• ICLUSIG™ to be PBS listed in Australia from November 1 2015
Melbourne, Australia, November 2, 2015: A treatment for patients with chronic myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant or intolerant to current therapies will be listed on the Australian Pharmaceutical Benefits Scheme (PBS) from November 1 2015.
Therapeutics Goods Administration (TGA) registered oral drug, Iclusig™ (ponatinib), is a new treatment option for adult patients with:
• Chronic phase, accelerated phase, or blast phase CML whose disease is resistant to, or who are intolerant of at least two prior tyrosine kinase inhibitors; or where there is a T315I mutation.
• Ph+ ALL whose disease is resistant to, or who are intolerant of dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or where there is a T315I mutation.1
Over 100 patients a year in Australia are now expected to access the potentially life saving treatment via the PBS.
The drug is made available in Australia by biopharmaceutical company Specialised Therapeutics Australia (STA) under license from ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA).
STA Chief Executive Officer Mr. Carlo Montagner welcomed the decision by the Pharmaceutical Benefits Advisory Committee (PBAC) and said it was a great step forward for this group of leukaemia patients for whom other treatments had failed.
“We are very pleased that Australian patients with resistant disease will now have equitable access to Iclusig which has been shown to deliver deep and durable responses,” he said.
Under the terms of the PBS listing, Iclusig will be reimbursed for:
• patients with CML who have been failed by first line therapy with imatinib or dasatinib or nilotinib and whose CML has the T315I mutation;
• patients with CML where both nilotinib and dasatinib have failed or where one of nilotinib or dasatinib has failed and who are intolerant of the other drug; and
• for the treatment of relapsed or refractory Philadelphia chromosome positive (Ph+ ) acute lymphoblastic leukaemia (ALL) in patients whose ALL has the T315I mutation.
Global and Australian leukaemia authority, Professor Tim Hughes, Beat Cancer Professor at the University of Adelaide and Cancer Theme Leader at SAHMRI (South Australian Health and Medical Research Institute), said Iclusig had been shown to be a valuable drug for patients for whom there were extremely limited options.
“Previously when patients developed resistance to current available therapies or developed the T315I mutation we had to consider embarking on an allogeneic stem cell transplant which is a high risk procedure in this patient group, or take a palliative approach,” he said.
“Iclusig has been shown to achieve a major molecular response in many of these patients, which is associated with long term disease control. We anticipate Iclusig will be a valuable tool, particularly in those patients with the T315I mutation.”
About Specialised Therapeutics Australia, Pty Ltd
Specialised Therapeutics Australia Pty Ltd (STA) is a biopharmaceutical company dedicated to working with leading international pharmaceutical and diagnostic companies to provide patient access to innovative healthcare solutions. With the highest professional and ethical standards, STA commercialises therapies and technologies that uniquely fulfil the unmet medical needs of our community.
The STA therapeutic portfolio and pipeline at present encompass oncology, haematology, urology and ophthalmology.
Additional information can be found at www.specialisedtherapeutics.com.au ?
About CML and Ph+ ALL
CML is characterised by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase or blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors (TKIs). The BCR-ABL protein is expressed in both of these diseases.
In Australia, approximately 330 patients are diagnosed with CML each year.3 The disease typically affects more men than women and is most prevalent in adults aged over 60.. It is estimated by the PBS Drug Utilisation Sub-Committee that around 2,500 patients are currently receiving therapy in Australia with PBS subsidised TKIs.
About Iclusig™ (ponatinib)
Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in CML and Ph+ ALL. Iclusig was designed using ARIAD’s computational and structure-based drug design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, a common mutation which has been associated with resistance to other approved TKIs.
The TGA approval of Iclusig was based on results from a pivotal Phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) international trial in patients with CML or Ph+ ALL who were resistant or intolerant to prior TKI therapy, or who had the T315I mutation of BCR-ABL.4
A total of 56% of chronic-phase CML patients, including 70% of patients with the T315I mutation, achieved a major cytogenetic response (MCyR) – the primary endpoint of the PACE trial for chronic-phase patients. In patients with advanced disease, 55% of accelerated-phase CML patients, 31% of blast-phase CML patients and 41% of Ph+ ALL patients achieved a major haematologic response (MaHR) to Iclusig. MaHR was the primary endpoint in the trial for patients with advanced disease.4
Minimum Product Information ICLUSIG™ (ponatinib HCl). Indications: Adult patients with: CML Chronic phase, accelerated phase, or blast phase chronic myeloid Ieukaemia (CML) whose disease is resistant to, or who are intolerant of at least two prior tyrosine kinase inhibitors; or where there is a T315I mutation. Ph+ ALL Philadelphia chromosome positive acute lymphoblastic Leukemia (Ph+ ALL) whose disease is resistant to, or who are intolerant of dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or where there is a T315I mutation. Therapy should be initiated and monitored by a haematologist with expertise in managing adult leukaemias. Contraindications: Hypersensitivity to ponatinib or excipients.
