This study will investigate if the drug sodium phenylbutyrate (NaPB) impacts blood pressure and vascular function in healthy volunteers and in patients with diabetes.

Start Date01 May 2025

Sponsor / Collaborator

University of Pennsylvania

[+1]

NCT06773026

/ RecruitingPhase 2IIT

A Phase 2, Open-label, Fixed-dose Study to Assess the Efficacy of Sodium Phenylbutyrate (ACER-001) in Treating Pediatric and Adult Patients with Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency Resulting from the Prevalent ACADM C.985 A>G (K304E) Mutation

This is a medical research study to test a medication in patients 4 years of age and older with a disease called medium-chain acyl-CoA dehydrogenase deficiency (MCADD) caused by the common ACADM c.985 A>G (K304E) mutation. The medication is sodium phenylbutyrate (ACER-001), which is currently FDA approved for the treatment of Urea Cyle Disorders. Previous research suggests that sodium phenylbutyrate may also be effective in the treatment MCADD. This study will investigate the safety and efficacy (how well it works) of sodium phenylbutyrate in patients with MCADD.

Start Date01 Apr 2025

Sponsor / Collaborator

University of Pittsburgh

[+1]

ChiCTR2400086139

/ SuspendedEarly Phase 1IIT

A clinical effectiveness study of Sodium phenylbutyrate in the treatment of polycystic ovary syndrome

Start Date01 Jul 2024

Sponsor / Collaborator

Zhongshan Hospital Fudan University

100 Clinical Results associated with Sodium Phenylbutyrate

100 Translational Medicine associated with Sodium Phenylbutyrate

100 Patents (Medical) associated with Sodium Phenylbutyrate

3,736

Literatures (Medical) associated with Sodium Phenylbutyrate

01 Apr 2025·Neural Regeneration Research

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell–derived exosomal vesicles: a case report

Article

Author: Pearse, Damien D. ; Dietrich, W. Dalton ; Levi, Allan D. ; Guest, James D. ; Silvera, Risset ; Goldschmidt, Alexander J.P. ; Brooks, Adriana ; Graham, Patricia ; Goldschmidt-Clermont, Pascal J. ; Jimsheleishvili, George ; Khan, Aisha

Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported. This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles, marking, to our knowledge, the first instance of such treatment. An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis. After initial diagnosis, the patient underwent a combination of generic riluzole, sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis, and taurursodiol. The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function. We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired (senescent) and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles, cultured expanded from a cadaver donor improved their growth capacity in vitro. After a period of observation lasting 10 weeks, during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored, the patient received weekly consecutive infusions of 1.54 × 1012 (×2), and then consecutive infusions of 7.5 × 1012 (×6) allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline. None of the infusions were associated with adverse events such as infusion reactions (allergic or otherwise) or changes in vital signs. Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend. A more sensitive in-house assay suggested possible inflammasome activation during the disease course. A trend for clinical stabilization was observed during the infusion period. Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles. Initial findings suggest that this approach is safe.

01 Apr 2025·FOOD CHEMISTRY

New insights into the tenderization pattern of yak meat by ROS-ERS: Promotion of ERS-associated apoptosis through feedback regulation of PERK/IRE1/ATF6 and caspase-12 activity

Article

Author: Shi, Hongmei ; Duan, Yufeng ; Yang, Xue ; Song, Rende ; Li, Yiheng ; Zhang, Li ; Kong, Xiangying ; Hua, Yongli ; Zhang, Xinjun ; Shen, Ruheng

This study aimed to investigate the molecular mechanisms of reactive oxygen species (ROS)-induced endoplasmic reticulum stress (ERS) in apoptosis and meat tenderization during postmortem aging. Yak longissimus dorsi muscle was incubated with N-acetylcysteine (NAC), 4-phenylbutyric acid (4-PBA) and NAC + 4-PBA, respectively, and stored at 4 °C for 0 h, 12 h, 24 h, 72 h, 120 h and 168 h. The results showed that NAC and 4-PBA treatments significantly reduced ROS content and endoplasmic reticulum stress levels. Meanwhile, the specific inhibitory effect of 4-PBA affected Ca²⁺ content, caspase-12 activity, endoplasmic reticulum apoptotic cascade reaction and meat tenderization by preventing myogenic fiber degradation. Additionally, the combined treatment of NAC + 4-PBA had a more significant effect than the other groups, confirming the necessity of targeted regulation of the ROS-ERS axis. Overall, our findings provide new insights into the critical role of ROS-mediated ERS in caspase-12-dependent apoptosis and yak meat tenderization during yak meat postmortem.

