After the US advisory panel’s unanimous vote in favour of Novartis’s Signifor to treat Cushing’s disease another rare condition looks set to be shaken up by big pharma.
The biggest casualty is Corcept Therapeutics, whose drug Korlym in April became the first endogenous Cushing’s syndrome treatment to be launched in the US. Corcept stock slumped 16% yesterday, and the company is now 64% off its February high. Although the FDA has of course been known to go against the advice of a panel there are several reasons why Corcept investors should now feel extremely nervous.
Not only is the clinical evidence backing Signifor stronger than that for Korlym – Novartis claims its pivotal Passport-Cushings study is the largest Cushing’s trial ever conducted – but the Swiss firm will have an immediate marketing advantage. Corcept launched Korlym with only the help of a distributor, and is continuing to hire and train a field force.
Pricing is one concern with which smaller players are increasingly having to contend after big pharma’s entry into the rare disease field. In Gaucher’s disease, for instance, Pfizer undercut the first market entrant by 25% when it launched its new treatment this year.
Signifor looks set to be approved broadly – indeed Novartis says it would become the first medication to treat US patients with Cushing’s. While it might be a question of semantics, strictly speaking Korlym is actually approved not for Cushing’s but for its symptoms – specifically hyperglycaemia due to high cortisol levels in endogenous Cushing’s syndrome adults with type 2 diabetes or glucose intolerance.
This is perhaps because Korlym does not reduce cortisol, whose excessive levels in the body characterise Cushing’s, but rather inhibits its effects. While Korlym blocks the glucocorticoid receptor to which cortisol normally binds, Signifor acts as a somatostatin analogue, targeting somatostatin receptors to inhibit secretion of ACTH, the hormone that stimulates adrenal release of cortisol.
Mechanistic subtleties aside, Korlym’s one advantage at present seems to be the fact that it is dosed orally, once daily. Signifor, meanwhile, is given by twice-daily subcutaneous injection.
Nevertheless, the threat from the Swiss giant is clear, and analysts have responded accordingly. Piper Jaffray, which had earlier downgraded Corcept citing the Novartis danger, drug-drug interactions and the fact Korlym tends to be given fourth line after generics, slashed their target price further after Signifor’s positive panel vote.
To make matters even worse for Corcept, Novartis is running a trial in 148 patients designed to test a once-monthly Signifor regimen – albeit given by intramuscular injection – and its aldosterone synthase inhibitor LCI699 is in a phase II Cushing’s trial (Event – Novartis looks to rain on Corcept’s Cushing’s parade, October 26, 2012).
And the Swiss firm is also ahead in Europe, where Signifor secured approval in April; analysts do not forecast an EU green light for Korlym until late next year, and Corcept has yet to sign up a rest-of-world partner for the drug.
Reported third-quarter Korlym revenues were $1.1m, net of rebates, bringing the total sold since launch to $2m; Piper Jaffray said uptake was slower than expected. With even the scaled-back consensus forecasts – Korlym revenue of $312m by 2018, according to EvaluatePharma – fast slipping from Corcept’s reach, investors are right to be worried.
Novartis’s grip on Cushing’s is set to tighten further still.
|Study detail||Trial ID|
|Pivotal Passport-Cushings trial, 162 patients, twice-daily sc injection of Signifor||NCT00434148|
|Expanded access study of sc Signifor||NCT01582061|
|148-patient phase III study of long-acting Signifor, once-monthly im injection||NCT01374906|
|39-patient phase II trial of LCI699||NCT01331239|
To contact the writer of this story email Jacob Plieth in London at email@example.com