Specialised Services Policy: Ivacaftor (Kalydeco) for Cystic Fibrosis (G551D and Specific Other Non G551D Mutations)

Transcription

1 Specialised Services Policy: Ivacaftor (Kalydeco) for Cystic Fibrosis (G551D and Specific Other Non G551D Mutations) Document Author: Welsh Health Specialised Services Committee Executive Lead: Medical Director Approved by: Joint Committee Issue Date: 21 June 2016 Review Date: June 2019 Document No: CP46 Page 1 of 17

2 Document History Revision History Version No. Revision date Summary of Changes Updated to version no.: Draft headings and content Collation of feedback from ID and adult CF team 0.3 re: edits Collation of feedback from paediatric and adult 0.4 CF team re: edits Collation of feedback and amendment to policy 0.5 template ID comments and amendments Minor amendments Ratified by Joint Committee Revised to Specialised Services Policy; inclusion 1.1 of more gene mutations Title amendment and other formatting 1.2 amendments Approved Expansion of policy to include children aged 2-5, 2.1 weighing <25kg Revised version including children aged Date of next revision January 2015 Consultation Name Date of Issue Version Number Lead clinician in Genetics Medical Director at WHSSC Lead clinicians in all specialist CF centres in Wales and lead CF centres for North Wales Lead clinicians in all specialist CF centres in Wales and lead CF centres for North Wales Women and Children and Cardiothoracic Programme Team Senior Operational Team Management Group Lead clinicians in all specialist CF centres in Wales Lead clinicians in lead CF centres for North Wales Joint Committee Corporate Directors Group Medical and Finance Directors NHS Wales WHSSC Management Group Medical Directors LHCH and Alder Hey Lead CF Clinicians in Wales Lead CF Clinicians LHCH and Alder Hey CF Trust Genetic Alliance Approvals Name Date of Issue Version No. Page 2 of 17

3 Management Group Joint Committee via Chair Action Management Group Chair s action Corporate Directors Group Distribution this document has been distributed to Name Date of Issue Version No. Page 3 of 17

4 Policy Statement Background Welsh Health Specialised Services Committee (WHSSC) will routinely commission Ivacaftor for patients aged 2-5 years weighing <25kg and those aged 6 years and older with cystic fibrosis and at least one copy of one of the following gene mutations: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D in accordance with the criteria outlined in this document and subject to the Patient Access Scheme. In creating this policy, WHSSC has considered the evidence base for clinical and cost effectiveness, the assessment made by All Wales Medicine Strategy Group and the Ministerial decision on options for treatment. Summary of Access Criteria Responsibilities This document outlines the clinical criteria, arrangements for commissioning and funding for Ivacaftor for the population of Wales. Ivacaftor will be routinely commissioned for all patients resident in Wales who are aged 2-5 years weighing <25kg and those aged 6 years and older with cystic fibrosis and at least one of the following gene mutations: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D. WHSSC will not routinely provide funding for Ivacaftor for cystic fibrosis patients with at least one copy of the gene mutations listed above in the following cases: Patients less than 2 years of age. Currently the efficacy and safety of Ivacaftor in children less than 2 years has not been evaluated; Patients with severe renal impairment (Creatinine clearance 30 ml/min) or in end stage renal failure. An Individual Patient Funding Request (IPFR) will be considered under the All Wales IPFR policy; Patients with severe hepatic impairment. Individual patient funding request will be considered under the All Wales Policy: Making Decisions on Individual Patient Funding Requests (IPFR). Referrers should: Inform the patient that this treatment is not routinely funded outside the criteria in this policy; and Refer via the agreed pathway Clinician considering treatment should: Discuss all the alternative treatment with the patient; Advise the patient of any side effects and risks of the potential treatment; Inform the patient that treatment is not routinely funded outside of the criteria in the policy; and Confirm that there is contractual agreement with WHSSC for the treatment. In all other circumstances submit an IPFR request Page 4 of 17

5 Table of Contents 1. Aim Introduction Relationship with other Policies and Service Specifications Scope Definition Codes Access Criteria Clinical Indications Clinical Assessment Treatment Stopping criteria Patient Pathway Exclusions Exceptions Responsibilities Quality Quality and Outcome Measures Clinical Audit Patient Experience Quality of Life Putting Things Right: Raising a Concern Equality Impact and Assessment References Annex (i) Ivacaftor Clinical Assessment Audit Form Page 5 of 17

