Frequently Asked Questions

What is Xen2174 and how was it discovered?
Xen2174 is a peptide modeled on the family of cone shell peptides known as chi-conopeptides. 

Chi-conopeptides were originally discovered by researchers at the University of Queensland characterising the various effects of the venom from Australian cone shell species.  Further development by Xenome scientists has resulted in the design of a peptide that targets a key process in the transmission of pain signals to the brain.

Xen2174 targets the Norepinephrine Transporter (NET). Inhibition of this transporter elevates the levels of norepinephrine (NE) in the spinal cord to prevent pain signals from reaching the brain.  Xen2174 is a synthetic peptide produced by standard peptide chemistry techniques.

How does Xen2174 work?
The electrical and chemical processes involved in the transmission, perception and interpretation of pain by our brain is extremely complex. The sensation of pain serves as an important alarm that warns us against the threat of, or ongoing, tissue damage. Without the ability to sense pain we could not function normally and our ability to stay alive would be seriously compromised.

In simple terms, our ability to sense pain is tightly regulated by specialised neuronal pathways; pathways which transmit pain signals to the brain and counterbalancing pathways that inhibit pain signals from reaching the brain. Under normal circumstances these pathways are in balance so that we sense pain through cuts, sunburn, or stubbing a toe but not in response to less damaging contact such as clapping.

When there are disturbances to this balance such as in conditions of chronic pain resulting from ongoing inflammation or nerve damage, the pathways transmitting pain signals to the brain are continually activated and normally non-painful contact can be painful (eg. allodynia).  Xen2174 acts to restore the balance by enhancing the activity of inhibitory pain pathways to selectively relieve the sensation of pain.

How is Xen2174 administered?
Xen2174 is administered by injection into the intrathecal space, which is the area immediately surrounding the spinal cord that contains the cerebrospinal fluid (CSF). Since this is the site of the drug’s action, delivering it here enables Xen2174 to exert its maximum effect.

Several methods are being investigated for delivering Xen2174 into the intrathecal space for the relief of pain, including direct injection and infusion via an implantable pump.

In what types of pain may Xen2174 be useful?
Xen2174 has the potential to provide therapeutic benefit in the treatment of moderate to severe pain in both acute (short-term) and chronic (long-term) settings.

In laboratory testing, Xen2174 has been shown to be effective in relieving both nociceptive pain (resulting from the injury to the body) and neuropathic pain (resulting from nerve damage or malfunction).

In the clinic, Xen2174 was tested in a recently completed phase II clinical trial to treat cancer patients with chronic pain who were no longer responsive, minimally responsive, or intolerant to routine pain treatments such as morphine and hydromorphone. A wide variety of pain states were experienced by these patients and included:

• Nociceptive Pain
• Somatic Pain (skin, muscles, bone)
• Visceral Pain (thorax, abdomen, pelvis)
• Neuropathic Pain

Xen2174 is also under clinical development for the treatment of acute post-operative pain, with an initial study currently underway using a bunionectomy model.

Where is Xen2174 in its development?
Xen2174 successfully completed a Phase I human safety trial in healthy volunteers, where it was administered intravenously to test the effects of systemic exposure to the drug.
 
The compound then moved on to a Phase II safety and tolerability trial in chronic pain patients who had a history of cancer.  This study, which was completed in early 2008, demonstrated the safety of Xen2174 across a wide range of doses. Though the primary intent of this study was safety, measures of the efficacy (effectiveness) of the drug were collected and pain relief was observed in some patients that lasted as long as several days following a single injection of Xen2174.

Xen2174 is currently being tested in a Phase II clinical trial in a model of post-operative pain.  This study will focus on the efficacy of Xen2174 given as a single intrathecal injection in the relief of pain following bunionectomy surgery.

Can I enrol in the clinical trials?
Before clinical trials with Xen2174 commenced, documentation supporting its safety were submitted for review to regulatory agencies including the US Food and Drug Administration (FDA).  Individual study protocols are also submitted to these regulatory agencies for review.

In addition, permission to conduct the study at each site also needs to be obtained from an Independent Review Board (IRB) or Ethics Committee to ensure that the rights and safety of each study subject are protected. 

A study of Xen2174 in bunionectomy is currently open for patient enrolment in the US and further studies of the drug will be initiated over the coming year. If you are seeking to enrol in a trial, please be aware that, while Xenome sponsors clinical trials with Xen2174 by developing the study protocols, supplying the drug, and funding the studies and the clinical trials themselves are independently conducted by internationally recognised hospitals and clinics.

The enrolment of patients into these trials is entirely the responsibility of the doctors at each study site and follows strict guidelines with respect to the entry criteria for patients entering the studies. There are also strict guidelines about maintaining confidentiality of patients and the on-going clinical trial. 

If you are a physician or a patient and wish to know more about Xenome or Xen2174, please email  enquiries@xenome.com