Miplyffa (arimoclomol) / LadRx, Orphazyme, Zevra Therap, Xoma - LARVOL DELTA

Zevra Therapeutics Submits Marketing Authorization Application to European Medicines Agency to Review Arimoclomol for the Treatment of Niemann-Pick Disease Type C (The Manila Times) - "Zevra Therapeutics, Inc...announced the company submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the evaluation of arimoclomol for the treatment of Niemann-Pick Disease Type C (NPC)...The EMA will review the application under the centralized marketing authorization procedure...'The extensive data generated for arimoclomol has shown long-term, meaningful clinical outcomes with 5 to 7 years of patient experience across more than 270 NPC patients through a Phase 2/3 clinical trial, Open-Label Extension (OLE) study, Expanded Access Programs (EAP), and a pediatric sub-study, which is the most expansive clinical development program in NPC to date.'"

EMA filing • Genetic Disorders

OR01. NEUROENDOCRINOLOGY AND PITUITARY: Mechanisms and Gene Changes (ENDO 2025) - No abstract available

Endocrine Disorders

OR01-1. Ambulatory Anesthesia - Oral Presentations (Non-CME) (ASA 2025) - No abstract available

Anesthesia

Game Changers: Blockbuster Small-Molecule Drugs Approved by the FDA in 2024. (PubMed, Pharmaceuticals (Basel)) - "Notably, eight of these drugs (including Rezdiffra®, Voydeya®, Iqirvo®, Voranigo®, Livdelzi®, Miplyffa®, Revuforj®, and Crenessity®) are classified as "first-in-class" and have received breakthrough therapy designation. These agents not only exhibit distinct mechanisms of action but also offer substantial improvements in efficacy for patients compared to prior therapeutic options. This article offers a comprehensive analysis of the mechanisms of action, clinical trials, drug design, and synthetic methodologies related to representative drugs, aiming to provide crucial insights for future pharmaceutical development."

FDA event • Journal • Review • Alopecia • Brain Cancer • Breast Cancer • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Congenital Adrenal Hyperplasia • Cystic Fibrosis • Dermatology • Duchenne Muscular Dystrophy • Endocrine Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Glioma • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Immunology • Infectious Disease • Leukemia • Lung Cancer • Lysosomal Storage Diseases • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Muscular Dystrophy • Nephrology • Non Small Cell Lung Cancer • Oncology • Primary Biliary Cholangitis • Psychiatry • Pulmonary Disease • Renal Disease • Respiratory Diseases • Schizophrenia • Solid Tumor • Ventricular Tachycardia

Zevra Announces Publication of MIPLYFFA Mechanism of Action Manuscript in Molecular Genetics and Metabolism (GlobeNewswire) - "The publication presents data demonstrating that arimoclomol enters the cell and increases the translocation of translation factors EB and E3 (FTEB & TFE3) from the cytosol to the nucleus, a key initial step for triggering a cascade of downstream events. Specifically, TFEB & TFE3 upregulate the coordinated lysosomal expression and regulation (CLEAR) genes including NPC1, which is essential for the regulation of lysosomal function. Increased CLEAR gene expression then causes higher NPC1 protein levels in the lysosomes, leading to greater correction of aberrant cholesterol trafficking. Of note, in animal NPC models, greater correction of aberrant cholesterol trafficking was shown to correlate with the improvement of specific neurological behaviors, such as rearing and gait."

Preclinical • Genetic Disorders • Lysosomal Storage Diseases • Rare Diseases

Mechanistic insights into arimoclomol mediated effects on lysosomal function in Niemann-pick type C disease. (PubMed, Mol Genet Metab) - "Arimoclomol, an orally available small molecule, is the first FDA-approved treatment for NPC when used in combination with miglustat...By also amplifying expression of CLEAR genes associated with autophagy, arimoclomol has the potential to act on different pathways and improve cell viability independent of NPC1 protein levels and functionality. In summary, the findings presented illustrate how arimoclomol improves lysosomal function and potentially autophagy flux to decrease lipid burden in NPC patient fibroblasts."

Journal • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • TFE3 • TFEB

Zevra Announces Closing of Sale of Rare Pediatric Disease Priority Review Voucher for $150 Million (GlobeNewswire) - "Zevra Therapeutics, Inc...announced the closing of the sale of its Rare Pediatric Disease Priority Review Voucher (PRV) for gross proceeds of $150 million. 'We have reached another key milestone with the closing on the sale of our PRV, which we received following the successful approval of MIPLYFFA (arimoclomol) from the U.S. Food and Drug Administration (FDA)'...'The $150 million in gross proceeds is non-dilutive capital that further enhances our financial flexibility to support our strategic priorities, which includes executing on the commercial launches of MIPLYFFA and OLPRUVA, supporting our ongoing Phase 3 trial for celiprolol, and augmenting our solid balance sheet to support future investments that are in alignment with our strategic plan'."

