CNS catalysts in 2013: Which new drugs are set to enter the market this year?

Transcription

1 White paper CNS catalysts in 2013: Which new drugs are set to enter the market this year? By Charlotte Mackey February

2 Charlotte Mackey Lead Analyst Central Nervous System I am the Lead Analyst of the Central Nervous System (CNS) team at. I joined Datamonitor in 2006, having previously worked in research at the National Spinal Injuries Center (Buckinghamshire Healthcare NHS Trust). I am responsible for ʼs CNS content which spans the neurology, psychiatry, and pain markets and I closely monitor developments in each of these sectors. If you have questions about the research, data, and findings within this document you can put your questions directly to the analysts. Simply your questions to info@datamonitorhealthcare.com. To find out more about Datamonitor Healthcare, contact us at: getcloser@datamonitorhealthcare.com phone Visit our website: Or follow us on DISCLAIMER While every care is taken to ensure the accuracy of the information contained in this material, the facts, estimates, and opinions stated are based on information and sources which, while we believe them to be reliable, are not guaranteed. In particular, it should not be relied upon as the sole source of referencee in relation to the subject matter. No liability can be accepted by Datamonitor, its directors, or employees for any loss occasioned to any person or entity acting or failing to act as a result of anything contained in or omitted from the content of this material, or our conclusions as stated. The findings are Datamonitor's current opinions; they are subject to change without notice. Datamonitor has no obligation to up or amend the research or to let anyone know if our opinions change materially. 2

3 In 2012, the FDA gave the go-ahead to 39 new drugs and biological entities, the mos st in over 16 years However, drugs approved for the treatment of disorders of the central nervous system (CNS) accounted for just two of these successful candis; Aubagio (teriflunomide) gained approval for multiple sclerosis (MS) and Fycompa (perampanel) for epilepsy. Looking ahead to FDA drug approval decisions on the horizon in 2013, Datamonitor believes that the tally of two FDA approvals for new CNS drugs in 2012 will be comfortably surpassed in Several promising candis for psychiatric and neurological indications were filed for approval in the US in 2012 and Datamonitor is optimistic that six will demonstratee significant clinical benefit to gain approval by the FDA over the next 12 months. 3

4 Key FDA drug approval decision s for CNS drugs, 2013 Date Drug Company Disease Event Expected outcome Q Feb 28 TH Abilify depot (aripiprazole once monthly) Lundbeck/ Otsuka Schizophrenia PDUFA action FDA approval US launch Q Fourth depot atypical antipsychotic to enter US market. Forecast to be market leader. Mar 28 th BG 12 (dimethyl fumarate) Biogen Idec Multiple sclerosis Datamonitor s expected PDUFA action FDA approval US launch: Q Third oral MS drug to launch in US. Q TBA levomilnacipr an Forest/ Pierre Fabre Major depressive disorder Datamonitor s expected PDUFA action FDA approval US launch: Q Forest s first SNRI product for depression. Q TBA suvorexant Merck Insomnia Datamonitor s expected PDUFA action FDA approval US launch: Q First to market orexin drug for insomnia. Oct 2 nd Brintellix (vortioxetine) Lundbeck, Takeda Major depressive disorder PDUFA action FDA approval US launch: Q TBA cariprazine Forest Gedeon Richter Schizophrenia and bipolar I disorder (manic/ mixed episodes) Datamonitor s expected PDUFA action FDA approval US launch: Q Fierce competition expected from generic atypical antipsychotics. CNS = central nervous system FDA= Food and Drug Administration TBA= To be announced PDUFA = Prescription Drug User Fee Act SNRI =serotonin-norepinephrine reuptake inhibitor 4

