Opicapone is a peripheral, selective and reversible catechol-o-methyltransferase (COMT) inhibitor 1.

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1 New Medicines Committee Briefing June 2017 Opicapone (Ongentys ) as adjunctive therapy in adult patients with Parkinson s disease and end-of-dose motor fluctuations Opicapone (Ongentys ) is to be reviewed for use within: Primary Care Secondary Care Summary: Opicapone is a peripheral, selective and reversible catechol-o-methyltransferase (COMT) inhibitor 1. Opicapone is licensed as a once daily oral adjunctive therapy to preparations of levodopa/dopa decarboxylase inhibitors (DDCI) in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations 1. The NICE evidence summary stated that opicapone, as an adjunct to levodopa, was more effective than placebo, and non-inferior to entacapone, at reducing off-time in people with Parkinson's disease 2. MTRAC stated that opicapone would be suitable for prescribing in primary care, following initiation in secondary care. The committee considered the evidence for efficacy to be relatively strong. MTRAC stated that some patients may benefit from the additional option offered by opicapone, especially those in whom entacapone is contraindicated, poorly tolerated or poorly effective 3. Two phase III randomised controlled trials (BIPARK I and BIPARK II) have demonstrated that opicapone is superior to placebo and non-inferior to entacapone in reducing off-time in patients with Parkinson s disease and end-of-dose motor fluctuations 4,5. Ongentys is a black triangle drug ( ) and is monitored intensively by the MHRA 1. 1 P a g e

2 Formulary application Consultants submitting application: Clinical Director: Dr Mann (Neurology Consultant) Dr Indira Natarajan (Clinical Director for Neurosciences) Dr Mann has requested for Opicapone (Ongentys ) to be considered for inclusion in the North Staffordshire Joint Formulary as adjunctive therapy to preparations of levodopa/dopa decarboxylase inhibitors (DDCI) in adult patients with Parkinson s disease and end-of-dose motor fluctuations who cannot be stabilised on these combinations. He intends that Opicapone (Ongentys ) will be initiated in hospital and subsequently continued in Primary Care as there is no monitoring required. Dr Mann estimates 10 patients per year will be treated with opicapone. Background 6 Parkinson s disease is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons within the substantia nigra region of the mid brain. The main features of Parkinson s disease are bradykinesia, tremor and rigidity, disturbances of movement, and problems with posture. Bradykinesia is characterized by difficulty in initiating, and slowness in executing movements. The tremor occurs in the limbs while at rest and disappears on movement and during sleep. Other common symptoms of the disease are autonomic disturbances (hypersalivation, constipation, micturition disturbances, sexual functioning, orthostatic hypotension, hyperhidrosis), sleep disturbances, and disturbances in the sense of smell or sense of temperature. Depression and cognitive dysfunction is also common in Parkinson s disease patients. Parkinson s disease usually begins later in life: it is rare before 50 years of age, with a mean age of onset of about 60 years. The overall prevalence of Parkinson s disease for subjects aged 65 years or older is 1.6%. Levodopa is an effective symptomatic treatment of Parkinson s disease; however progression of the disease requires gradual increases in levodopa dosage to achieve adequate motor control, which leads to development of motor complications such as motor fluctuations and dyskinesias. Levodopa is administered in conjunction with a peripheral DDCI - benserazide or carbidopa to prevent the peripheral conversion of levodopa to dopamine. This reduces side effects such as emesis, orthostatic hypotension, and cardiac arrhythmia. However, when administered together with a DDCI, only a relatively small amount of an oral dose of levodopa reaches the brain because COMT becomes the major metabolising enzyme for levodopa, and a considerable amount of the drug undergoes O- methylation to 3-O-methyl-levodopa (3-OMD) in the brain and periphery. COMT inhibitors prevent degradation of levodopa and are used in the treatment of Parkinson s disease. The COMT inhibitors marketed to date are tolcapone, entacapone and opicapone. Tolcapone is a more potent inhibitor of COMT than entacapone; it acts both in the periphery and central nervous system. However, due to an increased risk of hepatic toxicity with tolcapone, its use is limited to patients who have failed other therapies or are intolerant to entacapone. Entacapone is currently the standard COMT inhibitor used in the treatment of Parkinson s disease. It acts only in the periphery and is safer than tolcapone, however it is less efficacious than tolcapone and requires frequent dosing. Opicapone is a novel, once-daily, potent third-generation COMT inhibitor. It acts only in the periphery and is a selective and reversible COMT inhibitor. Opicapone is indicated as adjunctive therapy to 2 P a g e

