Rafael Holdings Announces Presentation of Preliminary Data from Ongoing Phase 3 TransportNPC™ Open-Label, Single-Arm Sub-Study in Patients Less Than 3 Years Old
Rafael Holdings (NYSE:RFL) announced preliminary data from Cyclo Therapeutics' Phase 3 TransportNPC™ open-label sub-study evaluating Trappsol® Cyclo™ for Niemann-Pick Disease Type C1 (NPC1). The data, presented at the 15th International Congress of Inborn Errors of Metabolism, showed promising results in patients under 3 years old.
Key findings after 48 weeks revealed that 7 out of 9 patients demonstrated stabilization or improvement in CGI-S scores, with three patients showing improvement. The safety profile remained consistent with previous studies, with 146 adverse events reported, mostly mild (69%) or moderate (29%). No serious adverse events were considered related to the study drug.
The TransportNPC™ study represents the most comprehensive controlled pivotal study for NPC1 treatment, with the drug having received Orphan Drug Designation in both U.S. and EU, along with Fast Track and Rare Pediatric Disease Designations in the U.S.
Rafael Holdings (NYSE:RFL) ha annunciato dati preliminari dallo studio aperto di fase 3 TransportNPC™ di Cyclo Therapeutics che valuta Trappsol® Cyclo™ per Niemann-Pick di tipo C1 (NPC1). I dati, presentati al 15° Congresso Internazionale sugli Errori Congeniti del Metabolismo, hanno mostrato risultati promettenti nei pazienti di età inferiore ai 3 anni.
Le principali evidenze a 48 settimane hanno mostrato che 7 su 9 pazienti hanno dimostrato stabilizzazione o miglioramento dei punteggio CGI-S, con tre pazienti che hanno registrato un miglioramento. Il profilo di sicurezza è rimasto coerente con gli studi precedenti, con 146 eventi avversi riportati, per lo più lievi (69%) o moderati (29%). Nessun evento avverso grave è risultato correlato al medicinale in studio.
Lo studio TransportNPC™ rappresenta lo studio controllato pivotale più completo per il trattamento della NPC1, con il farmaco che ha ricevuto la designazione di Orphan Drug sia negli Stati Uniti che nell’UE, insieme alle designazioni di Fast Track e Rare Pediatric Disease negli Stati Uniti.
Rafael Holdings (NYSE:RFL) anunció datos preliminares del subestudio abierto de Fase 3 TransportNPC™ de Cyclo Therapeutics, que evalúa Trappsol® Cyclo™ para Niemann-Pick Tipo C1 (NPC1). Los datos, presentados en el 15º Congreso Internacional de Errores Inbornos del Metabolismo, mostraron resultados prometedores en pacientes menores de 3 años.
Los hallazgos clave tras 48 semanas revelaron que 7 de 9 pacientes demostraron estabilización o mejora en las puntuaciones CGI-S, con tres pacientes mostrando mejora. El perfil de seguridad se mantuvo consistente con estudios anteriores, con 146 eventos adversos reportados, en su mayoría leves (69%) o moderados (29%). No se consideraron eventos adversos graves relacionados con el fármaco del estudio.
El estudio TransportNPC™ representa el ensayo pivotal controlado más completo para el tratamiento de NPC1, con el fármaco que ha recibido Designación de Medicamento Huérfano tanto en EE. UU. como en la UE, junto con Designaciones de Fast Track y Rare Pediatric Disease en EE. UU.
Rafael Holdings (NYSE:RFL)는 Cyclo Therapeutics의 3상 TransportNPC™ 개방형 하위 연구에서 Trappsol® Cyclo™를 NPC1(니만-픽 질환 1형)으로 평가한 예비 데이터를 발표했다. 데이터는 발생 대사 이상 국제 학술대회 15회에서 발표되었으며, 3세 미만 환자들에서 유망한 결과를 보였다.
48주 후 주요 발견으로 9명 중 7명의 환자에서 CGI-S 점수의 안정화 또는 개선이 관찰되었고, 그 중 3명의 환자에서 개선이 나타났다. 안전성 프로파일은 이전 연구와 일치하며, 146건의 이상반응이 보고되었고 대다수가 경증(69%) 또는 중등도(29%)였다. 연구 약물과 관련된 심각한 이상반응은 없었다.
TransportNPC™ 연구는 NPC1 치료를 위한 가장 포괄적인 조정된 결정적 연구이며, 미국과 EU에서의 고아 약물 지정을 받았고, 미국에서의 Fast Track 및 희귀 소아 질환 지정도 함께 부여되었다.
