CML

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Doctor evaluating a patient

Credit: CDC

Results of population-based research suggest that financial status may affect survival in patients with chronic myeloid leukemia (CML) living in the UK.

The study showed that, despite equal access to the same clinical care and treatment, survival rates were significantly lower for patients living in more deprived areas.

The researchers said this difference might be explained by lower rates of treatment compliance in the less affluent population.

“These findings highlight the importance of conducting comprehensive, population-based studies to examine treatment pathways across the entire patient population, rather than solely concentrating on findings from clinical trials,” said study author Alexandra Smith, PhD, of the University of York in the UK.

She and her colleagues recounted their findings in BMJ Open.

The team analyzed data from 242 patients who were diagnosed with CML from September 2004 to August 2011. Ninety-seven percent of patients had chronic-phase disease at presentation, and 86% were Ph-positive.

Fifty-five percent of patients were younger than 60 at diagnosis, and 60% were male. Fifty-nine percent lived in deprivation quintiles 1 to 3, and 41% lived in the less affluent quintiles 4 and 5.

Ninety-seven percent of patients received treatment with tyrosine kinase inhibitors (TKIs)—94% imatinib and the rest dasatinib. Three percent of patients were not treated with TKIs due to death, relocation, refusal, a more serious competing comorbidity, or the use of supportive care alone.

Factors affecting survival

The minimum follow-up was 1.5 years, and the maximum was 8.5 years. The overall 5-year survival was 79%. And the relative survival, which took into account the background mortality in the general population, was 89%.

The relative survival curves did not differ significantly between the 2 age groups. Five-year relative survival was 90% for patients younger than 60 and 87% for those older than 60.

Gender also had little impact on relative survival. The 5-year rates were 90% for men and 89% for women.

However, relative survival differed significantly according to affluence. The 5-year relative survival was 95% for the most affluent patients (quintiles 1 to 3) and 80% for the least affluent (quintiles 4 and 5).

Although 41% of all patients lived in the less affluent areas, this group accounted for about 60% of the deaths.

The researchers said this finding could not be attributed to biological features of disease or access to therapy. But they believe a lack of treatment compliance could be the cause.

“We suspect a major factor is that we are not supporting patients sufficiently to allow them to be fully compliant with a treatment that needs to be taken every day to be effective,” said Russell Patmore, MD, of Castle Hill Hospital in the UK.

“We would encourage all teams treating patients with CML to use these findings to focus their resource where it is likely to be most beneficial. This includes helping patients to manage their CML by explaining fully the importance of daily treatment and providing easy access to ongoing support.”

Doctor evaluating a patient

Credit: CDC

Results of population-based research suggest that financial status may affect survival in patients with chronic myeloid leukemia (CML) living in the UK.

The study showed that, despite equal access to the same clinical care and treatment, survival rates were significantly lower for patients living in more deprived areas.

The researchers said this difference might be explained by lower rates of treatment compliance in the less affluent population.

“These findings highlight the importance of conducting comprehensive, population-based studies to examine treatment pathways across the entire patient population, rather than solely concentrating on findings from clinical trials,” said study author Alexandra Smith, PhD, of the University of York in the UK.

She and her colleagues recounted their findings in BMJ Open.

The team analyzed data from 242 patients who were diagnosed with CML from September 2004 to August 2011. Ninety-seven percent of patients had chronic-phase disease at presentation, and 86% were Ph-positive.

Fifty-five percent of patients were younger than 60 at diagnosis, and 60% were male. Fifty-nine percent lived in deprivation quintiles 1 to 3, and 41% lived in the less affluent quintiles 4 and 5.

Ninety-seven percent of patients received treatment with tyrosine kinase inhibitors (TKIs)—94% imatinib and the rest dasatinib. Three percent of patients were not treated with TKIs due to death, relocation, refusal, a more serious competing comorbidity, or the use of supportive care alone.

Factors affecting survival

The minimum follow-up was 1.5 years, and the maximum was 8.5 years. The overall 5-year survival was 79%. And the relative survival, which took into account the background mortality in the general population, was 89%.