5 Q1: February 28 th PDUFA is expected to lead to Q1 launch for Abilify depot (Lundbeck/Otsuka) Datamonitor expects the FDA to grant approval of Lundbeck/Otsukaʼs once-monthly depot formulation of aripiprazole for the maintenance treatment of schizophrenia in adults on February 28. This future successor to oral Abilify was successful in significantly delaying time to impending relapse compared to placebo in both the interim and final analyses of a 52-week, Phase III trial (p<0.0001). Datamonitor projects US launch to take place in Q1 2013, providing a sizeable window of opportunity to switch patients from oral Abilify prior to its US patent expiration in Q Abilify depot is forecast to take over the mantle from Abilify oral as the highest selling schizophrenia drug and retain this status through to As the fourth depot atypical antipsychotic to enter the US market, Abilify depot will be competing with Risperdal Consta, Zyprexa Relprevv, and InvegaSustenna. Moreover, the Abilify depot will compete with Zyprexa Relprevv for the group of patients in which Risperdal Consta and InvegaSustenna do not show any efficacy. Positioning as a well-tolerated alternative to existing depot antipsychotics and as a more convenient treatment option than oral Abilify, along with inheritance of a strong patient base will ensure that revenues of Abilify depot outstrip those of its direct depot competitors. 5

6 Q1: Late March Go-ahead anticipated for BG-12 (Biogen Idec) in MS after FDA s 3 month extension to PDUFA Late March is expected to be when Biogen Idecʼs hotly anticipated BG-12 (dimethyl fumarate) receives FDA approval for the treatment of relapsing remitting multiple sclerosis (RRMS) with US launch tipped for Q BG-12ʼs late-stage efficacy data appears better than interferons and Copaxone and on a par with Gilenya. Assuming that Teva is not successful in its recent efforts to thwart BG-12ʼss market entry, Datamonitor forecastss BG-12 to overtakee older brands and become the highest-selling MS drug. Upon launch, BG-12 will represent the third oral treatment for MS to enter the US market, following Gilenya (fingolimod; Novartis) in September 2010 and Aubagio (teriflunomide; Genzyme) in September BG-1market share from existing first-line therapies, notably Gilenya. It will be is expected to be prescribed solely as a monotherapy therapy and will take used as a first-line therapy, given its relatively benign side-effect profile and high efficacy.biogen Idec has established itself as the leading player in the MS market, with two injectable products marketed for relapsing forms of MS; Tysabri (natalizumab) and Avonex (interferon beta-1a). Therefore, as an oral therapy, BG-12 will serve to augment Biogen Idecʼs already strong MS franchise and can expect to benefit from the companyʼs considerable experience in the MS field. Biogen Idecʼs FDA PDUFA for BG-12 was originally slated for December 28, However, the FDAʼs October 2012 announcement of a 3 month extension to review the application implies March 28, 2013 as the revised PDUFA.Importantly for Biogen Idec, the FDA didd not request additional studies, with ʻadditional time for review of the applicationʼ cited by the FDA as the reason for the extendedd PDUFA. BG-12ʼs delay is not without precedent; the FDA applied 3 month extensionss to the PDUFA s of Gilenya (fingolimod; Novartis) and Aubagio (teriflunomide; Sanofi) prior to their approvals. 6

7 Q3 Standard review expected to elicit FDA approval for Forest s levomilnacipran in depression Q is expected to be when the FDA approves Forestʼss levomilnacipran as a treatment for major depressive disorder (MDD). The candi has demonstrated a consistent antidepressant signal across late-stage studies with one of the four trials reporting a significant benefit over placebo after just one week. Upon projected US launch in Q4 2013, levomilnacipran will represent Forestʼs first serotonin- Pristiq(venlafaxine; Pfizer) and generic duloxetine. norepinephrine reuptake inhibitor (SNRI) product approved for MDD. In the US, levomilnacipran will experience strong competition from Effexor XR (venlafaxine; Pfizer), In the absence of standout antidepressant efficacy and little advance over current market players in its tolerability and side-effect profile, levomilnacipranʼs use will likely be limited to later lines of therapy and insurers will demand that venlafaxine and/or duloxetine are used first. The FDA has yet to publicly announce whether it has accepted Forestʼs NDA for levomilnacipran for review after the company filed for approval on September 27, Datamonitor assumes a standard 10 month review period. 7

