Pharmacy

Blood sample collection

Photo by Juan D. Alfonso

A single-center study has shown that laboratory testing among patients undergoing cardiac surgery can lead to excessive bloodletting.

This can increase the risk of hospital-acquired anemia and, therefore, the need for blood transfusions.

Among cardiac surgery patients, transfusions have been associated with an increased risk of infection, more time spent on a ventilator, and a higher likelihood of death, said Colleen G. Koch, MD, of the Cleveland Clinic in Ohio.

She and her colleagues conducted this research and published their findings in The Annals of Thoracic Surgery.

The researchers recorded every laboratory test performed on 1894 patients who underwent cardiac surgery at the Cleveland Clinic from January to June 2012.

The team evaluated the number and type of blood tests performed from the time patients met their surgeons until hospital discharge, tallying up the total amount of blood taken from each patient.

‘Astonishing’ amount of blood drawn

There were 221,498 laboratory tests performed during the study period, or an average of 115 tests per patient. The most common tests were blood gas analyses (n=88,068), coagulation tests (n=39,535), complete blood counts (n=30,421), and metabolic panels (n=29,374).

The cumulative median phlebotomy volume for the entire hospital stay was 454 mL per patient. Patients tended to have more blood drawn if they were in the intensive care unit as compared to other hospital floors, with median phlebotomy volumes of 332 mL and 118 mL, respectively.

“We were astonished by the amount of blood taken from our patients for laboratory testing,” Dr Koch said. “Total phlebotomy volumes approached 1 to 2 units of red blood cells, which is roughly equivalent to 1 to 2 cans of soda.”

More complex procedures were associated with higher overall phlebotomy volume. Patients undergoing combined coronary artery bypass grafting surgery (CABG) and valve procedures had the highest median cumulative phlebotomy volume. The median volume was 653 mL for CABG-valve procedures, 448 mL for CABG alone, and 338 mL for valve procedures alone.

Transfusion need

The researchers also found that an increase in cumulative phlebotomy volume was linked to an increased need for blood products. Similarly, the longer a patient was hospitalized, the more blood was taken, which increased the subsequent need for a transfusion.

Overall, 49% of patients received red blood cells (RBCs), 25% fresh-frozen plasma (FFP), 33% platelets, and 15% cryoprecipitate.

Patients in the lowest phlebotomy volume quartile (0%-25th%) were much less likely to receive transfusions than patients in the highest quartile (75th% to 100th%).

In the lowest quartile, 2% of patients received cryoprecipitate, 3% FFP, 7% platelets, and 12% RBCs. In the highest quartile, 31% of patients received cryoprecipitate, 54% FFP, 61% platelets, and 87% RBCs.

So to reduce the use of transfusions, we must curb the use of blood tests, Dr Koch said, noting that patients can help.

“Patients should feel empowered to ask their doctors whether a specific test is necessary—’What is the indication for the test?,’ ‘Will it change my care?,’ and ‘If so, do you need to do it every day?,’”  Dr Koch said.

“They should inquire whether smaller-volume test tubes could be used for the tests that are deemed necessary. Every attempt should be made to conserve the patient’s own blood. Every drop of blood counts.”

In an invited commentary, Milo Engoren, MD, of the University of Michigan in Ann Arbor, emphasized the importance of reducing blood loss to decrease possible complications during surgery.

“We make efforts to minimize intraoperative blood loss,” he noted. “Now, we need to make similar efforts postoperatively. While some may argue that transfusion itself is not harmful, but only a marker of a sicker patient, most would agree that avoiding anemia and transfusion is the best course for patients.”

Blood sample collection

Photo by Juan D. Alfonso

A single-center study has shown that laboratory testing among patients undergoing cardiac surgery can lead to excessive bloodletting.

This can increase the risk of hospital-acquired anemia and, therefore, the need for blood transfusions.

Among cardiac surgery patients, transfusions have been associated with an increased risk of infection, more time spent on a ventilator, and a higher likelihood of death, said Colleen G. Koch, MD, of the Cleveland Clinic in Ohio.

She and her colleagues conducted this research and published their findings in The Annals of Thoracic Surgery.

The researchers recorded every laboratory test performed on 1894 patients who underwent cardiac surgery at the Cleveland Clinic from January to June 2012.

The team evaluated the number and type of blood tests performed from the time patients met their surgeons until hospital discharge, tallying up the total amount of blood taken from each patient.

‘Astonishing’ amount of blood drawn

There were 221,498 laboratory tests performed during the study period, or an average of 115 tests per patient. The most common tests were blood gas analyses (n=88,068), coagulation tests (n=39,535), complete blood counts (n=30,421), and metabolic panels (n=29,374).

The cumulative median phlebotomy volume for the entire hospital stay was 454 mL per patient. Patients tended to have more blood drawn if they were in the intensive care unit as compared to other hospital floors, with median phlebotomy volumes of 332 mL and 118 mL, respectively.

“We were astonished by the amount of blood taken from our patients for laboratory testing,” Dr Koch said. “Total phlebotomy volumes approached 1 to 2 units of red blood cells, which is roughly equivalent to 1 to 2 cans of soda.”

More complex procedures were associated with higher overall phlebotomy volume. Patients undergoing combined coronary artery bypass grafting surgery (CABG) and valve procedures had the highest median cumulative phlebotomy volume. The median volume was 653 mL for CABG-valve procedures, 448 mL for CABG alone, and 338 mL for valve procedures alone.

Transfusion need

The researchers also found that an increase in cumulative phlebotomy volume was linked to an increased need for blood products. Similarly, the longer a patient was hospitalized, the more blood was taken, which increased the subsequent need for a transfusion.

Overall, 49% of patients received red blood cells (RBCs), 25% fresh-frozen plasma (FFP), 33% platelets, and 15% cryoprecipitate.

Patients in the lowest phlebotomy volume quartile (0%-25th%) were much less likely to receive transfusions than patients in the highest quartile (75th% to 100th%).

In the lowest quartile, 2% of patients received cryoprecipitate, 3% FFP, 7% platelets, and 12% RBCs. In the highest quartile, 31% of patients received cryoprecipitate, 54% FFP, 61% platelets, and 87% RBCs.

So to reduce the use of transfusions, we must curb the use of blood tests, Dr Koch said, noting that patients can help.

“Patients should feel empowered to ask their doctors whether a specific test is necessary—’What is the indication for the test?,’ ‘Will it change my care?,’ and ‘If so, do you need to do it every day?,’”  Dr Koch said.

“They should inquire whether smaller-volume test tubes could be used for the tests that are deemed necessary. Every attempt should be made to conserve the patient’s own blood. Every drop of blood counts.”

In an invited commentary, Milo Engoren, MD, of the University of Michigan in Ann Arbor, emphasized the importance of reducing blood loss to decrease possible complications during surgery.

“We make efforts to minimize intraoperative blood loss,” he noted. “Now, we need to make similar efforts postoperatively. While some may argue that transfusion itself is not harmful, but only a marker of a sicker patient, most would agree that avoiding anemia and transfusion is the best course for patients.”

Blood sample collection

Photo by Juan D. Alfonso

A single-center study has shown that laboratory testing among patients undergoing cardiac surgery can lead to excessive bloodletting.

This can increase the risk of hospital-acquired anemia and, therefore, the need for blood transfusions.

Among cardiac surgery patients, transfusions have been associated with an increased risk of infection, more time spent on a ventilator, and a higher likelihood of death, said Colleen G. Koch, MD, of the Cleveland Clinic in Ohio.

She and her colleagues conducted this research and published their findings in The Annals of Thoracic Surgery.

The researchers recorded every laboratory test performed on 1894 patients who underwent cardiac surgery at the Cleveland Clinic from January to June 2012.

The team evaluated the number and type of blood tests performed from the time patients met their surgeons until hospital discharge, tallying up the total amount of blood taken from each patient.

‘Astonishing’ amount of blood drawn

There were 221,498 laboratory tests performed during the study period, or an average of 115 tests per patient. The most common tests were blood gas analyses (n=88,068), coagulation tests (n=39,535), complete blood counts (n=30,421), and metabolic panels (n=29,374).

The cumulative median phlebotomy volume for the entire hospital stay was 454 mL per patient. Patients tended to have more blood drawn if they were in the intensive care unit as compared to other hospital floors, with median phlebotomy volumes of 332 mL and 118 mL, respectively.

“We were astonished by the amount of blood taken from our patients for laboratory testing,” Dr Koch said. “Total phlebotomy volumes approached 1 to 2 units of red blood cells, which is roughly equivalent to 1 to 2 cans of soda.”

More complex procedures were associated with higher overall phlebotomy volume. Patients undergoing combined coronary artery bypass grafting surgery (CABG) and valve procedures had the highest median cumulative phlebotomy volume. The median volume was 653 mL for CABG-valve procedures, 448 mL for CABG alone, and 338 mL for valve procedures alone.

Transfusion need

The researchers also found that an increase in cumulative phlebotomy volume was linked to an increased need for blood products. Similarly, the longer a patient was hospitalized, the more blood was taken, which increased the subsequent need for a transfusion.

Overall, 49% of patients received red blood cells (RBCs), 25% fresh-frozen plasma (FFP), 33% platelets, and 15% cryoprecipitate.

Patients in the lowest phlebotomy volume quartile (0%-25th%) were much less likely to receive transfusions than patients in the highest quartile (75th% to 100th%).

