Apr 12, 2018

Adynxx Announces Results of the ADYX-004 Phase 2 Study of Brivoligide (AYX1) for the Treatment of Post-Surgical Pain

Brivoligide reduced post-surgical pain, opioid use and time to achieve mild pain in an underserved patient population that suffers from inadequate pain relief following surgery

SAN FRANCISCO, April 12, 2018 – Adynxx Inc., a clinical stage biotechnology company developing a novel platform of first-in-class, disease-modifying, non-opioid pain therapeutics, today announced Phase 2 study results of its lead therapeutic candidate, brivoligide (AYX1) for the treatment of post-surgical pain. The ADYX-004 trial assessed safety and efficacy of a single preoperative dose of brivoligide compared to placebo in 210 subjects undergoing unilateral total knee arthroplasty where all subjects also received standard perioperative pain management.

Randomization into the study was stratified by a screening score of 20 or higher on the Pain Catastrophizing Scale (PCS) to balance subjects at higher risk of experiencing poor analgesic outcomes following surgery. While the primary endpoint of reduction in pain with walking from day 7 to 28 was not met in the total study population, in pre-specified analyses by PCS score, brivoligide showed a sustained and clinically meaningful reduction in pain and opioid use in subjects with higher PCS scores.

Specifically, in subjects that scored 20 or higher on the PCS, a single preoperative administration of brivoligide reduced the time to achieve mild pain by 26 days, from 41 days in the placebo group to 15 days in the brivoligide group. In addition to accelerating recovery from pain, subjects treated with brivoligide used 37% less opioids compared to the placebo group, an amount equal to more than 90 Vicodin tablets (5 mg) per subject. Additional analyses of brivoligide treatment effect in these subjects also showed a 30% reduction in pain at rest and a 25% reduction in pain with walking from day 7 to 28, the pre-specified time frame used for multiple efficacy assessments. Brivoligide continued to demonstrate an excellent safety profile with an adverse event profile typical for a population undergoing knee replacement surgery. Based on these results, Adynxx plans to initiate a Phase 3 clinical trial of brivoligide in subjects with high PCS scores.

“Brivoligide is a targeted therapy for post-surgical pain that specifically benefits patients with high PCS scores by preventing the exacerbation of pain,” added Donald C. Manning, M.D., Ph.D., Chief Medical Officer of Adynxx. “These findings support a role for brivoligide in the personalized medicine approach to post-surgical pain management, especially in patients who often have inadequate pain relief following surgery and may require increased doses of analgesic medication for longer periods of time in order to achieve adequate pain relief. In addition to reducing the magnitude and duration of post-surgical pain for these patients, our data show a single administration of brivoligide at the time of surgery can also provide a substantial and sustained reduction in opioid use during the critical outpatient period when diversion is a significant concern.”

“The number of prescriptions written for post-operative pain relief has recently come under intense scrutiny since the duration of opioid therapy greatly increases the quantity of opioid tablets in circulation and contributes to the ongoing opioid crisis in the United States,” said Joseph Gimbel, M.D., orthopedic surgeon, Chief Medical Director of Arizona Research Center in Phoenix, AZ and a Principal Investigator of the study. “The results of this study suggest brivoligide can play a meaningful role in reducing the need for opioid-based pain relief after surgery and significantly decrease the number of opioid tablets prescribed annually for post-surgical pain, without compromising patient comfort or safety.”

“With millions of patients in this targeted population undergoing surgery annually in the United States alone, brivoligide addresses a critical unmet need and represents a significant advancement in pain management for these patients,” commented Dennis Podlesak, Chairman and Partner of Domain Associates. “To address this critical need, our plan is to rapidly advance brivoligide into Phase 3 and to approval for the benefit of countless patients that would otherwise experience much greater pain and higher levels of opioid usage after surgery.”

About the Pain Catastrophizing Scale
The Pain Catastrophizing Scale (PCS) is a validated and sensitive 13-item clinical tool, developed in 1995, which assesses the 3 domains of the catastrophizing construct: rumination, helplessness and magnification. Each item is rated on a zero to four-point scale, with the total score ranging from zero to 52. Patients with a score of 16 or higher on the PCS are more likely to experience inadequate pain relief following surgery and represent 25-35% of all patients undergoing surgery. The relationship between PCS score and pain has been extensively documented and more than 600 papers have been published on use of the PCS in acute and chronic pain populations. The PCS can be provided to patients well in advance of surgery and easily integrated into the patient assessment and education flow to reliably identify patients suitable for brivoligide treatment. PCS data were collected in all Phase 2 studies of brivoligide (ADYX-002, ADYX-003 and ADYX-004) and show consistent effects in subjects with high PCS scores.

About Brivoligide
Brivoligide (AYX1) is an investigational drug intended to reduce acute post-surgical pain with a single administration at the time of surgery. It acts by locally inhibiting EGR1 activity at the time of surgery or trauma in neurons critical to pain sensation, switching off the sequence of events leading to exacerbated pain after surgery, including pain with movement. EGR1 is a transcription factor transiently upregulated in the spinal cord and dorsal root ganglia at the time of surgery or trauma. During this short period of upregulation, EGR1 triggers waves of gene transcription and subsequent protein expression that change neuronal properties, establishing mechanical hypersensitivity and leading to long-term pain arising from a single traumatic incident.