Arimoclomol

The mechanism(s) by which arimoclomol exerts its clinical effects in patients with NPC is unknown.

• 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. 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.

• None. None.contraindicated

Recommended MIPLYFFA oral dosage, in combination with miglustat, for patients with actual body weight of ( 2.1 ): 8 kg to 15 kg, is 47 mg three times a day > 15 kg to 30 kg, is 62 mg three times a day > 30 kg to 55 kg, is 93 mg three times a day > 55 kg, is 124 mg three times a day Administer with or without food. ( 2.1 ) See full prescribing information for recommended dosage in patients with an eGFR ≥ 15 to < 50 mL/minute. ( 2.2 ) See full prescribing information for instructions on preparation and administration. ( 2.3 ) 2.1 Recommended Dosage The recommended oral dosage of MIPLYFFA, in combination with miglustat, for patients with an actual body weight of: 8 kg to 15 kg, is 47 mg three times a day > 15 kg to 30 kg, is 62 mg three times a day > 30 kg to 55 kg, is 93 mg three times a day > 55 kg, is 124 mg three times a day Administer MIPLYFFA with or without food. Missed Dose If a dose of MIPLYFFA is missed, advise the patient to skip the missed dose and to resume taking the prescribed dose at the next scheduled time. 2.2 Recommended Dosage in Patients with Renal Impairment The recommended dosage of MIPLYFFA, in combination with miglustat, in patients with an eGFR ≥ 50 mL/minute is the same as the recommended dosage in patients with normal renal function [see Dosage and Administration ( 2.1 )].

Hypersensitivity Reactions : Urticaria and angioedema have been reported. Discontinue MIPLYFFA in patients who develop these adverse reactions. ( 5.1 ) Embryofetal Toxicity : May cause fetal harm. Advise pregnant females of the potential risk to the fetus and consider pregnancy planning and prevention. ( 5.2 ) Increased Creatinine without Affecting Glomerular Function: Mean increases in serum creatinine of 10-20% have been reported. Use alternative measures to assess renal function which are not based on creatinine. ( 5.3 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions such as urticaria and angioedema have been reported in patients treated with MIPLYFFA during Trial 1 [see Clinical Studies ( 14 )] : two patients reported both urticaria and angioedema (6%) and one patient (3%) experienced urticaria alone. The reactions occurred 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 [see Adverse Reactions ( 6.1 )]. 5.2 Embryofetal Toxicity Based on findings from animal reproduction studies, MIPLYFFA may cause embryofetal harm when administered during pregnancy. In animal reproduction studies, oral administration of arimoclomol to pregnant rats and rabbits resulted in post-implantation loss and structural abnormalities in offspring.

The following clinically significant adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions [see Warning and Precautions ( 5.1 )]. Increased Creatinine without Affecting Glomerular Function [see Warnings and Precautions ( 5.3 )]. Most common adverse reactions (≥15%) are: Upper respiratory tract infection, diarrhea, and decreased weight. ( 6.1 ) 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 . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of MIPLYFFA was evaluated in a randomized, double-blind, placebo-controlled, 12-month trial (Trial 1), which included 50 patients 2 to 19 years old with NPC [see Clinical Studies ( 14 )] . Patients received weight-adjusted doses of MIPLYFFA (31 to 124 mg orally three times daily); 28 of the patients were exposed to MIPLYFFA for one year. In Trial 1, 78% of patients received miglustat. Forty-one out of 50 patients that were enrolled in Trial 1 continued into an open-label extension trial, which included 39 patients treated with MIPLYFFA for more than 1 year, 34 patients treated with MIPLYFFA for more than 2 years, and 17 patients treated with MIPLYFFA for more than 5 years.

