- New 96-week data support durability and safety of Treatment-free Remission (TFR) in Ph+ CML-CP patients who stop taking Tasigna [1,2]
- More than 90% of Ph+ CML-CP patients in ENESTfreedom and ENESTop who stopped Tasigna and were in TFR at 48 weeks remained in TFR at 96 weeks [1,2]
- 48-week data from same trials recently added to Tasigna SmPC following EC approval; discussions with other regulatory authorities are underway worldwide
BASEL, Switzerland I June 23, 2017 I Novartis today announced results from additional analyses of the ENESTfreedom and ENESTop clinical trials, which found that approximately half of adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase (CP) who discontinued Tasigna [®] (nilotinib) remain in Treatment-free Remission (TFR) nearly two years after stopping treatment. The 96-week results from these two open-label Phase II trials, presented at the 22nd Congress of the European Hematology Association (EHA), add to the growing body of evidence examining the ability to remain in TFR in patients who achieved a sustained deep molecular response (DMR) with Tasigna and met additional eligibility criteria prior to discontinuing treatment. TFR is the ability to maintain molecular response (MR) after stopping tyrosine kinase inhibitor (TKI) therapy in patients with Ph+ CML-CP [3].
“These trials show that about half of Ph+ CML patients that met strict eligibility criteria and discontinued Tasigna continue to maintain TFR at 96 weeks, and demonstrate that more than 90% of patients who were in TFR at 48 weeks remain in TFR at 96 weeks,” said Timothy P. Hughes, M.D., ENESTop study investigator, Cancer Theme Leader at the South Australian Health and Medical Research Institute and Clinical Professor at the University of Adelaide, Australia. “Achieving deep molecular response is an important eligibility criteria prior to attempting TFR.”
ENESTfreedom and ENESTop evaluate the potential to maintain MR after stopping therapy in eligible adult patients with Ph+ CML-CP who achieved a sustained DMR with Tasigna [ ]in the first-line setting and in patients who achieved a sustained DMR with Tasigna after switching from Glivec [®] (imatinib)*, respectively.
“The findings from the 96-week analyses, as well as the recent regulatory decisions to add TFR data to the Tasigna product label in the European Union (EU), Chile and Ecuador, mark significant progress in the treatment of CML,” said Vas Narasimhan, M.D., Global Head Drug Development and Chief Medical Officer, Novartis. “We are proud that our innovation with Tasigna has contributed directly to this progress and that physicians now have the opportunity to consider TFR in both first- and second-line Tasigna patients.”
Results from ENESTfreedom, which evaluated the potential for discontinuing Tasigna in eligible Ph+ CML-CP patients who achieved a sustained DMR following at least three years of first-line treatment with Tasigna, found that 48.9% of 190 CML patients (confidence interval [CI] 95%: 41.6%-56.3%) were able to discontinue therapy and remain in major molecular response (MMR; BCR-ABL1 International Scale [IS] <= 0.1%) at 96 weeks. Of the 88 patients who restarted treatment with Tasigna due to loss of MMR by the cut-off date, 98.9% were able to regain MMR (n=87). One patient discontinued the study at 7.1 weeks without regaining MMR after reinitiating treatment with Tasigna [1]. No new major safety findings were observed in ENESTfreedom in patients treated with Tasigna beyond those in the known safety profile of Tasigna [1]. Among patients who remained in TFR for more than 48 weeks (n=100), the frequency of adverse events (AEs) was lower during the second 48 weeks of TFR compared to the first 48 weeks. AEs in the predefined musculoskeletal pain grouping also decreased from 34.0% to 9.0% during the first and second 48 weeks of the TFR phase, respectively [1], versus 17.0% during the treatment consolidation phase.
ENESTop, which evaluated the potential for discontinuing Tasigna in 126 eligible Ph+ CML-CP patients who were able to achieve a sustained DMR following at least three years of Tasigna therapy, but not with prior Glivec therapy, found that more than half (53.2%) of patients were able to remain in TFR at 96 weeks (95% CI: 44.1%-62.1%) [2]. In the study, 56 patients with confirmed loss of MR4.0 (BCR-ABL1 IS <= 0.01%) or loss of MMR restarted Tasigna by the cut-off date. Of these patients, 92.9% (n=52) regained both MR4.0 and MR4.5. By weeks 12.0 and 13.1 of treatment re-initiation with Tasigna, 50% of retreated patients achieved MR4.0 and MR4.5, respectively [2]. No new major safety findings were observed in ENESTop in patients treated with Tasigna beyond those in the known safety profile of Tasigna [2]. Among patients who remained in the TFR phase of the trial for more than 48 weeks (n=73), rates of all-grade AEs were 82.2% and 63.0% for the first 48 weeks and second 48 weeks of the TFR phase, respectively, versus 79.5% during the treatment consolidation phase. Rates of musculoskeletal pain-related AEs decreased from 47.9% to 15.1% during the first and second 48 weeks of the TFR phase, respectively, versus 13.7% during the treatment consolidation phase [2].
