Section 3 of 6

Product information and disease description

94 evidence topics · 55 sources

Product description

Phase of product development

FDA approval status

“Not FDA Approved for Orphan Indication” (opens the source at this quote in a new tab)

FDA submission and anticipated action date

“Saol resubmitted the NDA on June 30, 2026,” (opens the source at this quote in a new tab)
“a Prescription Drug User Fee Act (PDUFA) target action date of Dec. 30, 2026.” (opens the source at this quote in a new tab)

Regulatory submission: NDA resubmitted June 2026

“Saol resubmitted the NDA on June 30, 2026, after a productive Type A meeting in December 2025 and a Type C meeting in March 2026.” (opens the source at this quote in a new tab)

Launch

No evidence found.

Resubmission classification

“The FDA acknowledged the resubmission as complete, classified it as Class 2,” (opens the source at this quote in a new tab)

Special FDA designations

“06/11/1990” (opens the source at this quote in a new tab)
“Treatment of congenital lactic acidosis” (opens the source at this quote in a new tab)

Fast Track designation

“the FDA has granted Fast Track Designation for Dichloroacetate (DCA, SL-1009)” (opens the source at this quote in a new tab)

Additional FDA designations

“SL1009 has been granted Orphan Drug, Priority Review, and Rare Pediatric Disease Designations by the FDA.” (opens the source at this quote in a new tab)

FDA Advisory Committee

“No concerns were raised by the FDA about the adequacy of the filing or the need for an advisory committee meeting.” (opens the source at this quote in a new tab)

Product information

Generic, brand name and therapeutic class of product

Manufacturer: Saol Therapeutics

“Sponsor: Saol Therapeutics Inc.” (opens the source at this quote in a new tab)

Development code and product name

“SL1009, Sodium Dichloroacetate Oral Solution (DCA)” (opens the source at this quote in a new tab)

Dosage forms and strengths

Dosage form

“Oral Solution” (opens the source at this quote in a new tab)

Solution strength

No evidence found.

Material safety data sheet

No evidence found.

Average sales price and wholesale acquisition cost

Not applicable.

American hospital formulary service (AHFS), or other drug classification

Pharmacologic classification

“inhibits Pyruvate Dehydrogenase Kinase (PDK)” (opens the source at this quote in a new tab)

AHFS classification code

No evidence found.

Indication

Proposed indication

“for the treatment of pyruvate dehydrogenase complex deficiency (PDCD)” (opens the source at this quote in a new tab)

Pharmacology

Mechanism of action

Proposed mechanism of action

“inhibits Pyruvate Dehydrogenase Kinase (PDK) to stimulate residual Pyruvate Dehydrogenase Complex (PDC) activity and increase energy (ATP) production by mitochondria.” (opens the source at this quote in a new tab)

Pharmacodynamics

Preclinical peripheral nerve effects

“Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats.” (opens the source at this quote in a new tab)

Preclinical nematode model: preprint

“Significantly improved health, survival, tissue lactate levels, and mitochondrial physiology were observed at 25 mM in pdha-1(RNAi) knockdown animals.” (opens the source at this quote in a new tab)

Historical clinical review of dichloroacetate response

“The case histories of 46 subjects were analyzed with regard to diagnosis, clinical presentation and response to DCA.” (opens the source at this quote in a new tab)

Pharmacokinetics

Absorption and distribution

“An oral dose of DCA is rapidly absorbed and widely distributed within minutes of administration.” (opens the source at this quote in a new tab)

Central nervous system distribution

“It readily crosses the blood-brain barrier and can be measured in cerebrospinal fluid.” (opens the source at this quote in a new tab)

Metabolism and inhibition of clearance

“DCA inhibits GSTZ1/MAAI, leading to delayed plasma drug clearance and to accumulation of potentially toxic tyrosine intermediates.” (opens the source at this quote in a new tab)

Repeated dosing and phenoconversion

“DCA-induced inactivation of GSTZ1 resulted in phenoconversion of all subjects into slow metabolizers after repeated dosing.” (opens the source at this quote in a new tab)

Chronic dosing and accumulation

“Chronic administration of DCA leads to inhibition of DCA metabolism and potential accumulation to levels that result in side effects.” (opens the source at this quote in a new tab)

