Meplyffa

Refused

This medicine has been refused authorisation

arimoclomol

Overview

After re-examining its initial opinion, the European Medicines Agency has confirmed its recommendation to refuse marketing authorisation for the medicine Meplyffa. The medicine was intended for the treatment of Niemann-Pick disease type C.

The Agency issued its opinion after re-examination on 12 November 2026. The Agency had issued its initial opinion on 23 July 2026. The company that applied for authorisation of Meplyffa is Zevra Denmark A/S.

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Note: A previous application for this medicine (under the name Miplyffa) was withdrawn in March 2022.

What is Meplyffa and what was it intended to be used for?

Meplyffa was intended to be used together with miglustat, another medicine to treat symptoms of Niemann-Pick disease type C, in patients aged two years and older with the condition. Niemann-Pick disease type C is a progressive genetic disease that affects the body’s ability to transport fats inside cells. Over time, these fats build up in cells of the brain and other organs, causing the cells to stop working properly and eventually die. This leads to symptoms such as problems with balance, movement and swallowing, as well as behavioural problems and learning disabilities.

Meplyffa contains the active substance arimoclomol and was to be available as capsules to be taken by mouth.

Meplyffa was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 19 November 2014 for Niemann-Pick disease type C. Further information on the orphan designation can be found on the Agency’s website: ema.europa.eu/en/medicines/human/orphan-designations/eu-3-14-1376.

How does Meplyffa work?

Niemann-Pick disease type C is caused by mutations (changes) in genes that provide instructions for making proteins called NPC1 and NPC2. These proteins are normally involved in transporting fats within the cell. In people with Niemann-Pick disease type C, NPC1 or NPC2 do not function properly, leading to a harmful build-up of fat in cells. 

The active substance in Meplyffa, arimoclomol, increases the activation of proteins in the cell called TFEB and TFE3. These proteins stimulate the production of functioning NPC proteins, as well as other proteins that help cells clear fats. This is expected to prevent the build-up of fats in organs such as the brain and help reduce the symptoms of the disease.

What did the company present to support its application?

The company provided results of a main study that looked at the effectiveness of Meplyffa at slowing the progression of Niemann-Pick disease type C over time. The study involved 50 children and adolescents aged from 2 to 18 years who received either Meplyffa or placebo (a dummy treatment) for 1 year in addition to the standard care they were already receiving, which included miglustat in most cases. The main measure of effectiveness was a change in the disease severity score measured using a scale called the 5-domain NPCCSS. This scale rates disease severity based on a person’s ambulation (walking ability), swallowing ability, cognition (intellectual function), speech and fine motor (movement of hands and fingers) skills. 

What were the main reasons for refusing the marketing authorisation?

At the time of the initial evaluation, there were concerns about how the data had been handled and the results analysed, which led to uncertainties about the reliability and robustness of the results. Moreover, no benefit was seen in terms of ambulation and cognition. Although data for the subgroup of patients who were also taking miglustat showed a treatment effect favouring Meplyffa, this finding was not considered robust since effectiveness had not been demonstrated in the overall population. 

Therefore, the Agency’s opinion was that the benefits of Meplyffa were not sufficient to establish a positive benefit-risk balance of the medicine in the treatment of Niemann-Pick disease type C, and it recommended refusing marketing authorisation.

During the re-examination, the Agency re-assessed the available data and consulted experts in the field of Niemann-Pick disease type C, including patient representatives. The Agency also considered an intervention from a patient organisation providing insights from people living with Niemann-Pick disease type C and their carers on treatments for this condition. While recognising the unmet medical need in Niemann-Pick disease type C, the Agency considered that its concerns were not resolved after re‑examination and therefore confirmed the initial refusal.

Does this refusal affect patients in clinical trials or compassionate use programmes?

The company informed the Agency that it plans to continue with its ongoing compassionate use programmes pending discussions with national authorities that have granted approval for compassionate use.

If you are in a clinical trial or compassionate use programme and need more information about your treatment, speak with your doctor.

Questions and answer on the refusal of the marketing authorisation for Meplyffa (arimoclomol)

Adopted Reference Number: EMA/251490/2026

Product details

• Name of medicine:
  Meplyffa
• Active substance:
  arimoclomol citrate
• International non-proprietary name (INN) or common name:
  arimoclomol
• Therapeutic area (MeSH):
  Niemann-Pick Diseases
• Anatomical therapeutic chemical (ATC) code:
  N07XX17

Pharmacotherapeutic group

Other nervous system drugs

Application details

• EMA product number:
  EMEA/H/C/006736
• Orphan:

  This medicine was designated an orphan medicine. This means that it was developed for use against a rare, life-threatening or chronically debilitating condition or, for economic reasons, it would be unlikely to have been developed without incentives. For more information, see Orphan designation.

• Marketing authorisation applicant:
  Zevra Denmark A/S
• Opinion adopted:
  23/07/2026
• Opinion status:
  Negative