Rotigotine Transdermal Patch (Neupro) Lifecycle Strategy Analysis


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An analysis of R&D and marketing strategies for a TTS with rotigotine for the treatment of both Parkinson's Disease and Restless Legs Syndrome.

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Rotigotine Transdermal Patch (Neupro) Lifecycle Strategy Analysis

  1. 1. Life Cycle Strategy Analysis Rotigotine transdermal patch (Neupro®) Prepared by: Andrey Bayanov, MD, PhD Health Recode LLC, Copyright©, 2013
  2. 2. 2 Contents 1 2 3 4 5 Market Assessment ___________________________________________________ Preclinical Development _______________________________________________ Early Clinical Development ____________________________________________ Late Clinical Development ______________________________________________ 3 15 20 21 6 Intellectual Property Strategy ___________________________________________ 7 Marketing Strategy ___________________________________________________ 41 8 9 10 Sales Strategy & Managed Markets ______________________________________ 52 Final Remarks _______________________________________________________ 54 References __________________________________________________________ 55 Regulatory Strategy ___________________________________________________ 31 35
  3. 3. 1. Market Assessment 3 Unmet Medical Needs The Product Addresses Parkinson’s disease (PD) Background / Epidemiology • PD is the second most common neurodegenerative disorder after Alzheimer's disease, and affects about 7.0 mln people worldwide, and 1.0 mln people in the US {1,2}. • Main clinical symptoms: hand and foot tremor, muscular rigidity, akinesia, and postural instability resulting in lifelong disability and significant decrease of patient QOL. • Additional motor manifestations: freezing (loss of movement for a few seconds to be a frequent cause of falls), dysarthria, dysphagia, sialorrhea, and decreased ocular convergence. • Non-motor, psychiatric manifestations: depression (occurs in 50% of patients over the course of their illness), anxiety, apathy, psychosis, and cognitive impairment. Patient Groups • PD’s prevalence rises from 1% in 60+ y.o. to 4% of the population over 80 {1}. • About 85% diagnosed with PD are 65+ y.o. • 5–10% of patients have Parkinson's experience symptoms before the age of 40 {3}.
  4. 4. 1. Market Assessment 4 Unmet Medical Needs The Product Addresses Parkinson’s disease (PD) Primary needs related to treatment with standard antiparcinsonians • The major unmet need is motor complications – either dyskinesia or motor fluctuations, or wearing-off (“on/off”) episodes – affect 50% of patients being treated for 5 years with Levodopa or other dopaminergic medications {4}. The pathogenesis of the motor complications is believed to be caused by short half-life of dopaminergic medications (especially levodopa), the idiopathic deficit in dopamine production in the substantia nigra neurons, and the decreased buffering potential of the remaining functioning neurons that result in a nonphysiologic, pulsatile but not continuous delivery of dopamine from substantia nigra to striatum. That invokes an intermittent stimulation of dopamine receptors and postsynaptic alterations such as gene transcription and firing pattern of basal ganglia output neurons {21, 22}. The motor complications are a significant problem in the management of PD treatment. Therefore, the current trend is to develop strategies that provide steady dopaminergic stimulation through constant drug levels in plasma and continuous drug delivery over 24h.
  5. 5. 1. Market Assessment 5 Unmet Medical Needs The Product Addresses Parkinson’s disease (PD) Secondary needs related to treatment with standard antiparcinsonians • Oral route of administration + pill dosage form of most antiparkinsonians  low adherence to drug therapy of patients with advanced PD, due to the following reasons: – Hardly applicable for patients with dysphagia (difficulty wallowing) – Hardly applicable for patients with hand tremor (named “pill-rolling”) – Dose design often requires the administration of 2 to 3 antiparkinsonian medicines at once – Dose design often requires 3-time administration a day • A neuroprotective quality of the treatment. To date, there is no definite evidence for any of the marketed medications to be neuroprotective {20, 21,22}. Ideal medication qualities for the treatment of early and advanced PD: Providing constant drug levels in plasma over 24h Providing a steady dopaminergic stimulation Optimal dose design to decrease the frequency of drug administration a day Neuroprotecive specificity Not for oral administration Not pills/tabs Easy-to-use
  6. 6. 1. Market Assessment 6 Unmet Medical Needs The Product Addresses Restless Legs Syndrome (RLS) Background / Epidemiology • RLS is one of the most frequent neurological diseases, with an estimated prevalence of 7% to 11% of the general population in North America and Europe, and of 2 to 3% among the Mediterranean and Middle Eastern populations {45}. RLS may affect up to 23 mln Americans {15}. • Main clinical symptoms: uncomfortable sensations in the legs, feet, arms, torso or head that typically occur during periods of rest and inactivity, and predominantly at night, but may emerge at any point in the day or night. The severity of RLS symptoms ranges from mild to intolerable. Moderate-to-severe RLS, when patients experience symptoms two or more times a week, is considered poor manageable. Patient Group • RLS can begin at any age and generally gets worse with age. Statement of needs related to the treatment • Despite a number of medication classes helpful to relieve RLS symptoms, there is a big interindividual variability in therapeutic response to the treatment. • Although there is no one-size-fits-all therapy for RLS, dopaminergic drugs are considered the most target to control the condition, decrease symptoms, and improve sleep. The exploration of more target pharmaceutical agents to make manageable the moderate-tosevere RLS is a recent strategy of healthcare providers.
  7. 7. 1. Market Assessment 7 Market Analysis Market opportunity 1. Based on market segmentation: – Depending on chemical structure and mechanism of action: dopamine precursors (levodopa, Madopar), decarboxylase inhibitors (carbidopa, benserazide), dopamine agonists (pramipexole, Mirapex; ropinirole, Requip XL 24h; pergolide, bromocriptine, apomorphine, cabergoline, lisuride), COMT inhibitors (entacapone, Comtan; tolcapone), type B MAO inhibitors (selegiline; rasagiline, Azilect) and dopamine releaser/anti-glutamergic (amantadine). – Depending on dosage form: most antiparkinsonians are for only oral administration in tabs/pills. 2. Based on current GCP: – Current treatments for PD do control symptoms, but they do not halt or reverse the damage to dopamine-containing neurons. At the initial stages of PD, drug therapy may not be needed. When symptoms become disabling, clinicians may delay using levodopa, the “golden standard”, due to its risk of long-term motor complications and, instead, start patients on longer-acting oral dopamine agonists (e.g., ropinirole, pramipexole). However, levodopa is still widely used in both the early and later stages of PD, as it offers effective symptom control, and other antiparkinsonian drugs also provoke side effects. MAO-B inhibitors (e.g., rasagiline and selegiline) are also used as first-line therapy in the early stages of the illness.
