Addex Pharmaceuticals has announced its lead drug compound has passed mid stage clinical trials, with the company aiming towards a migraine prevention therapy.
The Swiss pharma said that ADX10059 has successfully passed a Phase II clinical trial and shown itself to be useful in treating migraine-related pain.
However, Vincent Mutel, Addex CEO, described this as: "just a validation that the concept [of this class of drug] works. It is a worst case scenario for development. Our target is the prevention of migraines."
The gold-standard for the prevention of migraines is Ortho-McNeil Neurologics' Topamax (topiramate). That drug is also used to prevent seizures in epilepsy patients but has side-effects related to the central nervous system (CNS) such as depression, mood disorders, confusion and tiredness.
Addex hopes that an improved side-effect profile for their drug will enable it to take some of Topamax's market share.
"The drug is extremely safe. In the Phase I trial we gave 100 people very high doses of the compound - up to 1000mg," Mutel told DrugResearcher.com. Another 100 people were dosed in the Phase II trial.
However, ADX10059 is not pinning all its hopes on migraine. The same drug has also passed another Phase II trial to treat acid reflux - specifically gastro-oesophageal reflux disease (GORD or GERD using US spelling) and a third Phase II trial for anxiety is underway.
If the drug proves successful in all three indications, its market potential is huge. The markets for migraine and acute anxiety are estimated at $2.5bn (€1.84bn) and $0.5bn, respectively. GERD is estimated to affect 2 per cent of the adult population in the US and represents a market size of some $19bn, according to Addex.
The Swiss pharma focuses its research on inhibiting the function of G protein coupled receptors (GPCRs) associated with the CNS. ADX10059 targets the metabotropic glutamate receptor 5 (mGluR5), although not through binding and blocking its active site as might be expected. Instead it is an allosteric modulator - it binds to another part of the protein, affecting the shape of the main binding site. ADX10059 renders the main binding site (and therefore protein) less functional - it is a negative modulator.
Addex claim to be the only company in the world focussing on this type of drug for GPCRs.
"I think the allosteric principle has an advantage over a classical approach as on its own, the drug has no effect. The receptor must be stimulated to see a response," said Mutel.
Triptan drugs such as sumatriptan are also used to treat migraines. However, as they act on blood vessels, it cannot prevent migraines, whereas ADX10059 and Topamax have neuronal targets and so can, Mutel explained. The results from the ADX10059 trial showed similar efficacy to triptans in achieving pain free status 2 hours after taking the drug. ADX10059 was 3.6 times better than placebo. Secondary endpoints of the trial were not met as the drug didn't decrease the severity of the migraine or the migraine recurrence rate with statistical significance - although Mutel said a clear trend was seen.
Addex has also announced its intention to float on the Swiss stock exchange to raise new funds for drug development. The company plans to initiate a Phase IIb trial this year, only now examining ADX10059 as a migraine prevention therapy. However, before moving to a subsequent Phase III trial, as is so often the case, Addex hopes to partner the development.
Mutel said: "We will need the arms and muscle of a big pharma to help us."