FDA designation highlights new treatment approach for DMD
Oral therapy explores muscle repair pathways beyond gene-specific drugs
The U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designation to (Z)-endoxifen for Duchenne muscular dystrophy (DMD), a step that could allow its developer, Atossa Therapeutics, to qualify for a future priority review benefit for another experimental treatment in its pipeline.
“This designation is an important regulatory milestone for Atossa, and we believe a strong validation of the science supporting the potential of (Z)-Endoxifen as a treatment for Duchenne Muscular Dystrophy,” Steven Quay, MD, PhD, Atossa’s president and CEO, said in a company press release.
The designation applies to treatments being developed for serious or life-threatening diseases that primarily affect people ages 18 or younger. If (Z)-endoxifen is approved, Atossa may receive a priority review voucher that can speed FDA review of another treatment or be sold to another company.
“[Rare pediatric disease] designation provides a regulatory framework and an enhanced level of interaction with the FDA as we define the clinical development path in DMD,” said Janet Rea, Atossa’s senior vice president of research and development.
What Duchenne muscular dystrophy is and how it affects muscles
DMD is a genetic disease that causes muscles to weaken over time. It is caused by mutations in the DMD gene, which provides instructions for making dystrophin — a protein that helps protect muscle fibers from damage. The disease mostly affects boys, with symptoms typically beginning in early childhood.
As DMD progresses, children often lose the ability to walk and may develop serious breathing and heart complications. Despite recent advances, current treatment options do not work for all patients.
“DMD is one of the most devastating childhood diseases. Families urgently need better options beyond steroids and gene-targeted approaches,” Quay said. Steroids, or corticosteroids, work to ease inflammation that damages muscles, while exon-skipping and other gene-targeted approaches address the cause of DMD.
(Z)-endoxifen is an oral small-molecule therapy designed for once-daily dosing. It acts as a selective estrogen receptor modulator/degrader, meaning it can alter how estrogen receptors function. Estrogen receptors play a role in muscle growth and repair after injury.
This designation is an important regulatory milestone for Atossa, and we believe a strong validation of the science supporting the potential of (Z)-Endoxifen as a treatment for Duchenne Muscular Dystrophy.
In addition to its investigation in cancer, Atossa is exploring (Z)-endoxifen as a potential add-on treatment for DMD, regardless of the specific genetic mutations, “potentially offering a broader and more accessible treatment approach,” Rea said. “I am excited to further Atossa’s DMD (Z)-endoxifen program.”
In cancer studies, (Z)-endoxifen has been associated with tumor reductions and disease stabilization. Its pharmacological behavior differs from that of tamoxifen, which has also been evaluated in DMD. (Z)-endoxifen is an active metabolite (breakdown product) of tamoxifen.
(Z)-endoxifen also inhibits protein kinase C, an enzyme involved in cell signaling that may contribute to muscle damage.
“We are very encouraged by emerging preclinical data and by (Z)-endoxifen’s potential to be a differentiated mechanism as a potent [selective estrogen receptor modulator/degrader], and look forward to our planned advancement of this program to the clinic for boys living with DMD,” Rea said.
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