Investor news
No. 07/2021
Company Registration No. 32266355
- Arimoclomol was well-tolerated with a statistically significant and clinically meaningful effect on disease progression
“We are pleased to share the data from our Phase 2/3 trial in JIMD. NPC is a rare, inherited progressive neurodegenerative disorder with a high unmet medical need for disease-modifying treatment options. This trial demonstrated a statistically significant and clinically meaningful treatment effect of arimoclomol in NPC supported by significant and consistent effects across several disease- and pharmacodynamic biomarkers. We believe these data establish the potential of arimoclomol as an efficacious and well-tolerated disease-modifying treatment for NPC” said
The Phase 2/3 trial (NPC-002; ClinicalTrials.gov identifier: NCT02612129), was a prospective, randomized, double-blind, placebo-controlled study. Fifty patients aged 2–18 years were randomized 2:1 to arimoclomol:placebo, stratified by miglustat use. Routine clinical care was maintained. Arimoclomol was administered orally three times daily. The primary endpoint was change in 5-domain NPC Clinical Severity Scale (NPCCSS) score from baseline to 12 months, as described by Mengel et al.1 and Patterson et al.2. The 5-domain NPCCSS comprises the domains determined to be most clinically relevant to patients, caregivers, and clinicians: ambulation, cognition, fine motor skills, speech, and swallowing (Cortina-Borja et al.3). A recent validation of the 5-domain NPCCSS shows that a change of 1 point or greater on the total score constitutes a clinically meaningful change for caregivers/patients and physicians (Patterson et al2).
At 12-months, a significant treatment effect in favor of arimoclomol of −1.40 points (95% CI: −2.76, −0.03; p = 0.046) was observed, corresponding to a 65% relative reduction in annual disease progression. In the prespecified subgroup of patients receiving miglustat as routine care, arimoclomol resulted in stabilization of disease severity with a treatment difference of −2.06 in favor of arimoclomol (p = 0.006). In the pre-specified subgroup of patients ≥4 years of age the mean treatment difference was −1.80 in favor of arimoclomol (p=0.016), corresponding to 82% relative reduction in annual disease progression.
Arimoclomol was well-tolerated, with adverse events occurring in 88.2% of patients receiving arimoclomol and 75.0% of patients receiving placebo. Fewer patients had serious adverse events with arimoclomol (14.7%) versus placebo (31.3%).
References:
1. Mengel E, Bembi B, Del Toro M, et al (2020) Clinical disease progression and biomarkers in Niemann–Pick disease type C: a prospective cohort study. Orphanet J Rare Dis 15: 328.
2. Patterson MC,
3. Cortina-Borja M, Vruchte D, Mengel E, et al (2018) Annual severity increment score as a tool for stratifying patients with Niemann-Pick disease type C and for recruitment to clinical trials. Orphanet J Rare Dis 13: 143. doi:110.1186/s13023-13018-10880-13029.
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About Niemann-Pick disease type C
Niemann-Pick disease type C (NPC) is a rare, genetic, progressively debilitating, and often fatal neurodegenerative disease. It belongs to a family known as lysosomal storage diseases and is caused by mutations leading to defective NPC protein. As a consequence, lipids that are normally cleared by the lysosome accumulate in tissues and organs, including the brain, and drive the disease pathology. We estimate the incidence of NPC to be one in 100,000 live births and the number of NPC patients in
About arimoclomol
Arimoclomol is an investigational drug candidate that amplifies the production of heat shock proteins (HSPs). HSPs can rescue defective misfolded proteins, clear protein aggregates, and improve the function of lysosomes. Arimoclomol is administered orally, and has now been studied in 10 Phase 1, four Phase 2, and three pivotal Phase 2/3 trials. Arimoclomol has received Orphan Drug Designation (ODD) for NPC in the US and EU. Arimoclomol has received Fast-Track Designation (FTD), Breakthrough Therapy Designation (BTD), and Rare Pediatric Disease Designation (RPDD) from the
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Attachment
- 07-2021
Orphazyme announces publication of results from its Ph 2-3 trial of ari in NPC in JIMD
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