Rafael Holdings Announces Topline Results from the Pivotal Phase 3 TransportNPC™ Study of Trappsol® Cyclo™ in Niemann-Pick Disease Type C (NPC)
A prespecified background-therapy subgroup showed a statistically significant effect, while the planned FDA application remains on track.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Summary
Rafael Holdings (RFL) reported Phase 3 TransportNPC results for Trappsol Cyclo in Niemann-Pick Disease Type C, missing statistical significance.
The 94-patient trial measured change in a four-domain clinical severity scale at Week 96. The primary endpoint showed directionally favorable 64% slowing of disease progression versus placebo (p=0.19). A prespecified analysis of 78 patients receiving background miglustat and/or leucine showed 71% slowing (p=0.046). Serious treatment-emergent adverse events occurred in 35.9% with treatment versus 16.7% with placebo; one treatment-related bilateral deafness event was severe.
Separate infantile-onset NPC analyses found treatment-associated mortality risk reductions versus external controls. Rafael expects to submit a new drug application in fourth-quarter 2026. The data remain subject to full analysis and FDA review.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Hollow bars mark forward-looking points. How the balance works
Positive
- Moderate point. Forward-looking: it has not happened yet and may not happen.Rafael remains on track for a fourth-quarter 2026 new drug application submission following its pre-application FDA meeting.
- Minor pointPrespecified background-therapy analysis showed 71% slowing of progression at Week 96 versus placebo (n=78; p=0.046).
- Minor pointInfantile-onset NPC treatment was associated with 85% lower mortality risk versus matched registry controls (41 versus 93 patients; p=0.044).
- Minor pointExpanded historical-control analysis associated treatment with 94% lower mortality risk (41 treated versus 133 controls; p=0.0008).
- Minor pointTreatment-emergent adverse events occurred in 93.8% versus 100.0% with placebo over 96 weeks.
3 minor points
- Minor pointTreatment-related serious adverse events occurred at similar rates: 3.1% versus 3.3% with placebo.
- Minor pointSafety monitoring found no new safety signals and no treatment-emergent adverse events resulting in death.
- Minor point. Forward-looking: it has not happened yet and may not happen.Rafael plans to present full results at an upcoming medical meeting.
Negative
- Major pointPrimary endpoint missed statistical significance despite directionally favorable 64% slowing versus placebo at Week 96 (p=0.19).
- Moderate pointSerious treatment-emergent adverse events were more frequent: 35.9% versus 16.7% with placebo.
- Minor pointHearing-related adverse events affected 15.6% versus 13.3% with placebo; one treatment-related bilateral deafness event was severe.
- Minor pointA treatment-emergent adverse event caused one Trappsol Cyclo participant to discontinue early.
- Minor pointTopline data, the complete dataset and survival analysis remain subject to full analysis and FDA regulatory review.
Details
Market move: RFL -34.88% vs previous close. Phase 3 clinical data
On Sep 30, the day this news came out, the latest delayed price for RFL is 34.88% below the previous close. Argus tracked a trough of -38.8% from its starting point during tracking. Our momentum scanner has recorded 10 alerts for this stock so far that day. The latest delayed price is $1.32.
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Key Figures
- Study enrollment
- 94 patients
- Pivotal Phase 3 TransportNPC study
- Primary endpoint difference
- −0.81 points; p=0.19
- Week 96 4DNPCSS; LS mean change 0.46 vs 1.28 points; 95% CI −2.04 to 0.41; not statistically significant
- Prespecified subgroup difference
- −1.11 points; p=0.046
- Week 96 4DNPCSS among patients receiving background miglustat and/or leucine; n=78; 95% CI −2.19 to −0.02
- Mortality risk reduction
- 85%; HR=0.154
- Separate analysis versus matched INPDR controls; 95% CI 0.025–0.950; p=0.044
- Mortality risk reduction
- 94%; HR=0.057
- Expanded historical-control analysis; 95% CI 0.011–0.306; p=0.0008
- Serious TEAEs
- 35.9% vs 16.7%
- Trappsol Cyclo vs placebo
- NDA submission timing
- Fourth quarter of 2026
- Company stated it remains on track to submit the NDA
Previous Clinical trial Reports
-
Completed the final 96-week visit in this pivotal study, with topline results still pending.