Discontinuation of treatment in ENESTfreedom and ENESTop was conducted under the conditions of the trials in patients who met the rigorous predefined criteria of the trials. An important part of the Tasigna TFR studies is regular and frequent molecular monitoring with a well-validated assay able to measure BCR-ABL transcript levels down to MR4.5. Frequent patient monitoring after discontinuation of Tasigna allows timely determination of loss of MR4.0 and MMR and prompt re-initiation of treatment [1,2].
On May 24, the European Commission (EC) approved an update of the Tasigna Summary of Product Characteristics (SmPC) to include data from the ENESTfreedom and ENESTop TFR clinical trials. With this EC approval, Tasigna is the first and only TKI to include information in its EU label on stopping therapy in eligible patients with Ph+ CML-CP in both the first-line setting and after switching from Glivec. The decision to add TFR data to the Tasigna SmPC is applicable to all 28 EU member states plus Iceland and Norway.
Information regarding TFR was also recently added to the Tasigna label in Chile and Ecuador.
In all other countries, discontinuation of Tasigna in patients who achieve a sustained DMR is being investigated and should only be attempted in the context of a clinical study. There is no guarantee Tasigna TFR data will be approved for inclusion in the label by other health authorities.
Novartis commitment to CML
Over the past several decades, Novartis research in Ph+ CML has helped transform the disease from a fatal leukemia to a chronic condition in most patients and, today, the company continues its long-standing commitment to the global CML community. Evaluating more than 1,000 patients, the Tasigna TFR studies, which include ENESTfreedom and ENESTop as well as two other ongoing company-sponsored TFR studies and multiple investigator-initiated studies, are part of a large international Ph+ CML-CP clinical trial program to assess TKI discontinuation. Novartis follows the science and builds upon existing evidence to explore what could be the next major contribution in the treatment of Ph+ CML through these TFR trials as well as investigational compounds, such as ABL001, which is currently being tested in patients who are relapsed, refractory or intolerant to existing TKIs in a Phase I trial as a single agent and in combination with several TKIs.
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 patients in the chronic phase, conducted at 132 sites across 19 countries. ENESTfreedom evaluated stopping treatment in 190 adults with Ph+ CML-CP receiving Tasigna for at least three years, after the patients had achieved a response of MR4.5 with Tasigna and a sustained DMR for one year as a first-line treatment. The study is ongoing with planned follow-up to evaluate the ability of patients to sustain remission for longer durations following discontinuation of Tasigna.
About ENESTop
ENESTop (Evaluating Nilotinib Efficacy and Safety Trial) is an open label Phase II study involving 163 Ph+ CML patients, conducted at 63 sites across 18 countries. The trial evaluated stopping treatment in 126 adults with Ph+ CML-CP receiving Tasigna for at least three years, after patients had achieved and sustained DMR for one year with Tasigna following Glivec. The study is ongoing with planned follow-up to evaluate the ability of patients to sustain remission for longer durations following discontinuation of Tasigna.
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 leukemia (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 Glivec (imatinib)
Glivec (imatinib) is approved in more than 110 countries, for the treatment of adult patients in all phases of Ph+ CML, for the treatment of patients with KIT (CD117)-positive gastrointestinal tumors (GIST), which cannot be surgically removed and/or have metastasized and for the treatment of adult patients following complete surgical removal of KIT+ GIST.
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.
Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis
For Novartis multimedia content, please visit www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com
References
| [1] |
Ross, D.M. 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. 24 June 2017. 22 [nd] Congress of the European Hematology Association (EHA) in Madrid, Spain. |
| [2] |
Hughes, T.P. 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. 23 June 2017. 22 [nd] Congress of the European Hematology Association (EHA) in Madrid, Spain. |
| [3] |
Hughes, T.P. and Ross, D.M. Moving treatment-free remission into mainstream clinical practice in CML. Blood. 2016. Advance online publication. doi# 10.1182/blood-2016-01-694265. |
SOURCE: Novartis
Post Views: 32
- New 96-week data support durability and safety of Treatment-free Remission (TFR) in Ph+ CML-CP patients who stop taking Tasigna [1,2]
- More than 90% of Ph+ CML-CP patients in ENESTfreedom and ENESTop who stopped Tasigna and were in TFR at 48 weeks remained in TFR at 96 weeks [1,2]
- 48-week data from same trials recently added to Tasigna SmPC following EC approval; discussions with other regulatory authorities are underway worldwide
BASEL, Switzerland I June 23, 2017 I Novartis today announced results from additional analyses of the ENESTfreedom and ENESTop clinical trials, which found that approximately half of adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase (CP) who discontinued Tasigna [®] (nilotinib) remain in Treatment-free Remission (TFR) nearly two years after stopping treatment. The 96-week results from these two open-label Phase II trials, presented at the 22nd Congress of the European Hematology Association (EHA), add to the growing body of evidence examining the ability to remain in TFR in patients who achieved a sustained deep molecular response (DMR) with Tasigna and met additional eligibility criteria prior to discontinuing treatment. TFR is the ability to maintain molecular response (MR) after stopping tyrosine kinase inhibitor (TKI) therapy in patients with Ph+ CML-CP [3].
“These trials show that about half of Ph+ CML patients that met strict eligibility criteria and discontinued Tasigna continue to maintain TFR at 96 weeks, and demonstrate that more than 90% of patients who were in TFR at 48 weeks remain in TFR at 96 weeks,” said Timothy P. Hughes, M.D., ENESTop study investigator, Cancer Theme Leader at the South Australian Health and Medical Research Institute and Clinical Professor at the University of Adelaide, Australia. “Achieving deep molecular response is an important eligibility criteria prior to attempting TFR.”
ENESTfreedom and ENESTop evaluate the potential to maintain MR after stopping therapy in eligible adult patients with Ph+ CML-CP who achieved a sustained DMR with Tasigna [ ]in the first-line setting and in patients who achieved a sustained DMR with Tasigna after switching from Glivec [®] (imatinib)*, respectively.
“The findings from the 96-week analyses, as well as the recent regulatory decisions to add TFR data to the Tasigna product label in the European Union (EU), Chile and Ecuador, mark significant progress in the treatment of CML,” said Vas Narasimhan, M.D., Global Head Drug Development and Chief Medical Officer, Novartis. “We are proud that our innovation with Tasigna has contributed directly to this progress and that physicians now have the opportunity to consider TFR in both first- and second-line Tasigna patients.”
Results from ENESTfreedom, which evaluated the potential for discontinuing Tasigna in eligible Ph+ CML-CP patients who achieved a sustained DMR following at least three years of first-line treatment with Tasigna, found that 48.9% of 190 CML patients (confidence interval [CI] 95%: 41.6%-56.3%) were able to discontinue therapy and remain in major molecular response (MMR; BCR-ABL1 International Scale [IS] <= 0.1%) at 96 weeks. Of the 88 patients who restarted treatment with Tasigna due to loss of MMR by the cut-off date, 98.9% were able to regain MMR (n=87). One patient discontinued the study at 7.1 weeks without regaining MMR after reinitiating treatment with Tasigna [1]. No new major safety findings were observed in ENESTfreedom in patients treated with Tasigna beyond those in the known safety profile of Tasigna [1]. Among patients who remained in TFR for more than 48 weeks (n=100), the frequency of adverse events (AEs) was lower during the second 48 weeks of TFR compared to the first 48 weeks. AEs in the predefined musculoskeletal pain grouping also decreased from 34.0% to 9.0% during the first and second 48 weeks of the TFR phase, respectively [1], versus 17.0% during the treatment consolidation phase.
ENESTop, which evaluated the potential for discontinuing Tasigna in 126 eligible Ph+ CML-CP patients who were able to achieve a sustained DMR following at least three years of Tasigna therapy, but not with prior Glivec therapy, found that more than half (53.2%) of patients were able to remain in TFR at 96 weeks (95% CI: 44.1%-62.1%) [2]. In the study, 56 patients with confirmed loss of MR4.0 (BCR-ABL1 IS <= 0.01%) or loss of MMR restarted Tasigna by the cut-off date. Of these patients, 92.9% (n=52) regained both MR4.0 and MR4.5. By weeks 12.0 and 13.1 of treatment re-initiation with Tasigna, 50% of retreated patients achieved MR4.0 and MR4.5, respectively [2]. No new major safety findings were observed in ENESTop in patients treated with Tasigna beyond those in the known safety profile of Tasigna [2]. Among patients who remained in the TFR phase of the trial for more than 48 weeks (n=73), rates of all-grade AEs were 82.2% and 63.0% for the first 48 weeks and second 48 weeks of the TFR phase, respectively, versus 79.5% during the treatment consolidation phase. Rates of musculoskeletal pain-related AEs decreased from 47.9% to 15.1% during the first and second 48 weeks of the TFR phase, respectively, versus 13.7% during the treatment consolidation phase [2].