The relative survival curves did not differ significantly between the 2 age groups. Five-year relative survival was 90% for patients younger than 60 and 87% for those older than 60.

Gender also had little impact on relative survival. The 5-year rates were 90% for men and 89% for women.

However, relative survival differed significantly according to affluence. The 5-year relative survival was 95% for the most affluent patients (quintiles 1 to 3) and 80% for the least affluent (quintiles 4 and 5).

Although 41% of all patients lived in the less affluent areas, this group accounted for about 60% of the deaths.

The researchers said this finding could not be attributed to biological features of disease or access to therapy. But they believe a lack of treatment compliance could be the cause.

“We suspect a major factor is that we are not supporting patients sufficiently to allow them to be fully compliant with a treatment that needs to be taken every day to be effective,” said Russell Patmore, MD, of Castle Hill Hospital in the UK.

“We would encourage all teams treating patients with CML to use these findings to focus their resource where it is likely to be most beneficial. This includes helping patients to manage their CML by explaining fully the importance of daily treatment and providing easy access to ongoing support.”

Doctor evaluating a patient

Credit: CDC

Results of population-based research suggest that financial status may affect survival in patients with chronic myeloid leukemia (CML) living in the UK.

The study showed that, despite equal access to the same clinical care and treatment, survival rates were significantly lower for patients living in more deprived areas.

The researchers said this difference might be explained by lower rates of treatment compliance in the less affluent population.

“These findings highlight the importance of conducting comprehensive, population-based studies to examine treatment pathways across the entire patient population, rather than solely concentrating on findings from clinical trials,” said study author Alexandra Smith, PhD, of the University of York in the UK.

She and her colleagues recounted their findings in BMJ Open.

The team analyzed data from 242 patients who were diagnosed with CML from September 2004 to August 2011. Ninety-seven percent of patients had chronic-phase disease at presentation, and 86% were Ph-positive.

Fifty-five percent of patients were younger than 60 at diagnosis, and 60% were male. Fifty-nine percent lived in deprivation quintiles 1 to 3, and 41% lived in the less affluent quintiles 4 and 5.

Ninety-seven percent of patients received treatment with tyrosine kinase inhibitors (TKIs)—94% imatinib and the rest dasatinib. Three percent of patients were not treated with TKIs due to death, relocation, refusal, a more serious competing comorbidity, or the use of supportive care alone.

Factors affecting survival

The minimum follow-up was 1.5 years, and the maximum was 8.5 years. The overall 5-year survival was 79%. And the relative survival, which took into account the background mortality in the general population, was 89%.

The relative survival curves did not differ significantly between the 2 age groups. Five-year relative survival was 90% for patients younger than 60 and 87% for those older than 60.

Gender also had little impact on relative survival. The 5-year rates were 90% for men and 89% for women.

However, relative survival differed significantly according to affluence. The 5-year relative survival was 95% for the most affluent patients (quintiles 1 to 3) and 80% for the least affluent (quintiles 4 and 5).

Although 41% of all patients lived in the less affluent areas, this group accounted for about 60% of the deaths.

The researchers said this finding could not be attributed to biological features of disease or access to therapy. But they believe a lack of treatment compliance could be the cause.

“We suspect a major factor is that we are not supporting patients sufficiently to allow them to be fully compliant with a treatment that needs to be taken every day to be effective,” said Russell Patmore, MD, of Castle Hill Hospital in the UK.

“We would encourage all teams treating patients with CML to use these findings to focus their resource where it is likely to be most beneficial. This includes helping patients to manage their CML by explaining fully the importance of daily treatment and providing easy access to ongoing support.”

Less than 3 months after it was pulled from the market due to safety concerns, ponatinib (Iclusig) is once again commercially available in the US.

Ariad Pharmaceuticals, Inc., has begun shipping the drug to Biologics, Inc., its exclusive specialty pharmacy. And the pharmacy has started filling prescriptions and distributing ponatinib to patients in need.

The drug is approved by the US Food and Drug Administration (FDA) to treat chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant to or intolerant of other tyrosine kinase inhibitors (TKIs).

