This is the text extract for Proposal for nilotinib and imatinib; Closing Date: Closed; Contact: Jackie Evans, browse documents here.

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24 February 2011

Proposal to widen funded access to imatinib and to fund nilotinib for patients with CML

PHARMAC is seeking feedback on a proposal to:

 

fund nilotinib (Tasigna) for patients with chronic myeloid leukaemia (CML); and widen funded access to imatinib mesylate (Glivec) to include: Funding for up to 600 mg/day for patients with chronic phase CML; and Funding for up to 400 mg/day for patients with c-kit negative unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST)

through a provisional agreement with Novartis New Zealand Limited. Further details of this proposal, including how to provide feedback and background information, can be found below and on the following pages. All changes would be implemented 1 May 2011 unless otherwise stated.

Feedback sought

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by 5 pm Thursday, 10 March 2011 to: Jackie Evans Therapeutic Group Manager PHARMAC Email: jackie.evans@pharmac.govt.nz Fax: 04 460 4995 Post PO Box 10 254, Wellington 6143

All feedback received before the closing date will be considered by PHARMAC’s Board (or Chief Executive acting under delegated authority) prior to making a decision on this proposal.

Details of the proposal

Funding of nilotinib  

Brand Tasigna Presentation 200 mg capsule Pack size 28 Price and subsidy $1,800.00

Nilotinib 200 mg capsules (Tasigna) would be listed in Section B and in Part II of Section H of the Pharmaceutical Schedule at the following prices and subsidies (exmanufacturer, excl. GST):

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Nilotinib 150 mg capsules (Tasigna) would be listed in Section B and in Part II of Section H of the Pharmaceutical Schedule as soon as practicable following Medsafe approval at the following prices and subsidies (ex-manufacturer, excl. GST):

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Brand Tasigna

Presentation 150 mg capsule

Pack size 28

Price and subsidy $1,350.00

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A confidential rebate would apply to all subsidies for Tasigna which would reduce its net price to the funder. Tasigna would be listed in Section B of the Pharmaceutical Schedule subject to Special Authority criteria as follows:

Special Authority for Subsidy Special Authority approved by PHARMAC. Notes: Application details may be obtained from http://www.pharmac.govt.nz, and prescriptions should be sent to: The Co-ordinator PHARMAC PO Box 10 254 Wellington

PHARMAC’s

website

Phone: (04) 460 4990 Facsimile: (04) 916 7571 Email: mary.chesterfield@pharmac.govt.nz

Special Authority criteria for CML – access by application to PHARMAC a) Funded for patients with diagnosis (confirmed by a haematologist) of a chronic myeloid leukaemia (CML) in blast crisis, accelerated phase, or in chronic phase. b) Maximum dose of 800 mg/day. c) Subsidised for use as monotherapy only. d) Initial approvals valid seven months. e) Subsequent approval(s) are granted on application and are valid for six months. The first reapplication (after seven months) should provide details of the haematological response. The third reapplication should provide details of the cytogenetic response after 14-18 months from initiating therapy. All other reapplications should provide details of haematological response, and cytogenetic response if such data is available. Applications to be made and subsequent prescriptions can be written by a haematologist or an oncologist. Note: Nilotinib is indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukaemia (CML) in adult patients resistant to or intolerant to at least one prior therapy including imatinib. Guideline on discontinuation of treatment for patients with CML a) Prescribers should consider discontinuation of treatment if, after 6 months from initiating therapy, a patient did not obtain a haematological response as defined as any one of the following three levels of response: 1) complete haematologic response (as characterised by an absolute neutrophil count (ANC) > 1.5 × 109/L, platelets > 100 × 109/L, absence of peripheral blood (PB) blasts, bone marrow (BM) blasts < 5% (or FISH Ph+ 0-35% metaphases), and absence of extramedullary disease); or 2) no evidence of leukaemia (as characterised by an absolute neutrophil count (ANC) > 1.0 × 109/L, platelets > 20 × 109/L, absence of peripheral blood (PB) blasts, bone marrow (BM) blasts < 5% (or FISH Ph+ 0-35% metaphases), and absence of extramedullary disease); or 3) return to chronic phase (as characterised by BM and PB blasts < 15%, BM and PB blasts and promyelocytes < 30%, PB basophils < 20% and absence of extramedullary disease other than spleen and liver). b) Prescribers should consider discontinuation of treatment if, after 18 months from initiating therapy, a patient did not obtain a major cytogenetic response defined as 035% Ph+ metaphases.