  8. 8. 8 1. Market Assessment Market Analysis Market opportunity Therapeutic Subcategory Total sales, US $ (mln) Ann. Growth Total • Despite a stagnation in annual growth in 2011, the total sales of antiparkinsonian drugs in 2010 figured up to US$ 3.4 bn worldwide. The market of antiparkinsonian drugs looks promising for the investment. Anti-Parkinson's agents 2009 3 282 2010 3 414 4% 2011 3 226 -6%
  9. 9. 9 1. Market Assessment Market Analysis Market opportunity Generic Name • Total sales, US $ (mln) Ann. Growth Total • • Despite the lack of rotigotine (Neupro) in the US market for 4 years, its world’s total sales in 2011 figured up to US$ 132.0 mln and made up 4% of all antiparkinsonians market sales. In the European market the drug recorded sales of €27 mln in the first quarter of 2012. Neupro sales demonstrate an excellent dynamic growth by over 22% annually. The Neupro re-launch on the US market will definitely increase its world sales many times. Rotigotine transdermal patch looks a good investment model. rotigotine 2009 85 2010 109 28% 2011 132 22%
  10. 10. 1. Market Assessment 10 Market Analysis Benchmarking analysis • A comparable, impressive “success story” of Exelon® Patch (rivastigmine TDS) for the treatment of Alzheimer’s disease, due to its comparable to Neupro qualities and marketing strategies, as follows: – “the first and the only” transdermal patch among nootropics for treating Alzheimer’s disease – providing constant drug levels in plasma and continuous drug delivery over 24h – providing significant reduction of symptoms of mild to moderate dementia of the Alzheimer’s type – compliance of good effectiveness and good safety, good benefits/risks balance – “easy-to-use” – once-daily administration – variability of dosage strengths and forms – good tolerability – good adherence of patients to the therapy • As a result, Exelon® Patch’s total sales worldwide in 2011 figured up to US$ 1032.0 mln and made up 16% of world total sales of the nootropics for treating Alzheimer’s dementia. Herein, Exelon’s sales demonstrate a good steady growth by over 5% annually. Neupro has all prerequisites to translate the Exelon’s “best practices” onto own marketing strategies to become a blockbuster in the category.
  11. 11. 11 1. Market Assessment Market Analysis Competitive landscape Direct competitors • • • In the segment of TDS for treatment of PD and RLS – NO COMPETITORS – to date, Neupro is “the first and the only” patch in the market* (see next slide). The Emsam TDS with selegiline, another efficient antiparkinsonian drug, is indicated for the treatment of major depressive disorder In the segment of Non-ergoline dopamine receptor agonists for treating PD and RLS – pramipexole (Mirapex, Mirapexin) – tabs; the top-selling antiparkinsonian drug in the world – ropinirole (Requip XL 24h, Ronirol, Adartrel) – extendedrelease tabs • Both competitors are of world’s Top-5 best-selling antiparkinsonian drugs. The total sales of Requip XL 24h + Mirapex in 2011 figured up to US$ 978.0 mln and made up 30% of the world’s antiparkinsonians sales. . The evident advantages of Neupro vs. Requip XL and Mirapex on the extended indications, dosage form, usability, etc. (see SWOT analysis) make the patch competitive to achieve a best-selling position in the segment. Rank World sales US $ (mln) 2011 Mirapex (BI) 755 Comtan (NVS) 614 Madopar (Roche) 332 Requip XL 24-Hour (GSK) 223 Azilect (LUN) 222 Other 1 081
  12. 12. 1. Market Assessment 12 Market Analysis Competitive landscape Direct competitors possible* • Otsuka Pharmaceutical Co., Ltd., a Japanese pharmaceutical company, in 2010-2012 finalized Phase II-III clinical trials to study the safety, effectiveness and dose regimen of an originally composed transdermal patch with SPM 962 (rotigotine) for both PD and RLS’s patients {39}. However, UCB has signed a co-marketing agreement with Otsuka Pharmaceutical Co., Ltd for Neupro. • Transdermal lisuride and apomorphine patches that are at early R&D phase have been shown to reduce motor fluctuations and duration of 'off' periods in advanced PD, while rotigotine allows significant down-titration of levodopa without severe adverse effects. Thus, parkinsonian patients with long-term levodopa syndrome or motor disorders during sleep could benefit from use of transdermal lisuride and apomorphine {40}.
  13. 13. 1. Market Assessment Market Analysis Competitive landscape Indirect competitors • entacapone (Comtan) – tabs indicated as an adjunct to levodopa/carbidopa to treat patients with idiopathic PD • rasagiline (Azilect) – tabs indicated as initial monotherapy and as adjunct therapy to levodopa • levodopa (Madopar) – tabs; the “golden standard” for the PD treatment The evident advantages of Neupro vs. Comtan, Azilect and Madopar on the decrease of “off” time episodes, as well as on dosage form and usability, make the patch highly competitive to achieve a bestselling position in the category. 13
  14. 14. 1. Market Assessment 14 Market Analysis Burden of Disease • The incidence of PD is about 14 per 100,000 population per year overall but increases to 160 for the population aged 70 years or older. The median prevalence is 9.4 per 1000 (0.3% of the whole population) with a 2% risk for developing PD by the age of 80. It affects approximately 1 mln individuals in the USA {18, 19, 22} with 60,000 new cases diagnosed each year (Parkinson's Action Network data), and about 7.0 mln people worldwide. • Mortality ratios are around twice those of unaffected people. The mortality rate was reported to be 3-fold greater in PD patients before the introduction of levodopa. This was reduced to 1.6fold in the post-levodopa era with a trend to increase again {23}. • Taking into account that by 2025 more than 20% of Europeans will be 65 y.o. or over, with a particularly rapid increase in the number of over 80s, the corresponding quantity of patients with PD will be double increased
  15. 15. 2. Preclinical Development 15 Product Profile • ATC code: N04BC09 – Rotigotine; Non-ergoline dopamine agonist; Parkinson's disease treatment drug. • Neupro is a branded transdermal patch that provides continuous delivery of rotigotine for 24 h following once-daily application to the skin. • License Possessor/Manufacturer: UCB Pharma /Schwarz Pharma.
