Date: 2015-07-23
Type of information: Termination of an agreement
Compound: remimazolam
Company: Paion (Germany) Ono Pharmaceutical (Japan)
Therapeutic area: CNS diseases
Type agreement: termination of a licensing agreement
Action mechanism: benzodiazepine derivative. Remimazolam is a short-acting general anaesthetic/sedative. Sedatives are used, for example, in endoscopic procedures such as colonoscopies. After intravenous administration remimazolam rapidly induces the desired sedation. Importantly, this sedative effect quickly disappears. This rapid offset of the effect of the substance is due to its metabolism by tissue esterase enzymes that are widely distributed throughout the body. Remimazolam is being developed as a sedative agent for day case procedures (procedural sedation) as well as for the induction and maintenance of anaesthesia. It could also be used as a sedative for patients in the Intensive Care Unit (ICU).
Disease: general anaesthesia
Details: * On November 5, 2014, Paion announced that its Japanese development partner, Ono Pharmaceutical Co, has informed Paion that they have decided \"to discontinue the project on strategic reasons considering issues inpharmacokinetic features, while no adverse events of concern were observed during clinical trials\". Ono successfully completed the Remimazolam development program in anaesthesia - the lead indication in Japan - in November 2013. The primary efficacy endpoint of effectiveness as a general anaesthetic was achieved by 100% of patients with no adverse events of concern and a clinically meaningfully less cardio depressive effect as compared to Propofol. After that the remaining development for a filing in Japan was finished including further studies to elucidate the pharmacokinetic findings seen in another development program ICU sedation, which supported Paions view that the data package can be filed for general anaesthesia.Ono now has decided to stop its development activities and to return the license. There will be no repayment for received milestone payments. Remimazolam is now available for licensing in Japan to other parties. Paion is evaluating an alternative filing strategy for Remimazolam in Japan in the indication general anaesthesia through Paion or another partner. Paion has full access to all data generated by Ono. The parties will closely work together in order to make the transition as fast as possible. Paion expects no impact on its ongoing development programs in General Anaesthesia in Europe and Procedural Sedation in the US. Ono entered into a license agreement with Paion UK (formerly CeNeS Limited) in 2007, acquiring the exclusive right to develop and market Remimazolam in Japan.
Financial terms:
Latest news: * On July 23, 2015, Paion announced that the company has completed the Remimazolam know-how and technology transfer from his former partner Ono. In the meantime, Ono has also returned its Remimazolam rights. Paion has received most of the data in electronic form and has access to the paper versions. Paion has successfully been assigned all IP that was generated in Japan on an exclusive and worldwide basis and has full access to all data generated by Ono. All investigational sites and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) have been informed by Ono that the development by Ono has been stopped “due to strategic reasons” and that Paion will be responsible for the future development and activities in Japan.
In June 2015, Paion requested an informal meeting with the PMDA to discuss the project status. The PMDA informed Paion that the company could directly apply for a Pre-NDA (New Drug Application) meeting. A Japanese CRO is already preparing the draft dossier that is required for this Pre-NDA meeting which is expected to take place in the beginning of 2016. The framework of the future production of Remimazolam for the Japanese market will be discussed with the PMDA in advance. The timing of a potential filing will be subject to the outcome of these meetings. In the meantime, Paion has held very productive meetings with Japanese Key Opinion Leaders involved in the general anesthesia studies as well as in the ICU sedation study. All KOLs confirmed that Remimazolam is regarded a needed innovation for the Japanese anesthesia market and that the improved cardio stability and the availability of a reversal agent are significant improvements over existing alternatives.
Two scientific abstracts based on the Japanese Phase I/II studies and the Phase III data have been accepted for oral presentation at the upcoming “Anesthesiology 2015 Annual Meeting“ (“ASA”) in San Diego, USA, in October 2015. Full publications of these trials are in preparation.
