Benzinga | Aug 23, 2021 05:07AM EDT

Orphazyme Announces Publication of Results From Its Phase 2/3 Trial of Arimoclomol in Niemann-pick Disease Type C in the Journal of Inherited Metabolic Disease; Trial Demonstrated a Statistically Significant and Clinically Meaningful Treatment Effect of Arimoclomol in NPC

Orphazyme A/S (ORPHA.CO; ORPH), a late-stage biopharmaceutical company, today announced that results from a Phase 2/3 trial of arimoclomol, an investigational heat-shock protein amplifier, in Niemann-Pick disease type C (NPC) have been published in the peer-reviewed Journal of Inherited Metabolic Disease (JIMD). The online publication is available here.

"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 Thomas Blaettler, Chief Medical Officer at Orphazyme. The Phase 2/3 trial (NPC-002; ClinicalTrials.gov identifier: NCT02612129), was a prospective, randomized, double-blind, placebo-controlled study. Fifty patients aged 218 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%).

Christophe Bourdon, Chief Executive Officer at Orphazyme added, "We are committed to serving the NPC community and are working expeditiously to deliver this potential new medicine to patients. Arimoclomol is under regulatory review in Europe, with an anticipated CHMP opinion in Q4 2021, and we continue to evaluate the path forward in the U.S. following the recent FDA response."

References:1. Mengel E, Bembi B, Del Toro M, et al (2020) Clinical disease progression and biomarkers in NiemannPick disease type C: a prospective cohort study. Orphanet J Rare Dis 15: 328.2. Patterson MC, Lloyd-Price L, Guldberg C, et al (2021) Validation of the 5-domain Niemann-Pick type C Clinical Severity Scale. Orphanet J Rare Dis 16: 79.3. 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.