6 1. AIM 1.1 Introduction Welsh Health Specialised Services Committee (WHSSC) will routinely commission Ivacaftor for patients aged 2-5 years weighing <25kg and those 6 years and above with cystic fibrosis and at least one copy of one of the following gene mutations: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D in accordance with the criteria outlined in this document and subject to the Patient Access Scheme. In creating this policy, WHSSC has considered the evidence base for clinical and cost effectiveness, the assessment made by All Wales Medicine Strategy Group and the Ministerial decision on options for treatment. This document outlines the clinical criteria, arrangements for commissioning and funding for Ivacaftor for the population of Wales. 1.2 Relationship with other Policies and Service Specifications This document should be read in conjunction with the following documents: All Wales Policy: Making Decisions on Individual Patient Funding Requests (IPFR). 2. SCOPE 2.1 Definition Cystic Fibrosis is the most common, life limiting, inherited disease in the UK. Cystic Fibrosis is caused by a single faulty gene that encodes the cystic fibrosis transmembrane conductance receptor (CFTR) that is vital to salt and fluid transport in the lining of many organs including lungs. G551D is a mutation affecting chloride transport in patients with Cystic Fibrosis causes a substitution of glycine (an amino acid) for aspartic acid (another amino acid) at amino acid 551 (G551D CFTR). This occurs in 3 5% of all patients with Cystic Fibrosis. Ivacaftor is a drug that increases the ion-channel function of CFTR. This drug has demonstrated evidence for effectiveness in G551D Cystic Fibrosis by improving sweat chloride, FEV1 and quality of life. There is no data demonstrating a survival benefit in G551D Cystic Fibrosis as yet. The sweat test measures the amount of chloride in sweat (sweat chloride), and is the basis for the diagnosis of CF. Patients with cystic fibrosis can have two to five times the normal amount of chloride in their sweat. In a sweat test, the skin is stimulated to produce enough sweat Page 6 of 17

7 (pilocarpine iontophoresis) to be absorbed into a special collector and then analyzed. FEV 1 is the maximal amount of air forcefully exhaled in one second. Absolute values are standardised by expressing them as a percentage of normal corrected for age, sex, height and ethnic origin. FEV 1 is a marker for the degree of airway obstruction, and is an important prognostic indicator of life expectancy in CF: FEV 1 greater 80% of predicted= normal FEV 1 60% to 79% of predicted = Mild obstruction FEV 1 40% to 59% of predicted = Moderate obstruction FEV 1 less than 40% of predicted = Severe obstruction FEV 1 is measured by spirometry, and the percent predicted is calculated automatically by the spirometer based on normal values and the individual demographics of the patient. Cystic Fibrosis Questionnaire Revised (CFQ-R) is a disease-specific health-related quality of life (HRQOL) measure for children, adolescents and adults with cystic fibrosis (CF). It is profile measure of HRQOL with several different domains. It was initially developed through focus groups and interviews with CF patients and health care professionals and has undergone extensive reliability and validity testing. It is one of the most widely used HRQOL measures for CF and was judged as well-established in a review of evidence-based measures. It is being used in the United States and internationally in a number of clinical trials. It is also used clinically during routine CF care Codes ICD-10 E84.9 Cystic Fibrosis, unspecified Cystic fibrosis with pulmonary manifestations E84.0 is a billable ICD-10-CM code that can be used to specify a diagnosis. Description Synonyms Cystic fibrosis of the lung Cystic fibrosis with pulmonary manifestation Cystic fibrosis, pulmonary Use Additional code to identify any infectious organism present, such as: Pseudomonas (B96.5) Page 7 of 17

