Orphazyme reports promising arimoclomol top-line clinical trial data

The Niemann-Pick disease Type C Phase II/III trial top-line results show a treatment benefit of arimoclomol over placebo; arimoclomol was well-tolerated in patients

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CopenhagenOrphazyme, a biopharmaceutical company dedicated to developing treatments for patients living with rare diseases, announced yesterday some encouraging top-line results for its clinical Phase II/III trial with orally administered arimoclomol for the treatment of patients with Niemann-Pick disease Type C (NPC).
NPC is a genetic, progressively debilitating and often fatal neurovisceral disease. It belongs to a family know 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 build-up in tissues and organs, including the brain, and drive the disease pathology. The estimated prevalence of NPC in the U.S. and Europe combined is 1,000-2,000. There are currently no approved treatments for NPC in the U.S., and only one approved product in Europe.
Arimoclomol amplifies the production of heat-shock proteins (HSPs), which can rescue defective misfolded proteins, clear protein aggregates, and improve the function of lysosomes. Arimoclomol is administered orally, crosses the blood brain barrier, and has been studied in seven Phase I and three Phase II trials. Arimoclomol has been granted Orphan Drug designation (EU and U.S.), Rare Pediatric Disease designation (U.S.), and Fast Track designation (U.S.) for the treatment of NPC.
This trial was a multi-center prospective double-blinded, placebo-controlled interventional study with a 12-month duration. In total, 50 patients were enrolled in the EU and U.S. The purpose of the trial was to assess the efficacy and safety of arimoclomol, compared to placebo in the treatment of NPC, administered in addition to the patient’s standard-of-care. The primary endpoints, 5-domain NPC-CSS and Clinical Global Impression of Improvement (CGI-I), evaluated the treatment difference between the arimoclomol-treated group and the placebo group after 12 months of treatment.
“We observed compelling, clinically-relevant trends in favor of arimoclomol in this first trial in NPC. I am encouraged by the 74% reduction in disease progression on the 5-domain NPC-CSS. This is further corroborated by a similar effect on the full scale. Assessing the effect in patients 4 years of age and older (44 out of 50 patients), the effect becomes even more pronounced, with a p-value of 0.027,” mentioned Thomas Blaettler, Chief Medical Officer of Orphazyme.
Overall, baseline characteristics were well balanced across treatment arms. Arimoclomol was well-tolerated by patients. The overall incidence of adverse events (AEs) was similar for arimoclomol (85.7%) and placebo (81.3%). Serious AEs occurred less frequently in the arimoclomol group (14.3%) compared to placebo (37.5%). The top-line data demonstrated a 74% reduction in progression on the primary endpoint, corroborated by consistent benefit across sub-populations. Placebo progression rates on the CGI-I were lower than expected, impeding the ability to show a positive effect.
The full data set, including biomarker data, will become available and be analyzed in Q4 2018. 24-month data will become available from the ongoing open-label extension trial in Q2 2019. Orphazyme plans to engage with the US Food and Drug Administration and the European Medicines Agency to determine the best path towards making arimoclomol available to those suffering from NPC.
Anders Hinsby, Chief Executive Officer of Orphazyme said, “We are highly encouraged that the top-line data show a strong positive trend on the 5-domain NPC-CSS. We now look forward to receiving the full analysis of data. In addition, the open-label extension trial will provide data on the clinical benefit of arimoclomol over a longer period of time. We are determined to make arimoclomol available to patients as quickly as possible. We are grateful for the strong support we have received from the patient community, the expert physicians, and especially the participants and their families.”

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