After first approval Synergy tackles differentiation

Yesterday's US approval of plecanatide in chronic idiopathic constipation is Synergy Pharmaceuticals' first, though the market's refusal to reward the group suggests that investors were hoping for a better label – one without a warning about severe diarrhoea.

The product has been given the trade name Trulance, and its responder rates are on par with the market leader, Linzess, owned by Allergan and Ironwood. Although both carry the warning Synergy's ultimately comes with lower rates of diarrhoea, and it will have to will have to play on this to make its mark. As plecanatide is unpartnered the news could even stoke further takeover rumours, though perhaps a deal will not materialise just yet.

Not so solid victory

Trulance is a guanylate cyclase type C receptor activator that aims to stimulate digestive fluid movement and promote regular bowel function.

It was tested in two double-blind, placebo-controlled trials in chronic idiopathic constipation (CIC). The phase III studies were in a total of 2,804 patients and both met the primary endpoint, yielding a significantly greater responder rate than placebo over 12 weeks. In the first study this was 21% versus 10%, and 21% versus 13% for the second trial (Synergy relaxes with positive constipation data, June 17, 2015).

Importantly it also had a relatively good safety profile, with low rates of diarrhoea. In an integrated analysis of both studies this side effect was reported in 5% of patients on the drug compared with 1% of those on placebo. Severe diarrhoea was reported in 0.6% of patients.

While Linzess is also a guanylate cyclase type C receptor activator its use is associated with higher rates of diarrhoea, 16% versus 5% for placebo, with 2% of patients reporting severe diarrhoea leading to a warning on its label. 

This suggests that Synergy's best bet for a superiority claim over Linzess lies in tolerability, though Trulance has also been approved with a severe diarrhoea warning – it has been contraindicated in children under six, and use is not advised in those aged six to 18 – which could explain Synergy's share reaction; opening intially up 4% the stock has now fallen 6% in early trading.

Linzess is approved in adults in CIC and irritable bowel syndrome with constipation (IBS-C) indications, and 2022 forecasts sit at $1.3bn according to consensus from EvaluatePharma.

Following through with a deal?

Synergy plans a supplemental filing in IBS-C later this quarter on the back of two positive phase III trials that it reported at the end of last year.

2022 sales of Trulance are forecast to reach $711m, according to consensus from EvaluatePharma, with an almost equal split between the two indications. It has an NPV of $949m, or 82% Synergy's market cap.

Synergy shares have been on a rally since of the release of Trulance data last year, and are up nearly 60% over the past 12 months. The product is still unpartnered and Valeant, once the obvious candidate for a deal, is no longer a realistic prospect.

Takeout speculations have followed the company for the past couple of years, and the approval might stoke further rumours, though real evidence of Trulance's potential on the market might be needed before anyone finally pulls the trigger.

To contact the writer of this story email Joanne Fagg in London at [email protected] or follow @JoEPVantage on Twitter

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