More Competition Coming To Cushing's Market
FDA Reviewing Strongbridge's Recorlev
Executive Summary
Having been given a PDUFA target date of 1 January, 2022, Strongbridge is already preparing for a happy new year challenging Recordati's Isturisa for market share in the Cushing's syndrome space
Patients suffering from Cushing’s syndrome, which caused by high levels of cortisol that are often the result of a benign tumor of the pituitary gland, could soon have a new treatment option now that US regulators are evaluating Strongbridge Biopharma plc's Recorlev.
The Food and Drug Administration has accepted for review the company’s new drug application for Recorlev (levoketoconazole) for the treatment of endogenous Cushing’s syndrome. Earlier than anticipated, Ireland-domiciled Strongbridge received the day 74 letter from the FDA which set a Prescription Drug User Fee Act (PDUFA) target action date of 1 January 2022 and the agency made no mention of a plan to hold an advisory committee meeting.
The submission for Recorlev is based on SONICS and LOGICS, two Phase III trials involving 166 patients with Cushing’s. The SONICS study met its primary and key secondary endpoints, demonstrating a significant rate of mean urinary free cortisol normalization after six months of maintenance therapy without a dose increase, while LOGICS confirmed that the long-term cortisol-normalizing efficacy demonstrated in SONICS was due to use of levoketoconazole specifically.
Recorlev is the 2S, 4R enantiomer of ketoconazole (Johnson & Johnson's Nizoral and generics) that has been used as an antifungal but is also used off label in Cushing's, although it has a black box warning for potentially fatal liver toxicity. Strongbridge is confident that Recorlev does not have the same liver toxicity issues and is actively preparing for the potential launch in the first quarter of 2022.
If approved, Recorlev will be going up against Recordati SpA's Isturisa (osilodrostat), a cortisol synthesis inhibitor that the Italian company licensed from Novartis AG in July 2019 for $390m upfront in a deal that also included rights to Signifor (pasireotide) and its long-acting version Signifor LAR. The latter two are also approved to improve the symptoms of Cushing’s as well as acromegaly in adults for whom surgery is not an option. (Also see "More Positive Data For Recordati Cushing's Drug" - Scrip, 19 Jun, 2020.)
Isturisa is approved in the US and the EU and the drug, which inhibits 11-beta-hydroxylase, also got approved in March this year by the Japanese Ministry of Health, Labour and Welfare (MHLW) for patients with endogenous Cushing’s syndrome for whom pituitary surgery is not an option or has not been curative. Recordati did not give any specific sales figures for Isturisa when it unveiled its first-quarter 2021 financials earlier this month but said that the drug was expected to achieve peak year sales of €300-350m.
Analysts at JMP Securities are forecasting $300m in Recorlev sales at peak compared with Strongbridge's own guidance of $250-350m. In a note issued on 13 May, they said that no plans for an FDA advisory committee was "likely reflective of a thorough submission [and] based on the positive Phase III data from the LOGICS and SONICS trials, we think Recorlev approval is likely, 90% POS (probability of success).
Sex A Potential Differentiator
Jefferies analysts "remain confident in the approval and adoption" of Recorlev, "particularly in women." Backing this claim, the broker said in a note that the drug's unique mechanism of action does not cause androgenic effects such as excessive hair growth and acne, differentiated from other steroidogenesis inhibitors such as Isturisa "and thus is likely to readily attract women," which make up 75% of the Cushing's patient population.
On a conference call to discuss Strongbridge's first quarter 2021 financials, which saw revenues rise $8.4m (+25%), due to sales of Keveyis (dichlorphenamide) for primary periodic paralysis, chief medical officer Fred Cohen said feedback from physicians had shown that sex was “an important potential differentiator between the drugs." He stressed that "the experience with Isturisa is relatively new and no single physician has treated more than one or two patients with it, so the jury remains out on what the ideal patient for that drug is going to look like.
"We do still believe that Recorlev is going to have a place most likely as a first line medical therapy and we think particularly in women who are having androgenic side effects or who are concerned about those."