In the lowest quartile, 2% of patients received cryoprecipitate, 3% FFP, 7% platelets, and 12% RBCs. In the highest quartile, 31% of patients received cryoprecipitate, 54% FFP, 61% platelets, and 87% RBCs.

So to reduce the use of transfusions, we must curb the use of blood tests, Dr Koch said, noting that patients can help.

“Patients should feel empowered to ask their doctors whether a specific test is necessary—’What is the indication for the test?,’ ‘Will it change my care?,’ and ‘If so, do you need to do it every day?,’”  Dr Koch said.

“They should inquire whether smaller-volume test tubes could be used for the tests that are deemed necessary. Every attempt should be made to conserve the patient’s own blood. Every drop of blood counts.”

In an invited commentary, Milo Engoren, MD, of the University of Michigan in Ann Arbor, emphasized the importance of reducing blood loss to decrease possible complications during surgery.

“We make efforts to minimize intraoperative blood loss,” he noted. “Now, we need to make similar efforts postoperatively. While some may argue that transfusion itself is not harmful, but only a marker of a sicker patient, most would agree that avoiding anemia and transfusion is the best course for patients.”

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted accelerated approval for panobinostat (Farydak) to treat patients with multiple myeloma (MM).

Panobinostat is the first histone deacetylase (HDAC) inhibitor approved to treat MM.

The drug can now be used in combination with bortezomib and dexamethasone to treat patients who have received at least 2 prior standard therapies, including bortezomib and an immunomodulatory agent (IMiD).

Panobinostat was approved with a boxed warning alerting patients and healthcare professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias, and electrocardiogram changes have occurred in patients receiving the drug.

Panobinostat was approved with a Risk Evaluation and Mitigation Strategy as well, which consists of a communication plan to inform healthcare professionals of these risks and how to minimize them.

Data supporting approval

In November 2014, the FDA’s Oncologic Drugs Advisory Committee advised the agency that, based on the data reviewed, the benefits of panobinostat did not outweigh its risks for patients with relapsed MM.

After the meeting, Novartis, the company developing the HDAC inhibitor, submitted additional information supporting the use of panobinostat for a different indication: MM patients who have received at least 2 prior standard therapies, including bortezomib and an IMiD.

The FDA’s accelerated approval of panobinostat is based on that data—efficacy and safety results in a subgroup analysis of 193 patients enrolled in the phase 3 PANORAMA-1 trial. These patients had received prior treatment with both bortezomib and an IMiD.

In these patients, treatment with panobinostat, bortezomib, and dexamethasone resulted in superior progression-free survival, when compared to treatment with bortezomib, dexamethasone, and placebo—10.6 months and 5.8 months, respectively (hazard ratio=0.52).

The most common adverse events (incidence ≥ 20%) in clinical studies of panobinostat have been diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, and vomiting.

The most common non-hematologic laboratory abnormalities (incidence ≥ 40%) were hypophosphatemia, hypokalemia, hyponatremia, and increased creatinine. The most common hematologic laboratory abnormalities (incidence ≥ 60%) were thrombocytopenia, lymphopenia, leukopenia, neutropenia, and anemia.

Panobinostat can cause fatal and serious toxicities, including severe diarrhea and cardiac toxicities.

The most frequent (≥ 5%) treatment-emergent serious adverse events for patients treated with the HDAC inhibitor were pneumonia (18%), diarrhea (11%), thrombocytopenia (7%), fatigue (6%), and sepsis (6%). Additional serious adverse events included hemorrhage, myelosuppression, infections, hepatotoxicity, and embryo-fetal toxicity.

Panobinostat development

The FDA previously granted panobinostat priority review and orphan product designation. Priority review provides an expedited review of drugs that are intended to treat a serious disease or condition and may provide a significant improvement over available therapy. Orphan product designation is given to drugs intended to treat rare diseases.

Now, the FDA has granted panobinostat accelerated approval, which allows for conditional approval of a drug based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Continued approval of panobinostat may be contingent upon verification of a clinical benefit in confirmatory trials conducted by Novartis. An improvement in overall survival or disease-related symptoms has not yet been established for the HDAC inhibitor.

For more details on panobinostat, see the full prescribing information.

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted accelerated approval for panobinostat (Farydak) to treat patients with multiple myeloma (MM).

Panobinostat is the first histone deacetylase (HDAC) inhibitor approved to treat MM.

The drug can now be used in combination with bortezomib and dexamethasone to treat patients who have received at least 2 prior standard therapies, including bortezomib and an immunomodulatory agent (IMiD).

Panobinostat was approved with a boxed warning alerting patients and healthcare professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias, and electrocardiogram changes have occurred in patients receiving the drug.

Panobinostat was approved with a Risk Evaluation and Mitigation Strategy as well, which consists of a communication plan to inform healthcare professionals of these risks and how to minimize them.

Data supporting approval

In November 2014, the FDA’s Oncologic Drugs Advisory Committee advised the agency that, based on the data reviewed, the benefits of panobinostat did not outweigh its risks for patients with relapsed MM.

After the meeting, Novartis, the company developing the HDAC inhibitor, submitted additional information supporting the use of panobinostat for a different indication: MM patients who have received at least 2 prior standard therapies, including bortezomib and an IMiD.

The FDA’s accelerated approval of panobinostat is based on that data—efficacy and safety results in a subgroup analysis of 193 patients enrolled in the phase 3 PANORAMA-1 trial. These patients had received prior treatment with both bortezomib and an IMiD.

In these patients, treatment with panobinostat, bortezomib, and dexamethasone resulted in superior progression-free survival, when compared to treatment with bortezomib, dexamethasone, and placebo—10.6 months and 5.8 months, respectively (hazard ratio=0.52).

The most common adverse events (incidence ≥ 20%) in clinical studies of panobinostat have been diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, and vomiting.

The most common non-hematologic laboratory abnormalities (incidence ≥ 40%) were hypophosphatemia, hypokalemia, hyponatremia, and increased creatinine. The most common hematologic laboratory abnormalities (incidence ≥ 60%) were thrombocytopenia, lymphopenia, leukopenia, neutropenia, and anemia.

Panobinostat can cause fatal and serious toxicities, including severe diarrhea and cardiac toxicities.

The most frequent (≥ 5%) treatment-emergent serious adverse events for patients treated with the HDAC inhibitor were pneumonia (18%), diarrhea (11%), thrombocytopenia (7%), fatigue (6%), and sepsis (6%). Additional serious adverse events included hemorrhage, myelosuppression, infections, hepatotoxicity, and embryo-fetal toxicity.

Panobinostat development

The FDA previously granted panobinostat priority review and orphan product designation. Priority review provides an expedited review of drugs that are intended to treat a serious disease or condition and may provide a significant improvement over available therapy. Orphan product designation is given to drugs intended to treat rare diseases.

Now, the FDA has granted panobinostat accelerated approval, which allows for conditional approval of a drug based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Continued approval of panobinostat may be contingent upon verification of a clinical benefit in confirmatory trials conducted by Novartis. An improvement in overall survival or disease-related symptoms has not yet been established for the HDAC inhibitor.

For more details on panobinostat, see the full prescribing information.

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted accelerated approval for panobinostat (Farydak) to treat patients with multiple myeloma (MM).

Panobinostat is the first histone deacetylase (HDAC) inhibitor approved to treat MM.

The drug can now be used in combination with bortezomib and dexamethasone to treat patients who have received at least 2 prior standard therapies, including bortezomib and an immunomodulatory agent (IMiD).

Panobinostat was approved with a boxed warning alerting patients and healthcare professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias, and electrocardiogram changes have occurred in patients receiving the drug.

Panobinostat was approved with a Risk Evaluation and Mitigation Strategy as well, which consists of a communication plan to inform healthcare professionals of these risks and how to minimize them.

Data supporting approval

In November 2014, the FDA’s Oncologic Drugs Advisory Committee advised the agency that, based on the data reviewed, the benefits of panobinostat did not outweigh its risks for patients with relapsed MM.

After the meeting, Novartis, the company developing the HDAC inhibitor, submitted additional information supporting the use of panobinostat for a different indication: MM patients who have received at least 2 prior standard therapies, including bortezomib and an IMiD.

The FDA’s accelerated approval of panobinostat is based on that data—efficacy and safety results in a subgroup analysis of 193 patients enrolled in the phase 3 PANORAMA-1 trial. These patients had received prior treatment with both bortezomib and an IMiD.

In these patients, treatment with panobinostat, bortezomib, and dexamethasone resulted in superior progression-free survival, when compared to treatment with bortezomib, dexamethasone, and placebo—10.6 months and 5.8 months, respectively (hazard ratio=0.52).

The most common adverse events (incidence ≥ 20%) in clinical studies of panobinostat have been diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, and vomiting.

The most common non-hematologic laboratory abnormalities (incidence ≥ 40%) were hypophosphatemia, hypokalemia, hyponatremia, and increased creatinine. The most common hematologic laboratory abnormalities (incidence ≥ 60%) were thrombocytopenia, lymphopenia, leukopenia, neutropenia, and anemia.

Panobinostat can cause fatal and serious toxicities, including severe diarrhea and cardiac toxicities.

The most frequent (≥ 5%) treatment-emergent serious adverse events for patients treated with the HDAC inhibitor were pneumonia (18%), diarrhea (11%), thrombocytopenia (7%), fatigue (6%), and sepsis (6%). Additional serious adverse events included hemorrhage, myelosuppression, infections, hepatotoxicity, and embryo-fetal toxicity.

