Brivoligide (AYX1)

 Post-Surgical Pain

Unmet Need

Post-surgical pain, particularly pain associated with movement, represents a significant unmet medical need for patients, physicians, hospitals and caregivers alike.

There are approximately 30 million inpatient surgical procedures performed annually in the United States1 and more than 70% of surgery patients experience moderate or severe post-surgical pain.2  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.3,4 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.5

Standard analgesic regimens for post-operative care can provide management of pain at rest, but often with troubling and dose-limiting side effects. Patient recovery is often limited by poorly controlled spikes in movement-evoked pain, which is currently not addressed by standard-of-care.  These aspects of pain remain inadequately addressed by current therapies and can impede normal activity, exacerbate depression and diminish overall quality of life.

Across the course of of post-surgical pain, current standard-of-care is not capable of modifying the course of pain and requires repeated administration to produce treatment effects.

There exists significant unmet need for pain treatments that can reduce post-surgical pain at rest and with movement, and modify the course of post-surgical pain, potentially preventing the development of chronic pain.

Therapeutic Approach

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 movement-evoked pain arising from a single traumatic incident.

Brivoligide, Adynxx’s lead product candidate, is an investigational drug intended to reduce acute post-surgical pain and prevent the transition to persistent or chronic 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 “pain neurons”, switching off the sequence of events leading to persistent movement-evoked pain after surgery.

Product Profile – Preventing Post-Surgical Pain

Brivoligide treatment is designed to produce a long-term benefit with a single intrathecal administration at the time of surgery, reducing both pain at rest and movement-evoked pain during recovery with a favorable safety profile, and without altering normal neuronal function which can result in numbness or weakness.

By switching off the cascade of protein expression responsible for establishing and maintaining mechanical hypersensitivity, a single brivoligide treatment at the time of surgery has the potential to:

• Reduce post-surgical pain, particularly pain with movement

• Prevent the transition to persistent and chronic post-surgical pain

Due to its unique mechanism of action, brivoligide has a favorable safety profile:

• Brivoligide has been well tolerated in clinical studies, with no observed drug related adverse events (such as cardiac, respiratory or endocrine effects)

• Brivoligide does not have abuse potential since it lacks reinforcing properties

• Brivoligide administration does not cause numbness or weakness as is the case with local anesthetics

Brivoligide has the potential to revolutionize the treatment of post-surgical pain, by pain with movement and pain at rest, and preventing the transition to chronic pain with a single administration at the time of surgery, and without the adverse effects associated with current standard of care.

  1. National Health Discharge Survey, 2010
  2. Institute of Medicine of the National Academies Report. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research, 2011. The National Academies Press, Washington DC
  3. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367:1618-1625
  4. Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth.2008;101(1):77-86
  5. Lavand’Homme P. Chronic post-surgical pain: 10 years on. Curr Opin Anaesthesiol. 2011 Oct;24(5):545-50