Safety concerns prompt action

Last October, the latest results of the phase 2 PACE trial revealed that ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the phase 3 EPIC trial, which was discontinued.

Then, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. But in December, the agency decided the drug could return to the market if new safety measures were implemented.

The FDA approved revised prescribing information and a communications Risk Evaluation and Mitigation Strategy for ponatinib. The prescribing information includes a revised indication statement and boxed warning, updated safety information, and recommendations regarding dosing considerations for prescribers.

Now, ponatinib is indicated for the treatment of:

• Adults with T315I-positive CML (chronic, accelerated, or blast phase)
• Adults with T315I-positive Ph+ ALL
• Adults with CML (chronic, accelerated, or blast phase) who cannot receive another TKI
• Adults with Ph+ ALL who cannot receive another TKI.

The starting dose of ponatinib remains 45 mg daily.

IND program

On November 1, 2013, there were approximately 640 patients receiving ponatinib through commercial channels in the US. Since then, the drug was only made available through emergency and single-patient investigational new drug (IND) applications, which were reviewed and approved by the FDA on a case-by-case basis.

The FDA has approved more than 370 INDs since early November, and more than 300 patients have received ponatinib at no cost through this process.

Ariad expects most of these patients, many of whom received a 3-month supply of ponatinib, to transition from the IND program to commercial therapy by the end of the first quarter of 2014. The IND program is now closed to new patients with Ph+ leukemias.

Ponatinib is currently priced in the US at approximately $125,000 per year. For more information on the drug, visit www.iclusig.com.

Less than 3 months after it was pulled from the market due to safety concerns, ponatinib (Iclusig) is once again commercially available in the US.

Ariad Pharmaceuticals, Inc., has begun shipping the drug to Biologics, Inc., its exclusive specialty pharmacy. And the pharmacy has started filling prescriptions and distributing ponatinib to patients in need.

The drug is approved by the US Food and Drug Administration (FDA) to treat chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant to or intolerant of other tyrosine kinase inhibitors (TKIs).

Safety concerns prompt action

Last October, the latest results of the phase 2 PACE trial revealed that ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the phase 3 EPIC trial, which was discontinued.

Then, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. But in December, the agency decided the drug could return to the market if new safety measures were implemented.

The FDA approved revised prescribing information and a communications Risk Evaluation and Mitigation Strategy for ponatinib. The prescribing information includes a revised indication statement and boxed warning, updated safety information, and recommendations regarding dosing considerations for prescribers.

Now, ponatinib is indicated for the treatment of:

• Adults with T315I-positive CML (chronic, accelerated, or blast phase)
• Adults with T315I-positive Ph+ ALL
• Adults with CML (chronic, accelerated, or blast phase) who cannot receive another TKI
• Adults with Ph+ ALL who cannot receive another TKI.

The starting dose of ponatinib remains 45 mg daily.

IND program

On November 1, 2013, there were approximately 640 patients receiving ponatinib through commercial channels in the US. Since then, the drug was only made available through emergency and single-patient investigational new drug (IND) applications, which were reviewed and approved by the FDA on a case-by-case basis.

The FDA has approved more than 370 INDs since early November, and more than 300 patients have received ponatinib at no cost through this process.

Ariad expects most of these patients, many of whom received a 3-month supply of ponatinib, to transition from the IND program to commercial therapy by the end of the first quarter of 2014. The IND program is now closed to new patients with Ph+ leukemias.

Ponatinib is currently priced in the US at approximately $125,000 per year. For more information on the drug, visit www.iclusig.com.

Less than 3 months after it was pulled from the market due to safety concerns, ponatinib (Iclusig) is once again commercially available in the US.

Ariad Pharmaceuticals, Inc., has begun shipping the drug to Biologics, Inc., its exclusive specialty pharmacy. And the pharmacy has started filling prescriptions and distributing ponatinib to patients in need.

The drug is approved by the US Food and Drug Administration (FDA) to treat chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant to or intolerant of other tyrosine kinase inhibitors (TKIs).