Panobinostat development

The FDA previously granted panobinostat priority review and orphan product designation. Priority review provides an expedited review of drugs that are intended to treat a serious disease or condition and may provide a significant improvement over available therapy. Orphan product designation is given to drugs intended to treat rare diseases.

Now, the FDA has granted panobinostat accelerated approval, which allows for conditional approval of a drug based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Continued approval of panobinostat may be contingent upon verification of a clinical benefit in confirmatory trials conducted by Novartis. An improvement in overall survival or disease-related symptoms has not yet been established for the HDAC inhibitor.

For more details on panobinostat, see the full prescribing information.

Revlimid (lenalidomide)

Photo courtesy of Celgene

The European Commission (EC) has expanded the marketing authorization for lenalidomide (Revlimid), just 2 days after the US Food and Drug Administration did the same.

Lenalidomide is now approved in the European Union (EU) to treat adults with previously untreated multiple myeloma (MM) who are not eligible for hematopoietic stem cell transplant. These patients can receive the drug continuously until

disease progression.

Lenalidomide was already approved in the EU for use in combination with dexamethasone to treat adults with MM who have received at least 1 prior therapy.

Lenalidomide is also approved in the EU to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with 5q deletion when other therapeutic options are insufficient or inadequate.

“Having a new treatment option now available for patients newly diagnosed with multiple myeloma is a real step forward,” said Thierry Facon, MD, of CHRU Lille in France.

“Treating patients continuously until disease progression is supported by several clinical studies and will have an important impact on how we manage the disease over the long-term.”

The EC’s decision to extend the approved use of lenalidomide was based on the results of 2 studies: MM-015 and MM-020, also known as FIRST.

The FIRST trial

In the phase 3 FIRST trial, researchers enrolled 1623 patients who were newly diagnosed with MM and not eligible for transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median progression-free survival was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT.

This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (hazard ratio[HR]=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival showed a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

Adverse events reported in 20% or more of patients in the continuous Rd, Rd18, or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%), and abdominal pain (20.5%, 14.4%, 11.1%).

The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

The MM-015 trial

In the phase 3 MM-015 study, researchers enrolled 459 patients who were 65 or older and newly diagnosed with MM.

The team compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo maintenance.

Patients who received MPR-R or MPR had significantly better response rates than patients who received MP, at 77%, 68%, and 50%, respectively (P<0.001 and P=0.002, respectively, for the comparison with MP).

And the median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months, HR=0.49, P<0.001) or MP (13 months, HR=0.40, P<0.001).

During induction, the most frequent adverse events were hematologic. Grade 4 neutropenia occurred in 35% of patients in the MPR-R arm, 32% in the MPR arm, and 8% in the MP arm. The 3-year rate of second primary malignancies was 7%, 7%, and 3%, respectively.

Revlimid (lenalidomide)

Photo courtesy of Celgene

The European Commission (EC) has expanded the marketing authorization for lenalidomide (Revlimid), just 2 days after the US Food and Drug Administration did the same.

Lenalidomide is now approved in the European Union (EU) to treat adults with previously untreated multiple myeloma (MM) who are not eligible for hematopoietic stem cell transplant. These patients can receive the drug continuously until

disease progression.

Lenalidomide was already approved in the EU for use in combination with dexamethasone to treat adults with MM who have received at least 1 prior therapy.

Lenalidomide is also approved in the EU to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with 5q deletion when other therapeutic options are insufficient or inadequate.

“Having a new treatment option now available for patients newly diagnosed with multiple myeloma is a real step forward,” said Thierry Facon, MD, of CHRU Lille in France.

“Treating patients continuously until disease progression is supported by several clinical studies and will have an important impact on how we manage the disease over the long-term.”

The EC’s decision to extend the approved use of lenalidomide was based on the results of 2 studies: MM-015 and MM-020, also known as FIRST.

The FIRST trial

In the phase 3 FIRST trial, researchers enrolled 1623 patients who were newly diagnosed with MM and not eligible for transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median progression-free survival was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT.

This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (hazard ratio[HR]=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival showed a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

Adverse events reported in 20% or more of patients in the continuous Rd, Rd18, or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%), and abdominal pain (20.5%, 14.4%, 11.1%).

The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

The MM-015 trial

In the phase 3 MM-015 study, researchers enrolled 459 patients who were 65 or older and newly diagnosed with MM.

The team compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo maintenance.

Patients who received MPR-R or MPR had significantly better response rates than patients who received MP, at 77%, 68%, and 50%, respectively (P<0.001 and P=0.002, respectively, for the comparison with MP).

And the median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months, HR=0.49, P<0.001) or MP (13 months, HR=0.40, P<0.001).

During induction, the most frequent adverse events were hematologic. Grade 4 neutropenia occurred in 35% of patients in the MPR-R arm, 32% in the MPR arm, and 8% in the MP arm. The 3-year rate of second primary malignancies was 7%, 7%, and 3%, respectively.

Revlimid (lenalidomide)

Photo courtesy of Celgene

The European Commission (EC) has expanded the marketing authorization for lenalidomide (Revlimid), just 2 days after the US Food and Drug Administration did the same.

Lenalidomide is now approved in the European Union (EU) to treat adults with previously untreated multiple myeloma (MM) who are not eligible for hematopoietic stem cell transplant. These patients can receive the drug continuously until

disease progression.

Lenalidomide was already approved in the EU for use in combination with dexamethasone to treat adults with MM who have received at least 1 prior therapy.

Lenalidomide is also approved in the EU to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with 5q deletion when other therapeutic options are insufficient or inadequate.

“Having a new treatment option now available for patients newly diagnosed with multiple myeloma is a real step forward,” said Thierry Facon, MD, of CHRU Lille in France.

“Treating patients continuously until disease progression is supported by several clinical studies and will have an important impact on how we manage the disease over the long-term.”

The EC’s decision to extend the approved use of lenalidomide was based on the results of 2 studies: MM-015 and MM-020, also known as FIRST.

The FIRST trial

In the phase 3 FIRST trial, researchers enrolled 1623 patients who were newly diagnosed with MM and not eligible for transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median progression-free survival was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT.

This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (hazard ratio[HR]=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival showed a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

Adverse events reported in 20% or more of patients in the continuous Rd, Rd18, or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%), and abdominal pain (20.5%, 14.4%, 11.1%).

The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

The MM-015 trial

In the phase 3 MM-015 study, researchers enrolled 459 patients who were 65 or older and newly diagnosed with MM.

The team compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo maintenance.

Patients who received MPR-R or MPR had significantly better response rates than patients who received MP, at 77%, 68%, and 50%, respectively (P<0.001 and P=0.002, respectively, for the comparison with MP).

And the median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months, HR=0.49, P<0.001) or MP (13 months, HR=0.40, P<0.001).

During induction, the most frequent adverse events were hematologic. Grade 4 neutropenia occurred in 35% of patients in the MPR-R arm, 32% in the MPR arm, and 8% in the MP arm. The 3-year rate of second primary malignancies was 7%, 7%, and 3%, respectively.

Thrombus

Image by Kevin MacKenzie

Teva Pharmaceutical Industries Ltd. has launched the generic equivalent of the low-molecular-weight heparin Lovenox (enoxaparin sodium injection) in 7 dosage strengths in the US.

Enoxaparin can be used to prevent deep vein thrombosis (DVT) in patients undergoing abdominal surgery, those receiving a hip or knee replacement, and patients at risk of thromboembolic complications due to severely restricted mobility during acute illness.

When administered with warfarin, enoxaparin can be used for inpatient treatment of acute DVT, with or without pulmonary embolism (PE). Enoxaparin given in conjunction with warfarin may also be used for outpatient treatment of acute DVT without PE.

When given concurrently with aspirin, enoxaparin can be used to prevent ischemic complications of unstable angina and non-Q-wave myocardial infarction. Enoxaparin may also be used to treat acute ST-segment elevation myocardial infarction that is managed medically or with subsequent percutaneous coronary intervention.

Teva’s Enoxaparin Sodium Injection USP is available in the following doses:

• 30 mg/0.3 mL syringe, 10 x 0.3 mL
• 40 mg/0.4 mL syringe, 10 x 0.4 mL
• 60 mg/0.6 mL syringe, 10 x 0.6 mL
• 80 mg/0.8 mL syringe, 10 x 0.8 mL
• 100 mg/mL syringe, 10 x 1 mL
• 120 mg/0.8 mL syringe, 10 x 0.8 mL
• 150 mg/mL syringe, 10 x 1 mL.

Safety information

Enoxaparin’s label contains a boxed warning detailing the risk of epidural or spinal hematomas that can occur in patients who are anticoagulated with low-molecular-weight heparins or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. The hematomas may result in long-term or permanent paralysis.

Enoxaparin is contraindicated in patients with active major bleeding, thrombocytopenia with a positive in vitro test for antiplatelet antibody in the presence of enoxaparin, or known hypersensitivity to enoxaparin, heparin, or pork products.

Serious adverse reactions reported with enoxaparin include increased risk of hemorrhage and thrombocytopenia.

Enoxaparin should be used with extreme caution in patients who have conditions with an increased risk of hemorrhage or in patients treated concomitantly with platelet inhibitors. Major hemorrhages, including retroperitoneal and intracranial bleeding, have been reported with enoxaparin. Some of these cases have been fatal.

Bleeding can occur at any site during enoxaparin treatment. The drug should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension, or a history of recent gastrointestinal ulceration, diabetic retinopathy, renal dysfunction, and hemorrhage.