Rafael Holdings (NYSE:RFL) a annoncé des données préliminaires du sous-étude ouverte de phase 3 TransportNPC™ de Cyclo Therapeutics évaluant Trappsol® Cyclo™ pour Niemann-Pick de type C1 (NPC1). Les données, présentées au 15e Congrès International sur les Erreurs Innées du Métabolisme, ont montré des résultats prometteurs chez les patients âgés de moins de 3 ans.
Les conclusions clés après 48 semaines indiquent que 7 sur 9 patients ont démontré une stabilisation ou une amélioration des scores CGI-S, trois patients montrant une amélioration. Le profil de sécurité est resté cohérent avec les études précédentes, avec 146 événements indésirables raportés, majoritairement bénins (69%) ou modérés (29%). Aucun événement indésirable grave n’a été jugé lié au médicament de l’étude.
L’étude TransportNPC™ représente l’étude pivotale contrôlée la plus complète pour le traitement de NPC1, le médicament ayant reçu une Désignation de Médicament Orphelin tant aux États-Unis qu'aux EU, ainsi que des Désignations Fast Track et Rare Pediatric Disease aux États-Unis.
Rafael Holdings (NYSE:RFL) gab vorläufige Daten aus Cyclo Therapeutics' Phase-3-TransportNPC™-Open-Label-Substudie bekannt, die Trappsol® Cyclo™ zur Niemann-Pick-Krankheit Typ C1 (NPC1) untersucht. Die Daten, präsentiert beim 15. Internationalen Kongress für angeborene Stoffwechselstörungen, zeigten vielversprechende Ergebnisse bei Kindern unter 3 Jahren.
Wichtige Ergebnisse nach 48 Wochen zeigten, dass 7 von 9 Patienten eine Stabilisierung oder Verbesserung der CGI-S-Werte zeigte, wobei drei Patienten eine Verbesserung aufwiesen. Das Sicherheitsprofil blieb konsistent mit früheren Studien, mit 146 unerwünschten Ereignissen gemeldet, überwiegend mild (69%) oder moderat (29%). Keine schweren unerwünschten Ereignisse wurden als mit dem Studienmedikament verbunden angesehen.
Die TransportNPC-Studie repräsentiert die umfassendste kontrollierte zentrale Studie zur NPC1-Behandlung, wobei das Medikament sowohl in den USA als auch in der EU die Orphan-Drug-Designation erhielt, ergänzt durch Fast-Track- und Rare-Pediatric-Disease-Designationen in den USA.
Rafael Holdings (NYSE:RFL) أعلنت عن بيانات أولية من فرع مفتوح من المرحلة 3 من TransportNPC™ لشركة Cyclo Therapeutics الذي يقيم Trappsol® Cyclo™ لعلاج Niemann-Pick من النوع C1 (NPC1). وتم عرض هذه البيانات في المؤتمر الدولي الخامس عشر لأخطاء التمثيل الوراثية المتورطة في التمثيل الغذائي، وأظهرت نتائج واعدة لدى الأطفال دون الثلاث سنوات.
بعد 48 أسبوعاً، أظهرت النتائج أن 7 من أصل 9 مرضى استقروا أو تحسنوا في درجات CGI-S، وبها أظهر ثلاثة مرضى تحسناً. كان ملف السلامة متسقاً مع الدراسات السابقة، مع إبلاغ 146 حدثاً ضاراً، مع الغالبية العظمى خفيفة (69%) أو معتدلة (29%). لم يُعتبر أي حدث ضار خطير مرتبطاً بعلاج الدراسة.
تمثل دراسة TransportNPC™ أوسع دراسة حاسمة محكومة لعلاج NPC1، مع تلقي الدواءDesignation دواء يتيم في كل من الولايات المتحدة والاتحاد الأوروبي، إلى جانب Designations Fast Track وRare Pediatric Disease في الولايات المتحدة.
