FDA Grants Orphan Drug Designation to ZMA001 for Pulmonary Arterial Hypertension

The FDA has granted orphan drug designation to ZMA001 (Zymedi), a first-in-class antibody for pulmonary arterial hypertension (PAH). ZMA001 is a human monoclonal antibody designed to block infiltration of inflammation-inducing macrophages in the lungs, which inhibits symptoms of PAH early.¹

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“With the orphan drug designation for ZMA001, we hope to provide a valuable treatment option for PAH patients in need of new therapies,” Nam Hoon Kwon, PhD, DVM, founder and CTO research and development, said in a news release. "The FDA's orphan drug designation offers various benefits, including tax credits for clinical trial costs, 7 years of market exclusivity upon approval, and assistance with the drug development process, which are particularly advantageous for startup companies with limited resources and time constraints, aiding in clinical progression and commercial success."¹

PAH is a leading cause of heart failure leading to patient death, with a 5-year survival rate of approximately 57% after diagnosis. Therapies that are currently available temporarily reduce blood pressure through dilating blood vessels, causing an unmet need for therapies to increase the survival rate.²

PAH is more frequent in women aged 30 to 60, and disproportionately impacts African American and Hispanic women, according to the American Lung Association. Further, those with a family history are also at an increased risk, with approximately 15% to 20% of patients having a genetic mutation for heritable PAH. Additionally, PAH has been associated with other conditions, including connective tissue disorders, infections, including HIV, cirrhosis of the liver, and congenital heart abnormalities.³

The treatment has shown improvements in right ventricular end-systolic pressure, monocytes, and macrophages infiltration to the lung as well as fibrosis in animal models. Survival rate also increased when combined with sildenafil, according to the company website. Furthermore, there were no adverse symptoms, including at the 100 mg/kg injection for the drug for rats and monkeys in a 4-week toxicity study.²

The designation is based on animal model studies that have demonstrated superior efficacy in comparison to existing drugs. A phase 1a clinical trial began at a National Institute of Health Clinical Center in January, which involved healthy individuals. The initial phase will evaluate the safety and tolerability of the drug in humans, with results helping to determine appropriate dosages and identify any potential adverse events.^1,4

The trial will be placebo-controlled and will be a collaborative effort between Zymedi and the National Heart, Lung, and Blood Institute.⁴

"We are excited to initiate this first in human trial of ZMA001, which marks a significant milestone for our company and the fight against PAH," Sunghoon Kim, PhD, CEO and founder of Zymedi, said in a news release. "We are scheduled to assess the safety and tolerability of ZMA001 through dose escalation clinical trials, systematically observing adverse reactions as dosage increases. Furthermore, we aim to establish the recommended dosage and determine the maximum tolerated dose for forthcoming phase 1b/2a clinical trials involving patients."⁴

References

1. FDA Grants Orphan Drug Designation (ODD) Status to Zymedi's ZMA001 for Pulmonary Arterial Hypertension. News release. Zymedi. July 30, 2024. Accessed July 31, 2024. https://prnmedia.prnewswire.com/news-releases/fda-grants-orphan-drug-designation-odd-status-to-zymedis-zma001-for-pulmonary-arterial-hypertension-302209679.html

2. Zymedi. PAH. Accessed July 31, 2024. https://zymedi.com/our-pipeline/pah/

3. American Lung Association. Learn About Pulmonary Arterial Hypertension. Updated June 7, 2024. Accessed July 31, 2024. https://www.lung.org/lung-health-diseases/lung-disease-lookup/pulmonary-arterial-hypertension/learn-about-pulmonary-arterial-hypertension

4. First in Human Dosed in Clinical Trial of ZMA001 for Treatment of Pulmonary Arterial Hypertension (PAH). News release. Zymedi. February 07, 2024. Accessed July 31, 2024. https://www.prnewswire.com/news-releases/first-in-human-dosed-in-clinical-trial-of-zma001-for-treatment-of-pulmonary-arterial-hypertension-pah-302056941.html