In clinical trials, the most common adverse reactions associated with enoxaparin (occurring in more than 1% of patients) were bleeding, anemia, thrombocytopenia, elevation of serum aminotransferase, diarrhea, and nausea. Mild local irritation, pain, hematoma, ecchymosis, and erythema may follow subcutaneous injection.

For additional information on enoxaparin, see the full prescribing information.

Thrombus

Image by Kevin MacKenzie

Teva Pharmaceutical Industries Ltd. has launched the generic equivalent of the low-molecular-weight heparin Lovenox (enoxaparin sodium injection) in 7 dosage strengths in the US.

Enoxaparin can be used to prevent deep vein thrombosis (DVT) in patients undergoing abdominal surgery, those receiving a hip or knee replacement, and patients at risk of thromboembolic complications due to severely restricted mobility during acute illness.

When administered with warfarin, enoxaparin can be used for inpatient treatment of acute DVT, with or without pulmonary embolism (PE). Enoxaparin given in conjunction with warfarin may also be used for outpatient treatment of acute DVT without PE.

When given concurrently with aspirin, enoxaparin can be used to prevent ischemic complications of unstable angina and non-Q-wave myocardial infarction. Enoxaparin may also be used to treat acute ST-segment elevation myocardial infarction that is managed medically or with subsequent percutaneous coronary intervention.

Teva’s Enoxaparin Sodium Injection USP is available in the following doses:

• 30 mg/0.3 mL syringe, 10 x 0.3 mL
• 40 mg/0.4 mL syringe, 10 x 0.4 mL
• 60 mg/0.6 mL syringe, 10 x 0.6 mL
• 80 mg/0.8 mL syringe, 10 x 0.8 mL
• 100 mg/mL syringe, 10 x 1 mL
• 120 mg/0.8 mL syringe, 10 x 0.8 mL
• 150 mg/mL syringe, 10 x 1 mL.

Safety information

Enoxaparin’s label contains a boxed warning detailing the risk of epidural or spinal hematomas that can occur in patients who are anticoagulated with low-molecular-weight heparins or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. The hematomas may result in long-term or permanent paralysis.

Enoxaparin is contraindicated in patients with active major bleeding, thrombocytopenia with a positive in vitro test for antiplatelet antibody in the presence of enoxaparin, or known hypersensitivity to enoxaparin, heparin, or pork products.

Serious adverse reactions reported with enoxaparin include increased risk of hemorrhage and thrombocytopenia.

Enoxaparin should be used with extreme caution in patients who have conditions with an increased risk of hemorrhage or in patients treated concomitantly with platelet inhibitors. Major hemorrhages, including retroperitoneal and intracranial bleeding, have been reported with enoxaparin. Some of these cases have been fatal.

Bleeding can occur at any site during enoxaparin treatment. The drug should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension, or a history of recent gastrointestinal ulceration, diabetic retinopathy, renal dysfunction, and hemorrhage.

In clinical trials, the most common adverse reactions associated with enoxaparin (occurring in more than 1% of patients) were bleeding, anemia, thrombocytopenia, elevation of serum aminotransferase, diarrhea, and nausea. Mild local irritation, pain, hematoma, ecchymosis, and erythema may follow subcutaneous injection.

For additional information on enoxaparin, see the full prescribing information.

Thrombus

Image by Kevin MacKenzie

Teva Pharmaceutical Industries Ltd. has launched the generic equivalent of the low-molecular-weight heparin Lovenox (enoxaparin sodium injection) in 7 dosage strengths in the US.

Enoxaparin can be used to prevent deep vein thrombosis (DVT) in patients undergoing abdominal surgery, those receiving a hip or knee replacement, and patients at risk of thromboembolic complications due to severely restricted mobility during acute illness.

When administered with warfarin, enoxaparin can be used for inpatient treatment of acute DVT, with or without pulmonary embolism (PE). Enoxaparin given in conjunction with warfarin may also be used for outpatient treatment of acute DVT without PE.

When given concurrently with aspirin, enoxaparin can be used to prevent ischemic complications of unstable angina and non-Q-wave myocardial infarction. Enoxaparin may also be used to treat acute ST-segment elevation myocardial infarction that is managed medically or with subsequent percutaneous coronary intervention.

Teva’s Enoxaparin Sodium Injection USP is available in the following doses:

• 30 mg/0.3 mL syringe, 10 x 0.3 mL
• 40 mg/0.4 mL syringe, 10 x 0.4 mL
• 60 mg/0.6 mL syringe, 10 x 0.6 mL
• 80 mg/0.8 mL syringe, 10 x 0.8 mL
• 100 mg/mL syringe, 10 x 1 mL
• 120 mg/0.8 mL syringe, 10 x 0.8 mL
• 150 mg/mL syringe, 10 x 1 mL.

Safety information

Enoxaparin’s label contains a boxed warning detailing the risk of epidural or spinal hematomas that can occur in patients who are anticoagulated with low-molecular-weight heparins or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. The hematomas may result in long-term or permanent paralysis.

Enoxaparin is contraindicated in patients with active major bleeding, thrombocytopenia with a positive in vitro test for antiplatelet antibody in the presence of enoxaparin, or known hypersensitivity to enoxaparin, heparin, or pork products.

Serious adverse reactions reported with enoxaparin include increased risk of hemorrhage and thrombocytopenia.

Enoxaparin should be used with extreme caution in patients who have conditions with an increased risk of hemorrhage or in patients treated concomitantly with platelet inhibitors. Major hemorrhages, including retroperitoneal and intracranial bleeding, have been reported with enoxaparin. Some of these cases have been fatal.

Bleeding can occur at any site during enoxaparin treatment. The drug should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension, or a history of recent gastrointestinal ulceration, diabetic retinopathy, renal dysfunction, and hemorrhage.

In clinical trials, the most common adverse reactions associated with enoxaparin (occurring in more than 1% of patients) were bleeding, anemia, thrombocytopenia, elevation of serum aminotransferase, diarrhea, and nausea. Mild local irritation, pain, hematoma, ecchymosis, and erythema may follow subcutaneous injection.

For additional information on enoxaparin, see the full prescribing information.

Capsules

The US Food and Drug Administration (FDA) has expanded the existing indication for lenalidomide (Revlimid)—in combination with dexamethasone—to include patients with newly diagnosed multiple myeloma (MM).

The FDA previously approved lenalidomide in combination with dexamethasone to treat MM patients who had received at least 1 prior therapy.

Lenalidomide is also FDA-approved to treat mantle cell lymphoma patients who have failed 2 prior therapies, including bortezomib.

And the drug is approved to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with 5q deletion, with or without additional cytogenetic abnormalities.

“The approval of Revlimid as an option for use in all patients with multiple myeloma represents a new paradigm in the management of this disease,” said Kenneth Anderson, MD, of Dana-Farber/Brigham and Women’s Cancer Center in Boston, Massachusetts.

“We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on Revlimid significantly improves progression-free survival.”

The FDA’s latest approval of lenalidomide was based on safety and efficacy results from phase 3 studies, particularly the FIRST trial.

The FIRST trial

In this phase 3 trial, researchers enrolled 1623 patients who were newly diagnosed with MM and not eligible for stem cell transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median progression-free survival was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT.

This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (hazard ratio[HR]=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival showed a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

Adverse events reported in 20% or more of patients in the continuous Rd, Rd18, or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%) and abdominal pain (20.5%, 14.4%, 11.1%).

The most frequently reported grade 3/4 events in the continuous Rd arm (until disease progression) were neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), deep vein thrombosis (5.6%), and hyperglycemia (5.3%).

The incidence of invasive second primary malignancies was 3% in the continuous Rd arm, 6% in the Rd18 arm, and 5% in the MPT arm. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

Capsules

The US Food and Drug Administration (FDA) has expanded the existing indication for lenalidomide (Revlimid)—in combination with dexamethasone—to include patients with newly diagnosed multiple myeloma (MM).

The FDA previously approved lenalidomide in combination with dexamethasone to treat MM patients who had received at least 1 prior therapy.

Lenalidomide is also FDA-approved to treat mantle cell lymphoma patients who have failed 2 prior therapies, including bortezomib.

And the drug is approved to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with 5q deletion, with or without additional cytogenetic abnormalities.

“The approval of Revlimid as an option for use in all patients with multiple myeloma represents a new paradigm in the management of this disease,” said Kenneth Anderson, MD, of Dana-Farber/Brigham and Women’s Cancer Center in Boston, Massachusetts.

“We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on Revlimid significantly improves progression-free survival.”

The FDA’s latest approval of lenalidomide was based on safety and efficacy results from phase 3 studies, particularly the FIRST trial.

The FIRST trial

In this phase 3 trial, researchers enrolled 1623 patients who were newly diagnosed with MM and not eligible for stem cell transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median progression-free survival was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT.

This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (hazard ratio[HR]=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival showed a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

Adverse events reported in 20% or more of patients in the continuous Rd, Rd18, or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%) and abdominal pain (20.5%, 14.4%, 11.1%).

The most frequently reported grade 3/4 events in the continuous Rd arm (until disease progression) were neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), deep vein thrombosis (5.6%), and hyperglycemia (5.3%).

The incidence of invasive second primary malignancies was 3% in the continuous Rd arm, 6% in the Rd18 arm, and 5% in the MPT arm. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

Capsules

The US Food and Drug Administration (FDA) has expanded the existing indication for lenalidomide (Revlimid)—in combination with dexamethasone—to include patients with newly diagnosed multiple myeloma (MM).