Rafael Holdings (NYSE:RFL) 宣布来自 Cyclo Therapeutics 的第三阶段 TransportNPC™ 开放标签子研究的初步数据，该研究评估 Trappsol® Cyclo™ 用于尼曼-皮克病类型C1（NPC1）。这些数据在第15届 国际先天性代谢疾病大会上公布，显示在3岁以下患者中取得了有希望的结果。
在< b>48周后，关键发现显示 9例中有7例患者在 CGI-S 评分方面实现了稳定或改善，其中有3例出现改善。安全性特征与以往研究一致，报告了 146 例不良事件，大多数为轻度（69%）或中度（29%）。未认为任何严重不良事件与研究药物相关。
TransportNPC™ 研究代表了对 NPC1 治疗最全面的有控关键性研究，该药在美国和欧盟均获得孤儿药 designation，并在美国还获得了快速通道（Fast Track）和稀有儿科疾病（Rare Pediatric Disease）指定。
- 7 of 9 patients showed stabilization or improvement in CGI-S scores at 48 weeks
- Majority of adverse events (69%) were mild, with no drug-related serious adverse events
- Drug received multiple regulatory designations including Orphan Drug, Fast Track, and Rare Pediatric Disease
- Study represents most comprehensive controlled pivotal trial for NPC1 treatment
- Two patients terminated participation after 48 weeks
- 146 adverse events reported, including some severe cases and serious adverse events (14%)
- Two patients showed deterioration of their CGI-S score
Insights
Rafael's Phase 3 sub-study shows promising early results for Trappsol® Cyclo™ in young NPC1 patients with manageable safety profile.
Rafael Holdings has released preliminary data from Cyclo Therapeutics' ongoing Phase 3 TransportNPC™ open-label, single-arm sub-study evaluating Trappsol® Cyclo™ (hydroxypropyl-beta-cyclodextrin) in children less than 3 years old with Niemann-Pick Disease Type C1 (NPC1). This represents the first dataset for this treatment in this particularly vulnerable age group.
The data shows that after 48 weeks of treatment, 7 out of 9 patients demonstrated stabilization or improvement in their Clinical Global Impression-Severity (CGI-S) scores, with 3 patients showing improvement. Two patients showed deterioration. This is particularly significant because NPC1 is a progressive, fatal genetic disorder where patients typically experience continuous deterioration.
The safety profile appears consistent with previous findings, with 69% of adverse events being mild and 29% moderate. While there were some serious adverse events (14%), none were considered by investigators to be related to the study drug. This safety profile is crucial for a pediatric population where treatment options must be especially well-tolerated.
NPC1 is characterized by cholesterol accumulation in cells leading to organ dysfunction, neurological deterioration, and premature death. There are limited treatment options available, making any potential therapy with positive signals highly relevant.
What makes this study particularly noteworthy is its focus on very young patients (under 3 years old) as part of a Pediatric Investigational Plan (PIP). Early intervention in progressive genetic disorders is often critical for maximizing treatment benefit before irreversible damage occurs.
The main Phase 3 study completed enrollment in May 2024 and is described as "the most comprehensive, controlled pivotal study" for an NPC1 therapy in terms of patient size, global reach, and duration. The regulatory designations already obtained (Orphan Drug, Fast Track, and Rare Pediatric Disease) could expedite approval pathways if final results prove positive.
First data on treatment of NPC1 with Trappsol® Cyclo™ (hydroxypropyl-beta-cyclodextrin) in this age group over a period of 48 weeks
At 48 weeks of the sub-study, 7 of 9 patients1 showed stabilization or improvement in CGI-S score
Data presented at the15th International Congress of Inborn Errors of Metabolism (ICIEM)
NEWARK, N.J., Sept. 16, 2025 (GLOBE NEWSWIRE) -- Rafael Holdings, Inc. (NYSE: RFL; NYSE American: RFL-WT) announced today that data from Cyclo Therapeutics’ Phase 3 TransportNPC™ open-label, single-arm sub-study evaluating Trappsol® Cyclo™ (hydroxypropyl-beta-cyclodextrin) for Niemann-Pick Disease Type C1 (“NPC1”) were presented at the 15th International Congress of Inborn Errors of Metabolism (ICIEM).
