FDA Hands Complete Response Letter to SL1009 for Pyruvate Dehydrogenase Complex Deficiency

Advertisement News|Articles|September 12, 2025 FDA Hands Complete Response Letter to SL1009 for Pyruvate Dehydrogenase Complex Deficiency Author(s)Marco Meglio Saol Therapeutics faces challenges after FDA's complete response letter for SL1009, a potential treatment for rare mitochondrial disorder PDCD. Advertisement In recent news, the FDA has issued Saol Therapeutics a complete response letter (CRL) for its investigational product SL1009 or sodium dichloroacetate oral solution (DCA) for the treatment of pyruvate dehydrogenase complex deficiency (PDCD), a rare mitochondrial metabolic disorder.1PDCD, caused by mutations in one of the components of the pyruvate dehydrogenase complex, affects fewer than 1000 individuals in the United States, with an incidence estimated at 1 in 40,000 live births. Neurological manifestations of the disorder include hypotonia, developmental delay, seizures, ataxia, and sometimes structural brain abnormalities visible on imaging like brain atrophy or abnormal white matter. Some patients present at infancy, while others may have attenuated forms that survive into childhood or adulthood.SL1009, a formulation of DCA, is an oral solution that was intended to be used in conjugation with a proprietary genetic test that helps determine appropriate dosing. In the CRL, the agency outlined specific issues that Saol must resolve in order to define the path forward, though none were related to SL1009’s manufacturing. Meeting these requirements will likely take several years and demand substantial financial investment, the company noted."Families living with PDCD face an urgent and life-threatening unmet need," Dave Penake, chief executive officer at Saol, said in a statement.1 "We are encouraged by recent FDA actions and commentary that recognize the importance of regulatory flexibility and speed for treating rare diseases. Traditional clinical trials often take many years; time that children with PDCD simply do not have. We remain committed to productive conversations with the Agency to identify a path forward that brings this therapy to patients as swiftly as possible."READ MORE: Claseprubart Heads to Phase 3 Study of Myasthenia Gravis Following Positive MaGic TrialThe new drug application (NDA), submitted in December 2024, was based on results from a phase 3, double-blind, placebo-controlled, crossover study (SL1009-01; NCT02616484) and a survival study (SL1009-02). In the phase 3 study, the primary end point, the Observer Reported Outcome (ObsRO) survey, did not demonstrate statistical significance in the double-blind portion. However, longer duration of the therapy, including the open-label extension (OLE), demonstrated a statistically significant improvement in motor function among those in the intent-to-treat (ITT) population (P = .002).2,3Key findings from the phase 3 study, presented earlier this year at the Mitochondrial Medicine 2025 conference in St. Louis, showed that DCA was well-tolerated, even upon chronic administration over 3 years. During that time, the most commonly reported adverse reaction, found in more than 5% of treated patients, was gastrointestinal disorders (n = 2; 5.9%). Additional data showed that DCA treatment significantly (P = .006) decreased plasma lactate concentrations while also improving survival (P = .027) compared with appropriately matched controls.To date, SL1009 has received priority review, orphan drug designation, and rare pediatric disease designation. Following the CRL, Saol reaffirmed that access to the agent will continue without interruption through both the ongoing open-label extension of the trial (NCT02616484) and the expanded access program (NCT06931262), which also includes emergency support for neonates with life-threatening lactic acidosis due to inborn errors of metabolism.1REFERENCES1. Saol Therapeutics Receives Complete Response Letter from FDA for SL1009 (DCA) for the Treatment of Pyruvate Dehydrogenase Complex Deficiency (PDCD). News release. Saol Therapeutics. September 8, 2025. Accessed September 11, 2025. https://www.prnewswire.com/news-releases/saol-therapeutics-receives-complete-response-letter-from-fda-for-sl1009-dca-for-the-treatment-of-pyruvate-dehydrogenase-complex-deficiency-pdcd-302548522.html2. Saol Therapeutics Announces Submission of New Drug Application (NDA) to the U.S. FDA for SL1009. Saol Therapeutics. December 3, 2025. Accessed September 11, 2025. https://saolrx.com/saol-therapeutics-announces-submission-of-new-drug-application-nda-to-the-u-s-fda-for-sl1009/3. Saol Therapeutics Announces Poster Presentation at the UMDF Mitochondrial Medicine 2025 Conference. News release. June 19, 2025. Accessed September 11, 2025. https://saolrx.com/saol-therapeutics-announces-poster-presentation-at-the-umdf-mitochondrial-medicine-2025-conference/ NewsletterKeep your finger on the pulse of neurology—subscribe to NeurologyLive for expert interviews, new data, and breakthrough treatment updates.Subscribe Now! 