Orphazyme announces the publication of its Phase results

Orphazyme A / S
Investor News

N ° 07/2021
Company registration number 32266355

  • Arimoclomol was finetolerated with a statistically significant and clinically significant effect on disease progression

Copenhagen – August 23, 2021 – Orphazyme A / S (ORPHA.CO; ORPH), an advanced stage biopharmaceutical company, today announced the results of a phase 2/3 trial of arimoclomol, an experimental heat shock protein enhancer, in Niemann-Pick disease type C (NPC) have been published in the peer-reviewed journal Journal of Inherited Metabolic Diseases (JIMD). The online publication is available here.

We are happy to share data from our Phase 2/3 trial in JIMD. NPC is a rare inherited progressive neurodegenerative disease with a high unmet medical need for disease-modifying treatment options. This trial demonstrated a statistically and clinically significant therapeutic effect of arimoclomol in NPC, supported by significant and consistent effects on several disease biomarkers and pharmacodynamics. We believe these data establish the potential of arimoclomol as an effective agent and a well-tolerated disease-modifying therapy for NPCSaid Thomas Blaettler, medical director of Orphazyme.

The Phase 2/3 trial (NPC-002; ClinicalTrials.gov ID: NCT02612129) was a prospective, randomized, double-blind, placebo-controlled study. Fifty patients aged 2 to 18 years were randomized 2: 1 to receive arimoclomol: placebo, stratified by miglustat use. Routine clinical care was maintained. Arimoclomol was administered orally three times a day. The primary endpoint was the change in the 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 includes the domains deemed to be the most clinically relevant for patients, caregivers, and clinicians: gait, 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 more in the total score constitutes a clinically significant change for caregivers / patients and physicians (Patterson et al.2).

At 12 months, a significant therapeutic effect in favor of arimoclomol of -1.40 points (95% CI: -2.76, -0.03; p = 0.046) was observed, corresponding to a relative reduction of 65% of the annual progression of the disease. In the predefined 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 predefined subgroup of patients ≥ 4 years of age, the mean difference in treatment was -1.80 in favor of arimoclomol (p = 0.016), corresponding to an 82% relative reduction in the annual progression of disease.

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%) compared to placebo (31.3%).

Christophe Bourdon, CEO of Orphazyme added: “We are committed to serving the NPC community and are working quickly to bring this potential new drug to patients. Arimoclomol is under regulatory review in Europe, with a CHMP opinion expected in Q4 2021, and we continue to assess the way forward in the US following the recent FDA response.

The references:
1. Mengel E, Bembi B, Del Toro M, et al (2020) Clinical disease progression and biomarkers in Niemann-Pick type C disease: 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 increase score as a tool for stratifying patients with Niemann-Pick type C disease and for recruitment into clinical trials. Orphanet J Rare Dis 13: 143. doi: 110.1186 / s13023-13018-10880-13029.

For more information, please contact

Orphazyme A / S

Anders Vadsholt, CFO +45 28 98 90 55

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 overload diseases and is caused by mutations leading to a defective NPC protein. As a result, the lipids that are normally eliminated by the lysosome accumulate in tissues and organs, including the brain, and lead to the pathology of the disease. We estimate the incidence of NPC at one live birth in 100,000 and the number of NPC patients in the United States and Europe at approximately 1,800 people. There are no approved treatments for NPC in the United States

About arimoclomol
Arimoclomol is an investigational drug candidate that enhances the production of heat shock proteins (HSPs). HSPs can rescue defective misfolded proteins, remove protein aggregates, and improve lysosome function. Arimoclomol is administered orally and has now been studied in 10 phase 1 trials, four phase 2 trials and three pivotal phase 2/3 trials. Arimoclomol has received Orphan Drug Designation (ODD) for NPC in the US and EU. Arimoclomol has received the Fast-Track Designation (FTD), Breakthrough Therapy Designation (BTD), and Rare Pediatric Disease Designation (RPDD) from the United States Food and Drug Administration (FDA) for NPC. On June 17, 2021, Orphazyme received a full response letter from the FDA regarding its new drug application for arimoclomol for the treatment of NPC. A Marketing Authorization Application (MAA) for arimoclomol in NPC has been filed with the European Medicines Agency and is under review.

About Orphazyme A / S
Orphazyme is a biopharmaceutical company in the late stages of development of arimoclomol for Niemann-Pick disease type C (NPC). Orphazyme is headquartered in Denmark and operates in the United States and Switzerland. ADSs representing Orphazyme shares are listed on Nasdaq US (ORPH) and its shares are listed on Nasdaq Copenhagen (ORPHA).

Forward-looking statement
This company announcement may contain certain forward-looking statements under the United States Private Securities Litigation Reform Act of 1995 and others, including its intention to seek regulatory approval of arimoclomol in the United States and Europe and the timing of clinical data. Although the Company believes that its expectations are based on reasonable assumptions, all statements other than statements of historical fact included in this Company’s announcement regarding future events are subject to (i) change without notice and (ii) to factors beyond the control of the Company. These statements may include, but are not limited to, statements preceded, followed or including words such as “target”, “believe”, “expect”, “aim”, “intend”, ” can “,” anticipate “,” “estimate”, “plan”, “project”, “will”, “may have”, “probably”, “should”, “would”, “could”, and other words and terms having a similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the control of the Company which could cause the actual results, performance or achievements of the Company to differ materially from the expected results, performance or achievements expressed or under- understood by these forward-looking statements, including the risks and uncertainties described in the Risk Factors section of the Company’s annual report on Form 20-F for the year ended December 31, 2020 filed with the Securities and Exchange Commission (SEC) of the United States on March 2, 2021, Report on Form 6-K filed with the SEC on June 11, 2021, and other documents filed by Orphazyme with the SEC from time to time. These documents are available in the “Investors & Media” section of the Orphazyme website at www.orphazyme.com. Except as required by law, the Company assumes no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

  • 07-2021 Orphazyme announces the publication of the results of its Ph 2-3 trial of ari in NPC in JIMD

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