01 Mar 2025·Molecular Genetics and Metabolism Reports

Single centre retrospective review of plasma branched-chain amino acid levels in children with urea cycle disorders: Impact of treatment modalities and disease severity

Article

Author: Dixon, Marjorie ; Yeo, Mildrid ; Rehsi, Preeya ; Chakrapani, Anupam ; Yeo, Jie Ming

Branched-chain amino acids (BCAAs) are important for normal growth, development, and function. In urea cycle disorders (UCDs), plasma BCAA levels can be relatively low; this has been attributed variously to low protein intake, hyperammonaemia, and nitrogen scavenger treatment. We undertook a retrospective review of plasma BCAA levels in individuals with UCDs comprising ornithine carbamoyltransferase deficiency (OTCD n = 22), arginosuccinate lyase deficiency (ASLD n = 12), and argininosuccinate synthase deficiency (ASSD n = 6). Scavenger treatment groups comprised sodium benzoate (NaBz, n = 20), sodium phenylbutyrate (NaPBA, n = 5), NaBz+NaPBA (n = 14), and a control group receiving neither NaBz nor NaPBA (n = 14). In these treatment groups, respectively, median (IQR) plasma levels of leucine were 54 (32), 55 (25), 58 (19), and 91 (70) μmol/L (leucine was lower in the NaBz group than the control, p = 0.0282) and numbers of individuals (%) with leucine below normal were 10/20 (50 %), 1/4 (25 %), 10/14 (71 %), and 2/9 (20 %). The pattern was similar for isoleucine and valine. In the NaBz group, plasma BCAA levels were inversely correlated with protein intake (p ≤ 0.01 to p ≤ 0.001), plasma ammonia level (p ≤ 0.01 to p ≤ 0.0001), and scavenger dose (p ≤ 0.0001). We speculate that individuals with greater disease severity may be prone to BCAA deficiency, caused by BCAA consumption when alternative urea disposal pathways are used. Practical reflections on our audit were that to increase the proportion of plasma BCAA levels in the normal range, we needed to alter the biological value of protein intake, prescribe higher doses of scavenger to facilitate safe levels of protein intake, and give EAA supplements if indicated.