Metabolic autoinhibition

“DCA inhibits GSTz1/MAAI, which leads to a marked decrease in its plasma clearance.” (opens the source at this quote in a new tab)

Contraindications/Warnings/Precautions/Adverse effects

Warnings and precautions

Investigational treatment: clinically limiting toxicity

“The main clinically limiting toxicity is reversible peripheral neuropathy.” (opens the source at this quote in a new tab)

Chronic exposure: sensory and motor neuropathy

“A reversible sensory/motor peripheral neuropathy is the clinically limiting adverse effect of chronic DCA exposure” (opens the source at this quote in a new tab)

Neuropathy character, dose dependence, and time to resolution

“DCA therefore appears to induce a dose-dependent, largely reversible, distal peripheral neuropathy that afflicts large and small fibers of motor and sensory nerves and causes both sensory loss and pain.” (opens the source at this quote in a new tab)
“In all studies, peripheral neuropathy generally resolved over 6–18 months following dose de-escalation or discontinuation, although in some cases it persisted.” (opens the source at this quote in a new tab)

Neuropathy risk by age

“Clinical descriptions of DCA-induced peripheral neuropathy have emphasized that it is more common and severe in adults than children” (opens the source at this quote in a new tab)
“In liver, cytosolic GSTZ1 expression (the dominant cellular fraction) reaches adult levels at around 7 years of age, while the mitochondrial form only reaches maximal expression and activity at around 21 years of age” (opens the source at this quote in a new tab)
“This explanation is supported by the finding that DCA clearance is reduced less in children than adults following 6 months DCA treatment” (opens the source at this quote in a new tab)

Special populations

Age-related pharmacokinetics

“a striking age-dependent decrease in its plasma clearance and an increase in its plasma half-life in patients and rats.” (opens the source at this quote in a new tab)

Pregnancy, lactation, and reproductive potential

No evidence found.

Renal impairment: SL1009-specific dosing

No evidence found.

Hepatic impairment: SL1009-specific dosing

No evidence found.

Drug/Drug, drug/disease interactions

Effects of other drugs on sodium dichloroacetate

No evidence found.

Effects of sodium dichloroacetate on other drugs

No evidence found.

Dosing and administration

Dosage

Genotype-directed dosing in the phase 3 trial

““fast” (12.5mg/kg/12h) or “slow” (6.25mg/kg/12h) DCA metabolizer” (opens the source at this quote in a new tab)

Dose-determining genetic test

“The test identifies each patient's GSTZ1 genotype to provide individualized dosing intended to reduce adverse events, such as peripheral neuropathy.” (opens the source at this quote in a new tab)

Clinical pharmacogenetic test validation

“The clinical genetic test for GSTZ1 was developed and validated at our CLIA-certified Clinical Laboratory.” (opens the source at this quote in a new tab)

Companion diagnostic: planned submission pathway

“will be filing a 510K for the dose-determining genetic test” (opens the source at this quote in a new tab)

Administration

Clinical administration routes

“by mouth or feeding tube” (opens the source at this quote in a new tab)

SL1009 administration relative to food

No evidence found.

Access and distribution

Expanded access: NCT06931262

“The patient is not eligible to participate in a clinical trial.” (opens the source at this quote in a new tab)
“The patient’s licensed physician (“physician”) submits an unsolicited request for expanded access.” (opens the source at this quote in a new tab)

Expanded-access request responsibility

“Only a qualified, licensed, treating physician may submit a request for expanded access to DCA for PDCD.” (opens the source at this quote in a new tab)

Genetic counseling and clinical-trial access

“After speaking with a genetic counselor, families interested in learning more about the clinical research study will be connected with a trial site.” (opens the source at this quote in a new tab)

Co-prescribed/Concomitant therapies

Phase 3 background treatment

“Enrolled subjects continued their ketogenic diets and other supplements.” (opens the source at this quote in a new tab)

Effect of sodium dichloroacetate on quality measures

No evidence found.