Discontinuation of treatment in ENESTfreedom and ENESTop was conducted under the conditions of the trials in patients who met the rigorous predefined criteria of the trials. An important part of the Tasigna TFR studies is regular and frequent molecular monitoring with a well-validated assay able to measure BCR-ABL transcript levels down to MR4.5. Frequent patient monitoring after discontinuation of Tasigna allows timely determination of loss of MR4.0 and MMR and prompt re-initiation of treatment [1,2].
On May 24, the European Commission (EC) approved an update of the Tasigna Summary of Product Characteristics (SmPC) to include data from the ENESTfreedom and ENESTop TFR clinical trials. With this EC approval, Tasigna is the first and only TKI to include information in its EU label on stopping therapy in eligible patients with Ph+ CML-CP in both the first-line setting and after switching from Glivec. The decision to add TFR data to the Tasigna SmPC is applicable to all 28 EU member states plus Iceland and Norway.
Information regarding TFR was also recently added to the Tasigna label in Chile and Ecuador.
In all other countries, discontinuation of Tasigna in patients who achieve a sustained DMR is being investigated and should only be attempted in the context of a clinical study. There is no guarantee Tasigna TFR data will be approved for inclusion in the label by other health authorities.
Novartis commitment to CML
Over the past several decades, Novartis research in Ph+ CML has helped transform the disease from a fatal leukemia to a chronic condition in most patients and, today, the company continues its long-standing commitment to the global CML community. Evaluating more than 1,000 patients, the Tasigna TFR studies, which include ENESTfreedom and ENESTop as well as two other ongoing company-sponsored TFR studies and multiple investigator-initiated studies, are part of a large international Ph+ CML-CP clinical trial program to assess TKI discontinuation. Novartis follows the science and builds upon existing evidence to explore what could be the next major contribution in the treatment of Ph+ CML through these TFR trials as well as investigational compounds, such as ABL001, which is currently being tested in patients who are relapsed, refractory or intolerant to existing TKIs in a Phase I trial as a single agent and in combination with several TKIs.
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 patients in the chronic phase, conducted at 132 sites across 19 countries. ENESTfreedom evaluated stopping treatment in 190 adults with Ph+ CML-CP receiving Tasigna for at least three years, after the patients had achieved a response of MR4.5 with Tasigna and a sustained DMR for one year as a first-line treatment. The study is ongoing with planned follow-up to evaluate the ability of patients to sustain remission for longer durations following discontinuation of Tasigna.
About ENESTop
ENESTop (Evaluating Nilotinib Efficacy and Safety Trial) is an open label Phase II study involving 163 Ph+ CML patients, conducted at 63 sites across 18 countries. The trial evaluated stopping treatment in 126 adults with Ph+ CML-CP receiving Tasigna for at least three years, after patients had achieved and sustained DMR for one year with Tasigna following Glivec. The study is ongoing with planned follow-up to evaluate the ability of patients to sustain remission for longer durations following discontinuation of Tasigna.
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 leukemia (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 Glivec (imatinib)
Glivec (imatinib) is approved in more than 110 countries, for the treatment of adult patients in all phases of Ph+ CML, for the treatment of patients with KIT (CD117)-positive gastrointestinal tumors (GIST), which cannot be surgically removed and/or have metastasized and for the treatment of adult patients following complete surgical removal of KIT+ GIST.
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.
Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis
For Novartis multimedia content, please visit www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com
References
| [1] |
Ross, D.M. 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. 24 June 2017. 22 [nd] Congress of the European Hematology Association (EHA) in Madrid, Spain. |
| [2] |
Hughes, T.P. 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. 23 June 2017. 22 [nd] Congress of the European Hematology Association (EHA) in Madrid, Spain. |
| [3] |
Hughes, T.P. and Ross, D.M. Moving treatment-free remission into mainstream clinical practice in CML. Blood. 2016. Advance online publication. doi# 10.1182/blood-2016-01-694265. |
SOURCE: Novartis
Post Views: 32
