EGFR-inhibitors have been used to treat cancer in millions of patients worldwide
A class effect in neuropathic pain - striking effects reported by 70% of patients treated.
EGFR-inhibitors do not have sedative side effects and are not addictive.
A well established drug class in oncology, but with novel mode of action against pain.
Pain relief already documented in >100 patients treated with EGFR-inhibitors at 10 clinics.
The EGFR and its
HER receptor family members
The EGFR is one of the most studied molecules in the human body.
It receives information from extracellular ligands and/or ligand independent activation, such as via SRC kinases, and transmits these signals into the cell, thereby modulating the cell’s behavior.
The EGFR can signal with another EGFR (its “twin”), as a homodimer, or it can signal with one of the other 3 HER family receptors, as a heterodimer.
Mode of action
in neuropathic pain
Since the serendipitous discovery that EGFR-inhibition leads to relief of neuropathic pain, at least five research groups have independently confirmed and/or explained the mode of action.
Although several of the EGFR's activating mechanisms, downstream signaling mediators, and end targets have been implicated, the EGFR itself has consistently been found to be critical in neuropathic pain.
Activation of the EGFR upon nerve damage, leading to translocation of critical ion channels and hyperexcitability of these neurons, is the most likely mechanism.
Potential for a targeted EGFR-inhibitor
When it comes to neuropathic pain: Not all EGFR-inhibitors are created equal – a window of opportunity?
EGFR inhibitors can be too toxic for long term use in non-cancer patients. AKIGAI founders have generated preclinical and clinical observations supporting the development of modified EGFR inhibitors that are targeted for the treatment of neuropathic pain. These modifications can lead to better pain relief, less side effects and better market protection.
Publications
Further prospective systematic observations from an exploratory study in patients with neuropathic cancer pain.
Positive signals in a randomized, phase-II placebo-controlled proof of concept trial using EGFR-inhibition in CRPS and compressed nerve injury.
Ten institutions have reported dramatic relief of neuropathic pain after treatment with EGFR-inhibitors in >100 patients.
In summary, AKIGAI founders Christian Kersten and Marte Cameron believe that EGFR-inhibitors could ultimately help 3 out of 4 patients with neuropathic pain. “We see almost immediate effects, sometimes like turning a switch, without the need for dose titration and without central nervous system side effects or problems related to abuse and addiction”.