DGAP-News: PAION AG / Key word(s): Research Update
PAION REPORTS POSITIVE REMIMAZOLAM TOPLINE DATA IN EU PHASE III TRIAL IN GENERAL ANESTHESIA
- Primary endpoint met: remimazolam demonstrated non-inferiority to propofol for anesthetic effect
- Key secondary endpoint met: remimazolam demonstrated superior hemodynamic stability compared to propofol
- EU Phase III program completed; data to serve as basis for MAA submission in general anesthesia
Aachen (Germany), 19 November 2020 - The Specialty Pharma Company PAION AG (ISIN DE000A0B65S3; Frankfurt Stock Exchange Prime Standard: PA8) today announces positive topline data from the pivotal remimazolam EU Phase III trial in general anesthesia. In the trial with 424 patients, remimazolam met both the primary and key secondary endpoints.
The randomized, single-blind, propofol-controlled, confirmatory Phase III trial enrolled 424 ASA III/IV patients (American Society of Anesthesiologists classification III to IV) undergoing planned surgery at more than 20 European sites.
The primary objective of the trial was to demonstrate non-inferiority of remimazolam compared to propofol for the induction and maintenance of general anesthesia during elective surgery. The primary efficacy endpoint was defined as the anesthetic effect of remimazolam and propofol assessed as a percentage of time of a Narcotrend (NCT) index below 60 (depth of anesthesia) during the maintenance phase of general anesthesia. In the final analysis, non-inferiority was demonstrated with an NCT index below 60 with 95.7% (n=235) of the time with remimazolam and 99.1% (n=92) with propofol at a significance level of p=0.0001.
The key secondary objective was to show improved hemodynamic stability compared to propofol. Hemodynamic stability is measured by avoidance of intraoperative drop in mean arterial blood pressure (MAP) between start of anesthesia and 15 minutes after the first skin incision, as well as usage of vasopressors. Although adjustments in the statistical testing were required based on the nature of the obtained data, a statistically significant superior hemodynamic stability of remimazolam compared to propofol could be shown with a number of hemodynamic events per patient of 62.62 ± 39.46 (n=270) with remimazolam and 71.03 ± 41.12 (n=95) with propofol at a significance level of p=0.0151.
Remimazolam is currently under regulatory review in the EU in procedural sedation. Assuming approval in procedural sedation, PAION plans to submit an extension of the marketing authorization for remimazolam for general anesthesia. A decision on market approval in procedural sedation is currently expected in the first half of 2021 with a CHMP opinion (Committee for Medicinal Products for Human Use) expected by the end of January 2021.
"The study results confirmed that remimazolam compared to propofol resulted in less events of critical intraoperative hypotension (IOH), defined as an arterial blood pressure decrease below 65 mm Hg (,), and therefore has the potential to be an important addition to existing options for induction and maintenance of general anesthesia in class ASA III/IV patients", commented Prof. Dr. Jörg Fechner, international coordinating and principal investigator, University Hospital Erlangen, and added: "I possibly will have the chance to present some study data during my presentation at the Euroanaesthesia virtual congress on 29th of November 2020."
Dr. Juergen Beck, Chief Development Officer at PAION AG, commented: "We are excited about the topline data and remimazolam's potential to serve as an effective, safe and efficient agent for general anesthesia. The efficacy and safety results we are reporting today confirm data from earlier studies. We look forward to preparing a marketing application also in general anesthesia."
Dr. Jim Phillips, CEO at PAION AG, commented: "I would like to thank the clinical study sites and patients who participated in this important study. As we have seen clearly during the ongoing coronavirus crisis, there is a need for more anesthesia options. We believe that remimazolam has the potential to play a significant role in improving patient care and we will make a supplementary submission to the EMA in 2021 for approval for use in general anesthesia, once we have received feedback (and we hope an approval) for procedural sedation."
In Japan, licensee Mundipharma received market approval in general anesthesia in January 2020. In the U.S., former licensee Cosmo Pharmaceuticals received market approval in procedural sedation in July 2020. In China, licensee Yichang Humanwell received market approval in procedural sedation in July 2020. In South Korea, licensee Hana Pharm filed for market approval in general anesthesia in December 2019. In Europe, PAION submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in procedural sedation in November 2019.
In addition to procedural sedation and general anesthesia, based on positive Phase II study results, ICU sedation is another possible indication for remimazolam.
Remimazolam is partnered in the U.S. (brand name BYFAVOTM) with Acacia Pharma, in Japan (brand name Anerem(R)) with Mundipharma, in China (brand name Ruima(R)) with Yichang Humanwell, in Canada with Pharmascience, in Russia/CIS, Turkey and the MENA region with R-Pharm, and in South Korea and Southeast Asia with Hana Pharm. For all other markets including parts of the EU, remimazolam is available for licensing.
In Europe, PAION is seeking approval of remimazolam for general anesthesia and for procedural sedation. PAION submitted a Marketing Authorization Application (MAA) for procedural sedation in November 2019.
PAION's mission is to be a leading specialty pharmaceutical company in the fields of anesthesia and critical care by bringing novel products to market to benefit patients, doctors & other stakeholders in healthcare.
PAION is headquartered in Aachen (Germany) with an additional site in Cambridge (United Kingdom).
1. Salmasi, V., et al., Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology, 2017. 126(1): p. 47-65.
2. Sessler, D.I., et al., Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery. Br J Anaesth, 2019. 122(5): p. 563-574.
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