Saol Therapeutics received a complete response letter for its pyruvate dehydrogenase complex deficiency treatment a week after the FDA unveiled its Rare Disease Evidence Principles program. On Dec. 18, in a Type A meeting, the biotech will attempt to convince the agency that its drug fits perfectly into the framework.
Three months after being hit with an FDA rejection for its ultrarare disease drug, Saol Therapeutics is back—with a plan. The company hopes to convince the FDA that SL1009 is the perfect “poster child” for the agency’s new Rare Disease Evidence Principles (RDEP) framework, which was unveiled just a week before the FDA shot down Saol’s therapy.
On Sept. 8, Saol (pronounced “Sail”) revealed that the FDA had issued a complete response letter (CRL) for SL1009, an oral formulation of sodium dichloroacetate intended to treat pyruvate dehydrogenase complex deficiency (PDCD) in children.
On Tuesday, Saol announced that it has been granted a Type A meeting with the regulator to discuss SL1009’s path forward. According to the biotech, a new clinical trial is not an option.
While Saol did not reveal the specific observations or objections laid out in the CRL, the letter “suggested that we would need to do an additional adequate and well controlled clinical trial,” Saol CEO Dave Penake told BioSpace on Tuesday, “and that’s not feasible to be done by our company and in this patient population.” Therefore, Penake said, the biotech’s “clear goal” is to find a path forward that does not involve the need to conduct another trial and bring the FDA onboard.
At the Type A meeting, which is scheduled to take place Dec. 18, Saol will present “new and expanded analyses” not yet seen by the FDA, according to its press release. These include additional analyses of functional benefit data, such as longer treatment duration, survival benefit, mechanistic support and safety, equaling over 100 patient-years of exposure.
Saol “believes these data reinforce the risk/benefit of SL1009 and demonstrate how the totality of evidence satisfies the FDA’s proposed Rare Disease Evidence Principles,” according to Tuesday’s press release.
Introduced by the FDA on Sept. 3, the FDA’s Rare Disease Evidence Principles (RDEP) framework is meant to streamline the approval of therapies for ultra-rare diseases. PDCD is a genetic disorder affecting less than 1,000 people in the U.S., Penake said, matching two key criteria for the RDEP program. According to the FDA’s announcement, the program “will encompass additional supportive data,” in reviews for such products.
“In PDCD, there’s a genetic defect that causes an enzyme deficiency. The drug that we use in SL1009, it’s very targeted, and it actually restores the enzyme activity,” Penake said. “The way we see the plausible mechanism [pathway] in RDEP is that it’s very targeted for populations like this, too small to maybe study in a reasonably coherent manner, a very clear cause of the disease, a very targeted mechanism that corrects the disease.”
PDCD is characterized by the toxic buildup of lactic acid in the body, leading to complications including nausea, vomiting, severe breathing problems, neurological impairments and an abnormal heartbeat. Most patients do not live beyond early childhood. There are no available treatments for this patient population, Penake said, and SL1009 “is a very targeted [treatment] and appears to be an effective one, so we certainly hope that we can find a good path forward.”