Females and Males of Reproductive Potential: Based on animal findings, MIPLYFFA may impair fertility. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, MIPLYFFA may cause embryofetal harm when administered during pregnancy. There are no available data on MIPLYFFA use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise pregnant females of the potential risk to the fetus. In animal reproduction studies, oral administration of arimoclomol to pregnant rats and rabbits during organogenesis resulted in post-implantation loss and structural abnormalities in offspring. These occurred at exposures equal to or greater than 10- and 5-fold, in rats and rabbits respectively, the human exposure at the maximum recommended human daily dose of 372 mg ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

Arimoclomol exhibited linear and dose proportional pharmacokinetics following oral administration of doses ranging from 62 to 372 mg (three times the maximum recommended dosage) three times a day in healthy subjects. The plasma C max and AUC 0-8hr of arimoclomol at the 248 mg dose (two times the maximum recommended dosage) are summarized in Table 2 .

• Sep 20, 2024NDANDA214927Zevra Denmark

1. 1Diarrhoea512%
2. 2Product Size Issue49.8%
3. 3Vomiting49.8%
4. 4Insomnia37.3%
5. 5Death24.9%
6. 6Fall24.9%
7. 7Fatigue24.9%
8. 8Gait Disturbance24.9%
9. 9Pneumonia24.9%
10. 10Pneumonia Aspiration24.9%
11. 11Product Administration Interrupted24.9%
12. 12Product Distribution Issue24.9%
13. 13Product Use Complaint24.9%
14. 14Seizure24.9%
15. 15Sepsis24.9%

The 10 most recently updated of 12 ClinicalTrials.gov registrations naming Arimoclomol as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Arimoclomol Prospective Study in Participants Diagnosed With Niemann-Pick Disease Type C
  Completed · Phase 2 · Phase 3 · Interventional · 50 enrolled · ZevraDenmark
  NCT02612129updated 2024-11-29
• Early Access Program With Arimoclomol in US Patients With NPC
  Available · Expanded access · ZevraDenmark
  NCT04316637updated 2024-08-16
• Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial
  Terminated · Phase 3 · Interventional · 121 enrolled · ZevraDenmark
  NCT04049097updated 2023-09-15
• Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
  Terminated · Phase 3 · Interventional · 120 enrolled · ZevraDenmark
  NCT03836716updated 2023-08-24
• Arimoclomol in Amyotropic Lateral Sclerosis
  Completed · Phase 3 · Interventional · 245 enrolled · ZevraDenmark
  NCT03491462updated 2023-08-24
• Study of Arimoclomol in Inclusion Body Myositis (IBM)
  Completed · Phase 2 · Interventional · 152 enrolled · ZevraDenmark
  NCT02753530updated 2023-05-10
• Study of Arimoclomol in Patients Diagnosed With Gaucher Disease Type 1 or 3
  Terminated · Phase 2 · Interventional · 39 enrolled · ZevraDenmark
  NCT03746587updated 2023-01-11
• Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis
  Completed · Phase 2 · Phase 3 · Interventional · 38 enrolled · University of Miami
  NCT00706147updated 2019-01-11
• A Prospective Non-therapeutic Study in Patients Diagnosed With Niemann-Pick Disease Type C
  Completed · Observational · 35 enrolled · ZevraDenmark
  NCT02435030updated 2017-05-18
• Arimoclomol in Sporadic Inclusion Body Myositis
  Completed · Phase 2 · Phase 3 · Interventional · 24 enrolled · Richard Barohn, MD
  NCT00769860updated 2017-01-19

Frequently asked questions

How does Arimoclomol work?

The mechanism(s) by which arimoclomol exerts its clinical effects in patients with NPC is unknown.

What is Arimoclomol used for?

According to FDA labeling, Arimoclomol carries indications including: 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. 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Arimoclomol?

Arimoclomol is classified as Other nervous system drugs, Organic Cation Transporter 2 Inhibitors, Transcription Factor Activity.

What are the brand names for Arimoclomol?

Arimoclomol is marketed under brand names including Miplyffa.

What are the contraindications for Arimoclomol?

Arimoclomol labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.