Event - Addex hoping for top marks in GERD trial

Before the year is out Addex will release the first set of phase IIb data due on its lead product, ADX10059, in gastro-oesophageal reflux disease (GERD). Positive results should pave the way to the Holy Grail, namely a licensing deal, meaning a successful study will almost guarantee an anticipatory jump in the Swiss company’s share price.

First to be announced will be a monotherapy study conducted in patients known to respond to proton pump inhibitors (PPIs), a class of drug that dominates the heartburn field and looks set to remain the first line therapy for the foreseeable future. Realistically this means that the fastest route to market for this drug will be GERD patients whose symptoms are not adequately treated by PPIs – the subject of the next study to report - however, these first data will be very revealing, particularly as they will help determine the market potential of ‘059, and importantly, how much a partner will be willing to pay for it.

Novel modulation

The incredibly strong hold that PPIs have in GERD, due to the fact that they actually work very well for most people, means cracking into this market will be tough. This will be made even harder when all the big names that currently dominate the market such as Nexium lose patent protection over the next couple of years. After raking in sales of $16.4bn last year, PPIs are set to generate $7.57bn in 2014, according to EvaluatePharma.

However, because Addex’s candidate, unlike the PPIs, targets the underlying disease mechanism, if it reaches the market there is a good chance it can carve out a share. The drug works by prompting loose sphincter muscles, which allow the contents of the stomach to travel back up the oesophagus, to tighten. PPIs suppress acid production in the stomach but do nothing to prevent reflux.

ADX10059 is a negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which is being targeted by a number of companies working in this field. As well as GERD, it is thought this target could lead to therapies addressing migraine, Parkinson’s disease, pain and depression.

Addex’s candidate is also in a phase IIb migraine prevention trial; results are due in the second quarter of next year. Given the much larger market potential in this indication due to the unmet need, particularly in a prophylactic setting, and the safety issues with current medicines, these results could well prove to be the most interesting in the long run. (Therapeutic focus - Lack of innovation in migraine market a headache, November 10, 2009).

All eyes on safety

The first GERD study to report will be 204, a relatively small study in 90 patients, looking at ‘059 dosed alone, in patients who previously responded well to PPIs. GERD is often mistaken for indigestion, however if a patient responds to PPIs the diagnosis can be largely confirmed.

This means study 204 will provide an important examination of the drug’s underlying efficacy in this disease and mechanisms of action, as well as potential in a monotherapy setting.

Despite the strong efficacy of the PPIs, anything from a fifth to half of all GERD patients do not respond adequately. Given that ‘059 works as a reflux inhibitor, it could be complementary to acid suppression therapies like PPIs, according to Addex. This second-line indication has been recognised as the route to market for ‘059, however given the size of the PPI field this is not exactly a niche setting.

This is being tested in the next phase IIb trial to report, called 205, due early next year, which enrolled almost 300 partial responders who were given '059 on top of their PPI.

Although it is crucial that ‘059 establishes strong efficacy in both of these trials, exhibiting a clean side effect profile is almost as important, considering how regularly heartburn drugs are taken. Therefore all eyes will be on tolerability, because this will equally determine the market potential.

Top marks needed

Success in both of these trials is important; encouraging earlier stage results and a new formulation that appears to have significantly improved tolerability means hopes are high for positive read outs on both efficacy and safety.

Some financial analysts have already upped their valuations in anticipation of positive results and a deal; earlier this month Jefferies upgraded to a “buy” recommendation and massively hiked its price target from SFr34 to SFr70. Piper Jaffray said recently that a successful trial would add SFr16 to their valuation of the company, which currently sits at SFr60.

Addex’s shares have a long way to go to reach those price targets; the stock closed today at SFr32, valuing the company at SFr182m ($181m).

To begin the journey to those heady heights, and attract partners willing to sign a top dollar deal, ‘059 has to achieve top marks on all measures.

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