SHERIDAN, WYOMING - December 11, 2025 - Saol Therapeutics is turning an FDA rejection into a potential regulatory test case, as the biotech prepares to argue that its pyruvate dehydrogenase complex deficiency (PDCD) drug SL1009 is the ideal "poster child" for the agency's new Rare Disease Evidence Principles (RDEP) framework at a Type A meeting on December 18.
Saol Recasts a Complete Response Letter as a Strategic Opening
On September 8, Saol disclosed that the FDA had issued a complete response letter (CRL) for SL1009, an oral formulation of sodium dichloroacetate for children with PDCD, a genetic disorder affecting fewer than 1,000 people in the U.S. The CRL, according to CEO Dave Penake, "suggested that we would need to do an additional adequate and well controlled clinical trial," and that "and that's not feasible to be done by our company and in this patient population."
Rather than accepting a lengthy and potentially impossible new trial requirement, Saol is using the recently announced RDEP framework as a pathway to keep the program alive. The company has secured a Type A meeting on December 18, where it will present "new and expanded analyses" of SL1009, with the goal of convincing the agency that an approval based on totality of evidence is justified in this ultra-rare setting.
Why a New Trial Is "Not Feasible" in an Ultra-Rare Population
PDCD is driven by a genetic defect that impairs pyruvate dehydrogenase enzyme activity, causing toxic lactic acid buildup. Patients suffer severe systemic complications, including nausea, vomiting, respiratory distress, neurological damage and arrhythmias; most do not survive beyond early childhood. In such a tiny and fragile population, traditional large, randomized trials are not realistic, either from a feasibility or ethical perspective.
Saol has already generated over 100 patient-years of exposure data with SL1009, including functional outcomes, survival signals, mechanistic evidence and safety. The company plans to bring these expanded analyses to the FDA, arguing that the dataset is sufficient when viewed through the RDEP lens. 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 its announcement.
RDEP: Matching a Targeted Mechanism to a Highly Defined Disease
The FDA introduced RDEP on September 3 as a flexible framework to support approvals in ultra-rare conditions, explicitly indicating that it "will encompass additional supportive data," beyond conventional trial designs. With PDCD affecting fewer than 1,000 U.S. patients and having a clear genetic and mechanistic basis, Saol sees a close alignment.
"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 explained. "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."
By anchoring its case in mechanism-based evidence, long-term exposure data and functional outcomes, Saol is effectively asking FDA to use SL1009 as a real-world demonstration of how RDEP could unlock approvals where classical trials are infeasible but biology is well understood.
Strategic Signals for Ultrarare Drug Developers and Investors
For other biotechs in ultra-rare indications, the SL1009 case will be closely watched. A positive outcome could confirm that well-constructed natural history data, mechanistic validation and long-term observational evidence can substitute for traditional pivotal trials in highly constrained populations. That would have direct implications for program design, capital allocation and partnering strategies across the rare disease ecosystem.
Conversely, if FDA maintains a strict "new trial" stance despite its own RDEP guidance, companies may question how much practical flexibility the framework really offers. Analysts and advocates have already raised concerns that rare disease initiatives risk becoming "all wrapper, no gift" if they do not materially change evidentiary expectations for conditions where traditional development is impossible.
Next Milestone: December 18 Type A Meeting and Beyond
The imminent Type A meeting is therefore pivotal not only for Saol but also for stakeholders evaluating the real-world impact of RDEP. Saol will argue that 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," Penake said, underscoring both the absence of approved therapies and the dire natural history of PDCD.
If FDA accepts a totality-of-evidence approach for SL1009, the decision could set a precedent for other ultra-rare programs with similar mechanistic clarity and severe unmet need. If not, developers may have to rethink the viability of pursuing certain ultra-rare targets at all. For now, all eyes are on December 18, when Saol will test whether the RDEP framework can translate from policy language into an actionable regulatory pathway for PDCD.
For more insight into SL1009 and Saol's evolving regulatory strategy in PDCD, industry stakeholders can monitor the company's future communications and FDA updates closely.