3 preparations of levodopa/ddci in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. Current formulary status Dopaminergic drugs used in Parkinson s disease APC Review: June 2011 Levodopa Levodopa and carbidopa with entacapone 2 Catechol-O-methyltransferase inhibitors Entacapone 2 Restriction: Initiation by specialist MTRAC Therapeutic class and mode of action 1 Opicapone is a peripheral, selective and reversible COMT inhibitor with a high binding affinity and a long duration of action (>24 hours). In the presence of a DDCI, COMT becomes the major metabolising enzyme for levodopa, catalysing its conversion to 3-OMD in the brain and periphery. In patients taking levodopa and a peripheral DDCI, such as carbidopa or benserazide, opicapone increases levodopa plasma levels thereby improving the clinical response to levodopa. Licensed indications 1 Ongentys is indicated as adjunctive therapy to preparations of levodopa/ddci in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. Dosage and administration 1 The recommended dose of opicapone is 50 mg once daily. The manufacturer recommends it to be taken once-daily at bedtime at least one hour before or after levodopa combinations. Opicapone enhances the effects of levodopa. Hence, it is often necessary to adjust levodopa dosage within the first days to first weeks after initiating the treatment with opicapone. Safety and adverse effects 1 Contraindications The following contraindications are listed in the Summary of Product Characteristics: Hypersensitivity to the active substance or to any of the excipients Phaeochromocytoma, paraganglioma, or other catecholamine secreting neoplasms History of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis 3 P a g e

4 Concomitant use with monoamine oxidase (MAO-A and MAO-B) inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson's disease. Special warnings and precautions for use Renal impairment: No dose adjustment is necessary in patients with renal impairment, as opicapone is not renally excreted. Hepatic impairment: No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh Class A). Caution, and possible dose reduction, is recommended in patients with moderate hepatic impairment (Childs-Pugh B). Treatment should be avoided in patients with severe (Childs-Pugh C) hepatic impairment. Dose adjustments of antiparkinsonian therapy: Ongentys is to be administered as an adjunct to levodopa treatment. Opicapone enhances the effects of levodopa. To reduce levodopa-related dopaminergic adverse reactions (e.g. dyskinesia, hallucinations, nausea, vomiting and orthostatic hypotension), it is often necessary to adjust the daily dose of levodopa by extending the dosing intervals and/or reducing the amount of levodopa per dose within the first days to first weeks after initiating treatment with Ongentys, according to the clinical condition of the patient. If Ongentys is discontinued it is necessary to adjust the dosing of the other antiparkinsonian treatments, especially levodopa, to achieve a sufficient level of control of the symptoms. Psychiatric disorders: Patients and care-givers should be made aware that impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments. Patients should be monitored regularly for the development of impulse control disorders and review of treatment is recommended if such symptoms develop. Raised Liver Enzymes: Increases in liver enzymes were reported in studies with COMT inhibitors. Liver functions tests should be considered in patients who experience progressive anorexia, asthenia and weight decrease within a relatively short period of time. Pregnancy and breastfeeding: Ongentys is not recommended during pregnancy, in women of childbearing potential not using contraception or in breastfeeding due to limited data on the use of opicapone in these patient groups. Effects on ability to drive and use machines: Opicapone in association with levodopa cause dizziness, symptomatic orthostatism and somnolence and therefore caution should be exercised when driving or using machines. Summary of the safety profile The most common adverse reactions reported were nervous system disorders. 4 P a g e

