Soliris (eculizumab, rmc) Section 100 Restriction Criteria

Transcription

1 Soliris (eculizumab, rmc) Section 100 Restriction Criteria A guide to initiation and ongoing access to (Section 100) funded Soliris for the treatment of patients with atypical Haemolytic Uraemic Syndrome (ahus) 1

2 PBS (Section 100) listing for the treatment of ahus an overview 1 0 Months 3 Months 6 Months WEEK 1-4 Initial treatment 1 New patient 12 Vials* WEEK 5-24 Initial treatment 1 New patient Balance of supply 40 Vials* WEEK Patients must be treated by a paediatric nephrologist, nephrologist, paediatric haematologist or haematologist or must be in consultation with one of the above. Once treatment with Soliris has started, 3-monthly monitoring of serial haematological results must be provided with every subsequent application for ongoing treatment. Ongoing access to PBS (Section 100) listed Soliris in ahus requires a series of applications, which vary according to the stage of treatment. Monitoring following discontinuation at 12 months 1,2 (1) Severe thrombotic microangiopathy (TMA) complications were observed after Soliris discontinuation in the ahus clinical studies. If ahus patients discontinue treatment with Soliris they should be monitored closely for signs and symptoms of severe TMA complications. Severe TMA complications post discontinuation can be identified by; a) any two, or repeated measurement of any one of the following: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during Soliris treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during Soliris treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during Soliris treatment; or b) any one of the following: a change in mental status or seizures; angina or dyspnoea; or thrombosis. 12 Months Treatment failure no further access to Soliris treatment New Patient 56 Vials* WEEK 53 ONWARDS WEEK 53 (2) Monitor any patient who discontinues Soliris for at least 12 weeks to detect severe TMA complications. (3) If severe TMA complications occur after Soliris discontinuation, consider reinstitution of Soliris treatment for eligible patients, supportive care with PE/PI, or appropriate organ-specific supportive measures including renal support with dialysis, respiratory support with mechanical ventilation or anticoagulation. treatment for patients with severe complications 52 Vials* Treatment break (4) Monitoring frequency should be on a case by case basis at treating physicians discretion. A treatment response is defined as: 18 Months At the time of each authority application medical practitioners must request the appropriate number of vials to provide sufficient drug for the treatment period, according to the specified dosage in the approved Product Information. Paediatric dosing is weight-based. Please refer to the Product Information to calculate the number of vials required. * Vials required for an adult patient. REACCESS WEEK 1-24 Initial Treatment 2 Recommencement 52 Vials* (includes induction dosing) WEEK 25 ONWARDS treatment after recommencement 56 Vials* No further TMA or deemed a treatment failure at 12 months (1) Normalisation of haematology as demonstrated by at least 2 of the following: platelet count, haptoglobin, and LDH; AND (2) One of the following: a) An increase in egfr of > 25% from baseline, where the baseline is the egfr measurement immediately prior to commencing treatment with Soliris or b) an egfr within ± 25% from baseline; or c) an avoidance of dialysis-dependence but worsening of kidney function with a reduction in egfr 25% from baseline. A treatment failure is defined as: (1) dialysis-dependent at the time of application and has failed to demonstrate significant resolution of extra-renal complications if originally presented; or (2) on dialysis and has been on dialysis for 4 months of the previous 6 months while receiving PBS-subsidised Soliris and has failed to demonstrate significant resolution of extra-renal complications if originally presented.

3 Restriction criteria for the initiation of PBS (Section 100) Soliris treatment 1 ACTIVE AND PROGRESSING TMA WEEK 1-4 Initial treatment 1 New patient WEEK 5-24 Initial treatment 1 New patient Balance of supply Current Thrombocytopenia Platelet count <150 x 10 9 /L Current Microangiopathic Haemolysis At least 2 of the following: Å Schistocytes and/or Å LDH > ULN and/or Å Low or absent haptoglobin Tissue Biopsy confirming TMA In patients who don t have thrombocytopenia and evidence of platelet consumption and haemolysis Active TMA related organ damage or impairment Kidney Impairment Å >20% decline in egfr* and/or Å scr > ULN^ or Å a renal biopsy One or more of the following: TMA-related: Å Neurological impairment and/or Å Cardiac impairment and/or Å Gastrointestinal impairment and/or Å Pulmonary impairment ADAMTS-13 10% (on blood taken pre-pe/pi) # In the case that a sample for ADAMTS-13 assay was not collected prior to plasma exchange or infusion, ADAMTS-13 activity must have been measured 1-2 weeks following the last plasma exchange or infusion, and must have been submitted to the Department of Human Services within 27 days of commencement of Soliris in order for the patient to be considered as eligible for further PBS-subsidised Soliris treatment. Platelet counts of greater than 30x10 9 /L and a serum creatinine of greater than 150 µmol/l These values have been identified as independently predictive of ADAMTS-13 deficiency 3 If treatment is initiated based on this criteria, an ADAMTS-13 assay must still be collected and the results sent to the Department of Human Services within 27 days of commencement of Soliris in order for the patient to be considered eligible for further PBS-subsidised Soliris treatment. Negative STEC result (if patient has had diarrhoea in the preceding 14 days) For all patients, measurement of egfr, platelets and 2 of either LDH, haptoglobin or schistocytes of < 1 week old at the time of application. * In a patient with pre-existing impairment. ^ In a patient with no history of pre-existing impairment or paediatric patients. # The date and time that the sample for the ADAMTS-13 assay was collected, and the dates and times of any PE/PI that were undertaken in the two weeks prior to collection of the ADAMTS-13 assay must be provided. Measurement of ADAMTS-13 activity must be taken 1-2 weeks following the last PE/PI. The ADAMTS-13 result must be submitted to the DHS.