  16. 16. 2. Preclinical Development 16 Mechanism of action • Rotigotine (Neupro) belongs to the group of non-ergolinic dopamine agonists and shows a close structural analogy to dopamine and apomorphine. At clinical doses rotigotine behaves mostly as a selective D2-like (D2, D3, D4) and D5 receptor agonist, and also as a partial agonist at the 5HT1A receptor {5}. PD is characterized by loss of the dopamine-producing neurons in the substantia nigra area of the brain, along with cell loss in other nerve pathways. • The precise mechanism of action of rotigotine as a treatment for both PD and RLS is not studied enough, although it is thought to be related to its ability to stimulate dopamine receptors within the caudate putamen in the brain.
  17. 17. 2. Preclinical Development 17 Animal model data • Efficacy – In in vitro (D2 receptor selective binding studies) and in vivo rat and monkey model studies from 1986 to 1996, was proved that rotigotine (N-0437, and later N-0923), to be efficacious in the treatment of experimental PD {6,7,8}. • Rotigotine general PK data – Intravenous, intraperitoneal, and oral administration in freely moving male and female rats: T1/2, the plasma clearance, and the apparent volume of distribution at steady state were studied. An extremely fast absorption was found after intraperitoneal administration. Maximal concentrations in plasma were often observed at the first time point 5 min after dosing. The bioavailability in male and female rats was also measured. An increase of the elimination half-life of at least 40% for male rats and 300% for female rats was observed, indicating dose-dependent kinetics after intraperitoneal administration {9}. – Intravenous administration in monkeys: T1/2 and mean clearance values were obtained for different doses of rotigotine. The steady-state volumes of distribution were estimated for the same doses {10}. – Oral and subcutaneous administration in monkeys {11}. Nonclinical studies with rotigotine were conducted in mice, rats, rabbits, and monkeys. Sufficient exposure multiples were achieved in vivo to allow comparison with clinical data, and in the calculation of safety margins.
  18. 18. 2. Preclinical Development 18 Animal model data • Toxicity studies – Retinal degeneration was observed at a dose equivalent to 2.8 times the maximum recommended human dose in a 3-month study in albino rats, mostly in females. At the histopathological evaluation of the eyes retinal degeneration was not observed in any of the toxicology studies in any species used. The relevance of these findings to humans is not known. – In a carcinogenicity study, male rats developed Leydig cell tumors and hyperplasia. Malignant tumors were noted mostly in the uterus of mid- and high-dose females. These changes are typical for dopamine agonists in rats after life-long therapy and assessed as not relevant to human. – The effects of rotigotine on reproduction have been studied in rats, rabbits and mice. Rotigotine was not teratogenic in all three species, but was embryotoxic in rats and mice at materno-toxic doses. Rotigotine did not influence male fertility in rats, but clearly reduced female fertility in rats and mice, because of the effects on prolactin levels which are particularly significant in rodents. – Rotigotine did not induce gene mutations in the Ames test, but did show effects in the in vitro Mouse Lymphoma Assay with metabolic activation and weaker effects without metabolic activation. This mutagenic effect could be attributed to a clastogenic effect of rotigotine. This effect was not confirmed in vivo in both the Mouse Micronucleus Test and the Rat Unscheduled DNA Synthesis (UDS) test. In repeated dose and long-term toxicity studies, the major effects were associated with the dopamine agonist related pharmacodynamic effects and the consequent decrease of prolactin secretion.
  19. 19. 2. Preclinical Development 19 Pharmaceutics, dosage forms and route of administration • Rotigotine chemical name: (6S)-6-{propyl[2-(2-thienyl)ethyl]amino}-5,6,7,8-tetrahydro-1naphthalenol. The empirical formula: C19H25NOS. The molecular weight: 315.48. • Retigotine active substance: a white to off-white powder. Its water solubility and lipophilicity are pH dependent: at neutral pH it poorly water-soluble and lipophilic (neutral form), and at more acidic pH rotigotine’s water solubility increases and its lipophilicity decreases (protonated form). • In preclinical trials in rats and monkey both powder and injectable dosage forms of rotigotine via oral or intravenous, intraperitoneal and subcutaneous administration have been studied. • Due to an extensive first-pass effect, rotigotine showed a very low bioavailability (below 1%) in rodents after oral administration. Based on rotigotine suitable physico-chemical properties for delivery through the skin (see active substance), a transdermal formulation has been developed to avoid the first-pass effect after oral administration and to enable continuous drug administration over 24 hours. A matrix transdermal patch, where the active substance is in the adhesive through which it diffuses to the skin surface, has been selected in order to keep the patch size as small as possible and to allow an easy application to the skin. Rotigotine’s high lipophilicity and the rapid first pass metabolism made oral administration difficult; however, these qualities made it suitable for a transdermal delivery system.
  20. 20. 3. Early Clinical Development 20 Early Stage Development in Humans Phase I safety studies • First In Man Phase 1 initiated in 1998, not in healthy volunteers but in patients with PD (n=9): a single-dose continuous intravenous infusion for 4.5 h provided an evident antiparcinsonian effect within minutes of the initiation, and maximum response was obtained at infusion rates varying from 216 microg/kg per hour and at blood levels of 0.11-1.49 microg/mL. The T1/2 was defined equal to 90 min. Good tolerability was detected {13}. • A double-blind, randomized, placebo- and positive-controlled, parallel-group QT/QTc trial to assess the potential electrocardiographic effects of rotigotine TDS up to 120 cm2/54.0 mg/day in patients with advanced-stage idiopathic PD was conducted in 2006 {34}. Phase II dose-response studies • Effect – A study to find out whether N-9023 is useful in treating the signs and symptoms of PD and to determine the best dose of N-9023 that is safe and effective has been performed {38}. • Dose ranging studies. – Rotigotine transdermal patch’s PK and various doses effectiveness were evaluated in a doubleblind, placebo-controlled study (n=85) {12}. Following the study, a more elastic and effective formulation was designed {14}.
  21. 21. 4. Late Clinical Development 21 Phase III clinical studies analysis Pivotal trials for PD • In five parallel group, randomized, double-blind placebo-controlled trials conducted in the U.S. and abroad the effectiveness of rotigotine in the treatment of the signs and symptoms of idiopathic PD was established. Depending on trial design, PD patients underwent a weekly titration of rotigotine in 2 mg/24 hours increments to either the randomized dose or optimal dose. • In four studies involving 830 patients with early-stage disease and 842 patients with advanced PD, Neupro has been compared with placebo (a dummy treatment). Two of these studies also compared Neupro with ropinirole in early-stage disease and pramipexole in advanced disease. The studies in early-stage disease looked at the number of patients who had at least a 20% improvement in symptoms, as measured with a standard symptom questionnaire. The studies in advanced disease measured the length of time during the day that the patients recorded as ‘off’ (when they had too many Parkinson’s disease symptoms to be able to live normally). Two smaller studies comparing Neupro with ropinirole were completed after the medicine’s authorisation.
