ZM001 for PAH gets FDA orphan drug designation
Zymedi investigational treatment is now in a first-in-humans Phase 1 study
The U.S. Food and Drug Administration (FDA) has given orphan drug designation to ZM001, a first-in-class investigational antibody from Zymedi for pulmonary arterial hypertension (PAH).
ZM001 is intended to reduce inflammation and tissue fibrosis (or scarring) in people with PAH. A Phase 1 clinical trial (NCT05967299) began dosing this year and is still recruiting participants at the National Institutes of Health Research Center in Bethesda, Maryland. It will evaluate the safety, tolerability, and pharmacological properties of ZMA001 in healthy volunteers.
“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, founder and chief technology officer, research and development at Zymedi, said in a company press release.
“The FDA’s Orphan Drug designation offers various benefits, including tax credits for clinical trial costs, seven 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,” she added.
A monoclonal antibody
PAH is marked by the narrowing of pulmonary arteries, the blood vessels that transport blood through the lungs, leading to high blood pressure (hypertension). As a result, the heart’s right side needs to work harder to pump blood.
Most approved treatments for PAH are vasodilators, medications that open (dilate) blood vessels and reduce blood pressure in the lungs. While they alleviate symptoms, such medications don’t address the underlying causes of the disease.
ZM001 is a human monoclonal antibody that blocks the activity of a pro-inflammatory enzyme, called lysyl-tRNA synthetase (KARS1). It is intended to suppress the infiltration of inflammatory cells, namely macrophages and monocytes, into the lungs.
In animal models of PAH, treatment with ZMA001 reduced the load of immune cells reaching the lungs, eased fibrosis, and improved heart health. In addition, positive effects were observed when combined with sildenafil (sold as Revatio and Liqrev), a standard vasodilator for PAH.
No signs of adverse events were found after four weeks in rats and monkeys, according to the company.
In the Phase 1 trial, participants are being randomly assigned to increasing doses of ZMA001 — range from 1.5 mg/kg to 20 mg/kg — or a placebo, administered by a one-time intravenous (into the vein) infusion. Participants will be followed for 113 days (slightly less than four months).
According to Zymedi, preliminary results will help establish the appropriate dosages and identify side effects associated with ZM001 to inform later stages of clinical testing.
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