Safety concerns prompt action

Last October, the latest results of the phase 2 PACE trial revealed that ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the phase 3 EPIC trial, which was discontinued.

Then, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. But in December, the agency decided the drug could return to the market if new safety measures were implemented.

The FDA approved revised prescribing information and a communications Risk Evaluation and Mitigation Strategy for ponatinib. The prescribing information includes a revised indication statement and boxed warning, updated safety information, and recommendations regarding dosing considerations for prescribers.

Now, ponatinib is indicated for the treatment of:

• Adults with T315I-positive CML (chronic, accelerated, or blast phase)
• Adults with T315I-positive Ph+ ALL
• Adults with CML (chronic, accelerated, or blast phase) who cannot receive another TKI
• Adults with Ph+ ALL who cannot receive another TKI.

The starting dose of ponatinib remains 45 mg daily.

IND program

On November 1, 2013, there were approximately 640 patients receiving ponatinib through commercial channels in the US. Since then, the drug was only made available through emergency and single-patient investigational new drug (IND) applications, which were reviewed and approved by the FDA on a case-by-case basis.

The FDA has approved more than 370 INDs since early November, and more than 300 patients have received ponatinib at no cost through this process.

Ariad expects most of these patients, many of whom received a 3-month supply of ponatinib, to transition from the IND program to commercial therapy by the end of the first quarter of 2014. The IND program is now closed to new patients with Ph+ leukemias.

Ponatinib is currently priced in the US at approximately $125,000 per year. For more information on the drug, visit www.iclusig.com.

Prescription drugs

Credit: CDC

When their share of prescription costs becomes too high, many patients with chronic myeloid leukemia (CML) will skip doses of imatinib or stop taking the drug entirely, new research suggests.

In a study of about 1500 patients, the median co-payment for an imatinib prescription was about $30 per fill, but the range was $0 to $4792.

Patients with higher co-payments were 70% more likely than their peers to stop taking imatinib and 42% more likely to skip doses of the drug.

Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill, and her colleagues conducted this research and described the results in the Journal of Clinical Oncology.

Co-payment requirements vary

The researchers analyzed health plan claims from privately insured adults (ages 18 to 64) from 2002 to 2011. The data included 1541 CML patients beginning treatment with imatinib.

For the whole study period, the mean co-payment was $108 for a 30-day supply of imatinib. Patients in the lowest 25th percentile paid a mean of $17, and patients in the upper 75th percentile paid a mean of $53.

As expected, monthly co-payments increased over time. They averaged $55 in 2002 and $145 in 2011, with 6.4% of patients paying more than $500 a month.

Dr Dusetzina noted that the data only included patients on employer-based insurance plans, and most individuals had low out-of-pocket costs.

“We studied people who are part of large employer groups, so their insurance is probably more generous than someone who is buying insurance on a private market that does not have a lot of negotiating power,” she said.

Costs correlate with adherence

In the first 180 days of treatment, 30% of patients with higher co-payments were non-adherent to imatinib treatment, compared to 21% of patients with lower co-payments. Non-adherence was defined as having less than 80% of days with imatinib available.

Seventeen percent of patients with higher co-payments discontinued taking imatinib, compared to 10% of patients with lower co-payments. Discontinuation was defined as having a gap of more than 60 days after the exhaustion of imatinib therapy.

These data did not include patients who could not begin taking imatinib due to costs. Therefore, Dr Dusetzina said this study likely underestimates the effects of drug costs on treatment adherence.

“If you went to the pharmacy to obtain your prescription, and they said it was $5000, and you walked away because you couldn’t afford to pay, you’re not in the data,” she said. “We could only study individuals who filled at least one prescription.”

Dr Dusetzina also said these findings have implications beyond imatinib and CML. Many new treatments for rare conditions can cost insurers and patients more than $100,000 year.

“Our results are particularly relevant for specialty pharmaceutical products—those that cost over $10,000 a month,” she said.

“However, the lessons learned likely relate to any pharmaceutical product that has high out-of-pocket costs. It is important that we identify strategies to make effective but expensive medications more affordable to patients.”