Financing • CNS Disorders • Metabolic Disorders

FDA approval of Miplyffa and Aqneursa: A dual breakthrough for the treatment of Neimann-Pick disease type C. (PubMed, Alzheimers Dement (N Y)) - No abstract available

FDA event • Journal • Frontotemporal Lobar Degeneration

Zevra Therapeutics Enters Agreement to Sell its Rare Pediatric Disease Priority Review Voucher for $150 Million (GlobeNewswire) - "Zevra Therapeutics, Inc...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...'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.'"

Financing • CNS Disorders • Metabolic Disorders

Arimoclomol: First Approval. (PubMed, Drugs) - "Arimoclomol (MIPLYFFA™), an oral small molecule that crosses the blood brain barrier and is thought to upregulate CLEAR (Coordinated Lysosomal Expression and Regulation) network genes and improve lysosomal function, is being developed by Zevra Therapeutics Inc., for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC). In September 2024, arimoclomol was approved for use in combination with miglustat for the treatment of neurological manifestations of NPC in adult and pediatric patients 2 years of age and older in the USA. This article summarizes the milestones in the development of arimoclomol leading to this first approval for use in combination with miglustat for the treatment of neurological manifestations of NPC in adult and pediatric patients aged ≥ 2 years."

Journal • Review • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics

Miplyffa (arimoclomol). (PubMed, Clin Ther) - No abstract available

Journal

OR01-1. Ambulatory Anesthesia - Oral Presentations (Non-CME) (ASA 2024) - No abstract available

Anesthesia

Zevra’s MIPLYFFA (arimoclomol) Receives Approval from U.S. Food and Drug Administration for Use in Patients with Niemann-Pick Disease Type C (NPC) (GlobeNewswire) - "XOMA Royalty Corporation...announced today Zevra Therapeutics has received approval from the U.S. Food and Drug Administration (FDA) for MIPLYFFA (arimoclomol). MIPLYFFA is approved for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients two years of age and older. It is the sixth commercial asset in XOMA Royalty’s growing royalty and milestone portfolio."

FDA approval • CNS Disorders • Lysosomal Storage Diseases

FDA Advisory Committee Votes Favorably that the Data Support Arimoclomol as Effective Treatment for Patients with Niemann-Pick Disease Type C (GlobeNewswire) - "Zevra Therapeutics...announced that the U.S. Food and Drug Administration (FDA) Genetic Metabolic Diseases Advisory Committee (GeMDAC) voted favorably (11 yes, 5 no) that the data support that arimoclomol is effective in the treatment of patients with Niemann-Pick disease type C (NPC)....'Based on the totality of the clinical data, including data from the pivotal trial, the long-term data from the arimoclomol open label extension study, and data from our expanded access programs (EAP: NCT04316637), we remain confident in the clinical benefit offered by arimoclomol as a treatment for NPC, and are optimistic about its continued path to approval'....The arimoclomol NDA has been assigned a Prescription Drug User Fee Act (PDUFA) action date of September 21, 2024."

FDA event • PDUFA • CNS Disorders • Lysosomal Storage Diseases

LadRx and ImmunityBio Mutually Agree to Terminate Aldoxorubicin License (Businesswire) - "LadRx Corporation...is pleased to announce that the Company and NantCell, Inc...together with NantCell’s parent company ImmunityBio, Inc. ('ImmunityBio'), have agreed to a mutual termination of the license of aldoxorubicin entered into in 2017...With the termination of the license agreement between LadRx and NantCell, LadRx regains control of aldoxorubicin...XOMA consented to the mutual termination of the LadRx-NantCell agreement in order to facilitate the return of the program to LadRx...The agreement between LadRx and XOMA regarding future royalties and milestones associated with arimoclomol is not affected by the termination of the aldoxorubicin license between LadRx and NantCell....'we continue to march LADR-7 towards the clinic and remain on track for filing an IND application for LADR-7 in the third or fourth quarter of 2024.'"

IND • Licensing / partnership • CNS Disorders • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. (PubMed, Lancet Neurol) - P3 | "Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated."

Journal • P3 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Gastrointestinal Disorder • Respiratory Diseases • KEAP1

OR01. Neuroendocrinology: Gene Regulation and Function (ENDO 2024) - "RF01-01 will also be presented as a poster on Sunday, board 076, SUN-076). Oral abstract presentations will only take place as oral abstracts and will not be presented as posters."