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Douglas Miles, MD, PhD, FAAN; Suma Satti, MDView moreVideoPatient, Provider, and Caregiver Connection: Improving Diagnosis and Care for Adolescent Myasthenia Gravis Patients – A New FrontierAbigail N. Schwaede, MD; Emmanuelle (Noelle) Tiongson, MDView moreVideoA New Era in NMOSD Treatment: Optimizing Therapeutic Transitions and Reducing Patient BurdenShamik Bhattacharyya, MD, MS, FAAN; Mirla Avila, MD; Dean Wingerchuk, MDView moreAudioPER Podcast™: Maximizing the Multidisciplinary Care Outcomes of Patients with Amyotrophic Lateral Sclerosis (ALS)Richard Bedlack, MD, PhDView moreAudioPER Podcast™: Best Strategies for Approaching the Diagnosis of Amyotrophic Lateral Sclerosis (ALS)Terry Heiman-Patterson, MDView moreVideoPER Postgame™: Updates from ANNA in the Management of IgA NephropathyGerald Bernard Appel, MD; Ellie Kelepouris, MD, FACP, FAHAView moreVideoPatient, Provider, and Caregiver Connection: Turning a New Leaf in Acute Pain Management – How Recent Advancements Impact the Treatment ParadigmJeffrey Gudin, MD; Jeffrey Bettinger, PharmDView morePrevious slideNext slide Advertisement Advertisement Trending on NeurologyLive1Enhancing Gene Therapy Safety for Duchenne Through New Recommendations: Barry Byrne, MD, PhD2Expanding the Alzheimer Drug Development Pipeline 3FDA Hands Complete Response Letter to SL1009 for Pyruvate Dehydrogenase Complex Deficiency4Patient-Reported Study Identifies Common Symptoms and Timing During Migraine Prodrome 5Setting Realistic Expectations for Antiamyloid Therapeutics Advertisement News|Articles|September 12, 2025 FDA Hands Complete Response Letter to SL1009 for Pyruvate Dehydrogenase Complex Deficiency Author(s)Marco Meglio Saol Therapeutics faces challenges after FDA's complete response letter for SL1009, a potential treatment for rare mitochondrial disorder PDCD. Advertisement In recent news, the FDA has issued Saol Therapeutics a complete response letter (CRL) for its investigational product SL1009 or sodium dichloroacetate oral solution (DCA) for the treatment of pyruvate dehydrogenase complex deficiency (PDCD), a rare mitochondrial metabolic disorder.1PDCD, caused by mutations in one of the components of the pyruvate dehydrogenase complex, affects fewer than 1000 individuals in the United States, with an incidence estimated at 1 in 40,000 live births. Neurological manifestations of the disorder include hypotonia, developmental delay, seizures, ataxia, and sometimes structural brain abnormalities visible on imaging like brain atrophy or abnormal white matter. Some patients present at infancy, while others may have attenuated forms that survive into childhood or adulthood.SL1009, a formulation of DCA, is an oral solution that was intended to be used in conjugation with a proprietary genetic test that helps determine appropriate dosing. In the CRL, the agency outlined specific issues that Saol must resolve in order to define the path forward, though none were related to SL1009’s manufacturing. Meeting these requirements will likely take several years and demand substantial financial investment, the company noted."Families living with PDCD face an urgent and life-threatening unmet need," Dave Penake, chief executive officer at Saol, said in a statement.1 "We are encouraged by recent FDA actions and commentary that recognize the importance of regulatory flexibility and speed for treating rare diseases. Traditional clinical trials often take many years; time that children with PDCD simply do not have. We remain committed to productive conversations with the Agency to identify a path forward that brings this therapy to patients as swiftly as possible."READ MORE: Claseprubart Heads to Phase 3 Study of Myasthenia Gravis Following Positive MaGic TrialThe new drug application (NDA), submitted in December 2024, was based on results from a phase 3, double-blind, placebo-controlled, crossover study (SL1009-01; NCT02616484) and a survival study (SL1009-02). In the phase 3 study, the primary end point, the Observer Reported Outcome (ObsRO) survey, did not demonstrate statistical significance in the double-blind portion. However, longer duration of the therapy, including the open-label extension (OLE), demonstrated a statistically significant improvement in motor function