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Key Terms
nda regulatory
treatment-emergent adverse events medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
Trappsol® Cyclo™ did not achieve statistical significance but demonstrated a directionally favorable treatment effect versus placebo on the primary endpoint of change in the 4-domain NPC Clinical Severity Scale (4DNPCSS) at Week 96
A prespecified analysis in patients receiving background miglustat and/or leucine therapy, representing approximately
Trappsol® Cyclo™ demonstrated a well-tolerated safety and tolerability profile consistent with previous studies, with no new safety signals observed
Based upon its previously announced pre-NDA meeting, the Company remains on track to submit the NDA in the fourth quarter of 2026, consistent with prior guidance
Company to host investor conference call and webcast today, September 30, at 8:30 a.m. ET
NEWARK, N.J., Sept. 30, 2026 (GLOBE NEWSWIRE) -- Rafael Holdings, Inc. (NYSE: RFL) today announced topline efficacy and safety data from its Cyclo Therapeutics, LLC subsidiary’s pivotal Phase 3 TransportNPC™ study (CTD-TCNPC-301) evaluating Trappsol® Cyclo™ (intravenous hydroxypropyl-β-cyclodextrin) in 94 patients diagnosed with Niemann-Pick Disease Type C (NPC). Trappsol® Cyclo™ was well tolerated and demonstrated a directionally favorable treatment effect on the primary endpoint, although the result did not achieve statistical significance. Notably, a prespecified analysis in patients receiving background miglustat and/or leucine therapy demonstrated a statistically significant and clinically meaningful treatment benefit. Based upon its previously announced pre-NDA meeting with the FDA, the Company remains on track to submit an NDA for Trappsol® Cyclo™ in the fourth quarter of 2026.
The Phase 3 TransportNPC™ Study
The global, double-blind, placebo-controlled Phase 3 TransportNPC™ study (CTD-TCNPC-301) enrolled 94 patients with NPC, ranging in age from 3 to 70 years. Patients were randomized to receive 2000 mg/kg of Trappsol® Cyclo™ administered intravenously every two weeks (n=63) or placebo (n=31) for a 96-week period to assess change in 4DNPCSS.
A prespecified analysis also evaluated change in 4DNPCSS among patients receiving background miglustat therapy and/or leucine (a food supplement available in some European countries), representing approximately
- Primary endpoint: Trappsol® Cyclo™ demonstrated a directionally favorable treatment effect compared with placebo, indicating slowing of disease progression by
64% on change in 4DNPCSS at Week 96 (LS mean change from baseline of 0.46 vs 1.28 points; difference −0.81 points [95% CI −2.04, 0.41]; p=0.19), the result did not achieve statistical significance. - Prespecified analysis: Among patients receiving background miglustat and/or leucine therapy (n=78), Trappsol® Cyclo™ indicating slowing of disease progression by
71% compared with placebo at Week 96 (LS mean change from baseline of 0.46 vs 1.57 points; difference −1.11 points [95% CI −2.19, −0.02]; p=0.046).
Safety and Tolerability
Over the 96-week treatment period, the safety profile of Trappsol® Cyclo™ was well tolerated. Adverse events were largely consistent with the underlying disease. Treatment-emergent adverse events (TEAEs) were reported as followed: Trappsol® Cyclo™,
Separate Overall Survival Analysis
The Company also conducted a separate overall survival analysis comparing patients with infantile-onset NPC treated with Trappsol® Cyclo™ across its clinical development program with well-matched external controls from the International Niemann-Pick Disease Registry (INPDR). The external control cohort included patients with similar baseline characteristics and disease progression. Results from the analysis provide supportive evidence of a treatment-associated survival benefit with Trappsol® Cyclo™.
Specifically, these data indicated:
- INPDR comparison: Treatment with Trappsol® Cyclo™ (n=41) was associated with an
85% reduction in the risk of mortality compared with matched INPDR controls (n=93), HR=0.154;95% CI: 0.025-0.950; p=0.044. - Expanded historical control analysis: In a secondary analysis that expanded the control group to include additional matched historical cohorts from published natural history studies (n=133), treatment with Trappsol® Cyclo™ (n=41) was associated with a
94% reduction in the risk of mortality, HR=0.057;95% CI: 0.011–0.306; p=0.0008.
