Novartis Announces Half of Eligible Ph+ CML-CP Patients Remain in Treatment-free Remission (TFR) Nearly Two Years After Stopping Tasigna® (nilotinib)

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Novartis UK

23 Jun, 2017, 06:40 GMT

CAMBERLEY, England, June 23, 2017 /PRNewswire/ --

  • Tasigna has become the first and only tyrosine kinase inhibitor (TKI) to include information on stopping therapy in Ph+ CML-CP patients in the EU product information 
  • Two clinical trials demonstrate that half of eligible patients were able to maintain TFR after stopping treatment with Tasigna both first-line and after switching from Glivec[1],[2]
  • More than 90% of Ph+ CML-CP patients in ENESTfreedom and ENESTop who stopped Tasigna were in TFR at 48-weeks remained in TFR at 96-weeks[1],[2]

Novartis today announced new data from two clinical trials, ENESTfreedom and ENESTop, which demonstrate that approximately half of adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) in the chronic phase (CP), were able to maintain TFR after stopping treatment with Tasigna (nilotinib) both in the first-line setting and after switching from Glivec (imatinib)[1],[2]. The studies were presented at 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain. Earlier analysis of the two trials at 48 weeks formed the basis for submission to the European Commission (EC), which approved the inclusion of TFR data in the Tasigna Summary of Product Characteristics (SmPC). Tasigna is the first and only tyrosine kinase inhibitor (TKI) to include information on TFR in the European Union (EU) label.

Results from the ENESTfreedom 96-week update found that nearly half of the 190 CML patients (48.9%, confidence interval [CI] 95%: 41.6% - 56.3%) who entered TFR, following at least three years of first-line treatment with Tasigna (and with a sustained deep molecular response (MR4.5) for a year prior to stopping), remained in major molecular response (MMR; BCR-ABL1 International Scale [IS] ≤ 0.1%) and off treatment at week 96, including 88 patients (46.3%) who were in MR4.5[1]. Among patients remaining in TFR for more than 48 weeks (n=100), less adverse events (AEs) were experienced during the second 48 weeks compared to the first 48 week period[1]. Rates of musculoskeletal pain-related AEs were 34% and 9% during first and second 48 week period respectively[1]. These results suggest a reduction in AEs the longer the patient is in TFR.

Professor Adam Mead, Associate Professor of Haematology, Weatherall Institute of Molecular Medicine (WIMM), University of Oxford said:  "The findings from these two trials, ENESTfreedom and ENESTop, demonstrating stability of the TFR rate between 48 and 96 weeks, provides further evidence of the durability of molecular response following discontinuation of tyrosine kinase inhibitor treatment in certain patients with CML. This is a significant milestone, supporting that we can now consider stopping treatment in carefully selected patients with this chronic condition."

An additional trial presented at EHA, updated 96-week data from ENESTop, evaluated TFR in 126 patients who previously switched from Glivec onto Tasigna and subsequently achieved a sustained deep molecular response (MR4.5). At week 96, 53.2% of the patients who entered TFR remained in TFR (confidence interval [CI] 95%: 44.1% - 62.1%)[2]. Among patients who remained in TFR for more than 48 weeks (n=73), rates of AEs were 82.2% and 63.0% during the first and second 48 week period of TFR respectively[2]. Rates of musculoskeletal pain-related AEs were 47.9% and 15.1% during the first and second 48 week period of TFR respectively[2].

The approval by the EC to update the Tasigna SmPC was based on efficacy and safety findings from the 48-week analyses of ENESTfreedom and ENESTop, which showed that more than 50% of Ph+ CML-CP patients who met the rigorous predefined response criteria of the trials were able to maintain TFR after stopping Tasigna in both in the first-line setting and after switching from Glivec[3],[4].

Barak Palatchi, Oncology General Manager, Novartis UK & Ireland, said: "The possibility for many patients to become treatment free is a huge step forward in the management of CML. We're proud to be leading the industry with this new advancement and our ongoing commitment to driving scientific research, which has helped transform this disease from a fatal leukaemia to a chronic condition for a majority of patients."