5 Table 1 Frequency of adverse reactions 1 System Organ Class Very common Common Uncommon Metabolism and nutrition disorders Psychiatric disorders Nervous system disorders Eye disorders Ear and labyrinth disorders Cardiac disorders Dyskinesia Abnormal dreams, Hallucination, Hallucination visual, Insomnia Dizziness, Headache, Somnolence Decreased appetite, Hypertriglyceridaemia Anxiety, Depression, Hallucination auditory, Nightmare, Sleep disorder Dysgeusia, Hyperkinesia, Syncope Dry eye Ear congestion Palpitations Vascular disorders Orthostatic Hypotension Hypertension, Hypotension Respiratory, thoracic and mediastinal disorders Gastrointestinal disorders Musculoskeletal and connective tissue disorders Renal and urinary disorders Investigations Constipation, Dry mouth, Vomiting Muscle spasms Blood creatine phosphokinase increased Dyspnoea Abdominal distention, Abdominal pain, Abdominal pain upper, Dyspepsia Muscle twitching, Musculoskeletal stiffness, Myalgia, Pain in extremity Chromaturia, Nocturia Weight decreased Drug Interactions 1 Monoamine oxidase (MAO) inhibitors: The concomitant use of opicapone with MAO inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson's disease is contraindicated. The concomitant use of the MAO-B inhibitor safinamide should be used with caution due to limited experience of use. Medicinal products metabolised by COMT: The effects of medicinal products metabolised by COMT (e.g. rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, dopexamine or dobutamine) may be potentiated, and therefore careful monitoring is advised. Tricyclic antidepressants and noradrenaline re-uptake inhibitors: The concomitant use of tricyclic antidepressants and noradrenaline re-uptake inhibitors (e.g. venlafaxine, maprotiline and desipramine) should be used with caution due to limited experience. Repaglinide: Opicapone is a weak inhibitor of CYP2C8. The concomitant use of opicapone and medicinal products metabolised by CYP2C8, such as repaglinide, should be avoided. OATP1B1 substrates: 5 P a g e

6 Opicapone is a weak inhibitor of OATP1B1. There is no experience with opicapone when used concomitantly with OATP1B1 substrates. Thus, particular consideration should be given to medicinal products transported by OATP1B1 and their concomitant use should be considered with appropriate caution. Presentation 1 Opicapone (Ongentys ) is formulated as a hard dark blue capsule, approximately 19 mm, and imprinted OPC 50 on the cap and Bial on the body. Guidance and Evidence Summary NICE Guidance No NICE Clinical Guideline CG35: Parkinson s disease in Over 20s Diagnosis and management 7 NICE state that there is not a universal first choice drug therapy for people with early or later Parkinson s disease. The choice of drug prescribed should take into account clinical and lifestyle characteristics and patient preference, after the patient has been informed of the short and long term benefits and drawbacks of the drug classes. Levodopa, dopamine agonists and MAO-B inhibitors are suitable for use in early and later Parkinson s disease. COMT inhibitors may be used to reduce motor fluctuations in people with later Parkinson s disease. NICE recommend that in view of problems with reduced concordance, for people with later Parkinsons s disease entacapone should be offered a triple combination preparation of levodopa, carbidopa and entacapone. Tolcapone should only be used after entacapone has failed in people with later Parkinson s disease due to lack of efficacy or side effects. NICE was published in 2006 while opicapone was launched in 2016 hence the reason it was not mentioned in NICE guideline. NICE Evidence Summary 2 : NICE published an evidence summary in March 2017 on the use Opicapone in Parkinson s Disease with end-of-dose motor fluctuations. The evidence summary reviewed the BIPARK I study 4 - a randomised placebo- and active-controlled trial in people with Parkinson's disease of at least 3-year duration, who were taking a stable dose of levodopa and experiencing end-of-dose motor fluctuations. The study reported that opicapone, as an adjunct to levodopa, was more effective than placebo at reducing off-time in people with Parkinson's disease over 15 weeks (mean difference of 60.8 minutes). Improvements in on-time without troublesome dyskinesia were also seen in people treated with opicapone (mean difference of 62.6 minutes compared with placebo). The effect was maintained at 1 year in an open-label extension study. Opicapone was shown to be non-inferior to entacapone for reducing off-time. Overall, opicapone was well tolerated with a relatively low incidence of adverse events compared with placebo and entacapone. NICE evidence summary noted that specialists who commented on the evidence summary suggested that opicapone may be an option to consider when entacapone is not tolerated or is inadequate at controlling symptoms. 6 P a g e