The FDA previously approved lenalidomide in combination with dexamethasone to treat MM patients who had received at least 1 prior therapy.

Lenalidomide is also FDA-approved to treat mantle cell lymphoma patients who have failed 2 prior therapies, including bortezomib.

And the drug is approved to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with 5q deletion, with or without additional cytogenetic abnormalities.

“The approval of Revlimid as an option for use in all patients with multiple myeloma represents a new paradigm in the management of this disease,” said Kenneth Anderson, MD, of Dana-Farber/Brigham and Women’s Cancer Center in Boston, Massachusetts.

“We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on Revlimid significantly improves progression-free survival.”

The FDA’s latest approval of lenalidomide was based on safety and efficacy results from phase 3 studies, particularly the FIRST trial.

The FIRST trial

In this phase 3 trial, researchers enrolled 1623 patients who were newly diagnosed with MM and not eligible for stem cell transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median progression-free survival was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT.

This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (hazard ratio[HR]=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival showed a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

Adverse events reported in 20% or more of patients in the continuous Rd, Rd18, or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%) and abdominal pain (20.5%, 14.4%, 11.1%).

The most frequently reported grade 3/4 events in the continuous Rd arm (until disease progression) were neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), deep vein thrombosis (5.6%), and hyperglycemia (5.3%).

The incidence of invasive second primary malignancies was 3% in the continuous Rd arm, 6% in the Rd18 arm, and 5% in the MPT arm. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

Patient and pharmacist

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued 5 draft documents related to drug compounding and repackaging that aim to help entities comply with public health provisions.

The agency said these draft documents are applicable to pharmacies, federal facilities, outsourcing facilities, and physicians.

The new category of outsourcing facilities was created under the Drug Quality and Security Act (DQSA), which was enacted by Congress in November 2013.

It was enacted in response to a deadly fungal meningitis outbreak that was linked to contaminated sterile compounded drug products.

Drugs compounded in an outsourcing facility that meet certain conditions may be entitled to exemptions from certain provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including the new drug approval requirements and the requirement to label drug products with adequate directions for use.

Outsourcing facilities are subject to current good manufacturing practice requirements and inspections by the FDA according to a risk-based schedule.

Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the FD&C Act, or they will be subject to all of the requirements applicable to drugs produced by conventional drug manufacturers.

“The draft guidance documents provide information to pharmacies, outsourcing facilities, healthcare entities, and others about these FDA-proposed policies, which are critical to protecting the public health,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

Descriptions of these documents follow.

Draft Guidance: For Entities Considering Whether to Register As Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

This draft guidance provides an entity considering whether to register with the FDA as an outsourcing facility with information about the regulatory impact of registering.

For example, it explains that a facility engaged in only certain activities, including repackaging human drugs and compounding non-sterile drugs, should not register as an outsourcing facility because its drug products will not qualify for the exemptions provided in section 503B, including the exemption from the new drug approval requirements.

Draft Guidance for Industry: Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities

This draft guidance describes the conditions under which the FDA does not intend to take action for certain violations of the law when state-licensed pharmacies, federal facilities, or outsourcing facilities repackage certain drug products.

Repackaged drug products are generally not exempt from any of the provisions of the FD&C Act related to the production of drugs, and the compounding provisions of the FD&C Act do not address repackaging. Therefore, the FDA is issuing guidance to describe how it intends to address repackaging when done in a state-licensed pharmacy, federal facility, or outsourcing facility.

Draft Guidance for Industry: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (BLA)

This draft guidance describes the conditions under which the FDA does not intend to take action for violations of certain sections of the Public Health Service Act (PHS Act) and the FD&C Act when state-licensed pharmacies, federal facilities, or outsourcing facilities mix, dilute, or repackage specific biological products without an approved BLA, or when such facilities or physicians prepare prescription sets of allergenic extracts without an approved BLA.

The draft guidance notes that a biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an unlicensed biological product under section 351 of the PHS Act and may not be legally marketed without an approved BLA.

Additionally, the compounding provisions of the FD&C Act do not address biological products subject to licensure under section 351 of the PHS Act. Therefore, the FDA is issuing the guidance to describe how it intends to address these practices.

Draft Guidance for Industry: Adverse Event Reporting for Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

Entities registered as outsourcing facilities are required to report adverse events to the FDA. This draft guidance explains adverse event reporting for such facilities.

Draft Memorandum of Understanding Between A State and the U.S. Food and Drug Administration Addressing Certain Distributions of Compounded Human Drug Products

The draft memorandum of understanding (MOU) under section 503A of the FD&C Act describes the responsibilities of a state that chooses to sign the MOU in investigating and responding to complaints related to compounded human drug products distributed outside the state, and in addressing the interstate distribution of “inordinate amounts” of compounded human drug products.

These documents are the latest in a series of policy documents related to FDA oversight of drugs produced by state-licensed pharmacies, federal facilities, and outsourcing facilities.

The draft guidance documents are available for public comment for 90 days. The public has 120 days to comment on the draft MOU between the states and the FDA.

Patient and pharmacist

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued 5 draft documents related to drug compounding and repackaging that aim to help entities comply with public health provisions.

The agency said these draft documents are applicable to pharmacies, federal facilities, outsourcing facilities, and physicians.

The new category of outsourcing facilities was created under the Drug Quality and Security Act (DQSA), which was enacted by Congress in November 2013.

It was enacted in response to a deadly fungal meningitis outbreak that was linked to contaminated sterile compounded drug products.

Drugs compounded in an outsourcing facility that meet certain conditions may be entitled to exemptions from certain provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including the new drug approval requirements and the requirement to label drug products with adequate directions for use.

Outsourcing facilities are subject to current good manufacturing practice requirements and inspections by the FDA according to a risk-based schedule.

Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the FD&C Act, or they will be subject to all of the requirements applicable to drugs produced by conventional drug manufacturers.

“The draft guidance documents provide information to pharmacies, outsourcing facilities, healthcare entities, and others about these FDA-proposed policies, which are critical to protecting the public health,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

Descriptions of these documents follow.

Draft Guidance: For Entities Considering Whether to Register As Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

This draft guidance provides an entity considering whether to register with the FDA as an outsourcing facility with information about the regulatory impact of registering.

For example, it explains that a facility engaged in only certain activities, including repackaging human drugs and compounding non-sterile drugs, should not register as an outsourcing facility because its drug products will not qualify for the exemptions provided in section 503B, including the exemption from the new drug approval requirements.

Draft Guidance for Industry: Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities

This draft guidance describes the conditions under which the FDA does not intend to take action for certain violations of the law when state-licensed pharmacies, federal facilities, or outsourcing facilities repackage certain drug products.

Repackaged drug products are generally not exempt from any of the provisions of the FD&C Act related to the production of drugs, and the compounding provisions of the FD&C Act do not address repackaging. Therefore, the FDA is issuing guidance to describe how it intends to address repackaging when done in a state-licensed pharmacy, federal facility, or outsourcing facility.

Draft Guidance for Industry: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (BLA)

This draft guidance describes the conditions under which the FDA does not intend to take action for violations of certain sections of the Public Health Service Act (PHS Act) and the FD&C Act when state-licensed pharmacies, federal facilities, or outsourcing facilities mix, dilute, or repackage specific biological products without an approved BLA, or when such facilities or physicians prepare prescription sets of allergenic extracts without an approved BLA.

The draft guidance notes that a biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an unlicensed biological product under section 351 of the PHS Act and may not be legally marketed without an approved BLA.

Additionally, the compounding provisions of the FD&C Act do not address biological products subject to licensure under section 351 of the PHS Act. Therefore, the FDA is issuing the guidance to describe how it intends to address these practices.

Draft Guidance for Industry: Adverse Event Reporting for Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

Entities registered as outsourcing facilities are required to report adverse events to the FDA. This draft guidance explains adverse event reporting for such facilities.

Draft Memorandum of Understanding Between A State and the U.S. Food and Drug Administration Addressing Certain Distributions of Compounded Human Drug Products

The draft memorandum of understanding (MOU) under section 503A of the FD&C Act describes the responsibilities of a state that chooses to sign the MOU in investigating and responding to complaints related to compounded human drug products distributed outside the state, and in addressing the interstate distribution of “inordinate amounts” of compounded human drug products.

These documents are the latest in a series of policy documents related to FDA oversight of drugs produced by state-licensed pharmacies, federal facilities, and outsourcing facilities.

The draft guidance documents are available for public comment for 90 days. The public has 120 days to comment on the draft MOU between the states and the FDA.

Patient and pharmacist

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued 5 draft documents related to drug compounding and repackaging that aim to help entities comply with public health provisions.

The agency said these draft documents are applicable to pharmacies, federal facilities, outsourcing facilities, and physicians.

The new category of outsourcing facilities was created under the Drug Quality and Security Act (DQSA), which was enacted by Congress in November 2013.

It was enacted in response to a deadly fungal meningitis outbreak that was linked to contaminated sterile compounded drug products.

Drugs compounded in an outsourcing facility that meet certain conditions may be entitled to exemptions from certain provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including the new drug approval requirements and the requirement to label drug products with adequate directions for use.

Outsourcing facilities are subject to current good manufacturing practice requirements and inspections by the FDA according to a risk-based schedule.

Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the FD&C Act, or they will be subject to all of the requirements applicable to drugs produced by conventional drug manufacturers.

“The draft guidance documents provide information to pharmacies, outsourcing facilities, healthcare entities, and others about these FDA-proposed policies, which are critical to protecting the public health,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

Descriptions of these documents follow.