307

News (Medical) associated with Sodium Phenylbutyrate

27 Feb 2025

·www.fiercepharma.com

Zevra to net $150M from priority review voucher sale tied to Miplyffa approval

The $150 million price tag for Zevra’s PRV is slightly above the $100 million mark that many vouchers have traded at in the past, though it’s in line with several other recent transactions. For Zevra Therapeutics, last year’s approval of the rare lysosomal storage disorder drug Miplyffa appears to be the gift that keeps on giving.After receiving a rare pediatric disease priority review voucher (PRV) in tandem with Miplyffa’s FDA green light in September, Zevra has locked in a deal to sell the PRV for $150 million.Zevra did not disclose the identity of the purchaser. The transaction itself is expected to occur within 30 to 45 days, the company said Thursday.The cash from the sale will be used to fuel R&D, plus the commercial rollouts of Miplyffa and the urea cycle disorder (UCD) medicine Olpruva, which Zevra picked up in its $91 million buyout of Acer Therapeutics in 2023, Zevra’s CFO, LaDuane Clifton, said in a statement.Miplyffa’s FDA approval last fall made it the first drug specifically cleared in the U.S. to treat Niemann-Pick disease type C (NPC), a rare lysosomal storage disorder that prevents the body from moving and using cholesterol and other lipids in cells. The disease can take a significant toll on patients’ speech, cognition, swallowing, movement and fine motor skills.Miplyffa is taken orally three times a day in conjunction with the enzyme inhibitor miglustat. Miglustat, which is sold by Johnson & Johnson as Zavesca, has long been used as the primary, albeit off-label, treatment for NPC patients.Zevra’s first-comer advantage was quickly challenged by Austin, Texas-based IntraBio, which scored an FDA thumbs up for its own NPC drug Aqneursa just one week after Miplyffa’s approval. Still, Zevra hasn’t been sweating the competition so far.“It’s really just hard to believe that you have two approvals within one week after literally decades of nothing available—so we’re thrilled for patients and the NPC community,” Zevra’s chief commercial officer, Josh Schafer, said in an interview last year.Miplyffa’s ability to halt the progression of disease, rather than just treating symptoms, will likely position the drug as the “foundation and the cornerstone” of NPC treatment, Schafer said, adding that he believes additional therapies will be prescribed based on patients’ individual symptoms and needs.The $150 million price tag for Zevra’s PRV is slightly above the $100 million mark that many vouchers have traded at in the past, though it’s in line with several other recent transactions.In late November, PTC Therapeutics said it had lined up a $150 million sale of the rare pediatric disease PRV it picked up through the approval of its gene therapy for the ultra-rare disease aromatic L-amino acid decarboxylase (AADC) deficiency. Earlier that same month, Acadia Pharmaceuticals also bagged a $150 million PRV sale tied to the approval of its Rett syndrome drug Daybue. In Acadia’s case, the company was only able to keep $100 million of the proceeds, with the rest going to the drug's licensor Neuren Pharmaceuticals.The recent voucher sales by Zevra, PTC and Acadia are likely to be among the last in the childhood rare disease space.Back in September, the FDA said it would sunset its rare pediatric disease PRV program beginning Dec. 20, 2024.

AcquisitionDrug ApprovalPriority Review

27 Feb 2025

·investors.zevra.com

Zevra Therapeutics Enters Agreement to Sell its Rare Pediatric Disease Priority Review Voucher for $150 Million

CELEBRATION, Fla., Feb. 27, 2025 (GLOBE NEWSWIRE) -- Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) (Zevra, or the Company), a commercial-stage company focused on providing therapies for people living with rare disease, today announced that it has entered into a definitive asset purchase agreement to sell its Rare Pediatric Disease Priority Review Voucher (PRV) for gross proceeds of $150 million upon the closing of the transaction, which is expected to take place within 30 to 45 days, subject to customary closing conditions. LaDuane Clifton, Zevra’s Chief Financial Officer said, “This non-dilutive capital strengthens our balance sheet by adding gross cash proceeds of $150 million, supporting continued investment in our strategic priorities, which include executing the commercial launches of MIPLYFFA™ and OLPRUVA®, and advancing our pipeline of product candidates to address unmet needs within the rare disease community.” The PRV was granted to Zevra in September 2024 following approval by the U.S. Food and Drug Administration of MIPLYFFA (arimoclomol), which is indicated for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients 2 years of age and older. The transaction is subject to customary closing conditions, including expiration of the applicable waiting period under the Hart-Scott Rodino Antitrust Improvements Act (HSR). Cantor Fitzgerald acted as Zevra’s exclusive financial advisor and Latham & Watkins LLP acted as Zevra’s legal advisor for this transaction. About Zevra Therapeutics, Inc. Zevra Therapeutics, Inc. is a commercial-stage company combining science, data, and patient need to create transformational therapies for rare diseases with limited or no treatment options. Our mission is to bring life-changing therapeutics to people living with rare diseases. With unique, data-driven development and commercialization strategies, the Company is overcoming complex drug development challenges to make new therapies available to the rare disease community. For more information, please visit www.zevra.com or follow us on X and LinkedIn. Cautionary Note Concerning Forward-Looking Statements This press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that do not relate solely to historical or current facts, including without limitation statements regarding the potential benefits of any of our products or product candidates for any specific disease or at any dosage; our strategic and product development objectives; the consummation and benefits of the transaction and its impact on the Company’s balance sheet; the outcome of any required filings under the HSR; prescription enrollments; our ability to support patients as they navigate the benefits verification process to obtain either MIPLYFFA™ or OLPRUVA®; availability of and access to MIPLYFFA and OLPRUVA; and the timing of any of the foregoing. Forward-looking statements are based on information currently available to Zevra and its current plans or expectations. They are subject to several known and unknown uncertainties, risks, assumptions, and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Given these risks and uncertainties, you should not place undue reliance on these forward-looking statements. These and other important factors are described in detail in the "Risk Factors" section of Zevra’s Annual Report on Form 10-K for the year ended December 31, 2023, Zevra’s Quarterly Report on Form 10-Q for the three and nine months ended September 30, 2024, and Zevra’s other filings with the Securities and Exchange Commission]. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. Although we believe the expectations reflected in such forward-looking statements are reasonable, we cannot assure that such expectations will prove correct. These forward-looking statements should not be relied upon as representing our views as of any date after the date of this press release. _____________________________________________ Zevra Contact Nichol Ochsner +1 (732) 754-2545 nochsner@zevra.com Russo Partners Contact David Schull +1 (858) 717-2310 david.schull@russopartnersllc.com