4 WEEK WEEK 52 ONWARDS TREATMENT PHASE: CONTINUING TREATMENT NEW PATIENT treatment new patients TREATMENT PHASE: CONTINUING TREATMENT BEYOND INITIAL 52 WEEKS OF TREATMENT treatment for patients with severe complications * Clinical criteria: Patient must have received 24 weeks therapy under the initial restriction with PBS subsidised Soliris for this condition Patient must have demonstrated on-going treatment response to PBS-subsidised Soliris treatment for this condition* Patient must not have experienced treatment failure with Soliris including PBS-subsidised Soliris for this condition Patient must not receive more than 28 weeks of treatment per continuing treatment course authorised under this restriction A treatment response is defined as: (1) normalisation of haematology as demonstrated by at least 2 of the following: platelet count, haptoglobin, and LDH; AND (2) one of the following: a) an increase in egfr of > 25% from baseline, where the baseline is the egfr measurement immediately prior to commencing treatment with eculizumab or b) an egfr within ± 25% from baseline; or c) an avoidance of dialysis-dependence but worsening of kidney function with a reduction in egfr 25% from baseline. PBS-subsidised treatment with eculizumab will not be permitted if a patient has experienced treatment failure A treatment failure is defined as a patient who is: (1) dialysis-dependent at the time of application and has failed to demonstrate significant resolution of extra-renal complications if originally presented; or (2) on dialysis and has been on dialysis for 4 months of the previous 6 months while receiving PBS-subsidised eculizumab and has failed to demonstrate significant resolution of extra-renal complications if originally presented. Serial haematological results (every 3 months while the patient is receiving treatment) must be provided. Clinical criteria: Patient must have received 52 weeks of treatment under Initial treatment-new patient, Initial treatment-balance of supply and treatment-new patient with PBS-subsidised Soliris for this condition Patient must have demonstrated on-going treatment response to PBS-subsidised Soliris for this condition* Patient must not have ever experienced treatment failure with Soliris including PBS-subsidised Soliris for this condition Patient must have a TMA-related cardiomyopathy as evidenced by left ventricular ejection fraction < 40% Patient must have severe TMA-related neurological impairment Patient must have severe TMA-related gastrointestinal impairment Patient must have severe TMA-related pulmonary impairment Patient must have grade 4 or 5 chronic kidney disease (egfr of less than 30 ml/min) Patient must not receive more than 24 weeks of treatment under this restriction