Draft Guidance: For Entities Considering Whether to Register As Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

This draft guidance provides an entity considering whether to register with the FDA as an outsourcing facility with information about the regulatory impact of registering.

For example, it explains that a facility engaged in only certain activities, including repackaging human drugs and compounding non-sterile drugs, should not register as an outsourcing facility because its drug products will not qualify for the exemptions provided in section 503B, including the exemption from the new drug approval requirements.

Draft Guidance for Industry: Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities

This draft guidance describes the conditions under which the FDA does not intend to take action for certain violations of the law when state-licensed pharmacies, federal facilities, or outsourcing facilities repackage certain drug products.

Repackaged drug products are generally not exempt from any of the provisions of the FD&C Act related to the production of drugs, and the compounding provisions of the FD&C Act do not address repackaging. Therefore, the FDA is issuing guidance to describe how it intends to address repackaging when done in a state-licensed pharmacy, federal facility, or outsourcing facility.

Draft Guidance for Industry: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (BLA)

This draft guidance describes the conditions under which the FDA does not intend to take action for violations of certain sections of the Public Health Service Act (PHS Act) and the FD&C Act when state-licensed pharmacies, federal facilities, or outsourcing facilities mix, dilute, or repackage specific biological products without an approved BLA, or when such facilities or physicians prepare prescription sets of allergenic extracts without an approved BLA.

The draft guidance notes that a biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an unlicensed biological product under section 351 of the PHS Act and may not be legally marketed without an approved BLA.

Additionally, the compounding provisions of the FD&C Act do not address biological products subject to licensure under section 351 of the PHS Act. Therefore, the FDA is issuing the guidance to describe how it intends to address these practices.

Draft Guidance for Industry: Adverse Event Reporting for Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

Entities registered as outsourcing facilities are required to report adverse events to the FDA. This draft guidance explains adverse event reporting for such facilities.

Draft Memorandum of Understanding Between A State and the U.S. Food and Drug Administration Addressing Certain Distributions of Compounded Human Drug Products

The draft memorandum of understanding (MOU) under section 503A of the FD&C Act describes the responsibilities of a state that chooses to sign the MOU in investigating and responding to complaints related to compounded human drug products distributed outside the state, and in addressing the interstate distribution of “inordinate amounts” of compounded human drug products.

These documents are the latest in a series of policy documents related to FDA oversight of drugs produced by state-licensed pharmacies, federal facilities, and outsourcing facilities.

The draft guidance documents are available for public comment for 90 days. The public has 120 days to comment on the draft MOU between the states and the FDA.

Micrograph showing MM

In a final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend pomalidomide (Imnovid) for the treatment of multiple myeloma (MM).

NICE recommends thalidomide for most MM patients as a first-line treatment and bortezomib for patients who are unable to receive thalidomide and those who fail first-line treatment.

For patients who have received 2 prior therapies, the agency recommends lenalidomide.

NICE considered pomalidomide for use in MM patients after their third or subsequent relapse.

The agency said it could not recommend pomalidomide, in combination with dexamethasone, within its marketing authorization, which is to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.

“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets pomalidomide, showed that the drug does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.

NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues its final guidance, National Health Service (NHS) bodies should make decisions locally on the funding of specific treatments.

This draft guidance does not mean that patients currently taking pomalidomide will stop receiving it. They have the option to continue treatment until they and their clinicians consider it appropriate to stop.

And pomalidomide is recommended for use within NHS Scotland.

Insufficient evidence

The committee advising NICE was not able to judge with any confidence how much more effective pomalidomide was compared with current treatment options based on the evidence provided by Celgene before and after consultation.

However, bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial, and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months, on average, when compared with standard NHS care.

Nevertheless, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years (QALYs) gained would be too high to consider pomalidomide a cost-effective use of NHS resources.

Also, the committee concluded that the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on the QALYs gained.

All cost-per-QALY figures presented by Celgene were over £50,000 compared with bortezomib and over £70,000 compared with bendamustine plus thalidomide and dexamethasone. And the figures would further increase when a number of more realistic assumptions were included in the model, the committee said.

A pack of pomalidomide (21 tablets of 1 mg, 2 mg, 3 mg, or 4 mg) costs £8884. The recommended dosage of the drug is 4 mg once daily, taken on days 1 to 21 of repeated 28 day cycles. Treatment should continue until disease progression.

Micrograph showing MM

In a final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend pomalidomide (Imnovid) for the treatment of multiple myeloma (MM).

NICE recommends thalidomide for most MM patients as a first-line treatment and bortezomib for patients who are unable to receive thalidomide and those who fail first-line treatment.

For patients who have received 2 prior therapies, the agency recommends lenalidomide.

NICE considered pomalidomide for use in MM patients after their third or subsequent relapse.

The agency said it could not recommend pomalidomide, in combination with dexamethasone, within its marketing authorization, which is to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.

“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets pomalidomide, showed that the drug does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.

NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues its final guidance, National Health Service (NHS) bodies should make decisions locally on the funding of specific treatments.

This draft guidance does not mean that patients currently taking pomalidomide will stop receiving it. They have the option to continue treatment until they and their clinicians consider it appropriate to stop.

And pomalidomide is recommended for use within NHS Scotland.

Insufficient evidence

The committee advising NICE was not able to judge with any confidence how much more effective pomalidomide was compared with current treatment options based on the evidence provided by Celgene before and after consultation.

However, bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial, and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months, on average, when compared with standard NHS care.

Nevertheless, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years (QALYs) gained would be too high to consider pomalidomide a cost-effective use of NHS resources.

Also, the committee concluded that the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on the QALYs gained.

All cost-per-QALY figures presented by Celgene were over £50,000 compared with bortezomib and over £70,000 compared with bendamustine plus thalidomide and dexamethasone. And the figures would further increase when a number of more realistic assumptions were included in the model, the committee said.

A pack of pomalidomide (21 tablets of 1 mg, 2 mg, 3 mg, or 4 mg) costs £8884. The recommended dosage of the drug is 4 mg once daily, taken on days 1 to 21 of repeated 28 day cycles. Treatment should continue until disease progression.

Micrograph showing MM

In a final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend pomalidomide (Imnovid) for the treatment of multiple myeloma (MM).

NICE recommends thalidomide for most MM patients as a first-line treatment and bortezomib for patients who are unable to receive thalidomide and those who fail first-line treatment.

For patients who have received 2 prior therapies, the agency recommends lenalidomide.

NICE considered pomalidomide for use in MM patients after their third or subsequent relapse.

The agency said it could not recommend pomalidomide, in combination with dexamethasone, within its marketing authorization, which is to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.

“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets pomalidomide, showed that the drug does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.

NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues its final guidance, National Health Service (NHS) bodies should make decisions locally on the funding of specific treatments.

This draft guidance does not mean that patients currently taking pomalidomide will stop receiving it. They have the option to continue treatment until they and their clinicians consider it appropriate to stop.

And pomalidomide is recommended for use within NHS Scotland.

Insufficient evidence

The committee advising NICE was not able to judge with any confidence how much more effective pomalidomide was compared with current treatment options based on the evidence provided by Celgene before and after consultation.

However, bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial, and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months, on average, when compared with standard NHS care.

Nevertheless, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years (QALYs) gained would be too high to consider pomalidomide a cost-effective use of NHS resources.

Also, the committee concluded that the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on the QALYs gained.

All cost-per-QALY figures presented by Celgene were over £50,000 compared with bortezomib and over £70,000 compared with bendamustine plus thalidomide and dexamethasone. And the figures would further increase when a number of more realistic assumptions were included in the model, the committee said.

A pack of pomalidomide (21 tablets of 1 mg, 2 mg, 3 mg, or 4 mg) costs £8884. The recommended dosage of the drug is 4 mg once daily, taken on days 1 to 21 of repeated 28 day cycles. Treatment should continue until disease progression.

Patient consults with pharmacist

Photo by Rhoda Baer

The oral factor Xa inhibitor edoxaban (Savaysa) is now available in US pharmacies, according to Daiichi Sankyo Company, Limited, the company developing the drug.

Savaysa is approved by the US Food and Drug Administration to reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis and pulmonary embolism following 5 to 10 days of initial therapy with a parenteral anticoagulant.

According to Savaysa’s label, it should not be used in NVAF patients with creatinine clearance levels greater than 95 mL/min because, in that population, there is an increased risk of ischemic stroke with the drug compared to warfarin.

Daiichi Sankyo has developed resources for physicians and patients to help ensure patients can begin and/or remain on Savaysa per physician instructions.

The Savaysa Savings Plus program will include a reimbursement hotline to assist patients and prescribers who request help understanding a patient’s available coverage. Eligible patients who are prescribed Savaysa can enroll in a copay savings program and pay $4 per month through the Savaysa Savings Card.

Vouchers will also be available to provide patients and doctors with a way to try Savaysa at no cost to see if it is right for the patient.

In addition, the Savaysa Patient Assistance Program will offer assistance to qualified individuals, providing free product to eligible patients who are prescribed Savaysa, are uninsured, and are unable to identify alternative payment sources.

The approval of Savaysa in the US is based on data from the ENGAGE AF-TIMI 48 trial and the Hokusai-VTE trial.

Patient consults with pharmacist

Photo by Rhoda Baer

The oral factor Xa inhibitor edoxaban (Savaysa) is now available in US pharmacies, according to Daiichi Sankyo Company, Limited, the company developing the drug.