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Tasigna when used in the community, would be distributed under a direct-to-patient mechanism, which would be funded by Novartis. DHB clinicians would be able to apply directly to PHARMAC for Special Authority approvals for existing patients (i.e. those being treated with nilotinib on 30 April 2011).but clinicians would need to demonstrate that the patient would have met the proposed Special Authority criteria prior to starting treatment with nilotinib. If the patient had been on nilotinib for longer than 7 months at 30 April 2011, the clinician would need to demonstrate,that the patient would also meet the proposed criteria for subsequent approval(s). Tasigna would have subsidy and delisting protection until 30 June 2013.

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Widening of access to imatinib  The Special Authority criteria applying to imatinib mesylate 100 mg tablet (Glivec) in Section B of the Pharmaceutical Schedule would be amended as follows (changes in bold and strikethrough):

Special Authority for Subsidy Special Authority approved by PHARMAC. Notes: Application details may be obtained from http://www.pharmac.govt.nz, and prescriptions should be sent to: The Co-ordinator PHARMAC PO Box 10 254 Wellington

PHARMAC’s

website

Phone: (04) 460 4990 Facsimile: (04) 916 7571 Email: mary.chesterfield@pharmac.govt.nz

Special Authority criteria for CML – access by application to PHARMAC a) Funded for patients with diagnosis (confirmed by a haematologist) of a chronic myeloid leukaemia (CML) in blast crisis, accelerated phase, or in chronic phase. b) Maximum dose of 600 mg/day for accelerated or blast phase, and 400 mg/day for chronic phase. c) Subsidised for use as monotherapy only. d) Initial approvals valid seven months. e) Subsequent approval(s) are granted on application and are valid for six months. The first reapplication (after seven months) should provide details of the haematological response. The third reapplication should provide details of the cytogenetic response after 14-18 months from initiating therapy. All other reapplications should provide details of haematological response, and cytogenetic response if such data is available. Applications to be made and subsequent prescriptions can be written by a haematologist or an oncologist. Guideline on discontinuation of treatment for patients with CML a) Prescribers should consider discontinuation of treatment if, after 6 months from initiating therapy, a patient did not obtain a haematological response as defined as any one of the following three levels of response: 1) complete haematologic response (as characterised by an absolute neutrophil 9 9 count (ANC) > 1.5 × 10 /L, platelets > 100 × 10 /L, absence of peripheral blood (PB) blasts, bone marrow (BM) blasts < 5% (or FISH Ph+ 0-35% metaphases), and absence of extramedullary disease); or 2) no evidence of leukaemia (as characterised by an absolute neutrophil count (ANC) > 1.0 × 109/L, platelets > 20 × 109/L, absence of peripheral blood (PB)

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blasts, bone marrow (BM) blasts < 5% (or FISH Ph+ 0-35% metaphases), and absence of extramedullary disease); or 3) return to chronic phase (as characterised by BM and PB blasts < 15%, BM and PB blasts and promyelocytes < 30%, PB basophils < 20% and absence of extramedullary disease other than spleen and liver). b) Prescribers should consider discontinuation of treatment if, after 18 months from initiating therapy, a patient did not obtain a major cytogenetic response defined as 035% Ph+ metaphases. Special Authority criteria for GIST – access by application a) Funded for patients: 1) with a diagnosis (confirmed by an oncologist) of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST); and 2) who have immunohistochemical documentation of c-kit (Cd117) expression by the tumour. b) Maximum dose of 400 mg/day. c) Applications to be made and subsequent prescriptions can be written by an oncologist. d) Initial and subsequent applications are valid for one year. The re-application criterion is an adequate clinical response to the treatment with imatinib (prescriber determined).

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The confidential rebate currently applying to Glivec would be increased reducing its net price to the funder. Glivec when used in the community, would remain distributed under a direct-to-patient mechanism, which would be funded by Novartis. Glivec would have subsidy and delisting protection until 1 April 2013.

