, including idiopathic pulmonary fibrosis and myelofibrosis. Promedior is backed by leading global healthcare venture investors and has a significant intellectual property estate relating to the discoveries and applications of pentraxin-2 therapeutics.
Additional information is available at www.promedior.com.
1 Raghu G, van den Blink B, Hamblin MJ, et al. Effect of recombinant human pentraxin 2 vs placebo on change in forced vital capacity in patients with idiopathic pulmonary fibrosis: a randomized clinical trial [published online May 20, 2018]. JAMA. doi:10.1001/jama.2018.6129
2 du Bois RM, et al. 6-Minute walk distance is an independent predictor of mortality in patients with idiopathic pulmonary fibrosis. Eur Respir J. 2014 May;43(5):1421-9. doi: 10.1183/09031936.00131813. Epub 2013 Dec 5.
3 Verstovsek, S. et al. 2016. Role of neoplastic monocyte derived fibrocytes in primary myelofibrosis. J. Exp. Med. 213:1723-1740.
4 Van Den Blink, B. et al. 2016. Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy. Respir. J.47:889-97. http://erj.ersjournals.com/content/47/3/889.long