Savaysa is approved by the US Food and Drug Administration to reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis and pulmonary embolism following 5 to 10 days of initial therapy with a parenteral anticoagulant.

According to Savaysa’s label, it should not be used in NVAF patients with creatinine clearance levels greater than 95 mL/min because, in that population, there is an increased risk of ischemic stroke with the drug compared to warfarin.

Daiichi Sankyo has developed resources for physicians and patients to help ensure patients can begin and/or remain on Savaysa per physician instructions.

The Savaysa Savings Plus program will include a reimbursement hotline to assist patients and prescribers who request help understanding a patient’s available coverage. Eligible patients who are prescribed Savaysa can enroll in a copay savings program and pay $4 per month through the Savaysa Savings Card.

Vouchers will also be available to provide patients and doctors with a way to try Savaysa at no cost to see if it is right for the patient.

In addition, the Savaysa Patient Assistance Program will offer assistance to qualified individuals, providing free product to eligible patients who are prescribed Savaysa, are uninsured, and are unable to identify alternative payment sources.

The approval of Savaysa in the US is based on data from the ENGAGE AF-TIMI 48 trial and the Hokusai-VTE trial.

Patient consults with pharmacist

Photo by Rhoda Baer

The oral factor Xa inhibitor edoxaban (Savaysa) is now available in US pharmacies, according to Daiichi Sankyo Company, Limited, the company developing the drug.

Savaysa is approved by the US Food and Drug Administration to reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis and pulmonary embolism following 5 to 10 days of initial therapy with a parenteral anticoagulant.

According to Savaysa’s label, it should not be used in NVAF patients with creatinine clearance levels greater than 95 mL/min because, in that population, there is an increased risk of ischemic stroke with the drug compared to warfarin.

Daiichi Sankyo has developed resources for physicians and patients to help ensure patients can begin and/or remain on Savaysa per physician instructions.

The Savaysa Savings Plus program will include a reimbursement hotline to assist patients and prescribers who request help understanding a patient’s available coverage. Eligible patients who are prescribed Savaysa can enroll in a copay savings program and pay $4 per month through the Savaysa Savings Card.

Vouchers will also be available to provide patients and doctors with a way to try Savaysa at no cost to see if it is right for the patient.

In addition, the Savaysa Patient Assistance Program will offer assistance to qualified individuals, providing free product to eligible patients who are prescribed Savaysa, are uninsured, and are unable to identify alternative payment sources.

The approval of Savaysa in the US is based on data from the ENGAGE AF-TIMI 48 trial and the Hokusai-VTE trial.

Drugs in vials

Photo by Bill Branson

A new analysis indicates that certain high-cost therapies for hematologic malignancies provide reasonable value for money spent.

Most cost-effectiveness ratios were lower than thresholds commonly used to establish cost-effectiveness in the US—$50,000 or $100,000 per quality-adjusted life year (QALY) gained.

The median cost-effectiveness ratio was highest for chronic myeloid leukemia (CML), at $55,000/QALY, and lowest for non-Hodgkin lymphoma (NHL), at $21,500/QALY.

Researchers presented these data in Blood.

“Given the increased discussion about the high cost of these treatments, we were somewhat surprised to discover that their cost-effectiveness ratios were lower than expected,” said study author Peter J. Neumann, ScD, of Tufts Medical Center in Boston.

“Our analysis had a small sample size and included both industry- and non-industry-funded studies. In addition, cost-effectiveness ratios may have changed over time as associated costs or benefits have changed. However, the study underscores that debates in healthcare should consider the value of breakthrough drugs and not just costs.”

With that issue in mind, Dr Neumann and his colleagues had conducted a systematic review of studies published between 1996 and 2012 that examined the cost utility of agents for hematologic malignancies. The cost utility of a drug was depicted as a ratio of a drug’s total cost per patient QALY gained.

The researchers identified 29 studies, 22 of which were industry-funded. Nine studies were conducted from a US perspective, 6 from the UK, 3 from Norway, 3 from Sweden, 2 from France, 1 from Canada, 1 from Finland, and 4 from “other” countries.

The team grouped studies according to malignancy—CML, chronic lymphocytic leukemia (CLL), NHL, and multiple myeloma (MM)—as well as by treatment—α interferon, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide.

The studies reported 44 cost-effectiveness ratios, most concerning interventions for NHL (41%) or CML (30%). Most ratios pertained to rituximab (43%), α interferon (18%), or imatinib (16%), and the most common intervention-disease combination was rituximab (alone or in combination) for NHL (36%).

The median cost-effectiveness ratios fluctuated over time, rising from $35,000/QALY (1996-2002) to $52,000/QALY (2003-2006), then falling to $22,000/QALY (2007-2012).

The median cost-effectiveness ratio reported by industry-funded studies was lower ($26,000/QALY) than for non-industry-funded studies ($33,000/QALY).

Four cost-effectiveness ratios, 1 from an industry-funded study, exceeded $100,000/QALY. This included 2 studies of bortezomib in MM, 1 of α interferon in CML, and 1 of imatinib in CML.

The researchers said these results suggest that many new treatments for hematologic malignancies may confer reasonable value for money spent. The distribution of cost-effectiveness ratios is comparable to those for cancers overall and for other healthcare fields, they said.

This study was funded by internal resources at the Center for the Evaluation of Value and Risk in Health. The center receives funding from federal, private foundation, and pharmaceutical industry sources.

Drugs in vials

Photo by Bill Branson

A new analysis indicates that certain high-cost therapies for hematologic malignancies provide reasonable value for money spent.

Most cost-effectiveness ratios were lower than thresholds commonly used to establish cost-effectiveness in the US—$50,000 or $100,000 per quality-adjusted life year (QALY) gained.

The median cost-effectiveness ratio was highest for chronic myeloid leukemia (CML), at $55,000/QALY, and lowest for non-Hodgkin lymphoma (NHL), at $21,500/QALY.

Researchers presented these data in Blood.

“Given the increased discussion about the high cost of these treatments, we were somewhat surprised to discover that their cost-effectiveness ratios were lower than expected,” said study author Peter J. Neumann, ScD, of Tufts Medical Center in Boston.

“Our analysis had a small sample size and included both industry- and non-industry-funded studies. In addition, cost-effectiveness ratios may have changed over time as associated costs or benefits have changed. However, the study underscores that debates in healthcare should consider the value of breakthrough drugs and not just costs.”

With that issue in mind, Dr Neumann and his colleagues had conducted a systematic review of studies published between 1996 and 2012 that examined the cost utility of agents for hematologic malignancies. The cost utility of a drug was depicted as a ratio of a drug’s total cost per patient QALY gained.

The researchers identified 29 studies, 22 of which were industry-funded. Nine studies were conducted from a US perspective, 6 from the UK, 3 from Norway, 3 from Sweden, 2 from France, 1 from Canada, 1 from Finland, and 4 from “other” countries.

The team grouped studies according to malignancy—CML, chronic lymphocytic leukemia (CLL), NHL, and multiple myeloma (MM)—as well as by treatment—α interferon, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide.

The studies reported 44 cost-effectiveness ratios, most concerning interventions for NHL (41%) or CML (30%). Most ratios pertained to rituximab (43%), α interferon (18%), or imatinib (16%), and the most common intervention-disease combination was rituximab (alone or in combination) for NHL (36%).

The median cost-effectiveness ratios fluctuated over time, rising from $35,000/QALY (1996-2002) to $52,000/QALY (2003-2006), then falling to $22,000/QALY (2007-2012).

The median cost-effectiveness ratio reported by industry-funded studies was lower ($26,000/QALY) than for non-industry-funded studies ($33,000/QALY).

Four cost-effectiveness ratios, 1 from an industry-funded study, exceeded $100,000/QALY. This included 2 studies of bortezomib in MM, 1 of α interferon in CML, and 1 of imatinib in CML.

The researchers said these results suggest that many new treatments for hematologic malignancies may confer reasonable value for money spent. The distribution of cost-effectiveness ratios is comparable to those for cancers overall and for other healthcare fields, they said.

This study was funded by internal resources at the Center for the Evaluation of Value and Risk in Health. The center receives funding from federal, private foundation, and pharmaceutical industry sources.

Drugs in vials

Photo by Bill Branson

A new analysis indicates that certain high-cost therapies for hematologic malignancies provide reasonable value for money spent.

Most cost-effectiveness ratios were lower than thresholds commonly used to establish cost-effectiveness in the US—$50,000 or $100,000 per quality-adjusted life year (QALY) gained.

The median cost-effectiveness ratio was highest for chronic myeloid leukemia (CML), at $55,000/QALY, and lowest for non-Hodgkin lymphoma (NHL), at $21,500/QALY.

Researchers presented these data in Blood.

“Given the increased discussion about the high cost of these treatments, we were somewhat surprised to discover that their cost-effectiveness ratios were lower than expected,” said study author Peter J. Neumann, ScD, of Tufts Medical Center in Boston.

“Our analysis had a small sample size and included both industry- and non-industry-funded studies. In addition, cost-effectiveness ratios may have changed over time as associated costs or benefits have changed. However, the study underscores that debates in healthcare should consider the value of breakthrough drugs and not just costs.”

With that issue in mind, Dr Neumann and his colleagues had conducted a systematic review of studies published between 1996 and 2012 that examined the cost utility of agents for hematologic malignancies. The cost utility of a drug was depicted as a ratio of a drug’s total cost per patient QALY gained.

