Any first-mover advantage that Corcept Therapeutics’ Korlym might have gained in February when it became the first drug to be approved for endogenous Cushing’s syndrome will quickly vanish if the FDA gives the go-ahead for Novartis’s Signifor by the end of the year.
Not that Signifor’s US approval is a dead cert. An FDA advisory committee is set to discuss the filing on November 7; Novartis pulled an earlier application over manufacturing issues before resubmitting it this year. Importantly, however, Signifor did secure a European green light in April, and a positive US panel endorsement would likely see Corcept’s already battered share price take another hit.
|% of market cap||2%|
|Event type||FDA advisory committee|
|Date||November 7, 2012|
Novartis expects a US regulatory decision in the fourth quarter, and is also hoping to file Signifor next year for treating acromegaly, a condition caused by excessive production of growth hormone. Consensus data compiled by EvaluatePharma forecast sales for Signifor of $610m by 2018.
First to market
Corcept’s Korlym secured US approval in February without an advisory panel, and was launched – with only the help of a distributor – two months later (Corcept scores a first with US Cushing’s approval, February 20, 2012).
But despite some early bullish expectations and the first-mover advantage, the drug has since come under increased scrutiny, and Corcept’s share price is presently 42% off the point it hit shortly after Korlym’s approval.
Last month Piper Jaffray downgraded the stock citing Korlym’s side-effect profile, the fact it tends to be given fourth line after generics, and the threat of Novartis’s Signifor. Korlym forecasts have been scaled back since launch, and it is currently expected to generate total revenue of only $312m by 2018, with an NPV of $280m – more than Corcept’s market capitalisation.
All of which works to Novartis’s advantage. Not only will the Swiss pharma giant have a bigger sales force to call on, its marketing muscle could also enable it to put pricing pressure on the smaller competitor.
Cushing’s syndrome is the result of excessive cortisol in the body, caused either by taking medication like prednisone, for inflammatory disorders, or – less commonly – by excess cortisol production by the adrenal glands as a result of a tumour. It is the latter type, exogenous Cushing’s, for which Korlym has been approved.
Signifor acts as a somatostatin analogue, and is thought to target somatostatin receptors to inhibit secretion of ACTH, the hormone that stimulates adrenal release of cortisol. Korlym blocks the glucocorticoid receptor type II to which cortisol normally binds, thus inhibiting the effects of excess cortisol. Korlym’s active ingredient, mifepristone, is better known as the generic ingredient of RU-486, the abortifacient that controversially received US approval in 2000.
While Korlym was approved on the basis of a single-arm, 50-patient study, with Signifor Novartis has carried out what it believes to have been the largest Cushing’s trial to date, in 162 patients, although this too had no control arm. In the Novartis study the higher, 900µg Signifor dose group met the primary endpoint of normalising urinary-free cortisol levels.
Clinicaltrials.gov lists another phase III study of Signifor, still recruiting 148 patients. The drug, known generically as pasireotide, is also available under a phase III expanded-access programme mainly across the US and Europe.
As if this were not enough, Novartis looks to put even more pressure on Corcept, saying it plans a filing in 2016 or later for LCI699, an aldosterone synthase inhibitor currently in phase II for Cushing’s. This and a proprietary mifepristone formulation in development by HRA Pharma specifically for treating Cushing’s caused by ectopic ACTH secretion, appear to be the only other clinical development programmes for the rare disorder.
Korlym might have beaten Signifor to the punch, but Novartis has come back swinging.
To contact the writer of this story email Jacob Plieth in London at firstname.lastname@example.org