The consistency and magnitude of the observed survival associations across both analyses provide additional supportive evidence for the potential clinical benefit of Trappsol® Cyclo™ in patients with infantile-onset NPC.
“The Phase 3 TransportNPC study is the most comprehensive trial in NPC conducted to date,” said Dr. Karen Mullen, Chief Medical Officer of Rafael Holdings. “We believe the totality of the data shared today provide a compelling rationale for the continued advancement of Trappsol Cyclo and its potential to offer clinically meaningful treatment benefit for those living with this devastating disease. We remain steadfast in our efforts to advance Trappsol Cyclo and are deeply grateful to the clinical investigators, patients, and caregivers whose courage and commitment were vital to completing this study.”
“NPC is a devastating, heterogeneous disease, and preserving function and stabilizing symptoms are critical,” said Dr. Caroline Hastings, Professor of Pediatric Hematology and Neurology at UCSF Benioff Children’s Hospital Oakland. “As a clinician who has cared for these patients for many years, I am encouraged by the clinically meaningful TransportNPC results. The study was rigorously conducted, and its findings align with the two prior trials for Trappsol Cyclo across a decade of development. I am hopeful that these data can move us closer to delivering a much-needed therapeutic option for families facing profound unmet need.”
NDA On Track for Fourth Quarter 2026
The Company remains on track to submit an NDA for Trappsol® Cyclo™ to the U.S. Food and Drug Administration in the fourth quarter of 2026 based upon its previously announced pre-NDA meeting. The topline data, complete dataset and overall survival analysis remain subject to full analysis and FDA regulatory review. The Company also plans to present the full results at an upcoming medical meeting.
Conference Call Information:
Date: Wednesday, September 30, 2026
Time: 8:30 a.m. ET
Domestic Dial-in Number: 1-877-425-9470
International Dial-in Number: 1-201-389-0878
Conference ID:13763049
Webcast Participant Link: https://viavid.webcasts.com/starthere.jsp?ei=1777956&tp_key=73c1065384
About Rafael Holdings, Inc.
Rafael Holdings, Inc. is a biotechnology company that develops pharmaceuticals and holds interests in clinical and early-stage companies that develop pharmaceuticals and medical devices. Our lead candidate is Trappsol® Cyclo™, and we have completed a pivotal Phase 3 study in NPC and are preparing for a planned NDA submission later this year. Niemann-Pick Disease Type C ("NPC") is a rare, fatal and progressive genetic disorder. We also hold interests in other clinical-stage and early-stage pharmaceutical development companies and an orthopedic-focused medical device company.
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. 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, the risk that the FDA may not accept for filing or approve an NDA for Trappsol® Cyclo™ based on the available data, and those disclosed under the caption "Risk Factors" in our Annual Report on Form 10-K for the year ended July 31, 2025, our subsequent Quarterly Reports on Form 10-Q, 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
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
Did Rafael Holdings' Trappsol Cyclo Phase 3 trial meet its primary endpoint?
The primary endpoint did not achieve statistical significance at Week 96 (p=0.19). The directionally favorable result indicated 64% slowing of disease progression versus placebo. The prespecified analysis in patients receiving background miglustat and/or leucine showed 71% slowing versus placebo (p=0.046).
When does Rafael Holdings plan to submit the Trappsol Cyclo FDA application?
Rafael remains on track to submit its new drug application in fourth-quarter 2026, based on its previously announced pre-application FDA meeting. The topline data, complete dataset and overall survival analysis remain subject to full analysis and FDA regulatory review.
How was Rafael Holdings' TransportNPC Phase 3 trial designed?
TransportNPC was a global, double-blind, placebo-controlled study enrolling patients aged 3 to 70 years. Patients were randomized to intravenous Trappsol Cyclo at 2000 mg/kg every two weeks (63 patients) or placebo (31 patients) for 96 weeks. The background miglustat and/or leucine subgroup represented approximately 83% of the population.
What controls were used in Rafael Holdings' Trappsol Cyclo survival analyses?
The separate survival analyses compared treated infantile-onset NPC patients with matched external controls, rather than the Phase 3 placebo group. The first used International Niemann-Pick Disease Registry patients with similar baseline characteristics and disease progression. The secondary analysis expanded the controls to include matched historical cohorts from published natural history studies.