Prescription drugs

Credit: CDC

When their share of prescription costs becomes too high, many patients with chronic myeloid leukemia (CML) will skip doses of imatinib or stop taking the drug entirely, new research suggests.

In a study of about 1500 patients, the median co-payment for an imatinib prescription was about $30 per fill, but the range was $0 to $4792.

Patients with higher co-payments were 70% more likely than their peers to stop taking imatinib and 42% more likely to skip doses of the drug.

Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill, and her colleagues conducted this research and described the results in the Journal of Clinical Oncology.

Co-payment requirements vary

The researchers analyzed health plan claims from privately insured adults (ages 18 to 64) from 2002 to 2011. The data included 1541 CML patients beginning treatment with imatinib.

For the whole study period, the mean co-payment was $108 for a 30-day supply of imatinib. Patients in the lowest 25th percentile paid a mean of $17, and patients in the upper 75th percentile paid a mean of $53.

As expected, monthly co-payments increased over time. They averaged $55 in 2002 and $145 in 2011, with 6.4% of patients paying more than $500 a month.

Dr Dusetzina noted that the data only included patients on employer-based insurance plans, and most individuals had low out-of-pocket costs.

“We studied people who are part of large employer groups, so their insurance is probably more generous than someone who is buying insurance on a private market that does not have a lot of negotiating power,” she said.

Costs correlate with adherence

In the first 180 days of treatment, 30% of patients with higher co-payments were non-adherent to imatinib treatment, compared to 21% of patients with lower co-payments. Non-adherence was defined as having less than 80% of days with imatinib available.

Seventeen percent of patients with higher co-payments discontinued taking imatinib, compared to 10% of patients with lower co-payments. Discontinuation was defined as having a gap of more than 60 days after the exhaustion of imatinib therapy.

These data did not include patients who could not begin taking imatinib due to costs. Therefore, Dr Dusetzina said this study likely underestimates the effects of drug costs on treatment adherence.

“If you went to the pharmacy to obtain your prescription, and they said it was $5000, and you walked away because you couldn’t afford to pay, you’re not in the data,” she said. “We could only study individuals who filled at least one prescription.”

Dr Dusetzina also said these findings have implications beyond imatinib and CML. Many new treatments for rare conditions can cost insurers and patients more than $100,000 year.

“Our results are particularly relevant for specialty pharmaceutical products—those that cost over $10,000 a month,” she said.

“However, the lessons learned likely relate to any pharmaceutical product that has high out-of-pocket costs. It is important that we identify strategies to make effective but expensive medications more affordable to patients.”

Prescription drugs

Credit: CDC

When their share of prescription costs becomes too high, many patients with chronic myeloid leukemia (CML) will skip doses of imatinib or stop taking the drug entirely, new research suggests.

In a study of about 1500 patients, the median co-payment for an imatinib prescription was about $30 per fill, but the range was $0 to $4792.

Patients with higher co-payments were 70% more likely than their peers to stop taking imatinib and 42% more likely to skip doses of the drug.

Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill, and her colleagues conducted this research and described the results in the Journal of Clinical Oncology.

Co-payment requirements vary

The researchers analyzed health plan claims from privately insured adults (ages 18 to 64) from 2002 to 2011. The data included 1541 CML patients beginning treatment with imatinib.

For the whole study period, the mean co-payment was $108 for a 30-day supply of imatinib. Patients in the lowest 25th percentile paid a mean of $17, and patients in the upper 75th percentile paid a mean of $53.

As expected, monthly co-payments increased over time. They averaged $55 in 2002 and $145 in 2011, with 6.4% of patients paying more than $500 a month.

Dr Dusetzina noted that the data only included patients on employer-based insurance plans, and most individuals had low out-of-pocket costs.

“We studied people who are part of large employer groups, so their insurance is probably more generous than someone who is buying insurance on a private market that does not have a lot of negotiating power,” she said.

