Promising oral IPF treatment earns FDA orphan drug designation
GRI-0621 shown in trial to improve lung function, cut inflammatory activity
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GRI Bio‘s experimental oral therapy GRI-0621 (tazarotene) has received orphan drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of idiopathic pulmonary fibrosis (IPF), a disease with no known cause that’s marked by inflammation and fibrosis, or scarring, that damages the lungs.
The developer called the FDA status “a significant regulatory milestone” in a company press release, noting that it “provides a potential pathway to seven years of U.S. market exclusivity” should the drug ultimately be approved.
The designation is intended to encourage the development of treatments for rare diseases — those affecting fewer than 200,000 people in the U.S — by offering incentives such as tax credits for certain research costs, waiver of regulatory fees, additional guidance from the FDA, and the promise of market exclusivity.
Its award follows positive Phase 2a clinical trial results showing the once-daily therapy was well tolerated when used alongside approved IPF treatments. GRI-0621 use was also associated with improved lung function, biomarker changes consistent with reduced fibrosis and enhanced tissue repair, and evidence of reduced inflammatory activity.
According to GRI, the FDA’s decision underscores both the seriousness of IPF and the need for therapies that target the biological processes driving the disease.
“Receiving FDA Orphan Drug Designation for GRI-0621 in IPF is an important validation of our development strategy and highlights the urgent need for innovative therapies capable of altering the course of this devastating disease,” said Marc Hertz, PhD, GRI’s CEO.
In IPF, a type of pulmonary fibrosis that occurs without a known cause, inflammation and progressive scarring gradually damage the lungs. As scar tissue builds up, the lungs become stiffer and less able to expand, making it harder to breathe and hindering the passage of oxygen into the bloodstream. This leads to symptoms such as shortness of breath, a persistent dry cough, and a decline in lung function.
GRI-0621 found safe in adults in small trial
GRI-0621 is a small molecule designed to suppress the activity of type 1 invariant natural killer T cells (iNKT), a type of immune cell believed to help drive the inflammation and scarring seen in IPF. It does so by activating retinoic acid receptors, which are known to play a role in dampening iNKT activity.
In the now-completed Phase 2a GRI-0621-IPF-02 study (NCT06331624), the therapy was tested in 35 adults with IPF in the U.S., the U.K., and Australia. The participants, ages 40 to 85, were randomly assigned to receive either 4.5 mg of GRI-0621 or a placebo once daily for 12 weeks, or about three months.
About 80% of the participants were also treated with the approved antifibrotic therapies pirfenidone (sold as Esbriet and generics) and Ofev (nintedanib) as standard of care.
Top-line data showed the study met its primary goal of demonstrating that GRI-0621 was safe and well tolerated. Patients receiving the therapy also showed improvements in measures of lung function relative to the placebo, along with biomarker changes consistent with reduced fibrosis and enhanced repair of damaged lung tissue. The researchers additionally reported reduced activity of neutrophils and macrophages, immune cells that are elevated in IPF and linked to disease progression.
We believe GRI-0621’s … mechanism of action has the potential to address key drivers of inflammation and fibrosis, and this designation strengthens our ability to advance the program.
Follow-up analyses provided further evidence that GRI-0621 was affecting its intended target. Patients treated with GRI-0621 showed increased expression of T cell receptors on iNKT, a change consistent with reduced activation of these immune cells.
More recent analyses also showed that treatment altered the activity of genes linked to inflammation, fibrosis, and lung injury while promoting gene signatures associated with lung tissue repair and fibrosis resolution.
“We believe GRI-0621’s differentiated mechanism of action has the potential to address key drivers of inflammation and fibrosis, and this designation strengthens our ability to advance the program efficiently while creating significant long-term value for patients and shareholders,” Hertz said. “We are committed to advancing GRI-0621 with urgency and discipline.”
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