  22. 22. 4. Late Clinical Development 22 Phase III clinical studies analysis Pivotal trials for RLS • The efficacy of rotigotine in the treatment of RLS was primarily evaluated in two fixed-dose, randomized, double-blind, placebo-controlled trials with six-month maintenance periods. Patients received rotigotine doses ranging from 0.5 mg/24 hours to 3 mg/24 hours, or placebo, once daily. In these trials, rotigotine provided significant RLS symptom improvement versus placebo for RLS patients, as measured by two widely-accepted tools that allowed patients and clinicians to assess and rank symptom improvement {37}. • In moderate to severe RLS, Neupro has been compared with placebo in two main studies involving a total of 963 patients. The main measure of effectiveness using two standard scales was the change in symptoms after six months of treatment with a stable dose {36}.
  23. 23. 4. Late Clinical Development 23 Phase III clinical studies analysis Primary endpoint • Effectiveness comparable to other efficient antiparkinsonians: – Neupro was more effective than placebo in treating PD. In early-stage disease, 48 to 52% of the patients using Neupro had an improvement in symptoms, compared with 19 to 30% of those using placebo. Neupro was less effective than ropinirole: an improvement was seen in 70% of the patients receiving ropinirole. In the smaller studies completed later, the effectiveness of Neupro was found to be comparable with ropinirole. The rotigotine transdermal system consistently demonstrated statistically significant and clinically relevant efficacy over placebo in patients with early PD and was well tolerated. – In RLS, patients using doses of Neupro between 1 and 3 mg/24 h had a greater improvement than those using placebo in the two studies, as measured on both symptom scales. Neupro is more effective than placebo and its effectiveness is comparable with ropinerole or pramipexole in patients with PD and RLS.
  24. 24. 4. Late Clinical Development 24 Phase III clinical studies analysis Secondary endpoint • Reducing “off’’ time and improving QOL of patients with advanced PD becomes possible if stable plasma levels of an antiparkinsonian agent over 24 h are achieved to provides continuous dopaminergic stimulation. • In an open-label, randomized, 2-site study the 24-hour pharmacokinetic profile of Neupro in early-stage PD patients has been assessed. Subjects received Neupro (8 mg/24 h) and plasma concentrations were measured on day 27 and day 30 during the maintenance phase. (See the diagram). In advanced PD, patients using Neupro had a greater decrease in their ‘off’ time than those taking placebo (a decrease of 2.1 to 2.7 h with Neupro compared with 0.9 h with placebo). The decrease seen with Neupro was similar to that seen with pramipexole (2.8 h). • Neupro provides stable plasma levels and continuous dopaminergic stimulation over 24 hours after reaching a steady state to cover the main unmet needs of PD patients.
  25. 25. 4. Late Clinical Development 25 Phase III clinical studies analysis Safety • • • • • A double-blind SP513 trial to assess the safety of long-term treatment of rotigotine in subjects with early-stage idiopathic PD has been performed. Based on the analysis of pooled placebo-controlled clinical trials comprising a total of 748 Neupro- and 214 placebo-treated patients, 65.2% of the patients on Neupro and 33.2% of patients on placebo reported at least one adverse drug reaction (ADR). The most common ADRs reported in more than 10% of PD and RLS patients treated with Neupro are nausea (feeling sick), application site reactions (redness, itching and irritation of the skin), asthenic conditions (tiredness, weakness and feeling unwell), somnolence, and headache. In trials where the application sites were rotated as reflected in the instructions provided in the SmPC and package leaflet, 34.2% of 748 patients using Neupro, experienced application site reactions. The majority of these reactions were mild or moderate in intensity, limited to the application areas and resulted in discontinuation of Neupro in 7.2% of subjects. Neupro must not be used in people who are hypersensitive (allergic) to rotigotine or any of the other ingredients. The backing layer of Neupro contains aluminium. To avoid skin burns, Neupro must be removed if the patient has to have magnetic resonance imaging (MRI) or cardioversion. Neupro has a good safety and tolerability profile comparable with the Requip XL and Mirapex’s ones.
  26. 26. 4. Late Clinical Development 26 Phase III clinical studies analysis Phase IIIB (upon the patch re-formulation) • In a multicenter, multinational, double-blind, placebo controlled, 2-arm trial the effectiveness of 24-hour transdermal delivery of rotigotine in the control of early morning motor function, sleep quality, nocturnal symptoms, and non-motor symptoms in patients with PD has been proven {31}. • A multicenter, randomized, double-blind, two-way cross-over study to compare the adhesiveness of two different rotigotine patch formulations in subjects with PD was conducted in 2011. • A double-blind, randomized, placebo-controlled study of rotigotine and its effect on all-day functioning and QOL in subjects with moderate to severe idiopathic RLS has been performed {35}. Re-formulated Neupro patch has a good effectiveness and good safety profiles for both PD and RLS patients.
  27. 27. 4. Late Clinical Development 27 Post-Marketing studies Defects in Manufacturing Processes • • • Due to some technology problems, the formation of rotigotine crystals in the patches was detected in April 2008. In order to improve the technology and avoid possible reputational risks, Schwarz Pharma, the Neupro manufacturer, recalled the drug from the US markets and partially from the EU market. {April 8, 2008, Drug Shortage Information, FDA}. Upon the patch been reformulated, a multicenter, randomized, double-blind, two-way cross-over study to compare the adhesiveness of two different rotigotine patch formulations in subjects with PD has been provided. The patch was reintroduced in the US in 2012. Safety and efficacy • • A post-hoc analysis of a prospective open-label study suggested that consistent with the results for the overall population, rotigotine transdermal patch at approved dosages of 1-3 mg/24 h was generally well tolerated after the first year, with sustained efficacy in patients who completed 5 years of treatment at dosages of 1-3 mg/24 h {16}. A multicenter, randomized, double-blind, placebo-controlled, 5-arm, parallel-group trial in subjects with advanced-stage PD showed rotigotine dose response at four its doses used with Ldopa in treating advanced stage PD has been completed in 2011 {33}.
