Zevra Therapeutics Presents Positive New Data Supporting Foundational Role of MIPLYFFA® (arimoclomol) for the Treatment of Niemann-Pick Disease Type C at the International Congress of Inborn Errors of Metabolism (ICIEM)

Rhea-AI Summary

Zevra Therapeutics (NASDAQ:ZVRA) presented new positive data for MIPLYFFA® (arimoclomol) in treating Niemann-Pick disease type C (NPC) at the International Congress of Inborn Errors of Metabolism. The company showcased multiple posters highlighting the drug's efficacy and safety profile.

Key findings include: MIPLYFFA's ability to upregulate CLEAR network genes and amplify NPC1 protein levels, reduced disease progression in patients switching from placebo while on miglustat, demonstrated safety in children aged 6 to 24 months, and confirmed effectiveness in real-world settings. The company's poster detailing MIPLYFFA's mechanism of action received a Best Poster Award nomination from ICIEM.

Positive

• MIPLYFFA demonstrated decline in annual disease progression for NPC patients switching from placebo
• Drug showed positive safety profile in young children aged 6 to 24 months
• Real-world data confirmed effectiveness consistent with Phase 3 study results
• Research poster nominated for Best Poster Award at ICIEM

Negative

• None.

Insights

Medical Research Specialist

New MIPLYFFA data shows positive clinical outcomes in NPC patients, including slowed disease progression and safety in young children, strengthening its therapeutic value.

Zevra Therapeutics has presented compelling new data for MIPLYFFA (arimoclomol) in treating Niemann-Pick disease type C (NPC), a rare lysosomal storage disorder. The findings, presented at the International Congress of Inborn Errors of Metabolism (ICIEM), strengthen the drug's clinical profile across multiple dimensions.

The mechanistic data, nominated for a Best Poster Award, demonstrates MIPLYFFA's ability to upregulate genes in the CLEAR network, directly addressing the underlying pathophysiology by amplifying NPC1 protein levels. This differentiates MIPLYFFA from symptom-focused treatments by targeting the disease's root cause.

Particularly notable are the long-term efficacy results showing patients who switched from placebo to MIPLYFFA while on concomitant miglustat experienced a decline in annual disease progression. This suggests additive benefits when MIPLYFFA is combined with the current standard of care.

The pediatric substudy data in very young patients (6 to <24 months) is especially significant given the aggressive nature of early-onset NPC. The 36-month safety profile with no new safety signals in this vulnerable population expands MIPLYFFA's potential patient population.

The real-world data from the expanded access program further validates MIPLYFFA's effectiveness both as monotherapy and in combination with miglustat, confirming that the controlled trial benefits translate to clinical practice.

These multi-faceted data points collectively strengthen MIPLYFFA's clinical foundation as a disease-modifying therapy for NPC, potentially establishing it as a cornerstone treatment for this devastating rare disease.

New data from pre-specified analysis shows patients on concomitant miglustat who switched from placebo to MIPLYFFA experienced a decline in annual disease progression

Nomination for Best Poster Award received for poster highlighting MIPLYFFA’s differentiated mechanism of action targets underlying pathology of NPC

CELEBRATION, Fla., Sept. 04, 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 the presentation of several posters highlighting new positive data on MIPLYFFA^® (MY-PLY-FAH) (arimoclomol) for the treatment of Niemann-Pick disease type C (NPC) at the International Congress of Inborn Errors of Metabolism (ICIEM).

“The efficacy and safety of MIPLYFFA have been substantiated by the most extensive clinical dataset currently available for patients with NPC,” said Adrian Quartel, M.D., FFPM, Zevra’s Chief Medical Officer. “Our commitment to the NPC community drives our ongoing efforts to publish additional data demonstrating the impact of MIPLYFFA across a heterogeneous population of NPC patients, including new findings in patients under the age of two and in patients who transitioned to MIPLYFFA after previously receiving placebo in our pivotal double-blind trial. We are also pleased that our poster detailing the pathways by which MIPLYFFA targets the underlying pathophysiology of NPC has been nominated for the Best Poster Award by ICIEM.”

Data Highlights

In a poster (BP-19) titled “Arimoclomol upregulates expression of genes belonging to the coordinated lysosomal expression and regulation (CLEAR) network,” it was demonstrated that MIPLYFFA activates transcription factors leading to the amplification of NPC1 protein levels and more successful NPC1 processing; thereby addressing the underlying NPC etiology through multiple mechanistic pathways.

In a poster (P-264) titled “Efficacy results across a 12-month double-blind randomized trial and an open-label extension phase of arimoclomol for the treatment of Niemann-Pick disease type C in patients treated with miglustat,” data demonstrated that patients who switched from placebo in the double-blind phase to MIPLYFFA in the open-label extension phase, while on continued concomitant miglustat treatment, experienced a decline in annual disease progression.

In a poster (P-261) titled “Safety and efficacy of arimoclomol in a pediatric substudy of Niemann-Pick disease type C patients aged 6 to <24 months at study enrollment,” data evaluating five patients for up to 36 months of treatment showed that MIPLYFFA was well tolerated in children in this age group with no new safety signals observed.

In a poster (P-76) titled “Arimoclomol for the treatment of Niemann-Pick disease type C in a real-world setting: long-term outcomes from an expanded access program in the United States,” the effectiveness and safety of MIPLYFFA for the treatment of NPC, including with and without miglustat as a component of routine clinical care, were further confirmed and were consistent with the benefits demonstrated in the pivotal, double-blind, placebo-controlled Phase 3 study.

