dm+d

Unassigned

New Medicines

Niemann-Pick disease, type C (NPC) in patients aged 2 years and older - first-line

Information

New molecular entity
Orphazyme
Orphazyme

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Not recommended for approval (Negative opinion)
Yes
Oct 21Orphazyme announced that it conducted a type A meeting with the US FDA, in which the US FDA recommended to submit additional data, information, and analyses to address certain topics in the Complete Response Letter (CRL) and engage in further interactions with the FDA to identify a pathway to resubmission [13]
Oct 21Orphazyme expects to receive an opinion on European regulatory approval from the Committee for Medicinal Products for Human Use (CHMP) for arimoclomol for Niemann-Pick disease type C, in Q1 2022 [13]
Jun 21FDA have issued a complete response letter requesting additional data on the benefits and risks of the heat shock protein amplifier before filing is progressed. Orphazyme is still hoping EU approval Q1 22 [11].
May 21Orphazyme expects to receive an opinion on European regulatory approval from the Committee for Medicinal Products for Human Use (CHMP) for arimoclomol for Niemann-Pick disease type C, in late 2021 [10]
Nov 20Orphazyme has submitted a Marketing Authorisation Application to the EMA for arimoclomol for the treatment of Niemann-Pick disease Type C [9].
Sep 20Filed in US with a priority review date of March 17, 2021. It was reported that the FDA felt that for a degenerative disease with no approved treatments it was “close enough” for a submission and a Priority Review. [8]
Jan 20EU MAA now expected 2H 2020, following FDA submission in 1H 2020 [7].
Jun 19Following discussions with the EMA and FDA, Orphazyme now expects to submit filings during the first half of 2020, with potential approval in the second half of 2020 and commercialisation starting in 2021 [5].
Dec 17If clinical trial results are favourable, the company expects to file in the EU and US during 2H 2019 with approval potentially 1H 2020 [4].
Nov 14Orphan designation (EU/3/14/1376) granted by the European Commission to Orphazyme ApS, Denmark, for arimoclomol citrate for the treatment of Niemann-Pick disease, type C [1].

Category

A hydroxylamine derivative thought to repair or induce destruction of misfolded proteins by amplifying molecular chaperone proteins and upregulating the cellular stress response.
Niemann-Pick disease, type C affects approximately 0.1 in 10,000 people in the European Union [1]
Niemann-Pick disease, type C (NPC) in patients aged 2 years and older - first-line
Oral

Further information

Yes

Trial or other data

Aug 21Orphazyme report positive data from PII/III NPC-002 trial (n=50). Arimoclomol improved Niemann-Pick type C Clinical Severity Scale score by 1.40 more points than placebo at 12 months (p=0.046), corresponding to a 65% relative reduction in annual disease progression [12].
Jan 20Data from the open-label extension phase of the PII/III trial demonstrate continued benefit over two years, according to a company media release. Neither the initial nor the extension-phase results have yet been published in full, however [7].
Sep 18Orphazyme announces ´promising´ results from the PII/III trial that did not reach statistical significance, stating that the top-line results show a treatment benefit of arimoclomol over placebo on the primary endpoint 5-domain NPC Clinical Severity Scale (NPC-CSS) (p-value 0.07). The company intends to analyse the data further, and indicated that progression in the placebo group was lower than expected [6].
Jan 17PII/III (NCT02612129) study is still recruiting. Collection of primary outcome data (Change in NPC disease severity score) is expected to complete Dec 17 [3].
Jun 16Orphazyme initiates a PII/III trial to assess the efficacy and safety of arimoclomol (150 - 600 mg/day) as an add-on therapy to the current prescribed best-standard-of-care, which may, or may not, include miglustat, in patients with Niemann-Pick disease type C (NP-C) (CT-ORZY-NPC-002; NCT02612129). The randomised, double-blind, placebo-controlled, parallel trial will enrol approximately 46 patients (aged 2 to 18 years). Enrolment is underway in Denmark and is expected to expand to the UK, France, Germany, Spain, Italy, Poland and Switzerland [2].

Evidence based evaluations

Amyotrophic lateral sclerosis (motor neurone disease)

Information

Licence extension / variation
Orphazyme
Orphazyme

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Yes
Yes
Aug 21Development discontinued [13].

Category

Molecular chaperone modulator
The incidence of ALS ranges from 1.8-2.2 per 100,000 population, with a prevalence of between 4.0-4.7 per 100,000 population in the UK. It is a form of motor neurone disease.
Amyotrophic lateral sclerosis (motor neurone disease)
Oral

Trial or other data

May 21PIII trial ORARIALS-01 of arimoclomol in amyotrophic lateral sclerosis (ALS) did not meet its primary and secondary endpoints to show benefit in people living with ALS [14].

Sporadic inclusion body myositis (sIBM) in adults aged 45 years and older

Information

Licence extension / variation
Orphazyme
Orphazyme

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Yes
Yes
Aug 21Development discontinued [9].

Category

A hydroxylamine derivative thought to repair or induce destruction of misfolded proteins by amplifying molecular chaperone proteins and upregulating the cellular stress response.
Inclusion body myositis (IBM) is a slowly progressive degenerative inflammatory disorder of skeletal muscles characterised by late onset weakness of specific muscles and distinctive histopathological features. IBM has a highly variable prevalence according to geographic, ethnic and age criteria. Prevalence in the general population ranges from 1:1,000,000 to 1:14,000 but a three-fold increase is observed when considering only a population over 50 years. No causal gene has been identified [1].
Sporadic inclusion body myositis (sIBM) in adults aged 45 years and older
Oral

Trial or other data

Mar 21Company announces that arimoclomol failed to hit both its primary and secondary endpoints. Further data from the trial to be released by June 2021 [6]