8 Q4 Positive FDA decision on Merck s suvorexant in insomnia anticipated; launch in Q Datamonitor expects Merckʼs novel insomnia candi, suvorexant, to receive FDA approval in September 2013, with US launch anticipated in Q Suvorexant (also known as MK-4305), an orexin receptor antagonist, was effective at improving both sleep onset and sleep maintenance during its Phase III program. A unique advantage over GSKʼs failed orexin targeted almorexant is the 12 month safety study which supports chronic use. Upon approval, suvorexant will represent the first major new approach to the treatment of insomnia in nearly 40 years and will likely generate much interest among physicians. However, Merckʼs debut insomnia drug will also be entering a highly competitive market dominated by generic versions of the current gold-standard treatment, zolpidem. Demonstration of superiority over zolpidem and lack of scheduling will therefore by key to suvorexant achieving a strong uptake. The agency accepted Merckʼs NDAA for suvorexant for standard review on November 8, In view of the requirement for the US Drug Enforcement Administration (DEA) to complete a schedule assessment and determination post approval, Datamonitor anticipates a delay of up to 6 months between FDA approval and US launch. 8

9 Q4: October 2 2 nd Go-ahead in depression predicted for Brintellix s ( Lundbeck/Takeda) October 2 PDUFA Datamonitor expects the FDA to grant approval of Brintellix (vortioxetine; Lundbeck/Takeda) in depression in early October, with US launch projected for Q This multimodal antidepressant boasts data from six short-term studies and one long-term maintenance study. After early failures in Phase III development, higher-dose Phase III trials provided strong evidence for vortioxetineʼs efficacy, including in relapse prevention and in elderly patients and demonstrated a good tolerability profile. Although Brintellix will benefit from Lundbeckʼs strong profile in the antidepressant sector, the drug will face competition from Forestʼs Viibryd (which shares some of vortioxetineʼsmodes of action) and generic duloxetine. The first clear evidence of vortioxetineʼs antidepressant efficacy in Phase III development only came after threee inconclusive studies and Datamonitor believes that the drug may have weaker perceived efficacy than its competitors as a result. In addition, compared to Valdoxan (agomelatine; Servier) and other approaches being explored in the pipeline, vortioxetine does not possess notable scientific innovation or differentiation from long-standing SSRI and SNRI antidepressants. In the absence of clear marketing, vortioxetine is in danger of being perceived as just another SSRI antidepressant that only offers incremental benefits in terms of tolerability. Datamonitor expects Brintellix willl take share from existing second and third line antidepressant brands, as well as slowly taking share from first-line generic monotherapies. The FDA is due to render a decision regarding Brintellix as a treatment for major depressive disorder on October 2,

10 Q4: Cariprazine (Forest/Gedeon Richter) poised for US sanctionn in both bipolar disorder and schizophrenia Datamonitor forecasts Q FDA approval of cariprazine (Forest/Gedeon Richter) as a treatment of both schizophrenia and bipolar I disorder (manic or mixed episodes). US launch of the highly potent dopamine receptor antagonist is projected for Q Forestʼs decision to file for approval of two psychiatricc indications concurrently echoes the approach Merck took when seeking sanction for Saphris (asenapine) in 2009, thereby indicating that developers now perceive bipolar disorders as a viable primary indicationn rather than a mere indication expansion. Cariprazine will be entering a mature and intensely competitive market, with the widespread availability of generic atypical antipsychotics chiefly olanzapine and quetiapine hindering uptake. Within the schizophrenia market, Datamonitor expects cariprazine to be positioned as an alternative to existing atypical antipsychotics for the treatment of predominantly negativee symptoms and take share from atypical antipsychotics at first and second lines. Cariprazineʼs uptake among bipolar disorder patients is expected to be weaker on account of its lack of efficacy in bipolar depression; the most important unmet need in the management of bipolar disorders. Demonstration of procognitive effects of cariprazine in patients with schizophrenia and bipolar disorder represents a key opportunity for product differentiation. On November 28, 2012, Forest Laboratories announced its submission of a NDA to the FDA for cariprazine. The FDA has yet to announce whether it has accepted the NDA for review. 10

11 Further reading R&D Trends: Depression Due for February publication. to find out more> >> Market and Product Forecasts: Top 10 Neurology Brands: Use a patient-based approach to size the commercial potential of Alzheimerʼs disease across the seven major markets (the US, Japan, France, Germany, Italy, Spain, and the UK) from 2011 to View in our online store >> Market and Product Forecasts: Alzheimer's Disease Multi-billion dollar potential in high-risk pipeline Assessment of the current and future top 10 neurology brands using a sales-based forecasting methodology. The analysis is designed to understand the future dynamics of the branded neurology market, with a particular focus on leading therapies. View in our online store >> 11

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