Costs correlate with adherence

In the first 180 days of treatment, 30% of patients with higher co-payments were non-adherent to imatinib treatment, compared to 21% of patients with lower co-payments. Non-adherence was defined as having less than 80% of days with imatinib available.

Seventeen percent of patients with higher co-payments discontinued taking imatinib, compared to 10% of patients with lower co-payments. Discontinuation was defined as having a gap of more than 60 days after the exhaustion of imatinib therapy.

These data did not include patients who could not begin taking imatinib due to costs. Therefore, Dr Dusetzina said this study likely underestimates the effects of drug costs on treatment adherence.

“If you went to the pharmacy to obtain your prescription, and they said it was $5000, and you walked away because you couldn’t afford to pay, you’re not in the data,” she said. “We could only study individuals who filled at least one prescription.”

Dr Dusetzina also said these findings have implications beyond imatinib and CML. Many new treatments for rare conditions can cost insurers and patients more than $100,000 year.

“Our results are particularly relevant for specialty pharmaceutical products—those that cost over $10,000 a month,” she said.

“However, the lessons learned likely relate to any pharmaceutical product that has high out-of-pocket costs. It is important that we identify strategies to make effective but expensive medications more affordable to patients.”

Omacetaxine mepesuccinate has been granted accelerated approval for the treatment of adult patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance or intolerance to 2 or more tyrosine kinase inhibitors (TKIs).^1,2 Approval was based on response rates observed in a combined cohort of adult CML patients from 2 clinical trials. As yet, no clinical trials have verified improved disease-related symptoms or increased survival with omacetaxine treatment.

Click on the PDF icon at the top of this introduction to read the full article.

Omacetaxine mepesuccinate has been granted accelerated approval for the treatment of adult patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance or intolerance to 2 or more tyrosine kinase inhibitors (TKIs).^1,2 Approval was based on response rates observed in a combined cohort of adult CML patients from 2 clinical trials. As yet, no clinical trials have verified improved disease-related symptoms or increased survival with omacetaxine treatment.

Click on the PDF icon at the top of this introduction to read the full article.

Omacetaxine mepesuccinate has been granted accelerated approval for the treatment of adult patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance or intolerance to 2 or more tyrosine kinase inhibitors (TKIs).^1,2 Approval was based on response rates observed in a combined cohort of adult CML patients from 2 clinical trials. As yet, no clinical trials have verified improved disease-related symptoms or increased survival with omacetaxine treatment.

Click on the PDF icon at the top of this introduction to read the full article.

The FDA has approved bosutinib (Bosulif), an Abl and Src kinase inhibitor, to treat patients with relapsed or refractory chronic myelogenous leukemia (CML).

Bosutinib is intended for use in patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who have failed therapy with first-generation and second-generation tyrosine kinase inhibitors (TKIs).

The recommended dose of bosutinib is 500 mg, taken once daily with food.

“[Bosutinib] is an important new addition to the CML treatment landscape,” said Jorge E. Cortes, MD, of MD Anderson Cancer Center in Houston.

“Despite recent advances, an unmet need remains for many CML patients who are refractory to one or more tyrosine kinase inhibitors.”

Dr Cortes was a lead investigator of the industry-sponsored study that led to bosutinib’s approval. The phase 1/2 trial included 546 adult patients who had chronic, accelerated, or blast phase CML.

Efficacy data

Patients were evaluable for efficacy if they had received at least one bosutinib dose and had a valid baseline efficacy assessment. Of the 546 patients enrolled, 503 were evaluable for efficacy.

Among the patients in chronic phase, 266 received prior treatment with imatinib only, and 108 received prior treatment with imatinib followed by dasatinib and/or nilotinib. There were 129 evaluable patients with advanced phase CML who were previously treated with at least one TKI.

The efficacy endpoints for patients with chronic phase CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The efficacy endpoints for patients with accelerated phase or blast phase CML were the rates of complete hematologic response (CHR) and overall hematologic response (OHR) by week 48.

In patients with chronic phase CML who received prior therapy with one TKI, 90 patients (33.8%) achieved an MCyR at week 24. Among the chronic phase CML patients who received prior therapy with more than one TKI, 29 (26.9%) achieved an MCyR by week 24.