Product comparison

Review of investigational dichloroacetate and phenylbutyrate

“This review analysed the efficacy of dichloroacetate and phenylbutyrate as potential treatments for PDH deficiency caused by PDHA1 pathogenic variants.” (opens the source at this quote in a new tab)

Place of product in therapy

Disease description

Definition and etiology

Genetic basis of disease

“PDCD is caused by abnormalities in the genes that encode the components of the pyruvate dehydrogenase complex.” (opens the source at this quote in a new tab)

Epidemiology

Incidence of Pyruvate dehydrogenase complex deficiency

U.S. incidence estimate

“1 in 40,000 live births, approximately 90 newborns annually” (opens the source at this quote in a new tab)

Prevalence of Pyruvate dehydrogenase complex deficiency

U.S. prevalence estimate

“fewer than 1,000 individuals in the U.S.” (opens the source at this quote in a new tab)

Swedish population-based cohort and birth prevalence

“54 patients (35 female patients)” (opens the source at this quote in a new tab)
“birth prevalence of 2.43 per 100,000 live births (95% CI 1.86–3.17)” (opens the source at this quote in a new tab)

Swedish point prevalence

“a point prevalence of 0.44 per 100,000 population (95% CI 0.40-0.65).” (opens the source at this quote in a new tab)

Natural history, survival, and mortality

Natural history and mortality

“39% of these subjects (23/59) have died.” (opens the source at this quote in a new tab)
“Causes of death included severe lactic acidosis, respiratory failure, and infection.” (opens the source at this quote in a new tab)

Age at death and mortality by sex

“Of these, 91% (21/23) died before age 4 years, 61% (14/23) before 1 year, and 43% (10/23) before 3 months.” (opens the source at this quote in a new tab)
“56% of males died compared with 25% of females.” (opens the source at this quote in a new tab)
“Neonatal or infant onset of symptoms was associated with poor outcomes. Males with PDHA1 mutations and low fibroblast PDC activity were less likely to survive beyond infancy.” (opens the source at this quote in a new tab)

Swedish population-based cohort: mortality

“Eight patients (15%) died during the study period.” (opens the source at this quote in a new tab)

Additional genotype, phenotype, and natural-history evidence

“Data from 891 individuals (45% unpublished) were included.” (opens the source at this quote in a new tab)

Pathophysiology

Pathophysiology and disease consequences

“chronic energy deficit leading to lactic acidosis, profound developmental problems, and early childhood death.” (opens the source at this quote in a new tab)

Impaired pyruvate metabolism

“pyruvate cannot be metabolized into acetyl‐CoA, resulting in a mitochondrial disorder with lactic acidosis, seizures, and severe encephalopathy.” (opens the source at this quote in a new tab)

Diagnosis

Molecular genetic testing

“molecular genetic testing for a mutation that causes PDCD” (opens the source at this quote in a new tab)

Previously unrecognized disease in female carriers

“We identified seven female PDHA1 carriers from five families.” (opens the source at this quote in a new tab)
“Five of them exhibited clinical features of the disease and were previously undiagnosed” (opens the source at this quote in a new tab)

Investigational amino-acid screening ratios

“Ala/Lys ≥3.0 and Ala/Leu ≥5.0” (opens the source at this quote in a new tab)
“identified patients with PDCD with 100% SN and ~85% SP.” (opens the source at this quote in a new tab)

Clinical presentation - signs and symptoms

Neurodevelopmental and motor symptoms

“Neurodevelopmental delay and hypotonia were the commonest clinical signs of PDC deficiency.” (opens the source at this quote in a new tab)

Structural brain abnormalities

“ventriculomegaly, dysgenesis of the corpus callosum” (opens the source at this quote in a new tab)

Epilepsy

“Lifetime epilepsy was present in 16/41 (39%) of individuals.” (opens the source at this quote in a new tab)

Long-term morbidity

Cognitive and adaptive functioning

“Intellectual disability was detected in 33/42 (79%) individuals, while 31/35 (89%) demonstrated significant impairments in adaptive functioning.” (opens the source at this quote in a new tab)