The Company’s ongoing TransportNPC™ study is a randomized, double-blind, placebo-controlled, parallel group, multicenter study designed to evaluate the safety, tolerability, and efficacy of 2,000 mg/kg doses of Trappsol® Cyclo™ administered intravenously and standard of care (SOC), compared to placebo administered intravenously and SOC alone, in patients with NPC1, a rare, genetic disease causing cholesterol accumulation in cells, leading to dysfunction primarily of the liver, lung, spleen and brain and premature death. The study duration is a 96-week study, with a 48-week comparative interim analysis. The TransportNPC™ study is the most comprehensive, controlled pivotal study with respect to patient size, global footprint, duration and clinical outcomes of an investigational therapy for NPC1. The study completed enrollment in May 2024. Additionally, the Company enrolled ten (10) patients in its single-arm sub-study per their adopted Pediatric Investigational Plan (PIP) treating newborns to 3 years of age. Two patients terminated participation in the sub-study after 48 weeks (caregiver decision). In accordance with the PIP, the sub-study will evaluate safety and tolerability, descriptive efficacy from both Investigator and patient perspectives via the Clinical Global Impression (CGI) scale and Pharmacokinetics. The sub-study is being conducted in countries outside of the United States per the Company’s adopted PIP.
As part of the ICIEM Congress, Dr. Orna Staretz-Chacham, Senior neonatologist and metabolic specialist, Director of the Rare Disease Center at Soroka Medical Center, Israel and associate professor at the Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel, and a Principal Investigator for the TransportNPC study presented a poster titled, “Trappsol Cyclo Open Label Treatment in the TransportNPC Sub-Study in Patients Under the Age of 3 Diagnosed with Niemann Pick Disease Type C1.”
Summary Of Data Presented In Dr. Staretz-Chacham’s Poster
- At baseline, sub-study patients had a mixture of very mild to severe disease based on the Clinical Global Impression – Severity (CGI-S) scale;
- Seven of nine patients who have reached 48 weeks participation in the study had an outcome of stabilization or improvement in CGI-S, with three patients showing improvement, and two patients showing deterioration of their CGI-S score;
- Adverse Event (AE) profile appears to be consistent with prior findings from earlier studies, and from the larger Phase 3 TransportNPC™ study that is irrespective of age and disease severity;
- As of May 14, 2025, there were 146 AEs, with the majority reported as mild (
69% ) or moderate (29% ), 3 reported as severe and the remainder reported as Serious Adverse Events(SAEs) (14% ); and - No SAEs were considered by the principal investigators as related to or possibly related to study drug.
The potential clinical significance of these preliminary data, if any, will be evaluated based upon the full results of the sub-study.
Dr. Staretz-Chacham commented, “This growing body of promising preliminary findings from the TransportNPC™ sub-study continues to strengthen the potential of Trappsol® Cyclo™ to address the significant unmet medical need in the treatment of NPC1. Importantly, at 48 weeks, the clinical improvements seen in patients is encouraging, and we look forward to gathering additional data from this ongoing study and further evaluating the potential effect of Trappsol® Cyclo™ on progression of NPC1.”
In addition to the poster presentation given by Dr. Staretz-Chacham, there was also an oral presentation given by Dr. Caroline Hastings, Pediatric hematologist oncologist, Director of Neuro-oncology, and Professor of Pediatrics at UCSF Benioff Children’s Hospital Oakland, and a Principal Investigator for the TransportNPC titled, “Hydroxypropyl-beta-cyclodextrin for the Long-Term Treatment of Niemann Pick Type C1: Efficacy and Safety Data from 4 Clinical Studies and the Ongoing Expanded Access Program.”
For more information about the Company’s TransportNPC™ pivotal Phase 3 study, visit www.ClinicalTrials.gov and reference identifier NCT04860960.
Cyclo Therapeutics received Orphan Drug Designation for Trappsol® Cyclo™ to treat NPC1 in both the U.S. and EU and Fast Track and Rare Pediatric Disease Designations in the U.S. The Rare Pediatric Disease Designation is one of the chief requirements for sponsors to receive a Priority Review Voucher in the U.S. upon marketing authorization.
About Trappsol® Cyclo™ (hydroxypropyl-beta-cyclodextrin)
Trappsol® Cyclo™ (hydroxypropyl-beta-cyclodextrin) is an investigational drug designed to deliver a first-in-class propriety cyclodextrin formulation that is administered intravenously (IV) in order to mobilize lysosomal cholesterol. Trappsol® Cyclo™ is designed to directly impact the root cause of Niemann-Pick Disease Type C1 (NPC1) by mobilizing cholesterol from late-stage endosomes and lysosomes. Trappsol® Cyclo™ has also been found in the completed Phase 1 study (CTD-TCNPC-101) and a Phase 2 study (CTD-TCNPC-201) to cross the blood-brain barrier after IV administration, suggesting that therapeutic concentrations have the potential to be reached in the central nervous system over the infusion time window. The potential clinical significance of those concentrations, if any, will be further evaluated based upon the results of the Phase 3 TransportNPC study.