  28. 28. 4. Late Clinical Development 28 Post-Marketing studies New indications • • • • A Phase IV open-label, multicenter, multinational study has proved the feasibility of switching therapy from pramipexole or ropinirole to the rotigotine transdermal system and its efficacy on motor and non-motor symptoms in subjects with advanced idiopathic PD {32} . A Phase IV multicenter, double-blind, placebo-controlled, parallel-group study has also proved a good efficacy of rotigotine on non-motor symptoms in patients with idiopathic PD (completed in 2012). A double-blind, placebo-controlled, parallel, multicenter, randomized interventional Phase IV study will evaluate the efficacy of rotigotine on depressive symptoms in idiopathic PD patients (expected completion in 2013) A multi-centre, randomized, double-blind, placebo controlled study to evaluate the effects of rotigotine on sleep efficiency in patients with advanced PD has just completed, and promising results were obtained. New patient population • An open-label, long-term, follow-up study to determine the safety, tolerability, and efficacy of rotigotine transdermal system as monotherapy in adolescents with RLS will start soon with expected completion in 2021. UCB is very resourceful, dynamic and pragmatic in the exploring new indications and new target patient populations.
  29. 29. 4. Late Clinical Development 29 Pharmacoeconomic trials • In the US, the average wholesale price for a one-month supply of the 6 mg/24h strength rotigotine patches is US$ 281.82 {27}. Monthly costs for other antiparkinsonian drugs, based on US average wholesale prices, range from about US$ 50.00 to US$ 450.00 {28}. • Health-related QOL Improvement: – Motor 'off-time‘ fluctuations are linked to poor QOL and higher healthcare costs. Minimizing off-time is an effective strategy for reducing costs associated with PD. – Adherence to treatment when taking numerous antiparkinsonian drugs may be an issue for both patients and caregivers. The rotigotine patch may improve treatment adherence due to its easy-to-use and once-daily administration schedule. Improved adherence was reported in a retrospective survey of 114 patients taking rotigotine over an average of 70 weeks {29}. Transdermal administration may also be of benefit to patients unable to take oral medications, or those with swallowing difficulties due to advanced disease {30}.
  30. 30. 4. Late Clinical Development 30 Pharmacoeconomic trials • Since there is no yet available statistic data on the number of cured PD and RLS’s patients treated with Neupro® – a study to evaluate QOL of RLS’s patient has just completed in 2013 {35}, a multisite, non-interventional, cross-sectional evaluation of the caregivers' and the physicians‘ preferred route of administration and the physicians‘ rationale for the choice of Neupro® in patients with PD requiring caregiver support has been performed in 2012, and a transdermal rotigotine user surveillance study (TRUST) is in effect to be completed in 2014 – it is hardly possible to calculate the cost-effectiveness and cost-benefit of the treatment. However, taking into account the Neupro’s quality to improve significantly the patient’s adherence to the treatment as well as to increase QALY, we can hypothesize a more high costutility of Neupro treatment compared to the standard treatment. Neupro is a medication of rather the “more costly more effective” category, and provides a good cost-utility treatment model.
  31. 31. 5. Regulatory Strategy 31 NDA and/or EMEA filing regulatory strategy • • • • • • Neupro® was approved first in Europe by the EMEA in February 2006 for PD treatment only. The application was received by the EMEA on 29 September 2004. The product was nowhere licensed else at the time of application submitting. In the US the drug has been approved by FDA in May, 2007 for PD treatment only. Since August 2008 Neupro® has been authorized as a RLS treatment by both the EMEA and FDA. In April 2008, Schwarz Pharma, the Neupro manufacturer, initiated on their own the recall of the Neupro TDS from the market, because of a technology problem associated with the formation of rotigotine crystals in the patches. The drug crystallization may cause less skin absorption and system availability of the drug, and finally increase the efficacy of the product. {April 8, 2008 Drug Shortage Information - FDA}. The same recall was done for some lots of the patch in Europe. After being reformulated and re-investigated in Phase I and Phase IIIB clinical trials in 2009-2011, the rotigotine transdermal patch was reapproved by FDA for the same as earlier indications and reintroduced to the US market in mid-2012. Despite such the circumstances for Neupro and its lack in the US market, the rotigotine transdermal patch still remains the first and the only TDS for the treatment of PD and RLS.
  32. 32. 5. Regulatory Strategy 32 Package insert FDA’s approved final indications • Parkinson's Disease – both early-stage and advanced-stage; • Moderate-to-severe primary Restless Legs Syndrome. EMEA’s approved final indications • Parkinson's Disease – monotherapy in early-stage disease, or in combination with levodopa at any stage of the disease; • Moderate-to-severe primary Restless Legs Syndrome in adults Patient populations • Neupro® may be prescribed for use in adult and elderly patients.
  33. 33. 5. Regulatory Strategy 33 Package insert Dosage form • The Neupro transdermal patch is a thin, matrix-type transdermal delivery system (TDS) consisting of three layers: 1. Backing, tan-colored layer: Polyester film, siliconized, aluminized, colour coated with a pigment (titanium dioxide (E171), pigment yellow 95, pigment red 166) layer and imprinted (pigment red 144, pigment yellow 95, pigment black 7). 2. Self adhesive matrix layer: Poly(dimethylsiloxane, trimethylsilyl silicate)-copolymerisate, Povidone K90, sodium metabisulphite (E223), ascorbyl palmitate (E304) and DL-α-tocopherol (E307). 3. Release liner: Transparent fluoropolymer coated polyester film.
  34. 34. 5. Regulatory Strategy 34 Package insert Dosing schedule • The treatment of PD with Neupro is designed to initiate at 2 mg/24 h and to be increased later in weekly increments of 2 mg/24 h to an effective dose up to a maximal dose of 8 mg/24 h. • The treatment of RLS should be initiated at 1 mg/24 h. Depending on the individual patient response, the dose may be increased in weekly increments of 1 mg/24 hours up to a maximal dose of 3 mg/24 h. • The patch is applied once-daily to the skin of the abdomen, thigh, hip, flank, shoulder, or upper arm and left in place for 24 hours. The prescribed dose may be achieved using single or multiple patches.