Distribution of intellectual outcomes among survivors

“Of 42 subjects whose intellectual abilities were professionally evaluated, 19% had normal or borderline intellectual ability (CQ/IQ ≥ 70), 10% had mild intellectual disability (ID) (CQ/IQ 55–69), 17% had moderate ID (CQ/IQ 40–54), 24% had severe ID (CQ/IQ 25–39) and 33% had profound ID (CQ/IQ < 25).” (opens the source at this quote in a new tab)
“The average outcome for females was severe-to-profound ID, whereas that of males was mild-to-moderate ID.” (opens the source at this quote in a new tab)
“Of 10 subjects who reached age 12 years, 9 had had professional IQ assessments, and only 4 had IQs ≥ 70” (opens the source at this quote in a new tab)

Ambulation and age-appropriate walking

“Although 27/39 (69%) were ambulatory, only 8/39 (21%) demonstrated age‐appropriate walking ability.” (opens the source at this quote in a new tab)

Burden of Pyruvate dehydrogenase complex deficiency

Humanistic burden and health-related quality of life

Patient-reported disease burden

“More than 84% of survey respondents cited muscle weakness as one of the three most impactful symptoms” (opens the source at this quote in a new tab)

Caregiver burden: broader mitochondrial disease

“often resulting in poor functional and survival outcomes for the patient and considerable psychosocial distress for the caregiver.” (opens the source at this quote in a new tab)

Broader mitochondrial disease review: utility evidence

“No studies reported utilities data.” (opens the source at this quote in a new tab)

Economic burden and healthcare resource utilization

Broader mitochondrial-disease population: Ontario, Canada

“(mean = CAD$24,023 in 12 months before first hospitalization)” (opens the source at this quote in a new tab)
“within the single-payer Ontario health care system.” (opens the source at this quote in a new tab)

Broader mitochondrial disease: U.S. healthcare costs

“Total allowed per member per month (PMPM) cost for pediatric patients was $4829 and $3100 for adults” (opens the source at this quote in a new tab)

Broader mitochondrial disease: treatment costs in China

“The average monthly treatment cost was 3000 RMB for children and 3100 RMB for adults.” (opens the source at this quote in a new tab)

Broader mitochondrial disease review: cost evidence

“No studies reported costs data.” (opens the source at this quote in a new tab)

Patient employment: adult PDCD

“This limits his ability to work” (opens the source at this quote in a new tab)

Economic impact of Pyruvate dehydrogenase complex deficiency on families

Broader mitochondrial disease: Australian household costs

“We estimated total annual average costs at AU$ 112 721 per household.” (opens the source at this quote in a new tab)
“a large proportion were societal costs (92%).” (opens the source at this quote in a new tab)

PDCD-specific household and caregiver costs

No evidence found.

Economic impact of diagnostic testing

Broader mitochondrial and rare disorders: proteomics micro-costing

“reported in 2023 Australian dollars (AUD).” (opens the source at this quote in a new tab)
“At an estimated average cost of $897 (US $607) per test” (opens the source at this quote in a new tab)

SL1009 dose-determining genetic test cost

No evidence found.

Approaches to treatment

Current treatment options and standard of care

Ketogenic dietary therapy

Primary PDCD management

“Ketogenic diet is the gold-standard therapy for individuals with primary PDCD” (opens the source at this quote in a new tab)
“Tolerance of the ketogenic diet varies and treatment must be individualized.” (opens the source at this quote in a new tab)

Ketogenic-diet clinical evidence

“Nineteen patients were assessed” (opens the source at this quote in a new tab)

Ketogenic diet therapies: International Ketogenic Diet Study Group recommendations

“KDTs are the treatment of first choice for 2 distinct disorders of brain energy metabolism: Glut1DS and PDHD.” (opens the source at this quote in a new tab)

Ketogenic-diet literature review and clinical-practice survey

“Forty studies describing 129 patients were identified, predominantly case reports or series.” (opens the source at this quote in a new tab)

Reported use of ketogenic diet in a natural-history cohort

“The next most common intervention was dietary, with 60% (35/58) of the subjects reportedly having used a “ketogenic” diet at some time.” (opens the source at this quote in a new tab)
“Altogether, 83% (24/29) of responding families reported that use of a ketogenic diet was “very helpful”, 10% said it was “somewhat helpful”, and 7% reported that it was “not helpful”” (opens the source at this quote in a new tab)
“No significant correlation was found between use of ketogenic diets and survival or cognitive function outcomes, which is not surprising since use of ketogenic diets varied by degree of severity, duration, and age of administration.” (opens the source at this quote in a new tab)
“ketogenic diet therapy does not reverse prior neurological damage and is not effective in sustaining survival in the most severe cases of PDC deficiency.” (opens the source at this quote in a new tab)