8 3. ACCESS CRITERIA 3.1 Clinical Indications Ivacaftor will be routinely commissioned for all patients resident in Wales who are aged 2-5 weighing <25 kg and those aged 6 years and older with cystic fibrosis and at least one of the following gene mutations: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D. WHSSC will not routinely provide funding for Ivacaftor for cystic fibrosis patients with at least one copy of the gene mutations listed above in the following cases: Patients less than 2 years of age. Currently the efficacy and safety of Ivacaftor in children less than 2 years has not been evaluated; Patients with severe renal impairment (Creatinine clearance 30 ml/min) or in end stage renal failure. An Individual Patient Funding Request (IPFR) will be considered under the All Wales IPFR policy; Patients with severe hepatic impairment. Individual patient funding request will be considered under the All Wales Policy: Making Decisions on Individual Patient Funding Requests (IPFR). 3.2 Clinical Assessment All patients will have a measurement of sweat chloride, spirometry including FEV 1 and quality of life assessment using the Cystic Fibrosis Questionnaire (revised instrument) prior to the initiation of treatment. They will have Liver function biochemistry measured. Spirometry including FEV 1 and liver function will be re-assessed after 2 months, and 4 months. A measurement of sweat chloride, spirometry including FEV 1 and quality of life assessment using the Cystic Fibrosis Questionnaire (revised instrument) and liver function will be repeated after 6 months. If treatment is continued measurement of sweat chloride, spirometry including FEV 1 and quality of life assessment using the Cystic Fibrosis Questionnaire (revised instrument) and liver function will be measured annually thereafter while remaining on treatment. The Specialist Cystic Fibrosis centre will be responsible for collecting the agreed clinical monitoring and outcome assessment data on each patient receiving Ivacaftor for a quality dashboard. This monitoring data will be provided to WHSSC on an agreed basis. 3.3 Treatment Ivacaftor will only be prescribed by the specialist Cystic Fibrosis centres commissioned by WHSSC. Page 8 of 17

9 Ivacaftor will only be funded in line with the Patient Access Scheme agreed and funded by Welsh Government; Ivacaftor will be commissioned in line with the following recommended doses 1) Children aged 2-5 years- Patients aged 2-5 <14 kg in weight: 50mg Ivacaftor granules taken orally every 12 hours (100 mg total daily dose). Patients aged kg to <25 kg in weight: 75mg Ivacaftor granules taken orally every 12 hours (150 mg total daily dose). 2) Patients aged 6 years and older- 150mg taken orally every 12 hours After 6 months, patients will be considered to have responded to treatment if either: Sweat chloride measurement falls below 60mmol/litre OR Sweat chloride measurement falls by 30% OR There is an absolute improvement in FEV 1 of 5% OR There is 4.0 improvement in the respiratory symptoms domain of CFQ. 3.4 Stopping criteria If the expected reduction in these clinical parameters does not occur, the patient s CF clinicians will explore any issues of patient compliance with taking the medication. Non responders will be reassessed 1 week following week 24 and the treatment will be discontinued immediately if the patient does not meet the above criteria. All assessments (including the assessment of non responders) will be required to be audited and presented to WHSSC on a timescale agreed by WHSSC and the CF Centre. The specialist CF centre must prescribe in line with the Summary of Product Characteristics. 3.5 Patient Pathway Ivacaftor should be considered as an additive therapy to usual care in patients with Cystic Fibrosis. Consideration of whether individual patients continue on Ivacaftor after transplant will be made on a case by case basis. Individual Patient Page 9 of 17

10 Requests in this context will be considered under the All Wales IPFR policy. 3.6 Exclusions WHSSC will not provide funding for Ivacaftor for cystic fibrosis patients with at least one copy of the G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D mutation in the following cases: Children < 2 years Children aged 2-5 years weighing <25kg Patients with severe renal impairment (Creatinine clearance 30 ml/ml0) or in end stage renal failure unless an Individual Patient Funding Request is considered and agreed under the All Wales IPFR policy. Patients with severe hepatic impairment unless an Individual Patient Funding Request is considered and agreed under the All Wales IPFR policy. 3.7 Exceptions If the patient does not meet the criteria for treatment, but the referring clinician believes that there are exceptional grounds for treatment, an Individual Patient Funding Request (IPFR) can be made to WHSSC under the All Wales Policy for Making Decisions on Individual Patient Funding Requests (IPFR). If the patient wishes to be referred to a provider out of the agreed pathway and the referring clinician believes that there are exceptional grounds for treatment at an alternative provider, an Individual Patient Funding Request (IPFR) can be made to WHSSC under the All Wales Policy for Making Decisions on Individual Patient Funding Requests (IPFR). Guidance on the IPFR process is available at Responsibilities Referrers should: Inform the patient that this treatment is not routinely funded outside the criteria in this policy; and Refer via the agreed pathway Clinician considering treatment should: Discuss all the alternative treatment with the patient; Advise the patient of any side effect and risks of the potential treatment; Inform the patient that treatment is not routinely funded outside of the criteria in the policy; and Confirm that there is contractual agreement with WHSSC for the treatment. Page 10 of 17