  35. 35. 6. Intellectual Property Strategy 35 Patent history Patents for active agent(s)/ methods of producing/ formulations/ compositions • A novel compound (named hereafter rotigotine) with a defined structural formula, and its pharmaceutically acceptable salts thereof, useful as dopamine receptor agonists for the treatment of various CNS diseases such as PD and related disorders, were patented by US 4564628 (1984). • A method for treating with rotigotine the symptoms of parkinsonism in human or other mammals suffering from the symptoms of parkinsonism, as well as a method of producing crystalline rotigotine and a process of obtaining of its two optical isomers: (+) and (−)-rotigotine, was patented by US 4885308 (1988). • A first rotigotine depot form, which achieves a therapeutically significant plasma level over at least 24 h after administration to a patient, was patented by WO 2001EP09595 20010821 (2000), EP 1313467 (2001), US 2003166709 (2003). • A transdermal therapeutic system (TTS) that comprises a rotigotine-containing cement layer, characterized in that the cement layer contains a hot-meltable adhesive in which rotigotine as the active substance is dispersed and partly or completely dissolved, was patented by US 8211462 (2003), EP 0663431 (1996). • An improved method of crystalline rotigotine preparation and purification, as well as a rotigotine dosage form as transdermal therapeutic system, and the therapeutic indications (PD and RLS) were patented by WO 2008/146284, EP 1325742 (2003), US 8344165 (2008).
  36. 36. 6. Intellectual Property Strategy 36 Patent history Patents for active agent(s)/ methods of producing/ formulations/ compositions • An improved transdermal delivery system with a self-adhesive matrix highly permeable to the free base of rotigotine and impermeable to the protonated form of rotigotine was patented by US 8246979 , US 8246980 (08/2003), EP1256340 (2002). • An additional method of converting rotigotine hydrochloride into rotigotine was protected by US Patent Application 2004/0048779. • A novel polymorphic form of rotigotine and a process for production thereof, which is useful for the manufacture of a stable medicament for treating or alleviating symptoms of Parkinson's disease and other dopamine-related disorders, were patented by US 8232414 (2008). • A new composition and formulation for rotigotine patch, as well as new therapeutic indications (prevention, alleviation and treatment of PD, PD Plus Syndrome, a depression, RLS, loss dopaminergic neurons and pain) were patented by US 61667528 (2012), EP 12797703 (2012) • A modified composition for rotigotine transdermal patch is protected by patents US 61667507 (2012), EP 12791699 (2012). • The use of rotigotine, its salts and prodrugs, as a medicament for preventing and/or treating Parkinson's plus syndrome is protected by patents US 7872041 (2005), EP 1256339 (2002).
  37. 37. 6. Intellectual Property Strategy 37 Patent history Patents for indications/ new formulations • A method of iontophoretic delivery of rotigotine for the treatment of Parkinson's disease is patented by US 7632859 (2003). • Novel injectable pharmaceutical compositions for the systemic administration of pharmacologically active ingredients, including rotigotine, whereby the ingredients are released from the pharmaceutical composition over a period of at least 12, preferably at least 24 hours, were patented by EP 0524775 (1993), US 7309497 (2001). • The treatment with rotigitine of hemispatial neglect and other deficits following stroke is protected by patent EP 2559435 (2011). • A liquid intranasal pharmaceutical formulation comprising a pharmaceutically acceptable acid addition salt of rotigotine and α-cyclodextrin is protected by patents US 7683040 (2004), EP 1256339 (2002). Rotigotine active substance, its isomers and pharmaceutically acceptable salts are free of patent protection. Rotigotine methods of producing, its compositions and several TTS formulations are patented by the manufacturer/license possessor. No one patent found on rotigotine combinations with other pharmaceutically active substances. Rotigotine TTS, injectable and intranasal formulations and compositions, as well as the use of rotigotine for the treatment of PD, PD Plus Syndrome, a depression, RLS, loss dopaminergic neurons and pain, consequences of stroke, are reliably patented.
  38. 38. 6. Intellectual Property Strategy 38 Patent time line, US & Europe Active agent(s)/substance(s) • Rotigotine, its isomers and pharmaceutically acceptable salts are free of patent protection in the US and EU since 2004. However, a novel polymorphic form of rotigotine and a process for its production is under patent protection until 2028 in the US. Methods of producing • The method of producing crystalline rotigotine is free of patent protection in the US and EU since 2008. However, an improved method of crystalline rotigotine preparation and purification is under patent protection until 2023 in the EU and until 2028 in the US. Compositions • A modified composition and also a new one, as well as formulations of rotigotine transdermal patch are under patent protection until 2022 in the EU and until 2024 in the US.
  39. 39. 6. Intellectual Property Strategy 39 Patent time line, US & Europe Formulations • The transdermal therapeutic system (TTS) as a rotigotine formulation and a method of its delivery is under patent protection until 2023 in the US, and is expected to expire in 2016 in the EU. Indications • The treatment with rotigotine and rotigotine transdermal patch of PD and other dopamine-related disorders is under patent protection until 2023 in both the EU and US. • The treatment and prevention with rotigotine, its salts and prodrugs of Parkinson's plus syndrome is under patent protection until 2022 in the EU and 2025 in the US. • New therapeutic indications (prevention, alleviation and treatment of PD, PD Plus Syndrome, a depression, RLS, loss dopaminergic neurons and pain) are under patent protection until 2032 in both the EU and US. New dosage forms • A liquid intranasal pharmaceutical formulation. A novel polymorphic form of rotigotine, its pharmaceutically acceptable salts and prodrugs, and a process for its production, as well as the rotigotine transdermal patch, its compositions and indications for the treatment of PD, PD Plus Syndrome, a depression, RLS, loss dopaminergic neurons and pain, consequences of stroke are reliably protected with patents for the next 9-15 years.
  40. 40. 6. Intellectual Property Strategy 40 Other IP issues Possible biomarkers filed as a companion for the drug • Despite a lot of researches on the PD etiology and pathogenesis, genetic causes account for only 10-15% of the cases. Some concepts of protein mishandling, mitochondrial dysfunction, apoptosis, and inflammation, as well as of the involvement of the ubiq-uitin-proteasomal system and lisosomes, do not match yet with a candidate biomarker/signature as therapeutic target {22, 24-26}. • At least 5% of people are now known to have forms of the disease that occur because of a mutation of one of several specific genes. Mutations in genes including SNCA, LRRK2 and GBA have been found to be risk factors for sporadic PD {41}. • More than 60% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance {42}. • Three genes, MEIS1, BTBD9 and MAP2K5, were found to be associated to RLS {43}. Their role in RLS pathogenesis is still unclear. More recently, a fourth gene, PTPRD was found to be associated to RLS {44}. No genetic biomarkers defined for both PD and RLS yet. No biologic or gene therapy designed for the treatment/co-treatment of both PD and RLS yet.
