Date: 2014-12-09
Type of information: Initiation of the trial
phase: 1
Announcement: initiation of the trial
Company: Saniona (Denmark)
Product: AN363
Action
mechanism: AN363 is a first-in-its-class pain-relieving compound, which has the potential of being a first choice drug for pain management in patients suffering from untreatable neuropathic pain disorders, either as standalone treatment or as add on medication to existing suboptimal therapies. Like the well-known Valium®, AN363 is acting on the receptors for GABA, the main inhibitory signalling compound in the nervous system. However, in contrast to Valium® and any other registered drugs in this class, AN363 works selectively on receptors containing the alpha2 and alpha3 proteins without efficacy on the main GABA-A receptors in the brain including the so-called alpha1 protein. This is important, since the sedative and hypnotic effects (both adverse effects) of Valium® is due to its action on the alpha1 containing receptors, whereas the pain killing and anxiolytic effects relies on its effects on the
alpha2 and alpha 3 containing receptors. This means that AN363 may regulate the body\'s own pain regulating system in the spinal cord without promoting unwanted side effects through activation of other GABA systems in the brain. The preclinical studies with the compound have confirmed efficacy in animal models of neuropathic pain without the sedative effect. AN363 was designed as a back-up candidate to AN721, which has been tested in humans. AN721 demonstrated the desired effects on relevant biomarkers in humans as well as lack of effect on unwanted markers such as sedation and coordination difficulties. AN363 is believed to have a better profile than AN721.
Disease: neuropathic pain
Therapeutic area: CNS diseases
Country:
Trial details:
Latest
news: * On December 9, 2014, Saniona announced that it expects to initiate Phase 1 clinical studies for AN363 in the fourth quarter of 2015. This is earlier than previously announced. AN363 is under development for neuropathic pain. “We have established the manufacturing process for large scale production, which means that we are able to advance initiation of the Phase 1 clinical trial to the fourth quarter 2015. I am thrilled that we have reached this significant milestone for this important internal program, which represents a major value driver for the company”, says Jørgen Drejer, CEO of Saniona. In July 2014, Saniona nominated AN363 as clinical candidate for formal pre-clinical development with the objective of entering into Phase 1 clinical trials during the first quarter of 2016. In October, Saniona entered into an agreement with its long-term co-operation partner Syngene for development of the pre-clinical package for AN363. The preclinical development package comprises scale-up of the manufacturing process, GMP production and various toxicology and safety studies. Combined this forms the basis for regulatory submission to begin clinical trials (“first in man-studies”). Saniona has now established the manufacturing process for large-scale production and will initiate manufacturing of the first batch of drug substance, which will be used to develop the final formulation for clinical trials. The achievement of this important milestone means that we now expect to initiate Phase 1 clinical trials during the fourth quarter of 2015. * On November 18, 2014, Saniona has presented positive preclinical data for the internal development candidate AN363 for treatment of neuropathic pain. The conclusion is that AN363 is highly efficacious and is well suited as a clinical development candidate. Saniona plans to initiate Phase 1 clinical trials for AN363 during the first quarter 2016. At the Annual Congress of International Drug Discovery Science & Technology in Suzhou, China, Dipak V. Amrutkar, Ph.D., Research Scientist, presented preclinical data suggesting that AN363 may represent a new treatment option for neuropathic pain where there is a significant medical need. At the congress, Dr. Amrutkar noted that AN363 is highly efficacious in both the capsaicin induced acute pain model and in the chronic constriction injury (CCI) induced neuropathic pain model in male rats. He showed that pre-treatment of AN363 before capsaicin injection significantly and dose dependently attenuated spontaneous nociceptive behaviour in response to hind paw injection of capsaicin. Similarly, in CCI, AN363 significantly reversed the mechanical allodynia 2 hours post treatment. Importantly, AN363 did not cause ataxia as measured by the rotarod in the therapeutic doses in rat. The robust therapeutic effect seen with AN363 in animal models of pain combined with its selective in vitro profile suggest that it could have potential benefit in treatment of pain in humans. * On July 4, 2014, Saniona announced that it has decided to initiate the formal preclinical development process for the drug candidate called AN363 for treatment of neuropathic pain. Saniona expects that the compound will be ready for Phase 1 first in man clinical studies in the first quarter of 2016. According to previously announced plans, Saniona is currently performing evaluation of AN346 and AN363 with the aim of selecting at least one of the compounds for formal preclinical development within 6 to 12 months. In line with these plans, Saniona has decided to initiate the formal preclinical development process for AN363. The preclinical development comprise upscaling of the manufacturing process, GMP production and various toxicology studies, which combined form the basis for regulatory approval to initiate clinical trials (first in man-studies). Saniona is currently setting up development contracts with its partners and expects to initiate the pre-clinical development of AN363 during the third quarter of 2014. Consequently, the objective is to make the compound ready for Phase 1 clinical trials during the first quarter of 2016. The planned evaluation for the other drug candidate, AN346 for inflammatory bowel disease, will continue in accordance with the previously announced plans.