About MIPLYFFA^® (arimoclomol)

MIPLYFFA (arimoclomol) is Zevra’s approved therapy for the treatment of Niemann-Pick disease type C (NPC). Approved by the U.S. Food and Drug Administration on Sep. 20, 2024, MIPLYFFA (arimoclomol) increases the activation of the transcription factors EB (TFEB) and E3 (TFE3) resulting in the upregulation of coordinated lysosomal expression and regulation (CLEAR) genes. MIPLYFFA has also been shown to reduce unesterified cholesterol in the lysosomes of human NPC fibroblasts. The clinical significance of these findings is not fully understood. In the pivotal Phase 3 trial, MIPLYFFA halted disease progression compared to placebo over the one-year duration of the trial when measured by the only validated disease progression measurement tool, the NPC Clinical Severity Scale. MIPLYFFA has also received Orphan Medicinal Product designation by the European Medicines Agency (EMA) for the treatment of NPC. MIPLYFFA, used in conjunction with miglustat, is the only treatment shown to halt disease progression by addressing the underlying pathology of NPC with improvement seen at the first evaluation at week 12, and durable effect for more than 5 years. More than 270 NPC patients worldwide have been treated with MIPLYFFA, including in a pivotal Phase 2/3 clinical trial, Open-Label Extension (OLE) study, Expanded Access Programs (EAP) for up to 7 years, and a pediatric sub-study, which is the most expansive clinical development program in NPC to date. A Marketing Authorization Application for the evaluation of arimoclomol for the treatment of Niemann-Pick disease type C is under review by the European Medicines Agency. 

INDICATIONS AND USAGE

MIPLYFFA 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. 

IMPORTANT SAFETY INFORMATION 

Hypersensitivity Reactions:

Hypersensitivity reactions such as urticaria and angioedema have been reported in patients treated with MIPLYFFA during Trial 1: two patients reported both urticaria and angioedema (6%) and one patient (3%) experienced urticaria alone within the first two months of treatment. Discontinue MIPLYFFA in patients who develop severe hypersensitivity reactions. If a mild or moderate hypersensitivity reaction occurs, stop MIPLYFFA and treat promptly. Monitor the patient until signs and symptoms resolve.

Embryofetal Toxicity:

MIPLYFFA may cause embryofetal harm when administered during pregnancy based on findings from animal reproduction studies. Advise pregnant females of the potential risk to the fetus and consider pregnancy planning and prevention for females of reproductive potential. 

Increased Creatinine without Affecting Glomerular Function:

Across clinical trials of MIPLYFFA, mean increases in serum creatinine of 10% to 20% compared to baseline were reported. These increases occurred mostly in the first month of MIPLYFFA treatment and were not associated with changes in glomerular function.

During MIPLYFFA treatment, use alternative measures that are not based on creatinine to assess renal function. Increases in creatinine reversed upon MIPLYFFA discontinuation. 

The most common adverse reactions in Trial 1 (≥15%) in MIPLYFFA-treated patients who also received miglustat were upper respiratory tract infection, diarrhea, and decreased weight.
Three (6%) of the MIPLYFFA-treated patients had the following adverse reactions that led to withdrawal from Trial 1: increased serum creatinine (one patient), and progressive urticaria and angioedema (two patients). Serious adverse reactions reported in MIPLYFFA-treated patients were hypersensitivity reactions including urticaria and angioedema. 

To report SUSPECTED ADVERSE REACTIONS, contact Zevra Therapeutics, Inc. at toll-free phone 1-844-600-2237 or FDA at 1 800-FDA-1088 or www.fda.gov/medwatch.

Drug Interaction(s):

Arimoclomol is an inhibitor of the organic cationic transporter 2 (OCT2) transporter and may increase the exposure of drugs that are OCT2 substrates. When MIPLYFFA is used concomitantly with OCT2 substrates, monitor for adverse reactions and reduce the dosage of the OCT2 substrate.

Use in Females and Males of Reproductive Potential:

Based on animal findings, MIPLYFFA may impair fertility and may increase post-implantation loss and reduce maternal, placental, and fetal weights.

Renal Impairment:

The recommended dosage of MIPLYFFA, in combination with miglustat, in patients with an eGFR ≥15 mL/minute to <50 mL/minute is lower than the recommended dosage (less frequent dosing) in patients with normal renal function.

MIPLYFFA capsules for oral use are available in the following strengths: 47 mg, 62 mg, 93 mg, and 124 mg.

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.

Caution 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 promise and potential impact of our preclinical or clinical trial data; or the potential benefits of any of our products or product candidates for any specific disease or at any dosage. 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, 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. 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, 2024, filed on March 12, 2025, and Zevra’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, filed on August 12, 2025, and Zevra’s other filings with the SEC. 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

FAQ

What new data did Zevra Therapeutics (ZVRA) present for MIPLYFFA at ICIEM 2025?

Zevra presented data showing MIPLYFFA's ability to reduce disease progression in NPC patients on miglustat, demonstrated safety in young children, and confirmed real-world effectiveness consistent with Phase 3 results.

How does MIPLYFFA work in treating Niemann-Pick disease type C?

MIPLYFFA activates transcription factors that amplify NPC1 protein levels and improve NPC1 processing, addressing the underlying disease pathology through multiple mechanistic pathways.

Is MIPLYFFA safe for young children with Niemann-Pick disease type C?

Yes, data from a study of children aged 6 to 24 months showed MIPLYFFA was well-tolerated with no new safety signals over up to 36 months of treatment.

What were the real-world outcomes of MIPLYFFA in treating NPC?

Real-world data from the expanded access program confirmed MIPLYFFA's effectiveness and safety both with and without miglustat, consistent with the Phase 3 study results.

How effective is MIPLYFFA when combined with miglustat for NPC treatment?

Patients on concomitant miglustat who switched from placebo to MIPLYFFA experienced a decline in annual disease progression, demonstrating positive combination effects.