About Ph+ CML 

CML is responsible for approximately 15% of all adult cases of leukaemia[5]. In the UK there are around 750 new cases each year[6]. CML is a type of cancer in which the body produces cancerous white blood cells. Almost all patients with CML have an abnormality known as the Philadelphia chromosome, which produces a protein called BCR-ABL1. BCR-ABL1 causes malignant white blood cells to proliferate. Generally more than 70% of men and almost 75% of women will survive with CML for 5 years or more after they are diagnosed[7].

About Tasigna (nilotinib)  

Tasigna® (nilotinib) is approved in more than 122 countries for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukaemia (Ph+ CML) in adult patients resistant or intolerant to at least one prior therapy, including Glivec® (imatinib), and in more than 110 countries for the treatment of adult patients with newly diagnosed Ph+ CML in chronic phase.

About ENESTfreedom 

ENESTfreedom (Evaluating Nilotinib Efficacy and Safety in Clinical Trials - Following REsponsE in De nOvo CML-CP Patients) is an open label Phase II study involving 215 Ph+ CML-CP patients, conducted at 132 sites across 19 countries. The trial evaluated stopping treatment in 190 adults with Ph+ CML-CP after the patients had achieved a response of MR4.5 with Tasigna as a first line treatment, and a sustained deep molecular (MR4.5) response for one year directly prior to entering TFR phase.

About ENESTop 

ENESTop (Evaluating Nilotinib Efficacy and Safety Trial) is an open label Phase II study involving 163 Ph+ CML-CP patients, conducted at 63 sites across 18 countries. The trial evaluated stopping treatment in 126 adults with Ph+ CML-CP after patients had previously been treated with Glivec, and then switched to treatment with Tasigna, and had achieved and sustained deep molecular response (MR4.5) for one year with Tasigna.

Novartis Commitment to CML  

Over the past several decades, Novartis research in Ph+ CML has helped transform the disease from a fatal leukaemia to a chronic condition in most patients, and today, the company continues its long-standing commitment to the global CML community. Novartis follows the science and builds upon existing evidence to explore what could be the next major contribution in the treatment of Ph+ CML. The company is evaluating more than 1,000 patients as part of the Tasigna ENEST studies, which include ENESTfreedom and ENESTop as well as two other ongoing company-sponsored TFR studies and multiple investigator-initiated studies, as well as investigational compounds.

About Novartis 

Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com (link is external).

In the UK, Novartis develops, manufactures and markets innovative medicines, devices and diagnostic tests, which help improve patient outcomes. Based on four sites across the north and south of England, we employ approximately 1,500 people to serve healthcare needs across the whole of the UK, as well as supporting the global operations of Novartis by manufacturing the active pharmaceutical ingredients used worldwide in many medicines. In 2015 Novartis in the UK invested over £50million in R&D and is the largest commercial sponsor of clinical trials. For more information, please visit http://www.novartis.co.uk.

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References 

  1. Ross, D. et al. Durable Treatment-free Remission (TFR) following frontline nilotinib (nil) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): ENESTfreedom 96-wk update. Poster presentation. Abstract #P601. 2017 European Hematology Association Congress in Madrid, Spain.
  2. Hughes, T. et al. Durable Treatment-free Remission (TFR) after stopping second-line nilotinib (nil) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): ENESTop 96-wk update. Poster presentation. Abstract #P257. 2017 European Hematology Association Congress in Madrid, Spain.
  3. Hochhaus, A. et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 17 March 2017. Advance online publication. doi# 10.1038/leu.2017.63.
  4. Hughes, T.P. et al. Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with second-line nilotinib (NIL): First results from the ENESTop study. Poster Presentation. Abstract #7054. 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, USA.
  5. Central European Leukemia Study Group. About CML. 2007. Available at: http://www.cml-info.com/de/healthcare-professionals/about-cml.html . Accessed June 2017.
  6. Cancer Research UK. CML Statistics. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/leukaemia-cml/incidence#heading-Zero. Accessed June 2017.
  7. Cancer Research UK. CML Survival. Available at: http://www.cancerresearchuk.org/about-cancer/chronic-myeloid-leukaemia-cml/survival. Accessed June 2017.

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TAS17-E008 Date of preparation: June 2017