COMMISSIONING POLICY RECOMMENDATION TREATMENT ADVISORY GROUP Policy agreed by (Vale of York CCG/date)

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1 COMMISSIONING POLICY RECOMMENDATION TREATMENT ADVISORY GROUP Policy agreed by (Vale of York CCG/date) Drug, Treatment, Device name Co-careldopa 2000mg/500mg intestinal gel (Duodopa, Solvay Pharmaceuticals) Licensed indication Treatment of advanced levodopa-responsive Parkinson's disease with severe motor fluctuations and hyper-/dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results Cost per patient (at recommended dose) Duodopa Individually adjusted doses including a morning bolus dose, continuous maintenance dose and extra bolus doses. 28,000-56,000 per year. Resource impact on population Predicted incidence figures is 1.1 patients requiring Duodopa treatment per 100,000 of the population per year but this is predicted to increase to 6.8 patients per 100,000 by 2015 (ref London new drugs group). Recommendation to Routinely Commission OR Not Routinely Commission OR Commission under criteria When is funding appropriate? Duodopa is not recommended for routinely commissioning for management of parkinson s disease. Clinical and cost effectiveness evidence Background Parkinson s disease (PD) is a progressive, neurodegenerative condition that is estimated to affect people per 100,000 of the population and has an annual incidence of 4 20 per 100,000. Individuals with PD classically present with the symptoms and signs associated with parkinsonism, namely bradykinesia, rigidity and rest tremor 3. Although predominantly a movement disorder, other impairments frequently develop including psychiatric problems such as depression and dementia. Autonomic disturbances and pain may later ensue, and the condition progresses to cause significant disability and handicap with impaired quality of life for the affected person Following diagnosis, drug treatment is not usually initiated until symptoms cause significant disruption of daily activities First-choice adjuvant drug therapy for later disease includes dopamine agonists, monoamine oxidase B inhibitors and catechol-o-methyl transferase (COMT) inhibitors. However, most people will develop, with time, motor complications and will

2 eventually require levodopa therapy. Levodopa is associated with response fluctuations and dyskinesias; large variations in motor performance occur, with normal function during ON periods and weakness and restricted mobility during OFF periods. Modified-release preparations of levodopa are able to help with end of dose deterioration and nocturnal immobility, in combination with other adjuvant agents 4. In advanced disease, subcutaneous injections or continuous infusions of apomorphine may be useful in patients experiencing unpredictable OFF periods and to reduce dyskinesias, but it is also highly emetogenic Around 5 10% of PD patients respond poorly to treatment, and in those who are, or who become, refractory to best available treatment, options are limited. Deep brain stimulation, involving the implantation of an electrode directly into a specific nucleus of the brain to allow its direct electrical stimulation, is an option for some patients. However, for most patients with this stage of PD, standard care involving palliative, best supportive care and continued conventional medication is all that is available. Co-careldopa intestinal gel is licensed for use in patients with advanced PD who are levodoparesponsive but who are experiencing severe response fluctuations despite optimised treatment with available alternative medications. Co-careldopa intestinal gel is therefore licensed for use as a last available medical treatment and may be viewed as having no direct comparators. NICE Clinical guideline 35: Parkinson s disease. June 2006 At the time of publishing Duodopa was not available so was not considered as part of the clinical guideline. It provides guidance on adjuvant pharmacotherapy options in later Parkinsons disease which include dopamine agonists, MAO-B inhibitors, COMT inhibitors, amantadine, apomorphine, and modified release levodopa. SMC guidance: co-careldopa intestinal gel, 20mg/5mg levodopa/carbidopa per ml for continuous intestinal infusion, (Duodopa). September Co-careldopa intestinal gel (Duodopa) is not recommended for use within NHS Scotland for the treatment of advanced levodopa-responsive Parkinson s disease with severe motor fluctuations and hyper-/dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results. In the pivotal study an increase in on time was achieved compared with individually optimised conventional combinations of Parkinson s disease medication. However, the economic case has not been demonstrated. All Wales Medicines Strategy Group: Co-careldopa intestinal gel (Duodopa ). August Co-careldopa intestinal gel (Duodopa ) should not be recommended for use within NHS Wales for the treatment of advanced levodopa-responsive Parkinson s disease. The clinical and cost effectiveness data presented was not sufficient for AWMSG to recommend its use.

