The National Institute for Health and Clinical Excellence (NICE) have recommended nilotinib (Tasigna) for the treatment of imatinib-resistant and imatinib-intolerant Philadelphia Chromosome (Ph+) chronic myeloid leukaemia (CML)[1]. 

Dasatinib and high dose imatinib were appraised in the same setting; neither are recommended. Final Guidance is expected in October 2011.

"Today's Final Appraisal Determination[1] recommending Tasigna is great news for CML patients across England and Wales as it provides access to a treatment option proven to be clinically-effective in this setting"[2], said Panos Alexakos, Oncology General Manager, Novartis UK & Ireland. "This decision should finally bring clarity on the most clinical and cost-effective second-line treatment for CML patients who are unable to continue with imatinib therapy when it has failed or is not suitable."

In second line, after 24 months of treatment, a study has shown that 87% of patients treated with nilotinib 400mg BD achieved overall survival, 44% achieved complete cytogenic response (CCyR) and more than 80% maintained their CCyR[2,3].

NICE's decision on nilotinib is an acknowledgement of nilotinib's clinical and cost-effectiveness and also of its innovation. Based on imatinib, nilotinib has been rationally designed to be more specific in its binding to the Bcr-Abl kinase domain[4], the single known cause of CML. Through preferential targeting of Bcr-Abl, nilotinib overcomes resistance or intolerance seen with imatinib therapy[5,6] , leading to 87% overall survival at 24 months[3]. The specificity in targeting Bcr-Abl leads to an improved safety profile compared to TKIs which have a multi-targeted approach that leads to off-target side-effects[7].

"At Novartis Oncology we are committed to ensuring that CML patients in the UK have access to effective life-extending medicines and receive parity of care with other Western European countries," said Panos Alexakos. "In that regard, we remain hopeful that the Department of Health (DH) and NICE will continue to work closely with the pharmaceutical industry and will focus their efforts on supporting patients and clinicians in the UK in accessing effective treatments in a timely way."

In order to maximise and ensure patient access to treatment in this setting, Novartis Oncology worked closely with the Department of Health (DH) to establish a Patient Access Scheme (PAS) for nilotinib.

The decision on nilotinib is particularly encouraging news for CML patients in Wales who have had difficulty in accessing this second-line therapy for over three years[8] whilst awaiting the outcome of the NICE review process.

Novartis Oncology therefore trusts that NICE will carry out its forthcoming review of CML therapies for newly-diagnosed CML patients swiftly and in the best interests of patients.

CML results from an increased production of abnormal (leukaemic) white blood cells by stem cells in the bone marrow. It is one of four most common types of leukaemia. It is estimated that about 560 people are diagnosed with CML in the UK each year[1]. Clinical trials suggest that, over an eight year period, approximately 16% of CML patients on imatinib discontinue treatment due to unsatisfactory therapeutic outcome, or resistance, and around 6% due to intolerance[9].



Source: Novartis Oncology

References:

 

[1]National Insititute for Clinical Excellence Final Appraisal Determination of nilotinib, high dose imatinib and dasatinib for Chronic Myeloid Leukaemia, August 2011: http://guidance.nice.org.uk/TA/WaveR/99 

[2]Kantarijan HM et al. Blood 2009;114:Poster, Presentation and Abstract 1129.Tasigna®

[3]Kantarjian, H. et al. Nilotinib is effective in patients with chronic myeloid leukaemia in chronic phase after imatinib resistance or intolerance: 24 month follow-up results. Blood 2011 117: 1141-1145

[4]Swords R, Mahalingam D, Padmanabhan S, et al. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib. Drug Des Devel Ther 2009 Sep 21;3:89-101

[5]Jabbour E et al. Minimal cross intolerance between nilotinib and imatinib in patients with imatinib-intolerant chronic myeloid leukaemia in chronic phase (CML-CP) or accelerated phase (CML-AP). Blood 2008; 112, 11 Abstract 3215 ASH Poster Presentation Dec 2008

[6]Kantarjian HM et. al.Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood 2007; 110 (10):3540-3546

[7]Giles F, Class effects of TKIs in treatment of CML. Leukaemia 2009; 23:1698-1707

[8]AWMSG, Medicines Not Meeting AWMSG Criteria for Appraisal, 2 June 2011

[10]Deininger M et al. 2009, International randomised study of interferon versus STI571 (IRIS) 8 year follow up: sustained survival and low risk of progression or events in patients with newly diagnosed Chronic Myeloid Leukaemia in the chronic phase (CP-CML) treated with imatinib. Abstract 1126, ASH 2008. Poster presentation

[11]Faderl S; Talpaz M; Estrov Z; O'Brien S; Kurzrock R; Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 341:164-72, 1999.

[12]Hughes et al. Reduction of BCR-ABL Transcript Levels at 6, 12, and 18 Months (mo) Correlates with Long-Term Outcomes on Imatinib (IM) at 72 Mo: An Analysis from the International Randomized Study of Interferon versus STI571 (IRIS) in Patients (pts) with Chronic Phase Chronic Myeloid Leukemia (CML-CP). ASH 2008. Abstract #334

[13]Tasigna (nilotinib) 200mg European Summary of Characteristics Novartis AG http://www.medicines.org.uk/emc/medicine/20827/SPC

[14]Scottish Medicines Consortium, August 2008 http://www.scottishmedicines.org.uk/SMC_Advice/Advice/440_08_nilotinib__Tasigna_/nilotinib__Tasigna

[15]Scottish Medicines Consortium, Detailed Advice Document (DAD), August 8 2011.