After receiving a complete response letter for its pyruvate dehydrogenase complex deficiency candidate, Saol Therapeutics anticipates it will need “several years” and “significant financial resources” to address the FDA’s concerns.
The FDA has rejected Saol Therapeutics’ application for SL1009, which it was proposing for the treatment of pyruvate dehydrogenase complex deficiency, an ultra-rare mitochondrial disease in children.
Saol did not reveal the regulator’s reasons for the rejection, only announcing that the Complete Response Letter detailed “specific observations” that the privately held biotech “will need to address to clarify the path forward.”
The FDA’s findings and recommendations for resolution could prove too burdensome for Saol. “To address the deficiencies as the FDA requested, it would take several years and require significant financial resources,” the company wrote on Monday. Currently, Saol is working with the FDA to find a way forward for SL1009 “that does not require an additional trial,” as per its announcement.
Affecting less than 1,000 patients in the U.S. and occurring in about 90 births per year, pyruvate dehydrogenase complex deficiency (PDCD) is characterized by the toxic buildup of lactic acid in the body, resulting in what Saol calls “overwhelming health challenges.” These include nausea, vomiting, severe breathing problems, neurological impairments and an abnormal heartbeat. Most patients with PDCD do not live beyond early childhood. There are no approved treatments for the disease.
Saol’s SL1009 is an oral formulation of sodium dichloroacetate that had previously won the FDA’s orphan drug, rare pediatric disease and priority review designations for PDCD. The drug is designed to be used with a proprietary genetic test.
In a statement on Friday, days before Saol’s formal announcement of the CRL, the United Mitochondrial Disease, a nonprofit pushing for diagnosis, treatment and cure of mitochondrial diseases, released an open letter to express its “deep disappointment” with the FDA’s rejection. The decision, according to the group, could delay access to life-saving therapies, in turn leading to “irreversible damage – or even death.”
“While we fully support rigorous scientific standards, regulatory flexibility is essential for rare disease populations like PDCD,” the open letter read. Other patient advocacy groups, including MitoAction, Cure Mito Foundation, Hope for PDCD and the Elizabeth Watt PDCD Research Fund, also signed the letter.
Monday’s PDCD rejection comes after a standout month for the rare disease space, which in August secured four regulatory firsts. Jazz Pharmaceuticals’ Modeyso, for instance, became the industry’s first drug for diffuse midline glioma with an H3 K27M mutation. Then, Insmed’s Brinsupri secured the FDA’s first approval for non-cystic fibrosis bronchiectasis—and also became the first therapy that blocks the DPP1 enzyme.
Last month, Precigen’s Papzimeos likewise became the “first-of-its-kind” non-replicating immunotherapy for recurrent respiratory papillomatosis. Finally, Ionis’ Dawnzera secured the industry’s first RNA-targeting prophylactic nod for hereditary angioedema.