WARNING: VASCULAR OCCLUSION AND HEART FAILURE
• Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 23% of ICLUSIG-treated patients, resulting in fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease (sometimes resulting in amputation), vision loss and the need for urgent revascularisation procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop ICLUSIG immediately for vascular occlusion (see Precautions, Vascular Occlusion).
• Heart Failure: Heart Failure, including fatalities, occurred in 8% of ICLUSIG-treated patients. Monitor cardiac function. Interrupt or stop ICLUSIG for new or worsening heart failure (see Precautions, Heart Failure).
• Hypertension: Hypertension, including hypertensive crisis, has been observed in ICLUSIG-treated patients (26% overall, 2% serious) (see Precautions, Hypertension).
Precautions: Actively monitor and manage patients for vascular occlusions, cardiac failure, hypertension, haemorrhage, myelosuppression, hepatotoxicity, pancreatitis and QT prolongation before and during treatment. Interrupt, reduce or discontinue ICLUSIG as clinically indicated (see full PI). Vascular occlusion: Do not use if history of myocardial infarction, prior revascularisation or stroke, unless the benefit outweighs the risk. Monitor cardiovascular status and optimise therapy throughout. Monitor patient for decreased or blurred vision. Cardiac failure: Monitor for heart failure and treat as clinically indicated. Hypertension: Hypertension may contribute to risk of arterial thrombotic and occlusive events including renal artery stenosis. Monitor at each clinic visit and treat hypertension to normalise blood pressure. Interrupt treatment if hypertension is not medically controlled and consider evaluating for renal artery stenosis. Haemorrhage, including fatalities occurred, mostly in patients with grade 4 thrombocytopaenia. Use anti-coagulants with caution in patients at risk of bleeding. Myelosuppression: Severe thrombocytopenia, neutropenia or anaemia. Perform complete blood counts every 2 weeks initially. Hepatotoxicity: Including severe drug induced liver injury and fatal hepatic failure. Monitor Liver Function Tests (LFT’s) at baseline and at least monthly. Pancreatitis and serum lipase: Monitor serum lipase every 2 weeks initially. QT prolongation: QT prolongation seen with other BCR-ABL inhibitors. Lactose: contains lactose. Special populations: Recommended starting dose of 30 mg for patients with hepatic impairment. Caution or avoid in patients with moderate to severe or end stage renal disease, pregnancy (category D), breastfeeding, the elderly, paediatric patients, or when driving or operating machinery (see full PI). Interactions with Other Medicines: Caution with concurrent strong CYP3A inhibitors and consider a starting dose of 30 mg. Caution with CYP3A inducers, P-glycoprotein (P-gp) substrates and breast cancer resistance protein (BCRP) (see full PI). Adverse Effects: Most common (= 20%) adverse drug reactions (ADRs): Platelet count decreased, rash, dry skin, and abdominal pain. Most common (> 1%) serious ADRs: Pancreatitis (5.1%), abdominal pain (1.8%), platelet count decreased (1.8%), lipase increased (1.3%), anaemia (1.3%), cardiac failure (1.3%), coronary artery disease (1.1%), diarrhoea (1.1%), neutrophil count decreased (1.1%), febrile neutropenia (1.1%), pancytopenia (1.1%), and pyrexia (1.1%). Other very common (> 10%) ADRs: Upper respiratory tract infection, anaemia, neutrophil count decreased, decreased appetite, insomnia, headache, dizziness, hypertension, dyspnoea, cough, diarrhoea, vomiting, constipation, nausea, lipase increased, ALA increased, AST increased, bone pain, arthralgia, myalgia, pain in extremity, back pain, muscle spasms, fatigue, asthenia, oedema peripheral, pyrexia, pain. This is not a full list of adverse effects – refer to full PI for more information on common (>1%) and uncommon (>0.1%) ADRs. Dosage and administration: Monitor and manage cardiovascular risk factors before and throughout treatment. Starting Dose: 45 mg once daily, with or without food; 30 mg for patients with hepatic impairment; 30 mg with concurrent strong CYP3A inhibitors. Dose adjustments based on disease response: Consider reducing the dose of ICLUSIG to 30 mg or 15 mg for chronic phase (CP) CML patients who have achieved a major cytogenetic response, especially in subjects at risk of vascular adverse events. Consider discontinuing ponatinib if a haematologic response has not occurred by 3 months (90 days) especially in subjects at risk of vascular adverse event. Dose adjustments for toxicity: Consider dose modification or treatment cessation to manage myelosuppression, vascular occlusion, uncontrolled hypertension, pancreatitis or elevated serum lipase, and other severe adverse reactions. Provide haematologic support (platelet transfusion or haematopoietic growth factors) if clinically indicated.
For further information or before prescribing, please consult the full ICLUSIG Product Information, available at www.specialisedtherapeutics.com.au.
References:
1. Australian Approved Product Information.
2. www.pbs.gov.au, Last accessed October 2015.
3. http://www.leukaemia.org.au/blood-cancers/leukaemias/chronic-myeloid-leukaemia-cml, Last accessed October 2015.
4. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A Phase 2 trial of ponatinib in Philadelphia chromosome positive leukaemias. N Engl J Med. 2013; 369(19): 1783-96.
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