7 Scottish Medicines Consortium (SMC) No The Scottish Medicines Consortium has not reviewed opicapone. All Wales Medicines Strategy Group (AWMSG) No The All Wales Medicines Strategy Group (AWMSG) has not reviewed opicapone and state that due to the absence of a submission from the marketing authorisation holder, opicapone (Ongentys ) cannot be endorsed for use within NHS Wales. Regional Drug and Therapeutic Centre (RDTC) 8 No RDTC are currently reviewing opicapone and are expected to publish a review in August Midlands Therapeutics Review and Advisory Committee (MTRAC) 3 Yes MTRAC stated that opicapone would be suitable for prescribing in primary care, following initiation in secondary care. The committee considered the evidence for efficacy to be relatively strong: opicapone was found to be non-inferior to entacapone in patients with Parkinson s disease and end of dose motor fluctuations. The committee noted that opicapone is a once daily treatment, unlike entacapone which is taken with every levodopa dose. However, patients can be prescribed a combined levodopa/ddci/entacapone combination which reduces the burden of tablets taken. Opicapone is taken one hour before or after the bedtime levodopa dose, which potentially increases dosing frequency. MTRAC stated that some patients may benefit from the additional option offered by opicapone, especially those in whom entacapone is contraindicated, poorly tolerated or poorly effective. Efficacy BIPARK I Trial 4 : Opicapone as an adjunct to levodopa in patients with Parkinson s disease and end of dose motor fluctuations: a randomised, double blind, controlled trial In a randomised, double-blind, placebo- and active-controlled study over weeks, opicapone (5mg, 25mg or 50mg once daily) was compared to entacapone (200mg with every levodopa dose) and placebo in patients with Parkinson's disease experiencing end-of-dose motor fluctuations. All participants (n=600) had a clinical diagnosis of Parkinson's disease for 3 or more years and were taking a stable dose of levodopa (3-8 daily doses). Concomitant treatment for Parkinson s disease was permitted, with the exception of apomorphine, tolcapone and entacapone (other than entacapone treatment which was supplied as part of the blinded trial). Patients who had previously taken entacapone or tolcapone, had severe dyskinesia and/or severe or unpredictable periods in the off state, or both were excluded from the study. The primary endpoint was the change from baseline in absolute off-time as assessed by patient diaries. The study evaluated the superiority of opicapone to placebo and also the non-inferiority of opicapone to entacapone 200mg. 7 P a g e

8 Motor symptoms (off and on state): The mean change from baseline in absolute time in the off state at weeks was minutes in the opicapone 50mg group, compared to 96.3minutes in the entacapone group and 56.0 minutes in the placebo group in the intention to treat analysis. The mean difference in change from baseline between opicapone 50mg and placebo was 60.8 minutes (95% confidence interval [CI] 97.2 to 24.2, p=0.0015) demonstrating superiority to placebo. In the non-inferiority analysis, the mean difference in the absolute time in the off state with opicapone 50mg compared with entacapone was 26.2 minutes (95% CI 63.8 to 11.4, p=0.0051) [per-protocol analysis]). Based on the pre-defined non-inferiority margin of 30 minutes, opicapone 50 mg was found to be non-inferior to entacapone. The proportion of patients with a reduction in time in the off state of at least 1 hour was significantly higher in the opicapone 50mg group compared to placebo (70% versus 48%, 95% CI ; p=0.001). The proportion of patient with an increase in on time of at least 1 hour was also significantly higher in the opicapone 50mg group compared to placebo (65% versus 46%, 95% CI ; p=0.003). No statistically significant difference was found for entacapone when compared with placebo or entacapone compared with opicapone 50 mg for these outcomes. Motor symptoms without troublesome dyskinesia: There was a statistically significant improvement in on-time without troublesome dyskinesia with opicapone 50mg when compared with placebo (62.6minutes; 95% CI , p=0.002), and entacapone compared with placebo (47.6 minutes, 95% CI 9.3 to 6.0, p=0.02). There was no statistically significant difference between opicapone 50mg and entacapone for this outcome (p=0.45). Clinician and patient global impression of change: A statistically significant difference was found in clinician global impression of change (CGI-C) and patient impression of change (PGI-C) with opicapone 50mg compared with placebo (p= and p= respectively). There was also a statistically significant improvement in CGI-C and PGI-C with opicapone 50mg compared with entacapone (p=0.007 and p= respectively). Health-related quality of life, motor and daily activities scores: There was an improvement in healthrelated quality of life, motor scores and daily activities scores (assessed using the Unified Parkinson s disease rating scale [UPDRS], Parkinson s Disease Sleep Scale [PDSS], 39 item Parkinson s Disease Questionnaire [PDQ-39] and Non-Motor Symptoms Scale [NMSS]) from baseline to end point in all treatment groups (including placebo). The differences between active treatment (opicapone 50mg and entacapone) and placebo groups were not statistically significant. Safety: The percentage of patients who discontinued treatment due to adverse effects were low and similar across the treatment groups (4% in opicapone 50mg group, 7% in the placebo group and 7% in the entacapone group). The number of participants experiencing at least 1 treatment-emergent adverse event was similar for all doses of opicapone and placebo (between 50-57% participants in each group). The number of participants with serious treatment-emergent adverse events was the greatest for entacapone (n=8), followed by placebo (n=6) and opicapone 50mg (n=4). Dyskinesia was the most common reported treatment-emergent adverse event across treatment groups. This was most commonly reported with opicapone 50mg (16%), when compared with entacapone (8%) and placebo (4%). Limitations: The BIPARK I study was carried out over a short period of up to 15 weeks. Patients who had previously taken entacapone or tolcapone, had severe dyskinesia and/or severe or unpredictable periods in the off state, or both were excluded from the study. The exclusion of patients previously treated with COMT inhibitors in the study does not provide evidence of efficacy for patients who have failed on other COMT inhibitors. 8 P a g e