among those in the intent-to-treat (ITT) population (P = .002).2,3Key findings from the phase 3 study, presented earlier this year at the Mitochondrial Medicine 2025 conference in St. Louis, showed that DCA was well-tolerated, even upon chronic administration over 3 years. During that time, the most commonly reported adverse reaction, found in more than 5% of treated patients, was gastrointestinal disorders (n = 2; 5.9%). Additional data showed that DCA treatment significantly (P = .006) decreased plasma lactate concentrations while also improving survival (P = .027) compared with appropriately matched controls.To date, SL1009 has received priority review, orphan drug designation, and rare pediatric disease designation. Following the CRL, Saol reaffirmed that access to the agent will continue without interruption through both the ongoing open-label extension of the trial (NCT02616484) and the expanded access program (NCT06931262), which also includes emergency support for neonates with life-threatening lactic acidosis due to inborn errors of metabolism.1REFERENCES1. Saol Therapeutics Receives Complete Response Letter from FDA for SL1009 (DCA) for the Treatment of Pyruvate Dehydrogenase Complex Deficiency (PDCD). News release. Saol Therapeutics. September 8, 2025. Accessed September 11, 2025. https://www.prnewswire.com/news-releases/saol-therapeutics-receives-complete-response-letter-from-fda-for-sl1009-dca-for-the-treatment-of-pyruvate-dehydrogenase-complex-deficiency-pdcd-302548522.html2. Saol Therapeutics Announces Submission of New Drug Application (NDA) to the U.S. FDA for SL1009. Saol Therapeutics. December 3, 2025. Accessed September 11, 2025. https://saolrx.com/saol-therapeutics-announces-submission-of-new-drug-application-nda-to-the-u-s-fda-for-sl1009/3. Saol Therapeutics Announces Poster Presentation at the UMDF Mitochondrial Medicine 2025 Conference. News release. June 19, 2025. Accessed September 11, 2025. https://saolrx.com/saol-therapeutics-announces-poster-presentation-at-the-umdf-mitochondrial-medicine-2025-conference/ NewsletterKeep your finger on the pulse of neurology—subscribe to NeurologyLive for expert interviews, new data, and breakthrough treatment updates.Subscribe Now! 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Hersh, DO, MSc, FAAN; Anna Shah, MDView moreMultimediaBurst CME™: Optimizing Migraine Management – Addressing Unmet Needs, Individualizing Care for Diverse Populations, and Utilizing CGRP Targeted AgentsJessica Ailani, MD, FAHS, FAAN; Paul G. Mathew, MD, DNBPAS, FAAN, FAHSView moreMultimediaBurst CME™: Setting the Stage – Individualizing Migraine Care for Diverse Populations Across Care SettingsJessica Ailani, MD, FAHS, FAAN; Paul G. Mathew, MD, DNBPAS, FAAN, FAHSView moreMultimediaCommunity Practice Connections™: Optimizing the Management of Tardive Dyskinesia—Addressing the Complexity of Care With Targeted TreatmentIlan Melnick, MD; Alejandro Alva, MD; Linda Trinh, DNP, PMHNP, FNP, MPHView moreMultimediaBurst CME™: Optimizing the Use of CGRP Targeted Agents for the Treatment of MigraineJessica Ailani, MD, FAHS, FAAN; Paul G. 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Douglas Miles, MD, PhD, FAAN; Suma Satti, MDView moreVideoPatient, Provider, and Caregiver Connection: Improving Diagnosis and Care for Adolescent Myasthenia Gravis Patients – A New FrontierAbigail N. Schwaede, MD; Emmanuelle (Noelle) Tiongson, MDView moreVideoA New Era in NMOSD Treatment: Optimizing Therapeutic Transitions and Reducing Patient BurdenShamik Bhattacharyya, MD, MS, FAAN; Mirla Avila, MD; Dean Wingerchuk, MDView moreAudioPER Podcast™: Maximizing the Multidisciplinary Care Outcomes of Patients with Amyotrophic Lateral Sclerosis (ALS)Richard Bedlack, MD, PhDView moreAudioPER Podcast™: Best Strategies for Approaching the Diagnosis of Amyotrophic Lateral Sclerosis (ALS)Terry Heiman-Patterson, MDView moreVideoPER Postgame™: Updates from ANNA in the Management of IgA NephropathyGerald Bernard Appel, MD; Ellie Kelepouris, MD, FACP, FAHAView moreVideoPatient, Provider, and Caregiver Connection: Turning a New Leaf in Acute Pain Management – How Recent Advancements Impact the Treatment ParadigmJeffrey Gudin, MD; Jeffrey Bettinger, PharmDView morePrevious slideNext slide Advertisement Advertisement Trending on NeurologyLive1Enhancing Gene Therapy Safety for Duchenne Through New Recommendations: Barry Byrne, MD, PhD2Expanding the Alzheimer Drug Development Pipeline 3FDA Hands Complete Response Letter to SL1009 for Pyruvate Dehydrogenase Complex Deficiency4Patient-Reported Study Identifies Common Symptoms and Timing During Migraine Prodrome 5Setting Realistic Expectations for Antiamyloid Therapeutics