Of the patients with chronic phase CML who had been treated with one prior TKI, 53.4% achieved an MCyR at any time during the trial. And 52.8% had a response lasting at least 18 months.

For the 32.4% of patients with chronic phase CML treated with more than one TKI who achieved an MCyR at any time, 51.4% had a response lasting at least 9 months.

In patients with accelerated phase CML who received at least one prior TKI, 21 (30.4%) achieved a CHR by week 48. And 38 patients (55.1%) achieved an OHR.

In the blast phase population, 9 patients (15%) achieved a CHR by week 48. And 17 patients (28.3%) achieved an OHR.

Safety data

The researchers evaluated bosutinib’s safety in all 546 patients. Of these patients, 287 had chronic phase CML, were previously treated with a single TKI, and had a median bosutinib treatment duration of 24 months.

There were 119 patients who had chronic phase CML, were previously treated with more than one TKI, and had a median bosutinib treatment duration of 9 months.

There were also 76 patients with accelerated phase CML and 64 patients with blast phase CML.  In these patients, the median treatment duration was 10 months and 3 months, respectively.

The most common adverse events observed in more than 20% of all patients were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue.

The most common grade 3 to 4 adverse events observed in more than 10% of patients were thrombocytopenia, anemia, and neutropenia. Other serious adverse events included anaphylactic shock, myelosuppression, gastrointestinal toxicity, fluid retention, hepatoxicity, and rash.

Bosutinib is marketed as Bosulif by Pfizer. For more information on bosutinib, see the package insert.

The FDA has approved bosutinib (Bosulif), an Abl and Src kinase inhibitor, to treat patients with relapsed or refractory chronic myelogenous leukemia (CML).

Bosutinib is intended for use in patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who have failed therapy with first-generation and second-generation tyrosine kinase inhibitors (TKIs).

The recommended dose of bosutinib is 500 mg, taken once daily with food.

“[Bosutinib] is an important new addition to the CML treatment landscape,” said Jorge E. Cortes, MD, of MD Anderson Cancer Center in Houston.

“Despite recent advances, an unmet need remains for many CML patients who are refractory to one or more tyrosine kinase inhibitors.”

Dr Cortes was a lead investigator of the industry-sponsored study that led to bosutinib’s approval. The phase 1/2 trial included 546 adult patients who had chronic, accelerated, or blast phase CML.

Efficacy data

Patients were evaluable for efficacy if they had received at least one bosutinib dose and had a valid baseline efficacy assessment. Of the 546 patients enrolled, 503 were evaluable for efficacy.

Among the patients in chronic phase, 266 received prior treatment with imatinib only, and 108 received prior treatment with imatinib followed by dasatinib and/or nilotinib. There were 129 evaluable patients with advanced phase CML who were previously treated with at least one TKI.

The efficacy endpoints for patients with chronic phase CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The efficacy endpoints for patients with accelerated phase or blast phase CML were the rates of complete hematologic response (CHR) and overall hematologic response (OHR) by week 48.

In patients with chronic phase CML who received prior therapy with one TKI, 90 patients (33.8%) achieved an MCyR at week 24. Among the chronic phase CML patients who received prior therapy with more than one TKI, 29 (26.9%) achieved an MCyR by week 24.

Of the patients with chronic phase CML who had been treated with one prior TKI, 53.4% achieved an MCyR at any time during the trial. And 52.8% had a response lasting at least 18 months.

For the 32.4% of patients with chronic phase CML treated with more than one TKI who achieved an MCyR at any time, 51.4% had a response lasting at least 9 months.

In patients with accelerated phase CML who received at least one prior TKI, 21 (30.4%) achieved a CHR by week 48. And 38 patients (55.1%) achieved an OHR.

In the blast phase population, 9 patients (15%) achieved a CHR by week 48. And 17 patients (28.3%) achieved an OHR.