5 Recommencement of Soliris treatment after a treatment break INITIAL TREATMENT 2: RECOMMENCEMENT OF TREATMENT AFTER AN INITIAL 52-WEEK PERIOD REACCESS WEEK 1-24 Active TMA anytime after a treatment break TREATMENT PHASE: CONTINUING TREATMENT FOLLOWING RECOMMENCEMENT OF TREATMENT AFTER AN INITIAL 52-WEEK PERIOD WEEK 25 ONWARDS treatment after recommencement Clinical criteria: Patient must have demonstrated treatment response to previous 52 weeks of treatment with PBS-subsidised Soliris for this condition* Clinical criteria: Patient must have received Initial treatment 2 Recommencement of treatment after an initial 52-week period with PBS-subsidised Soliris for this condition Patient must not have ever experienced treatment failure with Soliris including PBS-subsidised Soliris for this condition Patient must have demonstrated ongoing treatment response to the previous 24 weeks of PBS-subsidised Soliris for this condition* Patient must have the following clinical conditions: Either significant haemolysis as measured by low/absent haptoglobin; or presence of schistocytes on the blood film; or lactate dehydrogenase (LDH) above normal Patient must not have experienced treatment failure with Soliris including PBS-subsidised Soliris for this condition* Either platelet consumption as measured by either 25% decline from patient baseline or thrombocytopenia (platelet count <150 x 10 9 /L) TMA-related organ impairment including on recent biopsy Patient must not receive more than 24 weeks of treatment under this restriction Patient must not receive more than 28 weeks of treatment under this restriction. *A treatment response is defined as: (1) Normalisation of haematology as demonstrated by at least 2 of the following: platelet count, haptoglobin, and LDH; AND (2) One of the following: a) An increase in egfr of > 25% from baseline, where the baseline is the egfr measurement immediately prior to commencing treatment with Soliris or b) an egfr within ± 25% from baseline; or c) an avoidance of dialysis-dependence but worsening of kidney function with a reduction in egfr 25% from baseline. PBS-subsidised treatment with Soliris will not be permitted if a patient has experienced treatment failure. A treatment failure is defined as: (1) dialysis-dependent at the time of application and has failed to demonstrate significant resolution of extra-renal complications if originally presented; or (2) on dialysis and has been on dialysis for 4 months of the previous 6 months while receiving PBS-subsidised Soliris and has failed to demonstrate significant resolution of extra-renal complications if originally presented. NOTE A raise in LDH alone is not a sufficient reason to re-commence Soliris, but thrombocytopenia with one marker of haemolysis (such as raised LDH, presence of schistocytes, or low/absence of haptoglobin) is an accepted reason to consider re-commencement of Soliris treatment. NOTE Kidney transplantation/dialysis is not a contraindication to recommencement of Soliris treatment.

6 Assessment of Active Organ Damage or Impairment Assessment and recording of TMA-related organ damage is important for ongoing eligibility for Soliris therapy. 1 Ensure all signs of extra-renal TMA are documented in the application forms. CNS 48% of ahus patients experience neurological symptoms 4 EXTRA-RENAL THROMBI 37% of ahus patients experience thrombi outside of the kidney 12 Confusion 5 Stroke 5 Encephalopathy 6 Seizure 4,5 PULMONARY 47% of ahus patients experience pulmonary symptoms 7 Dyspnoea 8 Pulmonary haemorrhage 9 Pulmonary oedema 8 GASTROINTESTINAL 37% of ahus patients experience GI symptoms 12 Colitis 5 Gastroenteritis 6 Abdominal pain 5 Liver necrosis 10 Pancreatitis 13 Diarrhoea 13 Nausea/vomiting 12 CARDIOVASCULAR 43% of ahus patients experience cardiovascular symptoms 4 Myocardial infarction 8 Hypertension 10,11 Diffuse vasculopathy 10 RENAL More than 50% of ahus patients progress to end-stage renal disease 14 Proteinuria 4 Oedema, malignant hypertension 6,15 Decreased estimated glomerular filtration rate (egfr) 10,16 Elevated creatinine 15,16

7 In patients with TMA, the ADAMTS-13 and STEC tests can rule out TTP and STEC-HUS respectively and thereby confirm a diagnosis of ahus ADAMTS-13 Testing ADAMTS-13 testing 17 SPECIMEN REQUIREMENTS Specimen Type Container Type Minimum Adult Volume Minimum Paediatric Volume Storage and Transport Blood (Pre-plasma exchange or infusion) 2 x tubes Sodium Citrate (Light blue top) 4ml 1ml Centrifuge (double-spin), aliquot plasma and freeze (-20 C) within two hours of collection. Minimum plasma volume required is 0.5mL. Reference laboratories performing ADAMTS-13 activity assay Five reference laboratories offer ADAMTS-13 testing and act as referral laboratories for samples from other hospitals in Australia: STATE NAME CONTACT NO. New South Wales Hunter Area Pathology Services or New South Wales SEALS, Prince of Wales Hospital Send to Reference Laboratory marked as URGENT Please notify lab by phone ADAMTS-13 greater than or equal to 10% ; patient qualifies for PBS-funded eculizumab treatment. In the case that a sample for ADAMTS-13 assay was not collected prior to plasma exchange or infusion, a sample must be taken 1-2 weeks following the last plasma exchange or infusion. Victoria Monash Pathology, Monash Health Queensland Royal Brisbane and Women s Hospital Western Australia Fiona Stanley Hospital Expected turn-around time: All laboratories confirm they are able to produce a result in hours. Urgent requests require a phone call to advise laboratory of specimen arrival.