11 In all other circumstances submit an IPFR request. 4. QUALITY 4.1 Quality and Outcome Measures The Provider must work to written quality standards and provide monitoring information to the lead purchaser. Providers are expected to comply with the following: CF Core Standards as outlined by WHSSC Proportion of patients seen by specialist team for specialist annual review All providers should submit the minimum dataset data to the UK CF Registry within the required timescales. There is an expectation that data from all of Welsh CF patients would be entered onto the CF registry, but where it is not possible to obtain consent for registration and data entry the reasons should be documented for future audit. Serious incidents reported externally to STEIS, Welsh Government or equivalent must be shared at time of reporting Annual information to be received regarding: o Number of serious incidents reported externally o Number of concerns received, response timescales, lessons learnt and action plans o Compliance with safety notices e.g. NRLS Rapid Response Reports For those patients on Ivacaftor providers should complete the Ivacaftor Clinical Assessment Audit Form detailed in Annex (i) and report to WHSSC at each time specified time interval. This includes: providing baseline measures for the following measures: o Sweat Chloride o AST and ALT o FEV 1 and FEV 1 percentage predicted o FVC and FVC percentage predicted o Weight and weight centile or BMI o Quality of Life Score Report assessment at 8 weeks for the following measures o AST and ALT o FEV 1 and FEV 1 percentage predicted o FVC and FVC percentage predicted o Weight and weight centile or BMI o Quality of Life Score Report assessment at 16 weeks for the following measures o AST and ALT o FEV 1 and FEV 1 percentage predicted o FVC and FVC percentage predicted Page 11 of 17

12 o Weight and weight centile or BMI o Quality of Life Score Report assessment at 24 weeks for the following measures: o Sweat Chloride o AST and ALT o FEV 1 and FEV 1 percentage predicted o FVC and FVC percentage predicted o Weight and weight centile or BMI o Quality of Life Score Thereafter reporting assessment annually for the following measures: o Sweat Chloride o AST and ALT o FEV 1 and FEV 1 percentage predicted o FVC and FVC percentage predicted o Weight and weight centile or BMI o Quality of Life Score Report any adverse reactions including increased hepatic enzymes to be audited by Cystic Fibrosis Centres treating Welsh patients. Report any exacerbations 4.2 Clinical Audit An annual audit day will be held between providers and WHSSC to review the quality of services. All centres must participate and be compliant with the CF National Audit. 4.3 Patient Experience Providers should use a recognised validated patient experience tool for monitoring patient experience on an annual basis. 4.4 Quality of Life Measurement of the Quality of Life using the Cystic Fibrosis Revised Questionnaire Quality of Life tool with patients on inhaled antibiotic therapies is expected as a regular component of the annual review of patients. 5. PUTTING THINGS RIGHT: RAISING A CONCERN Whilst every effort has been made to ensure that decisions made under this policy are robust and appropriate for the patient group, it is acknowledged that there may be occasions when the patient or their representative are not happy with decisions made or the treatment provided. The patient or their representative should be guided by the clinician, or the member of NHS staff with whom the concern is raised, to the appropriate arrangements for management of their concern: Page 12 of 17

