An autumn approval of Cornerstone Therapeutics’s hyponatraemia therapy lixivaptan will go some way to compensate for the loss of the patent for Zyflo CR, the company’s asthma drug, which expired in June. First, though, lixivaptan must get a pass from an FDA advisory panel on September 13.
Cornerstone hopes to launch lixivaptan for the treatment of hospital-based patients with hyponatraemia – low levels of salt in the blood – in the first quarter of next year. This is not unrealistic; with the product backed by strong phase III data and a decent side-effect profile it would be a big surprise if the panel vote did not go Cornerstone’s way, and the FDA should follow its lead when making the approval decision on October 29.
Standing out from the crowd
Lixivaptan, previously called VPA-985, will have two competitors if it reaches market: Astellas’s Vaprisol and Otsuka’s Samsca, which had US sales of around $10m and $85m respectively in 2011. Samsca’s success is mostly due to its oral route of administration – Vaprisol is infused intravenously – so the orally dosed lixivaptan ought to be able to carve out a reasonable market share.
Lixivaptan's other advantage is its selectivity for the V2 vasopressin receptor, which is likely to appeal to physicians as the V2 receptor is better associated with serum sodium improvement in hyponatraemia patients. Samsca is a V2 antagonist, whereas Vaprisol inhibits both V2 and V1a receptors; V1a receptor activity is thought to have other downstream effects.
Hyponatraemia affects around 6 million people in the US. It is usually seen in patients with liver disease or congestive heart failure, which cause accumulation of fluids in the body. Cornerstone should be able to sell the drug directly to the 5,000 or so hospitals in the US, and has said that it will seek to partner lixivaptan in other territories.
Cornerstone expects to gain approval for lixivaptan for hospitalised patients with euvolemic hyponatraemia, in which total body water increases while the body's sodium content stays the same. With this indication most patients are treated on an acute basis, receiving eight to 21 days of lixivaptan therapy, with a small percentage receiving chronic therapy.
However, there is a slim chance that lixivaptan could be approved for a broader indication - hypervolemic hyponatraemia without the in-hospital requirement, allowing those with congestive heart failure to be treated as outpatients. In hypervolemic hyponatraemia both sodium and water content increase, but the water gain is greater. Data from the study to back this indication have not been released so the outcome on this decision is harder to call.
Ladenberg Thalmann analysts reckon the product could have US revenue of $30-50m if approved for hospitalised patients. Roth analysts have forecast US sales of around $25m, rising to $75m in the event that the broader indication is granted.
Nick of time
Approval of lixivaptan would come at a very useful time for Cornerstone. Not only is the firm set to lose revenues from Zyflo CR, but growth of its Curosurf infant respiratory distress syndrome treatment could be curtailed as Discovery Laboratories’ Surfaxin, approved in March, makes its presence felt.
The situation will be alleviated slightly by revenues from CRTX 067, a generic version of UCB’s antitussive/antihistamine Tussionex, which was approved in the US in July. This drug has been beset by delays, having originally been expected to gain approval in early 2011, and 2012 sales expectations are not exuberant (Event – Cornerstone eyes swift US approval before catching a cold, September 15, 2010). It is a grower, however, with analysts at Ladenberg Thalmann forecasting 2018 sales of $67m, up from just $2.8m this year.
Cornerstone is known as an acquisition-happy company. It obtained lixivaptan through its takeover of Cardiokine at the very end of last year, and has since merged with the acute hospital care specialist EKR Therapeutics in a $125m deal.
With cash reserves of $71m and no debt, analysts expect Cornerstone to do another acquisition by the year end, and lixivaptan could put the company in a good position for organic as well as inorganic growth.
To contact the writer of this story email Elizabeth Cairns in London at firstname.lastname@example.org