Vortioxetine Set For Japan Filing But Prospects Limited?
Executive Summary
Positive results from a Japanese trial of Takeda/Lundbeck’s vortioxetine pave way for a planned approval filing in the country this year, but how might drug fare in the market?
Takeda Pharmaceutical Co. Ltd. has reported “positive results” from a Japanese Phase III study with vortioxetine in major depressive disorder (MDD), clearing the path for an approval submission in the country.
Based on the results of the placebo-controlled trial (NCT02389816), initiated in 2015 in around 490 adults with recurrent MDD, “both companies intend to move forward with regulatory filing…later this year,” the Japanese firm and Danish co-development partner Lundbeck Inc. said.
Typical standard review times in Japan are around one year, which - depending on exact timings and the reimbursement price listing process - could potentially result in a launch sometime by the end of 2019 at the earliest. The multi-modal drug was commercialized for MDD in early 2014 in the US, its biggest market.
Neither company gave further details of the results of the study, which compared vortioxetine 10mg or 20mg a day with placebo, against the primary endpoint of change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score after eight weeks of treatment.
Secondary endpoints in the trial included MADRS response and remission, and change from baseline in Hamilton Rating Scale.
The molecule is known to act as a serotonin 5-HT reuptake inhibitor, thought to be its main mode of efficacy in MDD, but is also an agonist of 5-HT1A, a 5-HT1B partial agonist, and a 5-HT3, 5-HT1D and 5-HT7 antagonist, but its exact mechanism in the disorder is not clearly understood.
Limited Market?
Originally discovered by Lundbeck, the two companies will co-promote the drug in Japan, where the prevalence of diagnosed clinical depression is around 4%. Depression in general however remains relatively under-diagnosed in the country, as many patients do not present for diagnosis or treatment.
The antidepressant has already been launched in more than 60 countries as Brintellix and is enjoying generally strong growth in the US, where the two companies also co-promote it, as Trintellix. Takeda reported sales in this market of JPY48.4bn ($438m) in the fiscal year to March 31, and will like the US pay royalties to Lundbeck on its Japanese sales.
However, the product is a relative latecomer to the market, and Datamonitor Healthcare predicts Japanese sales of a modest $52m in 2024. Vortioxetine is usually approved and positioned as a later line depression therapy following initial treatment with SSRIs or SNRIs - some of which are now available generically in the country - and then tricyclic or tetracyclic drugs, which is likely to limit its potential commercial market.
However, Datamonitor Healthcare's patient-based forecast predicts that the overall depression market in Japan will decline over the coming years, from an estimated $1.25bn this year to $930m in 2024, in large part due to the continued genericization of mainstay therapies.
Expanded Claims
A planned US label update to include pro-cognitive benefits – a unique claim for an antidepressant - has been rejected twice by the FDA, which requested additional data in support of this, although the EU did approve the claim in March 2015. Up to around 30% of depressed patients experience declined executive function.
However, this May the companies successfully got an addition of data to the US product label showing improvement in the Digital Symbol Substitution Test, a neuropsychological assessment that measures processing speed, an important aspect of cognitive function that may be impaired in MDD. Takeda in Japan could not say at this stage whether a similar claim of pro-cognitive benefits would be sought as part of the local approval filing.
Vortioxetine was also submitted in the US last December for treatment-emergent sexual dysfunction. Elsewhere in Asia, the drug was approved in China late last year, as part of Takeda's push to introduce its global innovative products there. (Also see "China Approves Lundbeck Antidepressant In Year-End Dash" - Pink Sheet, 11 Dec, 2017.)
From the editors of PharmAsia News.