About the Trappsol® Cyclo™ Study Program
The ongoing Phase 3 TransportNPC study is a prospective, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Trappsol® Cyclo™ (hydroxypropyl-beta-cyclodextrin) administered intravenously (2000 mg/kg dose every 2 weeks) in patients aged 3 years and older with confirmed diagnosis of Niemann-Pick Disease Type C1 (NPC1) (CTD-TCNPC-301; NCT04860960). The TransportNPC study enrolled 94 patients in over 25 sites across 13 countries. The study duration is 96 weeks. An unblinded interim analysis was reviewed by an independent DMC when all patients reached 48 weeks. In June 2025, Cyclo Therapeutics announced the continuation of the study following the independent Data Monitoring Committee (DMC) review of safety and efficacy data at the prespecified 48-week interim analysis. As a result, the study is expected to continue for the full 96 weeks. A Phase 3 open-label extension study of up to 96 weeks follows the interventional study.
The primary endpoints of the Phase 3 TransportNPC study are the mean change in the 4-domain NPC Clinical Severity Scale (4D-NPC-CSS) score in the United States and the 5-domain NPC Clinical Severity Scale (5D-NPC-CSS) score in Europe. The 4D-NPC-CSS score (inclusive of ambulation, fine motor, speech, and swallow) and 5D-NPC-CSS score (inclusive of ambulation, fine motor, speech, swallow, and cognition) are measures of NPC disease progression that look at items that patients with NPC and their caregivers and physicians have identified as most relevant. Important secondary and exploratory endpoints will also be assessed across measures of disease activity.
As part of the Phase 3 study, a Phase 3 open-label sub-study is being conducted in NPC1 patients from birth to 3 years of age outside of the United States. Ten patients have been recruited and are continuing in the study. Outcomes for the sub-study include safety, clinical, and caregiver impression of the disease.
Cyclo Therapeutics has completed 2 studies, including a Phase 1 study (CTD-TCNPC-101; NCT02912793) and a Phase 2 study (CTD-TCNPC-201; NCT02912793). Patients who completed the Phase 1 study continue to receive Trappsol® Cyclo™ treatment in the ongoing Phase 1 open-label extension study (CTD-TCNPC-102; NCT03893071).
About Niemann-Pick Disease Type C1 (NPC1)
Niemann-Pick Disease Type C1 (NPC1) is a rare genetic disease that affects approximately 1 in 100,000 live births globally and often leads to premature death. NPC1 is characterized by an inability for cells to transport and process cholesterol, resulting in excessive amounts of cholesterol accumulating and damaging affected organs, including the liver, spleen, and brain. The disease can be life-limiting, with symptoms including progressive intellectual decline, loss of motor skills, seizures, and dementia. Approximately
About Rafael Holdings, Inc.
Rafael Holdings, Inc. is a biotechnology company with interests in clinical and early-stage pharmaceutical companies including a
About Cyclo Therapeutics, LLC
Cyclo Therapeutics, LLC ("Cyclo") is a wholly owned subsidiary of Rafael Holdings, Inc. (NYSE: RFL). Cyclo is a clinical-stage biotechnology company dedicated to developing life-changing medicines through science and innovation for patients and families living with rare and neurodegenerative diseases. The company's investigational drug Trappsol® Cyclo™ (hydroxypropyl-beta-cyclodextrin), which is orphan drug designated in the United States and Europe, is the subject of 4 formal clinical trials for Niemann-Pick Disease Type C1, a rare and fatal genetic disease, (www.ClinicalTrials.gov NCT02939547, NCT02912793, NCT03893071 and NCT04860960). Cyclo is also conducting a phase 2b clinical trial using Trappsol® Cyclo™ intravenously in early Alzheimer's disease (NCT05607615) based on encouraging data from an Expanded Access program for Alzheimer's disease (NCT03624842).
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential safety, efficacy, and regulatory and clinical progress of our product candidates; plans regarding the further evaluation of clinical data; and the potential of our pipeline, including our internal cancer metabolism research programs. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties 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, including, but not limited to, those disclosed under the caption "Risk Factors" in our Annual Report on Form 10-K for the year ended July 31, 2024, and our other filings with the SEC. These factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.
Contact:
Barbara Ryan
Barbara.ryan@rafaelholdings.com
(203) 274-2825
1 Patient 10 had not reached the 48 week treatment at the data cutoff used for this poster
FAQ
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