Lixudebart for IPF receives orphan drug status from FDA

Lixudebart designed to reverse organ fibrosis, disease course: Alentis

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by Mary Chapman |

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The U.S. Food and Drug Administration (FDA) has granted its orphan drug designation to Alentis Therapeutics’ antibody-based therapy lixudebart (ALE.F02) for idiopathic pulmonary fibrosis (IPF).

Orphan drug designation is given to support the accelerated development of investigational treatments for rare diseases, defined as those affecting fewer than 200,000 people in the U.S. The designation provides Alentis with regulatory support, financial incentives, and seven years of market exclusivity if lixudebart is approved.

“The Orphan Drug designation for lixudebart underscores the urgent medical need for an effective IPF treatment,” Luigi Manenti, MD, chief medical officer of Alentis, said in a company press release.

Estimated to affect up to one in every 5,000 people globally, IPF is the most common form of pulmonary fibrosis, a disorder of the respiratory system marked by scarring (fibrosis) in the lungs, which can make breathing more difficult. In IPF, the underlying cause of lung fibrosis is unclear.

“IPF patients do not have transformative treatment options and often experience tolerability challenges with the current standard of care drugs,” said Steven Nathan, MD, medical director of the advanced lung disease and transplant program at Inova Fairfax Hospital.

“Alentis is doing important work on developing lixudebart as a treatment targeting the root causes of disease,” Nathan said. “This molecule has shown a very favorable safety profile in Phase 1, and I would be thrilled to see lixudebart tested in IPF patients in the future.”

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Currently, the two antifibrotic medications approved for IPF are Esbriet (pirfenidone) and Ofev (nintedanib), both of which have been shown to slow lung function decline, but not halt progression or reverse lung fibrosis.

Lixudebart is a first-in-class antibody designed to reverse organ fibrosis by targeting Claudin-1 positive epitope (CLDN1), a protein that, when exposed outside cells, promotes tissue fibrosis.

In healthy cells, CLDN1 is hidden within tight junctions that allow cells to stick together. In fibrotic tissue, the protein is overproduced and exposed outside tight junctions, activating fibrotic signaling, and ultimately driving excessive buildup of extracellular matrix (ECM) components such as collagen.

ECM components surround cells and give structure to tissues, but when overproduced, they lead to tissue scarring.

Increasing accumulation of collagen creates a physical barrier that can, over time, cause organ failure. Lixudebart specifically binds to exposed Claudin-1 without interfering with the protein in tight junctions, ultimately leading to the erosion of the collagen barrier around the organ.

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“We have completed IND-enabling studies for our IPF program, and we strongly believe that targeting CLDN1 in fibrotic lungs with our highly specific antibody has the potential to reverse the course of the disease,” Manenti said.

Studies enabling an IND, or investigational new drug, are those conducted in preclinical models and whose results are used to support the filing of an IND application with the FDA, seeking clearance to conduct the first-in-human clinical trials with a new drug.

Notably, according to Alentis, single and multiples doses of lixudebart were well tolerated without serious safety concerns, in healthy volunteers participating in a Phase 1 trial.

Currently, the experimental therapy is in clinical trials for people with advanced liver fibrosis and ANCA-associated vasculitis.