Drug ApprovalPriority Review

27 Feb 2025

·www.pharmaceutical-technology.com

Zevra sells priority review voucher for $150m to support drug launches

The rare paediatric disease PRV program aims to incentivise drug development for rare paediatric diseases. Credit: MagicVectorCreation via Getty Images. Zevra has sold its US Food and Drug Administration (FDA) priority review voucher (PRV) for $150m to an undisclosed party. The US-based company received the PRV when its Niemann-Pick disease type C drug Miplyffa (arimoclomol) won FDA approval in September 2024. Zevra plans to use the funds from the voucher sale to support the commercial launches of Miplyffa and the company’s urea cycle disorder drug Olpruva, which it inherited as part of the $91m acquisition of Acer Therapeutics in 2023. Niemann-Pick disease type C is a progressive, neurodegenerative lysosomal storage disorder caused by the body’s inability to transport cholesterol and other lipids within cells. This leads to lipid accumulation in tissues, including the brain, resulting in severe physical and cognitive decline. Miplyffa was the first therapy approved for Niemann-Pick disease type C in the US. It is indicated for use alongside Johnson & Johnson’s (J&J’s) Zavesca (miglustat). Zavesca has long been used as the primary, but off-label treatment for Niemann-Pick disease type C patients in the US. It is however approved for the disease in the UK and Germany. Miplyffa works by inducing the heat shock response to address Niemann-Pick disease type C protein misfolding. Miplyffa’s approval followed a turbulent regulatory journey . The FDA initially rejected the drug in 2021, issuing a complete response letter (CRL) to its then-owner Orphazyme due to insufficient clinical data. The agency was not convinced by the clinical results and requested additional data. Orphazyme later sold the drug’s rights to KemPharma, which rebranded it as Zevra. According to GlobalData’s Pharma Intelligence Center, Miplyffa is forecast to generate $273m in global sales by 2030. GlobalData is the parent company of Pharmaceutical Technology. The FDA’s PRV programme was introduced to incentivise innovation in areas with limited commercial incentives, such as rare paediatric diseases and neglected tropical diseases. In February 2024, Valneva sold its PRV for $103m after securing FDA approval for its chikungunya vaccine, Ixchiq, in November 2023. However, not all companies have benefited as expected. In 2023, bluebird bio faced financial and strategic difficulties after failing to secure a PRV for Lyfgenia, a gene therapy it anticipated would qualify for a voucher. The company had pre-arranged a $103m sale of the voucher to Novartis, only for the FDA to deny it, citing similarities to the active ingredient in another of bluebird’s gene therapies called Zynteglo, which had already earned bluebird a PRV on its approval in 2022.

Drug ApprovalAcquisitionPriority Review

100 Deals associated with Sodium Phenylbutyrate

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KEGG	Wiki	ATC	Drug Bank
D05868	Sodium Phenylbutyrate	A16AX03	DB06819

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Citrullinemia	Canada	Médunik Canada, Inc.	30 Mar 2015
Urea Cycle Disorders, Inborn	United States	Horizon Therapeutics USA, Inc.	30 Apr 1996