8 Shiga Toxin/EHEC Testing Shiga Toxin/EHEC testing to rule out STEC-HUS 17 Å ahus patients can present with signs and symptoms similar to those with STEC-HUS. Å 25% of patients with ahus report diarrhoea as a presenting symptom. 18 Å Therefore, the presence of diarrhoea alone is not sufficient to either exclude ahus or to confirm a diagnosis of STEC-HUS. Å The absence of diarrhoea, however, is highly predictive that the TMA is not caused by STEC Infection, as 100% of children and adults with STEC-HUS infection have a history of diarrhoea. 19 Shiga Toxin/EHEC Testing: Positive culture and identification of bacteria in a faecal sample or by PCR (polymerase chain reaction) test in a pathology laboratory. Urgent requests, once the specimen has been received, can be processed in 48 hours by all laboratories, and requesting physicians should contact their local hospital laboratory to follow up for results. All laboratory confirmed cases of STEC infection are notifiable, in all states and territories, to the Public Health Unit. SPECIMEN REQUIREMENTS Specimen Container Type Specimen Volume Required Minimum Volume for Testing Storage and Transport Faeces preferred (or rectal swab) Brown Top Container 2-5 mls 1 gram Refrigerate Pathology laboratories Many laboratories are now able to provide STEC testing. Please confirm with your local Hospital Pathology Laboratory for their local STEC testing protocol. The 5 Reference Health Laboratories include: STATE NAME CONTACT NO. Queensland Public Health Microbiology Queensland New South Wales ICPMR, Westmead PHLN Victoria Microbiological Diagnostic Unit Public Health Laboratory South Australia Please refer to the SA state Wide STEC Testing Protocol Western Australia Pathwest Laboratory