Safety data

The researchers evaluated bosutinib’s safety in all 546 patients. Of these patients, 287 had chronic phase CML, were previously treated with a single TKI, and had a median bosutinib treatment duration of 24 months.

There were 119 patients who had chronic phase CML, were previously treated with more than one TKI, and had a median bosutinib treatment duration of 9 months.

There were also 76 patients with accelerated phase CML and 64 patients with blast phase CML.  In these patients, the median treatment duration was 10 months and 3 months, respectively.

The most common adverse events observed in more than 20% of all patients were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue.

The most common grade 3 to 4 adverse events observed in more than 10% of patients were thrombocytopenia, anemia, and neutropenia. Other serious adverse events included anaphylactic shock, myelosuppression, gastrointestinal toxicity, fluid retention, hepatoxicity, and rash.

Bosutinib is marketed as Bosulif by Pfizer. For more information on bosutinib, see the package insert.

The FDA has approved bosutinib (Bosulif), an Abl and Src kinase inhibitor, to treat patients with relapsed or refractory chronic myelogenous leukemia (CML).

Bosutinib is intended for use in patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who have failed therapy with first-generation and second-generation tyrosine kinase inhibitors (TKIs).

The recommended dose of bosutinib is 500 mg, taken once daily with food.

“[Bosutinib] is an important new addition to the CML treatment landscape,” said Jorge E. Cortes, MD, of MD Anderson Cancer Center in Houston.

“Despite recent advances, an unmet need remains for many CML patients who are refractory to one or more tyrosine kinase inhibitors.”

Dr Cortes was a lead investigator of the industry-sponsored study that led to bosutinib’s approval. The phase 1/2 trial included 546 adult patients who had chronic, accelerated, or blast phase CML.

Efficacy data

Patients were evaluable for efficacy if they had received at least one bosutinib dose and had a valid baseline efficacy assessment. Of the 546 patients enrolled, 503 were evaluable for efficacy.

Among the patients in chronic phase, 266 received prior treatment with imatinib only, and 108 received prior treatment with imatinib followed by dasatinib and/or nilotinib. There were 129 evaluable patients with advanced phase CML who were previously treated with at least one TKI.

The efficacy endpoints for patients with chronic phase CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The efficacy endpoints for patients with accelerated phase or blast phase CML were the rates of complete hematologic response (CHR) and overall hematologic response (OHR) by week 48.

In patients with chronic phase CML who received prior therapy with one TKI, 90 patients (33.8%) achieved an MCyR at week 24. Among the chronic phase CML patients who received prior therapy with more than one TKI, 29 (26.9%) achieved an MCyR by week 24.

Of the patients with chronic phase CML who had been treated with one prior TKI, 53.4% achieved an MCyR at any time during the trial. And 52.8% had a response lasting at least 18 months.

For the 32.4% of patients with chronic phase CML treated with more than one TKI who achieved an MCyR at any time, 51.4% had a response lasting at least 9 months.

In patients with accelerated phase CML who received at least one prior TKI, 21 (30.4%) achieved a CHR by week 48. And 38 patients (55.1%) achieved an OHR.

In the blast phase population, 9 patients (15%) achieved a CHR by week 48. And 17 patients (28.3%) achieved an OHR.

Safety data

The researchers evaluated bosutinib’s safety in all 546 patients. Of these patients, 287 had chronic phase CML, were previously treated with a single TKI, and had a median bosutinib treatment duration of 24 months.

There were 119 patients who had chronic phase CML, were previously treated with more than one TKI, and had a median bosutinib treatment duration of 9 months.

There were also 76 patients with accelerated phase CML and 64 patients with blast phase CML.  In these patients, the median treatment duration was 10 months and 3 months, respectively.

The most common adverse events observed in more than 20% of all patients were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue.

The most common grade 3 to 4 adverse events observed in more than 10% of patients were thrombocytopenia, anemia, and neutropenia. Other serious adverse events included anaphylactic shock, myelosuppression, gastrointestinal toxicity, fluid retention, hepatoxicity, and rash.

Bosutinib is marketed as Bosulif by Pfizer. For more information on bosutinib, see the package insert.