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Medium Chain Acyl CoA Dehydrogenase Deficiency	Phase 2	United States	Zevra Therapeutics, Inc.	01 Apr 2025
Maple Syrup Urine Disease	Phase 2	United States	Acer Therapeutics, Inc.	19 Sep 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CENTAUR (AAN2023)	Not Applicable	Amyotrophic Lateral Sclerosis	-	Sodium Phenylbutyrate and Taurursodiol	qzfabbcfgx(jukzbjybmn) = hjkdikmzqx pgpkpcquny (rxacsmgqyz )	-	25 Apr 2023
				Placebo	qzfabbcfgx(jukzbjybmn) = gamiyetmnu pgpkpcquny (rxacsmgqyz )
SSIEM2022	Not Applicable	homozygous p.L483P mutation	-	Phenylbutyrate	upipbhsfcz(akgbjuquqf) = hqkomwhucj dkqyfcmivk (njsffdgrhi )	-	30 Aug 2022
				Ursodeoxycholic acid	upipbhsfcz(akgbjuquqf) = krhtwzqibf dkqyfcmivk (njsffdgrhi )
NCT01529060 (MSUD, CTgov)	Phase 2/3	Maple Syrup Urine Disease	20	Phenylbutyrate (Phenylbutyrate)	unsatnmqxr(maoahmimeo) = nzvbkpicxo faeabbakbi (zxnikplxkj, 5168) View more	-	06 Mar 2019
				Placebo powder (Inactive Powder)	lvvukqeavx(jzggdamtpb) = uxoxumcszf mubcidjvva (rqzfxoewza, ekfgywxpmy - okqojamlhn) View more
NCT00771901 (TUDCA/PBA, CTgov)	Not Applicable	Insulin Resistance \| Diabetes Mellitus \| Obesity	101	placebo (Placebo)	lqdwevtvtc(vuregwujsa) = bzkkibqndi xuwiamqfla (olnaocldvv, 7) View more	-	29 May 2018
				tauroursodeoxycholic acid (Tauroursodeoxycholic Acid)	lqdwevtvtc(vuregwujsa) = kfxezksptk xuwiamqfla (olnaocldvv, 8) View more
NCT02111200 (BPA/Benzoate, CTgov)	Not Applicable	Urea Cycle Disorders, Inborn	7	Sodium Benzoate (Sodium Benzoate Arm)	vrkpunbvjh(xclqitgxsg) = flcopdweme fcnotlafec (eaytlqpnlf, 3.1) View more	-	08 Dec 2017
				Sodium Phenylbutyrate (Sodium Phenylbutyrate Arm)	vrkpunbvjh(xclqitgxsg) = fzapotbsjg fcnotlafec (eaytlqpnlf, 0) View more
NCT00528268 (STOPSMA, CTgov)	Phase 1/2	HMN (Hereditary Motor Neuropathy) Proximal Type I \| Spinal Muscular Atrophy \| Muscular Atrophy, Spinal, Type II	22	Sodium phenylbutyrate (Cohort 1)	guiclmrimo = iqupmrcfkt eagltyexhv (rmjwwessct, ehuivwvbqv - tnigrypwku) View more	-	03 Jul 2015
				Sodium phenylbutyrate (Cohort 2)	guiclmrimo = uvfppvjtpk eagltyexhv (rmjwwessct, streuzkvwn - xpnzzzyosm) View more
NCT00551200 (CTgov)	Phase 2	Urea Cycle Disorders, Inborn	14	NaPBA+HPN-100 (NaPBA Steady State)	ywhidmmfff(tiezubcodm) = rduuholxvr brdzifnpam (fhnyklmgth, 40.1) View more	-	12 May 2015
				HPN-100 (HPN-100 Steady State)	ywhidmmfff(tiezubcodm) = znizccglqv brdzifnpam (fhnyklmgth, 27.9) View more
NCT00345605 (CTgov)	Phase 2	Argininosuccinic Aciduria	12	Buphenyl+Arginine (Low-dose Arginine Plus Buphenyl)	nuvhvstddm(dlbkhdookt) = mhpkzbcphe zkqxbmffbu (okfttpbnbw, 10.9) View more	-	05 Nov 2014
				Arginine (High Dose Arginine Alone)	nuvhvstddm(dlbkhdookt) = xkhlqiukjw zkqxbmffbu (okfttpbnbw, 15.7) View more

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