OR01: Oral Comm.1 - Anxiety Disorders and Somatoform Disorders - Obsessive-Compulsive Disorder - Post-Traumatic Stress Disorder - Psychophysiology (EPA 2024) - No abstract available

CNS Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Post-traumatic Stress Disorder • Psychiatry • Psychosomatic Disorders

Zevra Therapeutics Provides FDA Update on the PDUFA Action Date for Arimoclomol as a Treatment for Niemann-Pick Disease Type C (GlobeNewswire) - "Zevra Therapeutics, Inc...announced the U.S. Food and Drug Administration (FDA) has extended the review period for the New Drug Application (NDA) for arimoclomol, an investigational orally delivered, first-in-class treatment for Niemann-Pick disease type C (NPC). In addition, the FDA has set a new Prescription Drug User Fee Act ('PDUFA') action date of September 21, 2024, and has re-affirmed its intent to present the resubmission for discussion at an advisory committee meeting to be scheduled."

PDUFA date • CNS Disorders

Zevra Therapeutics Receives FDA Acceptance of Resubmission of NDA for Arimoclomol as a Treatment for Niemann-Pick Disease Type C (GlobeNewswire) - "Zevra Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has acknowledged receipt of the resubmission of the New Drug Application (NDA) for arimoclomol as an orally-delivered, first-in-class treatment for Niemann-Pick disease type C. Under the Prescription Drug User Fee Act ('PDUFA'), the FDA has deemed the arimoclomol NDA resubmission to be a Class II complete response which has a six-month review period from the date of resubmission. As a result, the FDA has assigned a PDUFA action date of June 21, 2024, and currently intends to present the resubmission for discussion in an advisory committee."

NDA • PDUFA date • CNS Disorders

Zevra Therapeutics Announces Resubmission of Arimoclomol New Drug Application to the U.S. Food and Drug Administration (GlobeNewswire) - "Zevra Therapeutics, Inc...announced it resubmitted its New Drug Application (NDA) for arimoclomol, an investigational therapeutic candidate for the treatment of Niemann-Pick disease type C (NPC) to the U.S. Food and Drug Administration (FDA) on December 22, 2023. Based on standard NDA resubmission review timelines, an acknowledgment letter from the FDA that the resubmission is complete and setting the PDUFA date is expected within 30 days. Zevra expects the NDA to be classified as a Class II submission which would be subject to a review period by the FDA within six months from the date of submission....Additionally, new data included in the resubmission comes from multiple non-clinical studies..."

NDA • PDUFA date • CNS Disorders

Safety and efficacy of arimoclomol for inclusion body myositis: a multicentre, randomised, double-blind, placebo-controlled trial. (PubMed, Lancet Neurol) - P2 | "Arimoclomol did not improve efficacy outcomes, relative to placebo, but had an acceptable safety profile in individuals with inclusion body myositis. This is one of the largest trials done in people with inclusion body myositis, providing data on disease progression that might be used for subsequent clinical trial design."

Journal • Immunology • Myositis • Nephrology

[VIRTUAL] A Randomized, Double-Blind, Placebo Controlled Study of Arimoclomol in Patients with Inclusion Body Myositis (ANA 2021) - P2 | "This trial did not demonstrate a benefit of arimoclomol in IBM with respect to its primary and second ary efficacy endpoints"

Clinical • Late-breaking abstract • CNS Disorders

KemPharm Announces Corporate Name Change to Zevra Therapeutics (GlobeNewswire) - “KemPharm, Inc…announced today that it changed its name to Zevra Therapeutics, Inc. (‘Zevra’). This name change reflects the Company’s intensified focus and dedication to developing transformational, patient-focused therapies for rare diseases with limited or no treatment options. In conjunction with the name change, the Company will begin trading under the new ticker symbol ‘ZVRA’ on The Nasdaq Global Market on or about March 1, 2023….Zevra looks ahead to key milestones in 2023, including the resubmission of arimoclomol New Drug Application (‘NDA’) to the FDA as early as Q3 2023…and the potential achievement of certain commercial sales milestones for our partnered asset, AZSTARYS^®.”

Commercial • NDA • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease

Heat shock protein amplification improves cerebellar myelination in the Npc1 mouse model. (PubMed, EBioMedicine) - "These data increase our understanding of the mechanisms by which HSP70 regulates myelination and provide further support for the clinical development of HSP-amplifying therapies in the treatment of NPC."

Journal • Preclinical • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • Solid Tumor