Background

CML Chronic myeloid leukaemia (CML) is a disease characterised by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. Allogeneic haematopoietic stem cell transplantation remains the only known curative treatment in CML. Use of this treatment is limited by donor availability and the high risk of the procedure. The disease course of CML is grouped into three phases; chronic, accelerated and blast phases, based on clinical characteristics and laboratory findings. Imatinib mesylate (Glivec) and dasatinib (Sprycel) are currently funded via a PHARMAC co-ordinated special access program for the treatment of patients with CML and imatinib is also funded for patients with c-kit positive GIST. Dasatinib is currently funded for patients with CML up to a maximum dose of 100 mg/day for patients in chronic phase or up to 140 mg/day in the accelerated or blast phase. Imatinib is currently funded for patients with CML up to a maximum dose of 400 mg/day for patients in chronic phase or up to 600 mg/day in the accelerated or blast phase.

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Currently, 319 patients are accessing funded imatinib (240 CML, 79 GIST) and 30 patients are accessing funded dasatinib. Imatinib and dasatinib are tyrosine kinase inhibitors and although recent evidence suggests a role for dasatinib in the first line treatment of CML, it is currently generally used in the second line treatment following resistance or intolerance to imatinib. The 2-year incidence of resistance is estimated to be 80% in blast phase, 40% to 50% in accelerated phase, and at least 10% in chronic phase. Nilotinib - CML Nilotinib is an oral tyrosine kinase inhibitor, selective for BCR-ABL, derived from imatinib. Nilotinib is currently indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive CML in adult patients resistant to or intolerant to at least one prior therapy including imatinib. Although nilotinib is not currently approved by MedSafe for use in newly diagnosed CML, under this proposal it would be funded if clinicians wish to use it in this setting. Results from a randomised phase III study comparing nilotinib (at a dose of either 300 mg or 400 mg twice daily) or imatinib (400 mg once daily) demonstrated that in newly diagnosed chronicphase CML patients, nilotinib was superior to imatinib (Saglio et al N Engl J Med June 2010;362:2251-9). The efficacy of the 300 mg and 400 mg doses of nilotinib were similar, however the 300 mg dose was associated with a lower rate of discontinuation, dose reductions and dose delays. The funding of nilotinib has been reviewed by PTAC at its May 2008, February 2009, November 2009 and February 2011 meetings and its Cancer Treatments Subcommittee (CaTSoP) at its June 2008 and June 2009 meetings1. Initially PTAC recommended that the application be declined due to its limited, short-term data and high cost. However, at its most recent review, following pricing negotiations and the provision of additional evidence, the Committee recommended that nilotinib be funded for patients with CML with a medium priority (minute not yet available). Imatinib - CML As discussed above, imatinib is currently funded for patients with CML up to a maximum dose of 400 mg/day for patients in chronic phase or up to 600 mg/day in accelerated or blast phase. Doses of up to 800 mg/day imatinib are approved by Medsafe for use in all phases of CML but this dose is not funded, nor is it proposed for funding. This proposal is for dosing of up to 600 mg/day to be funded for patients with chronic phase CML. The funding of 600 mg imatinib has been reviewed by PTAC at its February 2007 meeting and CaTSoP at its December 2007 and June 2008 meetings1. CaTSoP recommended that doses up to 600 mg/day imatinib should be funded with high priority for patients with chronic phase CML who do not respond to 400 mg/day treatment, with non-response defined as per the European Leukaemia Net (ELN) classification system. However, CaTSoP noted that its high priority recommendation was on the basis of there being no other funded option at that time for these patients. PTAC agreed with this view. GIST

1

Relevant PTAC and CaTSoP minutes are available at www.pharmac.govt.nz/PTAC/PTACminutes and www.pharmac.govt.nz/PTAC/PTACSCMinutes A409294 - T10-464 Page 5 of 6

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Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms of the gastrointestinal tract. They are rare tumours and constitute about 1% of all malignant tumours of the GI tract. Surgical resection remains the treatment of choice and offers the only chance of cure from GIST. Where surgery is not an option, imatinib is useful to induce remission, reduce morbidity and prevent complications. Imatinib is currently funded for patients with c-kit positive unresectable and/or metastatic malignant GIST. Imatinib - GIST The funding of imatinib for patients with c-kit negative GIST has been reviewed by CaTSoP at its December 2007 meeting1. The Subcommittee noted that approximately 25% of GIST tumours were c-kit negative, and that approximately 33% of c-kit negative GIST tumours harboured imatinib-sensitive platelet-derived growth factor receptor (PDGFR-A) mutations. However, members noted that clinical responses to imatinib have been observed in some GIST patients in the absence of either c-kit or PDGFR-A mutations. CaTSoP recommended that access to imatinib should be widened to include treatment of c-kit negative patients with high priority.

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