Zevra Therapeutics Announces Open Label Extension Data Showing Sustained Long-Term Efficacy of MIPLYFFA for the Treatment of NPC Published in the Journal of Molecular Genetics and Metabolism

CELEBRATION, Fla., July 16, 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, announced the publication of “Long-term Efficacy and Safety of Arimoclomol in Niemann-Pick Disease Type C: Final Results of the Phase 2/3 NPC-002 48-month Open-label Extension Trial” in the peer-reviewed journal, Molecular Genetics and Metabolism (). MIPLYFFA^® (arimoclomol) is an approved treatment for Niemann-Pick disease type C (NPC), a neurodegenerative disease caused by lysosomal dysfunction.

“NPC is a debilitating and ultimately fatal disease,” said Adrian Quartel, M.D., FFPM, Zevra’s Chief Medical Officer. “With MIPLYFFA, we have demonstrated its ability to halt disease progression through twelve months in our pivotal, double-blind, randomized, placebo-controlled study. For those patients who are continuing to receive treatment through the open-label extension study, we have also shown that MIPLYFFA’s clinically-meaningful impact on disease progression is sustained over multiple years, with safety and efficacy data extending through five years in more than 270 patients worldwide, and in some patients as long as seven years on treatment. This impact on disease progression represents a critical advancement in care for people living with NPC, and we are humbled by the opportunity to support this community.”

This paper presents long-term efficacy and safety outcomes for NPC patients treated with MIPLYFFA in the 48-month open-label extension (OLE) phase following the end of the 12-month, pivotal, placebo-controlled, double-blind, Phase 2/3 trial. Efficacy was calculated using the 5- and rescored 4-domain NPC Clinical Severity Scale, the only validated measurement of NPC progression. The data from the OLE phase showed a sustained reduction in disease progression for at least 5 years in a heterogeneous population of NPC patients receiving MIPLYFFA in addition to routine clinical care, with no new safety concerns. These results align with the pivotal Phase 2/3 trial, which showed that MIPLYFFA halted disease progression compared to placebo over the one-year duration.

About MIPLYFFA^® (arimoclomol)

MIPLYFFA (arimoclomol) is Zevra’s approved therapy for use in combination with miglustat 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.

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 /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 rare disease company combining science, data, and patient needs to create transformational therapies for 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 or follow us on and .

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 promise and potential impact of our preclinical or clinical trial data; or the potential benefits of any of our products for any specific disease. 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 March 31, 2025, filed on May 13, 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

This press release was published by a CLEAR® Verified individual.