13 When a patient or their representative is unhappy with the decision that the patient does not meet the criteria for treatment further information can be provided demonstrating exceptionality. The request will then be considered by the All Wales IPFR Panel. If the patient or their representative is not happy with the decision of the All Wales IPFR Panel the patient and/or their representative has a right to ask for this decision to be reviewed. The grounds for the review, which are detailed in the All Wales Policy: Making Decisions on Individual Patient Funding Requests (IPFR), must be clearly stated. The review should be undertaken, by the patient's Local Health Board; When a patient or their representative is unhappy with the care provided during the treatment or the clinical decision to withdraw treatment provided under this policy, the patient and/or their representative should be guided to the LHB for NHS Putting Things Right. For services provided outside NHS Wales the patient or their representative should be guided to the NHS Trust Concerns Procedure, with a copy of the concern being sent to WHSSC. 6. EQUALITY IMPACT AND ASSESSMENT The Equality Impact Assessment (EQIA) process has been developed to help promote fair and equal treatment in the delivery of health services. It aims to enable Welsh Health Specialised Services Committee to identify and eliminate detrimental treatment caused by the adverse impact of health service policies upon groups and individuals for reasons of race, gender re-assignment, disability, sex, sexual orientation, age, religion and belief, marriage and civil partnership, pregnancy and maternity and language (welsh). This policy has been subjected to an Equality Impact Assessment. The Assessment demonstrates the policy is robust and there is no potential for discrimination or adverse impact. All opportunities to promote equality have been taken. 7. REFERENCES Accurso FJ, Rowe SM, Durie PR, Konstan MW, Dunitz J, Hornick DB et al. (2008). Interim results of a phase 2a study of VX-770 to evaluate safety, pharmacokinetics and biomarkers of CFTR activity in cystic fibrosis subjects with G551D. Pediatr Pulmonol Suppl 31: 295. Page 13 of 17

14 Ballard ST, Trout L, Bebok Z, Sorscher EJ, Crews A (1999). CFTR involvement in chloride, bicarbonate, and liquid secretion by airway submucosal glands. Am J Physiol 277: L694 L699. Berdiev BK, Qadri YJ, Benos DJ (2009). Assessment of the CFTR and ENaC association. Mol Biosyst 5: Bijvelds MJC, Bot AGM, Escher JC, De Jonge HR (2009). Activation of intestinal chloride secreion by lubprostone requires the cystic fibrosis transmembrane conductance regulator. Gastroenterology 137: Conese M, Romano M, Furnari ML, Copreni E, Fino ID, Pardo F et al. (2009). New genetic and pharmacological treatments for cystic fibrosis. Curr Ped Rev 5: Donaldson SH, Boucher RC (2007). Sodium channels and cystic fibrosis. Chest 132: Dormer RL, Derand R, McNeilly CM, Mettey Y, Bulteau-Pignoux L, Metaye T et al. (2001). Correction of delf508-cftr activity with benzo(c) quinolizinium compounds through facilitation of its processing in cystic fibrosis airway cells. J Cell Sci 114: Hirsh AJ, Sabater JR, Zamurs A, Smith RT, Paradiso AM, Hopkins S et al. (2004). Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease. J Pharmacol Exp Ther 311: Knowles MR, Clarke LL, Boucher RC (1991). Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. N Engl J Med 325: Van Goor F, Hadida S, Grootenhuis PDJ, Burton B, Cao D, Neuberger T et al. (2009). Rescue of a CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Nat Acad Sci USA 106: Page 14 of 17

15 Annex (i) Ivacaftor Clinical Assessment Audit Form NAME: DOB: NHS NO: CF GENOTYPE: / HOSPITAL: CONSULTANT: AT BASELINE DATE SWEAT CHLORIDE mmols/l AST ALT FEV1 FEV1 % PRED FVC FVC % PRED WEIGHT WEIGHT CENTILE / BMI QUALITY of LIFE SCORE CONTRAINDICATIONS OR DOSING CONSIDERATIONS AT BASELINE: THERAPY START DATE: DOSING REGIMEN: CONTRAINDICATIONS OR DOSING CONSIDERATIONS DATE DATE DOSING REGIMEN DOSING REGIMEN DATA POINT DATE SWEAT CHLORIDE mmols/l AST ALT FEV1 FEV1 % PRED FVC FVC % PRED WEIGHT WEIGHT CENTILE / BMI QUALITY of LIFE SCORE 8 weeks NA Ivacaftor Clinical Access Policy Version: 3.0 Page 15 of 17 version to ensure the version to hand is the most recent.

16 DATA POINT DATE SWEAT CHLORIDE mmols/l AST ALT FEV1 FEV1 % PRED FVC FVC % PRED WEIGHT WEIGHT CENTILE / BMI QUALITY of LIFE SCORE 16 weeks NA 24 weeks Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 Y9 Y10 Y11 Y12 Ivacaftor Clinical Access Policy Version: 3.0 Page 16 of 17 version to ensure the version to hand is the most recent.

17 ADVERSE REACTIONS EXACERBATIONS DETAIL DATE ACTION Po Abx Iv Abx Ivacaftor Clinical Access Policy Version: 3.0 Page 17 of 17 version to ensure the version to hand is the most recent.