9 The study was carried out in Europe (excluding the UK) and Russia, and participants may not reflect UK population and routine clinical practice. Some of the participants were taking anticholinergics (5%) and medicines for Parkinson's disease that are not available in the UK. In the NICE guideline on Parkinson's disease, anticholinergics are not included as an option for adjuvant therapy in people with later Parkinson's disease. BIPARK II Trial 5 : Opicapone as Adjunct to Levodopa Therapy in Patients with Parkinson s Disease and Motor Fluctuations: A Randomised Clinical Trial The BIPARK II study, a multi-centre (including the UK) week randomised controlled trial (n=427) mirrored the design of the trial mirrored the BIPARKI study with the exceptions of no active comparator (entacapone) being included or 5mg dose of opicapone. The primary objective was to investigate the efficacy of opicapone 25mg and 50mg compared with placebo, by measuring the change from baseline in off-time versus placebo. Motor symptoms (off and on state): The study reported a change from baseline in absolute off-time at week 15 of 64.5 minutes for placebo and minutes for opicapone 50mg producing a significant difference of 54.3 minutes (95% CI , adjusted p=0.008). There was no significant difference in the opicapone 25mg group. Secondary efficacy endpoints measured included proportional off-time and on-time responders at the end of the double blind period. 50.4% of placebo patients were assessed as off-time responders (offtime reduction of 1 hour) compared with 66.0% of patients treated with opicapone 50mg (p=0.009). Similarly 45.2% of the placebo group were evaluated as on-time responders (increase in on-time of 1 hour) compared with 61.9% in the group taking opicapone 50mg (p=0.006). Health-related quality of life, motor and daily activities scores: As in the BIPARK I study there were improvements in health-related quality of life, motor scores and daily activities scores (assessed using the Unified Parkinson s disease rating scale [UPDRS], Parkinson s Disease Sleep Scale [PDSS], 39 item Parkinson s Disease Questionnaire [PDQ-39] and Non-Motor Symptoms Scale [NMSS]) across all treatment groups, but no significant differences between them. There was no significant difference in the clinician global impression of change (CGI-C) or patient impression of change (PGI-C) between the treatment groups. Extended open-label phase: The study also reported findings from a 1-year open-label phase during which all participants received active treatment with opicapone (n=367). The participants started open-label treatment with 25 mg opicapone, which could be titrated up to 50 mg if greater symptom control was needed. The adjusted mean change in off-time from the start to the end of the open-label phase was minutes (95% CI to +6.95). Safety: More than half of patients in each group experienced at least 1 adverse event, most were mild or moderate in intensity. The most common adverse events occurring in the opicapone group compared with the placebo group were dyskinesias, constipation and dry mouth. The number of patients who discontinued treatment due to adverse effects was higher in the opicapone 50mg group compared to the placebo group (11.3% vs 6.6%). The most common adverse event leading to discontinuation was dyskinesia. Limitations: The sample size required to ensure at least 95% power to confirm a treatment effect compared to placebo was based on a much lower placebo response (30 minutes) than that which the study reported (64.5 minutes reduction in off-time) and therefore it is possible that the study may have been underpowered to detect treatment differences between the groups. 9 P a g e

