| Drug Name |
MIPLYFFA™ (arimoclomol) |
| Active Ingredient |
arimoclomol |
| Date of Approval |
September 20, 2024 |
| Manufacturer |
Zevra Therapeutics, Inc. |
| Approval Pathways and Indications |
Approval Pathway: NDA
Indication: 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. |
| Therapeutic Class |
Niemann-Pick disease type C Agent |
| Formulation |
Capsules: 47 mg, 62 mg, 93 mg and 124 mg of arimoclomol |
| MoA |
The mechanism by which arimoclomol exerts its clinical effects in patients with NPC is unknown |
| Dosing and Administration |
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
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.
For patients with an eGFR ≥ 15 to < 50 mL/minute, 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 two times a day
- > 15 kg to 30 kg, is 62 mg two times a day
- > 30 kg to 55 kg, is 93 mg two times a day
- > 55 kg, is 124 mg two times a day
MIPLYFFA™ should be taken with or without food. 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. |
| Administered by self or by HCP |
Administered by Self |
| Place in Therapy |
Niemann-Pick disease type C (NPC) is an ultra-rare, relentlessly progressive, degenerative, and fatal disease affecting an estimated 900 children and adults in the U.S., with approximately one-third being formally diagnosed. Those living with NPC experience progressive physical and cognitive limitations, with key neurological impairments present in speech, cognition, swallowing, ambulation, and fine motor skills. Effective management of NPC requires multiple treatment options due to the complexity of the disease. Based on data of MIPLYFFA™ with miglustat, MIPLYFFA™ became the first approved therapy in the U.S. for NPC. .
The most common adverse reactions (≥15%) are upper respiratory tract infection, diarrhea, and decreased weight. Therapy should be discontinued in patients who develop urticaria and angioedema. Female patients should consider pregnancy planning and prevention, as this medication can cause fetal harm. |
| Expected Market Launch Date |
Zevra will immediately initiate its launch activities for MIPLYFFA™, which is expected to be commercially available in the U.S. in eight to 12 weeks. |
| New Molecular Entity (NME) or Existing Formulation |
New Molecular Entity |
| Expected Cost |
$40,000 and $106,000 per month depending on dosage; At the highest dose the annual price comes to about $1.3 million |
| Product Discontinuation |
N/A |
| Clinical Trials |
Safety and effectiveness of MIPLYFFA™ were assessed in Trial 1, a randomized, double-blind, placebo controlled, 12-month trial in patients 2 to 19 years of age who had a molecularly confirmed diagnosis of NPC (NCT02612129). Fifty patients were randomized 2:1 to treatment with weight-adjusted MIPLYFFA™ (31 to 124 mg) or placebo orally three times per day. The randomization was stratified by miglustat-use status at baseline, with 76% and 81% of patients in the MIPLYFFA and placebo groups, respectively, receiving miglustat six months or longer prior to the time of enrollment. Efficacy was assessed using the rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS), which measures ambulation, speech, swallowing, and fine motor skills. Results showed that MIPLYFFA™ slowed disease progression, with a decrease of 0.2 points on the R4DNPCCSS compared to a progression of 1.9 points for those on miglustat alone. The approval of MIPLYFFA™ was supported by this trial's data, FDA-preferred analyses, and additional confirmatory evidence from a 48-month open-label extension study, indicating improved outcomes compared to a matched NPC natural history cohort. |
| Sources |
U.S. Food and Drug Administration. Miplyffa (arimoclomol) prescribing information. Accessed September 23, 2024. Available at: https://www.accessdata.fda.gov/drugsatfda
_docs/label/2024/214927s000lbl.pdf
Drugs.com. Miplyffa history. Accessed September 23, 2024. Available at: https://www.drugs.com/history/miplyffa.html
Drugs.com. FDA approves Miplyffa (arimoclomol) for Niemann-Pick type C. Accessed September 23, 2024. Available at: https://www.drugs.com/
newdrugs/fda-approves-miplyffa-arimoclomol
-niemann-pick-type-c-6370.html
U.S. Food and Drug Administration. FDA approves first treatment for Niemann-Pick disease type C. Accessed September 23, 2024. Available at: https://www.fda.gov/news-events/press-announcements/
fda-approves-first-treatment-niemann-pick-disease-type-c
Reuters. Zevra Therapeutics prices rare genetic disorder drug at up to $106,000 per month. Accessed September 23, 2024. Available at: https://www.reuters.com/business/healthcare-pharmaceuticals/
zevra-therapeutics-prices-rare-genetic-disorder-drug-up-
106000-per-month-2024-09-23/ |