  41. 41. 7. Marketing Strategy 41 Marketing strategy for the drug • US & EU – despite the re-launch in the US market after the lack for 4 years, the Neupro’s marketing strategy for both the US and EU does not look large-scale, aggressive and expensive. The drug still remains the first and unique transdermal patch in its therapeutic segment as well as in overall category of antiparkinsonians, and has definitive advantages over competitor’s products. Moreover, a very flexible and cooperative marketing behavior in respect of the closest competitors is detected. As a result, the dynamic growth of Neupro‘s sales by 22% annually for the past 3 years looks a good trend for the rest of the world. The current marketing strategy includes: 1. Continuing promo activities via public awareness and loyalty program development through Medical Science Liaisons for: – Target specialist groups: – out-patient neurologists – neurologists of geriatric centers/homes – family practitioners – in-patient neurologists/neuropsychiatrists – Target patients groups/ patient societies/ funds 2. Continuing post-marketing studies 3. Qualitative marketing researches Positioning (see slide #48): 1. A drug having a multimodal versatility in the treatment of both DP and RLS: – For early-stage and the advanced diseases – For monotherapy and in combination with small doses of pramipexole or ropinirole 2. Key messages: – “The first and the only” transdermal patch for symptom control of PD and RLS – An excellent alternative to pills/tabs – Exceptional “easy-to-use”/usability qualities
  42. 42. 7. Marketing Strategy 42 Marketing strategy for the drug • Asian Markets (Japan, Malaysia, South Korea, Singapore, Taiwan, China) – the recent main strategic direction needs a more careful and flexible regulatory strategy to approve and launch finally the patch in the markets. A wide range of local clinical trials taking ethnic peculiarities (metabolism, genetic polymorphism, dosage strengths) into account, as a part of international trials, is provided there, as follows: • Three parallel group trials to evaluate the PK, safety and tolerability of repeated dose treatment with rotigotine TDS in Japanese and Caucasian healthy subjects have been completed in 2002 and 2012. • A single-site, single-dose and multiple-dose study to evaluate the PK, safety, and tolerability of rotigotine transdermal patch in healthy Chinese subjects has been completed in 2012. • An open-label, multicenter, multinational study to assess the feasibility of switching therapy from pramipexole or ropinirole to the rotigotine TDS and its effect on motor and non-motor symptoms in subjects with advanced PD Phase IV has been completed in 2013 {32}. • A study investigated the safety and efficacy of rotigotine add-on therapy with low doses of pramipexole or ropinirole in patients with advanced-stage PD who have insufficient response to L-dopa and low doses dopamine receptor agonists has been completed in 2013. • A double-blind, placebo-controlled, parallel, multicenter, randomized interventional Phase IV study to evaluate the efficacy of rotigotine in depressive symptoms in PD patients (expected completion in 2013)
  43. 43. 7. Marketing Strategy Marketing strategy for the drug • Emerging markets (Brazil, Russia, India) – a forward looking and very profitable strategic direction commercialize the patch there. • to Neupro® is authorized in 36 countries. 43
  44. 44. 44 7. Marketing Strategy SWOT Analysis + “The first and the only”– no one else transdermal patch analogue for the treatment of PD and RLS in the market + Good adherence of patients to the antiparcinsonian therapy + Strengths Variability of dosage strengths + Excellent “easy-to-use”/ usability qualities for target patient groups, and specifically, for 80+ y.o. + Providing continuous drug delivery and constant drug levels in plasma over 24 h + + Significant reduction of endof-dose “off” symptoms and dyskenesia + Non-aggressive marketing strategy + Significant reduction of symptoms of both early and advanced PD, and RLS + Very friendly, flexible and collaborative marketing strategy in regards with direct competitors + A very customer-centric product development ant business model + Compliance of good safety and good effectiveness, good benefits/risks balance + Good tolerability + Significantly improving HR-QOL + A cost-effective and cost-utility model of the treatment of PD and RLS Excellent patent protection for the molecule, dosage form, compositions, and for therapeutic indications
  45. 45. 7. Marketing Strategy 45 SWOT Analysis Weaknesses • • • • • • No evident neuroprotecive specificity required for an “ideal” antiparkinsonian drug Distribution in the retail pharmacy segment only Rather not enough affordable while distributing through retail pharmacies Shady, unaccountable sales on on-line market Side effects such as skin irritation and topical allergy at the place of application may reduce the quantity of target patients Not in the US and EU essential drug lists
  46. 46. 46 7. Marketing Strategy SWOT Analysis Opportunities • • • Potent for sharing the market with bestselling products for the treatment of earlystage and advanced both PD and RLS to achieve more significant sales Potent for launching the Asian and emerging markets Very resourceful and flexible marketing strategy development in regards to closest competitors Threats • • • • Retail pharmacies as the only distribution channel may affect sales strategy High price of the patch may diminish sales and distribution Not clear reimbursement strategy Several new technological developments for treating PD (sublingual films, biodegradable implants) to provide 24h constant drug plasma levels and delivery are patented recently (2013) by outside investors, and are potent to become strong competitors in the market
  47. 47. 7. Marketing Strategy 47 Drug value proposition Neupro® vs Requip XL® or Mirapex® • FDA and EMEA approved for the treatment of the signs and symptoms of idiopathic PD and moderate-to-severe primary RLS. • Neupro benefits: – Unique dosage form – the incremental benefit – Highly selective to D2-like and D5 receptors – Providing constant drug levels and continuous drug delivery over 24 hours  increasing treatment effectiveness – Favorable safety profile – Good tolerability, few local topical reactions / allergy events reported – Once-daily administration – Excellent “easy-to-use”/usability quality – Wide range of dosage strengths and very convenient dosing regimen – Significant improvement in patient’s adherence to drug therapy – Additional improvement in the treatment effectiveness – Significant improvement of QOL in patients with PD and RLS. – Cost-effective and cost-utility Neupro through proven good efficacy and tolerability, and excellent usability offers a new standard of the treatment and convenient care management for PD and RLS patients.
  48. 48. 7. Marketing Strategy 48 Positioning statement • Market category / segment: Antiparkinsonians / Non-ergoline dopamine receptor agonists • Direct competitors: pramipexole and ropinirole. • Equal to pramipexole and ropinirole effectiveness for symptom control in PD and RLS. • Offers the potential benefits of once-daily, topical administration and continuous drug delivery over 24 hours, which results in more constant drug levels than with oral medications. • Non-oral administration and “easy-to-use” quality – an additional benefit for patients and specifically for those who have hand tremor and difficulty swallowing. • Significantly improves patient’s adherence to drug therapy resulting in the increase of treatment effectiveness and QOL. • Drug for mostly elderly individuals • Outpatient drug • Mid-to-high price segment while selling through pharmacy retail • A cost-effective and cost-utility model for the treatment of both PD and RLS. Neupro has strong strengths and positioning qualities among competitors in the market.