Vitamin and cofactor supplementation

Thiamine supplementation

“thiamine (may benefit rare individuals)” (opens the source at this quote in a new tab)

Reported use of thiamine in a natural-history cohort

“Thiamine was the most frequently employed intervention, with 68% (39/57) of subjects reporting some use.” (opens the source at this quote in a new tab)
“Doses ranged widely from 25 mg to 2000 mg/day (average dose: 174 mg; median dose: 150 mg/dl).” (opens the source at this quote in a new tab)
“No subject reportedly had a remarkable beneficial response to thiamine treatment.” (opens the source at this quote in a new tab)

Rehabilitation and supportive care

Muscle function and rehabilitation

“physical and occupational therapy to help with muscle function” (opens the source at this quote in a new tab)

Symptom-directed neurologic therapies

Seizure management

“Standard anti-seizure therapy as needed” (opens the source at this quote in a new tab)

Paroxysmal dystonia

“Benzodiazepines” (opens the source at this quote in a new tab)

Chronic dystonia

“Botulinum toxin injections” (opens the source at this quote in a new tab)

Buffer therapy for acidosis

Correction of acidosis

“Bicarbonate or buffer therapy” (opens the source at this quote in a new tab)

Genotype-specific metabolic management

DLD-related disease: dietary and acute metabolic management

“Branched-chain amino acid restriction” (opens the source at this quote in a new tab)
“Dextrose-containing IV fluids” (opens the source at this quote in a new tab)

Limitations of current therapies

Summary

Ketogenic dietary treatment must be individualized because tolerance varies. A clinical-practice review identified 40 studies describing 129 participants, predominantly case reports or case series. A separate treatment scoping review included seven preclinical and ten human studies and concluded that most interventions had not been rigorously investigated. These evidence designs limit the certainty of comparative treatment effects.

Unmet treatment need

“There are currently no FDA-approved therapies for PDCD.” (opens the source at this quote in a new tab)

Cochrane review: mitochondrial disorders, literature search through July 2011

“three trials in children showed a statistically significant improvement in biochemical measurements but no clinical benefit on physiological measurements and exercise tests” (opens the source at this quote in a new tab)

PDCD scoping review and case series

“We reviewed and summarized findings from seven preclinical studies and ten human studies” (opens the source at this quote in a new tab)
“However, most interventions have yet to be rigorously investigated.” (opens the source at this quote in a new tab)

Natural-history cohort: absence of demonstrated benefit for any intervention

“Five subjects had used DCA, and one family reported that it was “very helpful”.” (opens the source at this quote in a new tab)
“Subjective retrospective assessments of the benefits of these various interventions were most favorable for ketogenic diet treatment, but we cannot confidently determine from these data benefit or lack thereof for any of these interventions.” (opens the source at this quote in a new tab)
“This retrospective correlation of PDC activity, mutations, and outcomes was not designed to assess whether specific treatments were effective in improving outcomes.” (opens the source at this quote in a new tab)

Place in treatment, anticipated use, and care setting

Summary

SL1009 is an investigational oral treatment with genotype-directed dosing. In the phase 3 study, participants continued ketogenic diets and other supplements; the available evidence therefore concerns use with background treatment rather than replacement of that care. The application remains under FDA review, with a target action date of December 30, 2026. Expanded access is physician-directed, and the published policy requires that the patient be ineligible for a clinical trial and that a licensed treating physician submit the request.

Heterogeneity of treatment effect

Ketogenic diet: disease phenotype and ketosis

“Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.” (opens the source at this quote in a new tab)

Care management intervention strategies

Paroxysmal dystonia: minimizing provoking stressors

“Minimize stressors (e.g., fever).” (opens the source at this quote in a new tab)

Ongoing post-approval monitoring

Not applicable.

Expected outcomes of therapy

Investigational biochemical outcome

“A key secondary endpoint measured the reduction in plasma lactate of SL1009 compared to placebo.” (opens the source at this quote in a new tab)