Event – Plecanatide data could secure a partner for Synergy

Top-line data from a phase II/III trial of Synergy Pharmaceuticals’ constipation therapy plecanatide will be a significant catalyst for the company when they are released in January, and if positive ought to see the Synergy in a strong position for sale or partnership.

On Tuesday, Synergy said it was on track to complete the 951-patient chronic idiopathic constipation study, called SP304-20210, in early December, with results a month later. Synergy will also start a US phase IIb trial of the drug in irritable bowel syndrome with associated constipation (IBS-C) by the end of 2012. Synergy’s share price jumped 20% to close at $3.75 yesterday, adding $41m to the company’s market cap, which now stands at $248m.

Plecanatide, Synergy’s lead candidate, is a uroguanylin analogue that activates guanylate cyclase type-C receptors to increase the flow of water into the intestine. Expectations for the drug are extraordinarily high; its net present value dwarfs Synergy’s market cap.  

Competition

This is despite the fact that the first-in-class guanylate cyclase-C agonist, Linzess (linaclotide), gained FDA approval in chronic constipation in August. Developed by Ironwood Pharmaceuticals and sold in the US by Forest Laboratories, Linzess is forecast to be a blockbuster by 2018, EvaluatePharma’s consensus data show. Plecanatide is not expected to reach market until 2015, and its 2018 sales are pegged at $475m.

But while Linzess is first to market, plecanatide might have the edge when it comes to safety. Around 70% of patients with severe chronic constipation who failed over-the-counter treatments are also unsatisfied with prescriptions therapies. And Linzess, while usually effective, can cause severe diarrhoea in around 15-20% of those who take it, and has warning on the label to this effect.

Ritu Baral, an analyst at Canaccord Genuity, said that compared with Linzess plecanatide might have better tolerability, as no patients had had diarrhoea in phase IIa trials. Ms Baral added that if no safety worries arose, plecanatide could end up being used widely for severe chronic constipation, thus taking share from Linzess.

The planned phase IIb trial in IBS-C will enrol 350 patients and report data in the first quarter of 2014. Around 40 million people in the US have either chronic constipation or IBS-C, and approximately half of them would be likely to benefit from plecanatide.

Ms Baral suggested that plecanatide could end up a near-blockbuster, with a 12% share of the CC and IBS markets, meaning sales of $400m in each indication.

Collaboration

If the drug is shown safe and effective in the study, chances are good that a partner will come knocking. Scott Henry, an analyst at Roth Capital Partners, said that Synergy is expected to outlicense, partner, or sell its clinical programmes before launch. Companies active in the gastrointestinal area, such as Salix Pharmaceuticals or Santarus, could make a good fit.

From Synergy’s perspective a partner would be welcome; the company raised $52m in June, but cash is expected to run out next year without additional financing.

Synergy says that the SP304-20210 trial is designed to meet registration requirements for a pivotal study, and if the company can submit the findings as part of an NDA approval could come earlier than expected. Most analysts, though, suggest that the FDA will request at least one further phase III trial.

Whenever it is approved, plecanatide could see fairly rapid uptake, thanks to Linzess establishing awareness of this mechanism of action. And a good choice of partner could boost uptake significantly; it is just possible that plecanatide could end up the market leading guanylate cyclase-C agonist.

To contact the writer of this story email Elizabeth Cairns in London at [email protected]