The U.S. Food and Drug Administration (FDA) granted PRM-151, a novel investigational anti-fibrotic immunomodulator, Breakthrough Therapy designation 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.
According to the FDA, a breakthrough therapy is a drug that is:
- Intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition
- Preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development
If a drug is designated as breakthrough therapy, FDA will expedite the development and review of such drug. All requests for breakthrough therapy designation will be reviewed within 60 days of receipt, and FDA will either grant or deny the request.
Breakthrough Therapy designation 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. Breakthrough Therapy designation 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. Breakthrough Therapy designation 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.
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. 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 IPF.
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.