SAN FRANCISCO, Aug. 11, 2015 /PRNewswire/ -- Adynxx, a clinical-stage pharmaceutical company developing a transformative, first-in-class platform of therapeutics to alter the course of pain by addressing its molecular roots, today announced positive results from a Phase 2 dose-ranging clinical study of its lead product candidate, AYX1. AYX1 is under development for the reduction of acute pain and the prevention of chronic pain following surgery. There are approximately 30 million inpatient surgical procedures performed annually in the United States and more than 70% of surgery patients experience moderate or severe post-surgical pain. Of those patients, fewer than half report adequate pain relief with standard of care. Depending on the surgical procedure, 10 to 50% of patients will go on to develop chronic pain after major surgery. More than 50 million people in the US suffer from chronic pain, and more than 15% of those cases are a result of surgery or trauma.
The 120 subject, multi-center, double-blind, placebo-controlled study followed subjects for 42 days after knee replacement surgery, with patients receiving standard of care pain management plus either a single preoperative intrathecal injection of AYX1 or placebo. AYX1 demonstrated a statistically significant difference and clinically meaningful reduction in pain with walking from day 7 to 28 compared to placebo, the primary post-discharge endpoint. The treatment effect was sustained through the 42-day study period, highlighting the unique pain-modifying properties of AYX1. AYX1 also demonstrated a statistically significant difference and clinically meaningful reduction in pain at rest from day 7 to 28, a key secondary endpoint, similarly maintained through the 42-day study period. Consistent with prior trials, AYX1 had an excellent safety profile and the adverse-event rate observed during the trial was typical for a population undergoing knee replacement.
The data will be submitted to future medical conferences for presentation and to a peer-reviewed journal for publication.
"With a single preoperative administration, AYX1 was able to provide a significant and sustained reduction in pain after surgery with an excellent safety profile," said Donald Manning, M.D., Ph.D., chief medical officer of Adynxx. "Given these results, we believe AYX1 has the potential to be a disease-modifying treatment for post-surgical pain and a significant benefit to patients and their surgeons who are in urgent need of new, non-opioid treatment options."
Henrik Kehlet, M.D., Ph.D., professor of perioperative therapy and head of Section of Surgical Pathophysiology, The Juliane Marie Centre Section, Copenhagen, Denmark, and member of the Adynxx Clinical Advisory Board added, "Despite major advances in our understanding of postsurgical pain mechanisms, there is an important unmet need for new analgesics, especially for the many patients undergoing major joint replacement and where persistent pain remains a significant problem. It is therefore of major interest that this study of AYX1 has demonstrated clinically relevant analgesic effects, including pain with walking, extending to more than 1 month after knee replacement. These results urgently call for advancing this program into Phase 3 clinical trials."
AYX1 is an investigational drug designed to reduce acute post-surgical pain and prevent chronic pain with a single administration at the time of surgery. It acts by locally inhibiting the activity of EGR1, a transcription factor that is transiently upregulated in the spinal cord and dorsal root ganglia at the time of surgery or trauma. During this short period of induction, EGR1 triggers waves of gene transcription and subsequent protein expression that can pathologically alter the action and sensitivity of critical neurons in the pain pathway, resulting in pain at rest, during walking, and with movement. In some people this altered neuronal function persists and leads to chronic pain. It is this long-term effect deriving from a brief EGR1 induction that allows a single administration of AYX1, a drug with a relatively short half-life, to alter the long-term course of pain and potentially prevent chronic pain. In 2013 the U.S. Food and Drug Administration (FDA) granted Fast Track designation to AYX1 Injection for the prevention of chronic pain.
Rick Orr, chief executive officer of Adynxx noted, "With the ground-breaking results seen in this study, we look forward to initiating Phase 3 clinical trials of AYX1 in the coming year. We are pleased to continue our rapid progress toward meeting the needs of millions of patients who every year suffer from chronic post-surgical pain."
Adynxx, located in San Francisco, California, is a clinical-stage pharmaceutical company developing a transformative technology platform addressing pain at its molecular roots, preventing the development of pain following surgery or trauma and resolving established chronic pain syndromes. Adynxx's unique approach is to transform pain management by approaching pain as a disease rather than a symptom.
Funded by Domain Associates, Adynxx has successfully completed two Phase 2 studies of AYX1 for the reduction of acute pain and the prevention of chronic pain following total knee replacement surgery. Additional compounds targeting a range of intractable neuropathic and inflammatory pain syndromes are in the pre-clinical stage.