10 As with the BIPARK I study, patients who had previously taken entacapone or tolcapone, had severe dyskinesia and/or severe or unpredictable periods in the off state, or both were excluded from the study. Cost Analysis Comparative Costs of COMT inhibitors and combination products containing a COMT inhibitor in Secondary Care (UHNM) May 2016 April 2017: Medicine Description Dose Pack size OPICAPONE 50mg CAPSULES 50mg OD 30 ENTACAPONE 200mg Up to 2000mg/day 30 TOLCAPONE 100mg mg TDS 100 SASTRAVI Up to (all available strengths) tablets/day STANEK 50mg/12.5mg/200mg tabs tablets/day 30/100 STANEK 75mg/18.75mg/200mg tabs tablets/day 100 STANEK 100mg/25mg/200mg tabs tablets/day 100 STANEK 125mg/31.25mg/200mg tabs tablets/day 100 STANEK 150mg/37.5mg/200mg tabs tablets/day 100 STANEK 175mg/43.75mg/200mg tabs Up to 8 tablets/day 100 STANEK 200mg/50mg/200mg tabs Up to 7 tablets/day 100 UHNM (incl. VAT) Price per pack UHNM (incl. VAT) Price per tablet Comparative Expenditure of COMT inhibitors and combination products containing a COMT inhibitor in Secondary Care (UHNM) May 2016 April 2017: Medicine Description TOTAL QUANTITY UHNM EXPENDITURE (VAT applied as appropriate) OPICAPONE 50mg CAPSULES ENTACAPONE 200mg TOLCAPONE 100mg 0.00 LEVODOPA/CARBIDOPA/ENTACAPONE 50mg/12.5mg/200mg LEVODOPA/CARBIDOPA/ENTACAPONE 75mg/18.75mg/200mg LEVODOPA/CARBIDOPA/ENTACAPONE 100mg/25mg/200mg LEVODOPA/CARBIDOPA/ENTACAPONE125mg/31.25mg/200mg LEVODOPA/CARBIDOPA/ENTACAPONE 150mg/37.5mg/200mg LEVODOPA/CARBIDOPA/ENTACAPONE 175mg/43.75mg/200mg LEVODOPA/CARBIDOPA/ENTACAPONE 200mg/50mg/200mg TOTAL 1, P a g e

11 Comparative Costs and Expenditure of COMT inhibitors and combination products containing a COMT inhibitor in Primary Care April 2016 March 2017: Medicine Description OPICAPONE 50mg CAPSULES ENTACAPONE 200mg TOLCAPONE 100mg SASTRAVI 100mg/25mg/200mg SASTRAVI 50mg/12.5mg/200mg 100mg/25mg/200mg 125mg/31.25mg/200mg 150mg/37.5mg/200mg 175mg/43.75mg/200mg 200mg/50mg/200mg 50mg/12.5mg/200mg 75mg/18.75mg/200mg STANEK 175mg/43.75mg/200mg STANEK 50mg/12.5mg/200mg STANEK 75mg/18.75mg/200mg Dose Pack Size Current Price Primary Care (excl. VAT) Cost per tablet (excl. VAT) Total Quantity North Staffs CCGs Sum of Total Nic 50mg OD Up to 30 2g/day , mg TDS tablets/day 30/ / / tablets/day 30/ / / tablets/day 30/ / / , tablets/day 30/ / / , tablets/day 30/ / / , Up to 8 tablets/day 30/ / / , Up to 7 tablets/day 30/ / / , tablets/day 30/ / / , tablets/day 30/ / / , Up to 8 tablets/day 30/ / / tablets/day 30/ / / tablets/day 30/ / / TOTAL 65, Predicted Annual Cost of Opicapone: Annual Cost of Opicapone Per Patient (based on secondary care prices) Annual Cost of Opicapone for 10 patients (based on secondary care prices) 11 P a g e

12 References 1 Summary of Product Characteristics. Ongentys. Bial Pharma UK Ltd. Last updated on 21 st September Accessed via: 2 National Institute for Health and Clinical Excellence (2017). Evidence summary ES9: Parkinson s disease with end-of-dose motor fluctuations: opicapone. Accessed online via: 3 Midlands Therapeutic Review and Advisory Committee (MTRAC) Commissioning Support: Opicapone (Ongentys ) Midlands Therapeutics Review & Advisory Committee. January Accessed online via 4 Ferreira JJ, Lees A, Rocha JF et al. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. The Lancet Neurology 2016; 15: Lees A, Ferreira JJ, Rascol O, et al. Opicapone as Adjunct to Levodopa Therapy in Patients with Parkinson s Disease and Motor Fluctuations: A Randomised Clinical Trial. JAMA Neurology 2017; 72(2): European Medicines Agency. Ongentys - European Public Assessment Report; 28 April National Institute for Health and Clinical Excellence (NICE) Clinical Guidelines 35. Parkinson s disease in Over 20s: Diagnosis and management. June Access online via: 8 Specialist Pharmacy Service. New product evaluations - a resource for medicines management. Available from: [Accessed 7 June 2017] Produced by Helen Wrightson Specialist Rotational Pharmacist - Medicines Management University Hospital of North Midlands Telephone: helen.wrightson@uhnm.nhs.uk Produced for use within the NHS. Not to be reproduced for commercial purposes. 12 P a g e