  49. 49. 7. Marketing Strategy 49 Pricing strategy • In the US, the average wholesale price for a one-month supply of the 28-film 6 mg/24h strength rotigotine patches is US$ 281.82 {27}. In the EU countries except UK* the price varies from € 136 to 168 per the same patch. • Due to only retail pharmacy distribution and sales, the patch price varies significantly, depending on its dosage strengths, and is rather of mid-to-high price segment. Thanks to such a wide choice of patch dosage strengths and prices, the patients sometime optimize on their own the daily/weekly/monthly prescribed dose to achieve a costeffectiveness compliance. • Finally, the monthly average cost of the treatment with Neupro varies from US$ 100 to 200 for patients with early stage PD, and figures up to US$ 300 for patients with advanced stage PD, depending on the country. (The data were obtained on multiple Internet forums for PD patients). Despite the patch price is perceived rather high, the final cost of monthly treatment with Neupro looks generally affordable. The Neupro pricing strategy looks rather “more costly more effective”.
  50. 50. 7. Marketing Strategy 50 Other Marketing Issues Reimbursement strategy • No involvement in the essential drug list. • No direct participation in and reimbursements by the US federal-state health assistance programs (Medicaid, Medicare). • No data available on covering the treatment expenses by private insurance funds both in the USA and EU. Line extensions • Novel dosage form – rotigotine nasal spray – is still at the stage of early-to-mid R&D since 2006. A double-blind, placebo-controlled, parallel-group, proof of concept trial to assess the tolerability, safety, and efficacy of the rotigotin for the acute treatment of “off“ symptoms in patients with advanced-stage, idiopathic PD, as well as a study of the same design to assess the efficacy, safety and tolerability of ascending doses of the spray for the treatment of RLS Symptoms have been completed, and their results are promising.
  51. 51. 7. Marketing Strategy 51 Other Marketing Issues Novel indications • Fibromyalgia Syndrome – A parallel, randomized, double-blind, placebo-controlled, multicenter proof of concept trial to assess the efficacy and safety of 2 different doses of rotigotine in patients with signs and symptoms associated with fibromyalgia syndrome was completed in 2008, and its results are promising. • Depression – A double-blind, placebo-controlled, parallel, multicenter, randomized interventional Phase IV study to evaluate the efficacy of rotigotine in depressive symptoms in PD patients has been continuing; the expected study completion in 2013. • Sleep Disorders – A multi-centre, randomized, double-blind, placebo controlled study to evaluate the effects of rotigotine on sleep efficiency in patients with advanced PD has just completed. – A study on the effect of rotigotine on motor symptoms in patients with advanced PD with motor fluctuations and symptoms of gastrointestinal dysfunction is expected to complete in 2013. – A multicenter, double-blind, placebo-controlled, parallel-group, Phase IV study has shown a good efficacy of rotigotine in the relief of non-motor symptoms in patients with PD (completed in 2012). • Stroke – A multi-centre exploratory study to evaluate the efficacy of rotigotine in the treatment of hemispatial neglect and motor deficits following stroke has shown excellent results (2010).
  52. 52. 8. Sales Strategy & Managed Markets 52 Other Marketing Issues Sales strategy • The retail pharmacy segment seems to be the only channel of Neupro distribution and sales. No reimbursement strategy detected. However, a “more costly more effective” positioning and sales strategy achieves excellent results. Hospital vs. Primary care / Family practitioners vs. specialists? • Neupro is definitely an outpatient care segment medication. So, a Neupro promo campaign to engage family practitioners as the primary target specialist group will be successful in the US but not in the EU, Asian countries and not for the emerging markets where family practitioners are not widely spread. Advertising campaigns – promo activity messages are, as follows: • The first and the only TDS for the treatment of PD • Effective symptom control in Parkinson’s disease, etc. (See slides # 41, #44) The differences by markets • Since the PD is less prevalent in Asian populations than in the North American and European ones, the patch is to be positioned and co-strengthen strategically there as a “2 in 1” medicine for the relief not only motor but also non-motor symptoms of PD (depression, sleep disorders, gastrointestinal disorders). The relevant clinical trials in Asian countries are in effect or have just been completed.
  53. 53. 8. Sales Strategy & Managed Markets 53 Other Marketing Issues Unique tools used by the company to differentiate their drug • Large-scale well-designed clinical and post-marketing trials to explore new indications and new patient populations, as well as the unmet needs of prospective markets. • Studies to unite competitors into a shared marketing strategy to co-strengthen the own and competitor’s products. For instance, a study on the safety and efficacy of rotigotine add-on therapy with low doses of pramipexole or ropinirole in patients with advanced-stage PD who have insufficient response to L-dopa and low doses dopamine receptor agonists (2013). Innovative uses of social media or technology • Neupro’s overall possible information for both patients and physician specialists is available on the UCB’s official web site. Also, a separated, specially designed site, as a part of UCB’s public awareness campaign, contains Neupro overall possible information for each target audience Sales volume the company has achieved • Despite the lack of rotigotine patch (Neupro) in the US market for 4 years, its world’s total sales in 2011 figured up to US$ 132.0 mln and made up 4% of all antiparkinsonians market sales. In the European market the drug recorded sales of €27 mln in the first quarter of 2012. To date, Neupro® is authorized and selling in 36 countries. (See slide #9)
  54. 54. 9. Final Remarks 54 Anything should be done the company has an even more successful product? • Despite the Neupro’s lack in the US market for 4 years, the recent local product-related marketing/promo behaviors may appear paradoxically passive and blear-eyed. • However, to date, the manufacturer is likely has been focused on more promising strategies in the product lifecycle development – an extensive investment in clinical trials for new indications, new patient populations, new markets worldwide, and even for a new, non-patch dosage form (nasal spray), as well as in continuing extensive post-marketing researches for the current indications. • Moreover, the other core strategy to develop partnership with the product’s direct competitors looks paradoxical as well, although actually is exceptionally resourceful and pragmatic. The final goal of this alliance seems to reduce levodopa market share or drive levodopa out of the market. Did they miss anything? • The gaining and maintenance of Federal listing status for Neupro (EDL, price, reimbursement status) if not in the US but in other countries will significantly increase its availability and affordability for the target patients, and facilitate finally the sales strategy. Neupro is at an intermediate stage of its life cycle. That is why their recent large-scale clinical trials to explore new indications and new patient populations are anticipatory and pragmatic. The product lifecycle development and marketing strategies look more than adequate and impressive, and potent to repeat the Exelon’s “success story” in the world market.
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