The researchers identified 29 studies, 22 of which were industry-funded. Nine studies were conducted from a US perspective, 6 from the UK, 3 from Norway, 3 from Sweden, 2 from France, 1 from Canada, 1 from Finland, and 4 from “other” countries.

The team grouped studies according to malignancy—CML, chronic lymphocytic leukemia (CLL), NHL, and multiple myeloma (MM)—as well as by treatment—α interferon, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide.

The studies reported 44 cost-effectiveness ratios, most concerning interventions for NHL (41%) or CML (30%). Most ratios pertained to rituximab (43%), α interferon (18%), or imatinib (16%), and the most common intervention-disease combination was rituximab (alone or in combination) for NHL (36%).

The median cost-effectiveness ratios fluctuated over time, rising from $35,000/QALY (1996-2002) to $52,000/QALY (2003-2006), then falling to $22,000/QALY (2007-2012).

The median cost-effectiveness ratio reported by industry-funded studies was lower ($26,000/QALY) than for non-industry-funded studies ($33,000/QALY).

Four cost-effectiveness ratios, 1 from an industry-funded study, exceeded $100,000/QALY. This included 2 studies of bortezomib in MM, 1 of α interferon in CML, and 1 of imatinib in CML.

The researchers said these results suggest that many new treatments for hematologic malignancies may confer reasonable value for money spent. The distribution of cost-effectiveness ratios is comparable to those for cancers overall and for other healthcare fields, they said.

This study was funded by internal resources at the Center for the Evaluation of Value and Risk in Health. The center receives funding from federal, private foundation, and pharmaceutical industry sources.

Velcade (bortezomib)

Photo courtesy of Millennium

The European Commission (EC) has approved bortezomib (Velcade) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) to treat adults with previously untreated mantle cell lymphoma (MCL) in whom hematopoietic stem cell transplant (HSCT) is considered unsuitable.

Now, bortezomib can be marketed for this indication in all 28 countries of the European Union (EU).

Bortezomib is already approved in the EU to treat multiple myeloma (MM), either as monotherapy or in combination with other agents.

The EC’s approval of bortezomib in MCL is based on data from a phase 3 study known as LYM-3002.

This randomized trial included 487 patients with newly diagnosed MCL who were ineligible, or not considered, for HSCT. Patients were randomized to receive VR-CAP or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

The VR-CAP regimen significantly improved progression-free survival (PFS), the primary endpoint, when compared to R-CHOP.

According to an independent review committee, there was a 59% improvement in PFS for the VR-CAP arm compared to the R-CHOP arm, with median times of 24.7 months and 14.4 months, respectively (hazard ratio=0.63; P<0.001).

Study investigators reported a 96% increase in PFS with VR-CAP compared to R-CHOP, with median times of 30.7 months and 16.1 months, respectively (hazard ratio=0.51, P<0.001).

VR-CAP was associated with additional, but manageable, toxicity when compared to R-CHOP. Serious adverse events (AEs) were reported in 38% and 30% of patients, respectively. And grade 3 or higher AEs were reported in 93% and 85% of patients, respectively.

Treatment discontinuation due to AEs occurred in 9% of patients in the VR-CAP arm and 7% in the R-CHOP arm. On-treatment, drug-related deaths occurred in 2% and 3% of patients, respectively.

About bortezomib

Bortezomib works by reversibly interrupting the normal working of cell proteasomes, inducing cancerous cells to stop growing and die.

In addition to the new MCL indication, the drug is approved in the EU to treat various stages of MM. It’s approved in combination with melphalan and prednisone to treat previously untreated adults with MM who are unsuitable for high-dose chemotherapy with HSCT.

Bortezomib is also approved in combination with dexamethasone, or with dexamethasone plus thalidomide, to treat previously untreated MM patients set to receive high-dose chemotherapy followed by HSCT.

And the drug is approved as monotherapy or in combination with pegylated liposomal doxorubicin or dexamethasone to treat adults with MM whose disease has progressed after at least one other treatment and who have already had, or cannot undergo, HSCT.

Bortezomib is approved in more than 90 countries and has been used to treat more than 550,000 patients worldwide.

The product is co-developed by Millennium, the Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and Janssen Pharmaceutical Companies.

Millennium is responsible for commercialization in the US. Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote the drug in Japan.

Velcade (bortezomib)

Photo courtesy of Millennium

The European Commission (EC) has approved bortezomib (Velcade) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) to treat adults with previously untreated mantle cell lymphoma (MCL) in whom hematopoietic stem cell transplant (HSCT) is considered unsuitable.

Now, bortezomib can be marketed for this indication in all 28 countries of the European Union (EU).

Bortezomib is already approved in the EU to treat multiple myeloma (MM), either as monotherapy or in combination with other agents.

The EC’s approval of bortezomib in MCL is based on data from a phase 3 study known as LYM-3002.

This randomized trial included 487 patients with newly diagnosed MCL who were ineligible, or not considered, for HSCT. Patients were randomized to receive VR-CAP or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

The VR-CAP regimen significantly improved progression-free survival (PFS), the primary endpoint, when compared to R-CHOP.

According to an independent review committee, there was a 59% improvement in PFS for the VR-CAP arm compared to the R-CHOP arm, with median times of 24.7 months and 14.4 months, respectively (hazard ratio=0.63; P<0.001).

Study investigators reported a 96% increase in PFS with VR-CAP compared to R-CHOP, with median times of 30.7 months and 16.1 months, respectively (hazard ratio=0.51, P<0.001).

VR-CAP was associated with additional, but manageable, toxicity when compared to R-CHOP. Serious adverse events (AEs) were reported in 38% and 30% of patients, respectively. And grade 3 or higher AEs were reported in 93% and 85% of patients, respectively.

Treatment discontinuation due to AEs occurred in 9% of patients in the VR-CAP arm and 7% in the R-CHOP arm. On-treatment, drug-related deaths occurred in 2% and 3% of patients, respectively.

About bortezomib

Bortezomib works by reversibly interrupting the normal working of cell proteasomes, inducing cancerous cells to stop growing and die.

In addition to the new MCL indication, the drug is approved in the EU to treat various stages of MM. It’s approved in combination with melphalan and prednisone to treat previously untreated adults with MM who are unsuitable for high-dose chemotherapy with HSCT.

Bortezomib is also approved in combination with dexamethasone, or with dexamethasone plus thalidomide, to treat previously untreated MM patients set to receive high-dose chemotherapy followed by HSCT.

And the drug is approved as monotherapy or in combination with pegylated liposomal doxorubicin or dexamethasone to treat adults with MM whose disease has progressed after at least one other treatment and who have already had, or cannot undergo, HSCT.

Bortezomib is approved in more than 90 countries and has been used to treat more than 550,000 patients worldwide.

The product is co-developed by Millennium, the Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and Janssen Pharmaceutical Companies.

Millennium is responsible for commercialization in the US. Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote the drug in Japan.

Velcade (bortezomib)

Photo courtesy of Millennium

The European Commission (EC) has approved bortezomib (Velcade) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) to treat adults with previously untreated mantle cell lymphoma (MCL) in whom hematopoietic stem cell transplant (HSCT) is considered unsuitable.

Now, bortezomib can be marketed for this indication in all 28 countries of the European Union (EU).

Bortezomib is already approved in the EU to treat multiple myeloma (MM), either as monotherapy or in combination with other agents.

The EC’s approval of bortezomib in MCL is based on data from a phase 3 study known as LYM-3002.

This randomized trial included 487 patients with newly diagnosed MCL who were ineligible, or not considered, for HSCT. Patients were randomized to receive VR-CAP or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

The VR-CAP regimen significantly improved progression-free survival (PFS), the primary endpoint, when compared to R-CHOP.

According to an independent review committee, there was a 59% improvement in PFS for the VR-CAP arm compared to the R-CHOP arm, with median times of 24.7 months and 14.4 months, respectively (hazard ratio=0.63; P<0.001).

Study investigators reported a 96% increase in PFS with VR-CAP compared to R-CHOP, with median times of 30.7 months and 16.1 months, respectively (hazard ratio=0.51, P<0.001).

VR-CAP was associated with additional, but manageable, toxicity when compared to R-CHOP. Serious adverse events (AEs) were reported in 38% and 30% of patients, respectively. And grade 3 or higher AEs were reported in 93% and 85% of patients, respectively.

Treatment discontinuation due to AEs occurred in 9% of patients in the VR-CAP arm and 7% in the R-CHOP arm. On-treatment, drug-related deaths occurred in 2% and 3% of patients, respectively.

About bortezomib

Bortezomib works by reversibly interrupting the normal working of cell proteasomes, inducing cancerous cells to stop growing and die.

In addition to the new MCL indication, the drug is approved in the EU to treat various stages of MM. It’s approved in combination with melphalan and prednisone to treat previously untreated adults with MM who are unsuitable for high-dose chemotherapy with HSCT.

Bortezomib is also approved in combination with dexamethasone, or with dexamethasone plus thalidomide, to treat previously untreated MM patients set to receive high-dose chemotherapy followed by HSCT.

And the drug is approved as monotherapy or in combination with pegylated liposomal doxorubicin or dexamethasone to treat adults with MM whose disease has progressed after at least one other treatment and who have already had, or cannot undergo, HSCT.

Bortezomib is approved in more than 90 countries and has been used to treat more than 550,000 patients worldwide.

The product is co-developed by Millennium, the Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and Janssen Pharmaceutical Companies.

Millennium is responsible for commercialization in the US. Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote the drug in Japan.