3 London New Drugs Group; Duodopa. August The clinical trial associated with this drug is the DIREQT study which was a single blinded, cross over study. 24 patients were initially randomized into 2 groups, group 1 received conventional treatment for 3 weeks, followed by Duodopa for 3 weeks. Group 2 received the treatments in the opposite order. Naso-jejunal tubes were used to avoid unnecessary surgery but this did mean that it would not necessarily reflect patients on long term treatment. Dose adjustments for individual optimization occurred during the first week of each treatment period and were allowed throughout the study. Patients were also allowed to use rescue medication throughout the study if needed. A treatment response scale (TRS) was used for assessment of clinical response, ranging from -3 (severe OFF) to +3 (on with severe dyskinesias) where 0 is on without any dyskinesias. The primary efficacy variable was the percentage of ratings from the TRS within the interval -1 to +1, a clinically desirable functional on state accepting mild parkinsonism or mild dyskinesia and percentage of ratings within the -3 to -2 and +2 to +3. In the intention to treat (ITT)population, compared with conventional medication, the infusion achieved a significant increase in time spent in the on state, 90.7% vs 74.5%, mean difference 13.7% (± 20.62); and corresponding significant reduction in off time, 1.8% vs 19.2%, mean difference -13.5% (± 16.47). Secondary efficacy measures in the per protocol population (n=18) demonstrated a significant improvement with the infusion, compared with conventional medication, of 14.1 points (mean ± 19.3) in the Unified Parkinson s Disease Rating Scale (range 0-199); 9.5 points (mean ± 9.5) out of 100 in the mean Parkinson s Disease Questionnaire (PDQ-39) summary index; and 0.06 (median) on a total scale of 1.0 in the generic 15-D Quality of Life instrument. Self-assessment of motor function and quality of life by patients in electronic home diaries showed a significant improvement in 5 out of 9 items. Points to consider Due to small numbers of patients, evidence of efficacy is very limited. The phase III DIREQT study provides only two weeks of efficacy data for co-careldopa intestinal gel. It is therefore not possible to assess long term efficacy of this treatment. The patients enrolled in the DIREQT study meet the licensed indication for co-careldopa intestinal gel, but are not necessarily representative of the broad patient population with advanced PD. Many patients in clinical practice will have atypical PD, dementia or psychiatric disorders.such patients were excluded from the study as they would generally not be eligible for this treatment due to the difficulty in managing the device on an ongoing basis. Many antiparkinsonism agents require slow titration and gradual withdrawal. The crossover design of the DIREQT study required patients to switch between treatments rapidly and, although a dose adjustment period was built into each three-week treatment period, the effects of this switching are not explored. Co-careldopa intestinal gel requires administration via a transabdominal tube when used

4 long term. Given that the SPC notes that complications with the device are very common, the short term DIREQT trial and the pharmacokinetic study, in which the gel was administered via a nasoduodenal rather than a transabdominal tube, provide very limited information in relation to patient experience and quality of life with usual long term use of this product. The cost of the CADD pump tube and all materials required for Duodopa administration is included in the cassette price. It is anticipated by the manufacturer, that a 9 day inpatient stay will be required for treatment initiation. This cost is estimated to by Solvay as 3823 (the cost of duodopa used during the trial period will be paid by Solvay). The overall cost will range from 28,000-56,000 per year dependent on the dose Place in therapy relative to available treatments Duodopa may have benefit for a small number of patients with very advanced Parkinson s disease. Patients suitable will either have failed to tolerate, all existing available pharmacological therapies including apomorphine. They are also likely to be unsuitable for or have refused surgical options including deep brain stimulation. Patient monitoring / impact Adverse effects Stoma site Disease progression Patient safety / pharmacovigilance Complications with the duodopa device are very common (>1/10) and include- Dislocation of the intestinal tube backwards into the stomach. Occlusion or kinking of the tube Abdominal pain infection and leakage of gastric fluid may occur shortly after surgery. Local infections around the stoma. When to stop treatment Negative response to initial trial. Gradual deterioration of condition resulting in ability to manage pump and replacement of drug cassettes Who prescribes? It is not recommended to be commissioned. Stakeholder views Equity of access SPECIFICATION DATE, REVIEW DATE, AND LEAD NAME/JOB TITLE Origin Date: July 2013 Originator:Historical Y&H SCG policy

5 TAG Review Date: TAG Recommendation Date: Reviewer: Christopher Ranson Impact on individual clinical commissioning groups CCG Population Cost Impact Vale of York 337, ,000 Harrogate and Rural District 160,100 49,310 Scarborough & Ryedale 118,000 36,344 Hambleton, Richmondshire & Whitby 141,600 43,612 East Riding of Yorkshire 320, Hull 295, North Lincolnshire 168, North East Lincolnshire 167,