9 WARNING: SERIOUS MENINGOCOCCAL INFECTION. SOLIRIS increases the risk of meningococcal infections Vaccinate patients with a meningococcal vaccine at least 2 weeks prior to receiving the first dose of SOLIRIS; revaccinate according to current medical guidelines for vaccine use. Patients less than 2 years of age and those who are treated with SOLIRIS less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Monitor patients for early signs of meningococcal infections, evaluate immediately if infection is suspected, and treat with antibiotics if necessary. Soliris (eculizumab, rmc) Minimum Product Information INDICATIONS: Treatment of paroxysmal nocturnal haemoglobinuria (PNH) to reduce haemolysis; treatment of atypical haemolytic uraemic syndrome (ahus). CONTRAINDICATIONS: eculizumab or murine protein hypersensitivity; unresolved Neisseria meningitidis infection; unvaccinated against Neisseria meningitidis (including ahus patients who have not received prophylactic treatment with appropriate antibiotics until 2 wks after vaccination). PRECAUTIONS: Meningococcal Infection/Immunisation: meningococcal infection susceptibility (vaccinate all patients at least 2 wks prior to receiving SOLIRIS, strongly recommend vaccination against serotypes A, B*, C, Y and W135, if available, preferably, quadrivalent or conjugated vaccines); monitor for early signs of infection, including fever > 39 deg C, headache ± stiff neck, light sensitivity; if treated < 2 weeks after meningococcal vaccination, admin prophylactic antibiotics for 2 wks after vaccination; admin prophylactic antibiotics in children < 2 yrs of age; maintain immunisation currency (esp < 18 yrs of age against Haemophilus influenza, pneumococcal); admin with caution with active systemic infections. Laboratory Monitoring: (PNH) monitor serum LDH for intravascular haemolysis; (ahus) monitor serum LDH, serum creatinine and platelet count for TMA. Discontinuation: (PNH) closely monitor for at least 8 wks for serious intravascular haemolysis and other reactions; (ahus) closely monitor for at least 12 wks for severe thrombotic microangiopathy complications. Anticoagulation Therapy: the effect of withdrawal of anticoagulant therapy during SOLIRIS treatment has not been established.* Other: classic ahus; Na restricted diet, elderly 65 yrs of age. Use in Pregnancy- Category B2: women of childbearing potential should use adequate contraception during treatment with SOLIRIS, and for up to 5 months after treatment.* Use in Lactation: discontinue breastfeeding during treatment, and up to 5 months after treatment. Paediatric Use: safety and effectiveness not been established in PNH patients < 18 yrs of age. Educational Materials: All prescribing physicians must be familiar with the physician s guide to prescribing, discuss the benefits and risks of treatment with patients and provide them with patient safety card and information brochure. ADVERSE EFFECTS: Infections (including meningococcal, sepsis, Aspergillus), blood dyscrasia (esp leukopenia), hypersensitivity (including anaphylaxis), decreased appetite, headache, dizziness, nausea, dysgeusia, paraesthesia, vertigo, hypotension*, dyspnoea*, cough, nasal congestion, pharyngolaryngeal pain, rhinorrhoea, throat irritation, GI upset, alopecia, dry skin, pruritis, rash, arthralgia, back/neck/muscle/ extremity pain, muscle spasms, bone pain, dysuria, spontaneous penile erection, chest discomfort, chills, fatigue, asthenia, oedema, pyrexia, influenza-like illness*, Coombs test +ve and others, see full PI. DOSAGE: (PNH) initial phase: 600 mg/wk for 4 wks, followed by maintenance phase: 900 mg in wk 5, then every 14 ± 2 days thereafter; (ahus adults) initial phase: 900mg/wk for 4 wks, followed by maintenance phase: 1200mg in wk 5, then every 14 days ± 2 days thereafter; (ahus children < 18 yrs of age) initial phase: 900 mg/wk for 4 wks ( 40 kg), 600 mg/wk for 2 wks (20-40 kg), 600 mg in wk 1 (10-20 kg), 300 mg in wk 1 (5-10 kg), then followed by maintenance phase: 1200 mg in wk 5 and every 2 wks after ( 40 kg), 900 mg in wk 3 and every 2 wks after (30-40 kg), 600 mg in wk 3 and every 2 wks after (20-30 kg), 300 mg in wk 2 and every 2 wks thereafter (10-20 kg), 300mg in wk 2 and every 3 wks after (5-10 kg). Dose modification: Supplemental dosing with concomitant PE/PI (see full PI). ADMINISTRATION: reconstitute to 5mg/mL with 0.9%, 0.45% Sodium Chloride Injection, 5% Dextrose in Water for Injection, or Ringer s Injection; admin as IV infusion over min (max 2 hrs in adults and adolescents, 4 hrs in children < 12 yrs of age). Monitor for at least 1 hr for signs of an infusion reaction. Date of most recent amendment: 26 June *Please note changes in product information. Please refer to the full Product Information before prescribing, including Black Box Warning regarding meningococcal infection and vaccination. Please contact Alexion Pharmaceuticals Australasia Pty Ltd on to request the Full Product Information. PBS Information: This product is listed on the PBS as a Section 100 item for the treatment of ahus. Refer to PBS Schedule for full authority information. Soliris (eculizumab) is funded on the Life Saving Drug Programme for the treatment of PNH. Application and consent forms for Soliris treatment are available from the LSDP website: References 1. Australian Government. Department of Health Australian Product Information for Soliris (eculizumab). Approved 25th January Coppo P, et al. PLOS ONE 2010;5:e Neuhaus TJ, et al. Arch Dis Child. 1997;76: Ohanian M, et al. Clin Pharmacol. 2011;3: Noris M, et al. Clin J Am Soc Nephrol. 2010;5: Muus P, et al. Presented at: 18th Congress of the European Hematology Association; June 13-16, 2013; Stockholm, Sweden. Abstract B Sallée M, et al. Nephrol Dial Transplant. 2010;25: Sellier-Leclerc A-L, et al; French Society of Pediatric Nephrology. J Am Soc Nephrol. 2007;18: Loirat C, et al. Pediatr Nephrol. 2008;23: Kavanagh D, et al. Br Med Bull. 2006;77-78: Langman CB. Haematologica. 2012;97(supp1):Abstract Dragon-Durey M-A, et al. J Am Soc Nephrol. 2010;21: Caprioli J, et al; for the International Registry of Recurrent and Familial HUS/TTP. Blood. 2006;108: Ståhl A-L, et al. Blood. 2008;111: Ariceta G, et al; for the European Paediatric Study Group for HUS. Pediatr Nephrol. 2009;24: Data on file, Alexion. 18. Geerdink LM et al. Pediatr Nephrol Piercefield E W. et al Arch Intern Med. 2010;170(18): Alexion Pharmaceuticals Australasia Pty Limited. All rights reserved. Alexion Pharmaceuticals Australasia Pty Limited. ACN Suite 401, Level 4, Building A, 20 Rodborough Rd, Frenchs Forest. NSW 2086 Australia. November 2015 AU/SOL-aHUS/15/0017

10 Notes USEFUL CONTACTS / RESOURCES Alexion Australasia Adverse Event Reporting Pharmacovigilance.Australasia@alxn.com Medical Information STEPP A support program for clinicians prescribing STEPP@partizanhealth.com PBS (Section 100) Soliris

11 Soliris is a registered trademark of Alexion Pharmaceuticals, Inc. Copyright 2015, Alexion Pharmaceuticals, Inc. All rights reserved.