Pharmacy

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Commission (EC) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least one prior therapy.

Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein expressed on myeloma cells, natural killer (NK) cells, plasma cells, and specific immune cell subsets of differentiated cells in the hematopoietic lineage.

Elotuzumab has a dual mechanism of action. It directly activates the immune system through NK cells via the SLAMF7 pathway, and it targets SLAMF7 on myeloma cells, tagging them for NK-cell-mediated destruction via antibody-dependent cellular toxicity.

Elotuzumab is the first immunostimulatory antibody approved to treat MM in the European Union.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Phase 3 trial

The EC approved elotuzumab based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies.

The patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

Baseline patient demographics and disease characteristics were well balanced between treatment arms.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Commission (EC) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least one prior therapy.

Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein expressed on myeloma cells, natural killer (NK) cells, plasma cells, and specific immune cell subsets of differentiated cells in the hematopoietic lineage.

Elotuzumab has a dual mechanism of action. It directly activates the immune system through NK cells via the SLAMF7 pathway, and it targets SLAMF7 on myeloma cells, tagging them for NK-cell-mediated destruction via antibody-dependent cellular toxicity.

Elotuzumab is the first immunostimulatory antibody approved to treat MM in the European Union.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Phase 3 trial

The EC approved elotuzumab based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies.

The patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

Baseline patient demographics and disease characteristics were well balanced between treatment arms.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Commission (EC) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least one prior therapy.

Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein expressed on myeloma cells, natural killer (NK) cells, plasma cells, and specific immune cell subsets of differentiated cells in the hematopoietic lineage.

Elotuzumab has a dual mechanism of action. It directly activates the immune system through NK cells via the SLAMF7 pathway, and it targets SLAMF7 on myeloma cells, tagging them for NK-cell-mediated destruction via antibody-dependent cellular toxicity.

Elotuzumab is the first immunostimulatory antibody approved to treat MM in the European Union.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Phase 3 trial

The EC approved elotuzumab based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies.

The patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

Baseline patient demographics and disease characteristics were well balanced between treatment arms.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.

Antihemophilic factor

The European Commission (EC) has approved albutrepenonacog alfa (Idelvion) to treat and prevent bleeding in children and adults with hemophilia B.

Albutrepenonacog alfa is a long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin.

The product is now approved for use as routine prophylaxis, for on-demand control of bleeding, and for the perioperative management of bleeding.

Appropriate patients age 12 and older can go up to 14 days between albutrepenonacog alfa infusions. This dosing interval has been achieved while maintaining high levels of factor IX activity—above 5% over 14 days at 75 IU/kg.

“Offering 14-day dosing, Idelvion helps patients maintain higher factor IX levels over a long period of time, providing them with greater freedom from frequent infusions,” said Elena Santagostino, MD, PhD, of the University of Milan/IRCCS Maggiore Hospital in Italy.

“This is an important attribute for my patients who require a prophylactic regimen but don’t want treatment to disrupt their active lives.”

Albutrepenonacog alfa is being developed by CSL Behring. The company said the product will be launched in European markets in the coming months, as market access and pricing are obtained.

Phase 3 trial

The EC approved albutrepenonacog alfa based on results of the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.

Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).

The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks,

followed by a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.

Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).

The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.

For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).

Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.

None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).

There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).

Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.

Antihemophilic factor

The European Commission (EC) has approved albutrepenonacog alfa (Idelvion) to treat and prevent bleeding in children and adults with hemophilia B.

Albutrepenonacog alfa is a long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin.

The product is now approved for use as routine prophylaxis, for on-demand control of bleeding, and for the perioperative management of bleeding.

Appropriate patients age 12 and older can go up to 14 days between albutrepenonacog alfa infusions. This dosing interval has been achieved while maintaining high levels of factor IX activity—above 5% over 14 days at 75 IU/kg.

“Offering 14-day dosing, Idelvion helps patients maintain higher factor IX levels over a long period of time, providing them with greater freedom from frequent infusions,” said Elena Santagostino, MD, PhD, of the University of Milan/IRCCS Maggiore Hospital in Italy.

“This is an important attribute for my patients who require a prophylactic regimen but don’t want treatment to disrupt their active lives.”

Albutrepenonacog alfa is being developed by CSL Behring. The company said the product will be launched in European markets in the coming months, as market access and pricing are obtained.

Phase 3 trial

The EC approved albutrepenonacog alfa based on results of the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.

Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).

The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks,

followed by a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.

Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).

The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.

For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).

Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.

None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).

There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).

Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.

Antihemophilic factor

The European Commission (EC) has approved albutrepenonacog alfa (Idelvion) to treat and prevent bleeding in children and adults with hemophilia B.

Albutrepenonacog alfa is a long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin.

The product is now approved for use as routine prophylaxis, for on-demand control of bleeding, and for the perioperative management of bleeding.

Appropriate patients age 12 and older can go up to 14 days between albutrepenonacog alfa infusions. This dosing interval has been achieved while maintaining high levels of factor IX activity—above 5% over 14 days at 75 IU/kg.

“Offering 14-day dosing, Idelvion helps patients maintain higher factor IX levels over a long period of time, providing them with greater freedom from frequent infusions,” said Elena Santagostino, MD, PhD, of the University of Milan/IRCCS Maggiore Hospital in Italy.

“This is an important attribute for my patients who require a prophylactic regimen but don’t want treatment to disrupt their active lives.”

Albutrepenonacog alfa is being developed by CSL Behring. The company said the product will be launched in European markets in the coming months, as market access and pricing are obtained.

Phase 3 trial

The EC approved albutrepenonacog alfa based on results of the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.

Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).

The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks,

followed by a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.

Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).

The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.

For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).

Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.

None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).

There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).

Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.

Doctor and patient

Photo courtesy of NIH

Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.

The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.

To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”

The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.

“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”

For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.

Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.

When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.

The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).

The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).

The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.

The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.

“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.

“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”

Doctor and patient

Photo courtesy of NIH

Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.

The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.

To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”

The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.

“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”

For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.

Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.

When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.

The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).

The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).

The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.

The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.

“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.

“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”

Doctor and patient

Photo courtesy of NIH

Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.

The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.

To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”

The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.

“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”

For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.

Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.

When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.

The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).

The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).

The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.

The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.

“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.

“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”

Vials of drug

Photo by Bill Branson

Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.

The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.

However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.

BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.

Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.

Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.

Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.

Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.

Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.

Vials of drug

Photo by Bill Branson

Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.

The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.

However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.

BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.

Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.

Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.

Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.

Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.

Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.

Vials of drug

Photo by Bill Branson

Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.

The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.

However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.

BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.

Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.

Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.

Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.

Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.

Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application for blinatumomab (Blincyto) as a treatment for pediatric and adolescent patients with Philadelphia chromosome negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.

The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.

The Prescription Drug User Fee Act target action date for the supplemental biologics license application for blinatumomab is September 1, 2016.

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

Blinatumomab was previously granted breakthrough therapy and priority review designations by the FDA and is now approved in the US for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.

This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is marketed by Amgen as Blincyto. The full US prescribing information is available at www.BLINCYTO.com.

‘205 trial

The supplemental biologics license application for blinatumomab in pediatric and adolescent patients is based on data from the phase 1/2 '205 trial.

In this study, researchers evaluated blinatumomab in patients younger than 18 years of age. The patients had B-cell precursor ALL that was refractory, had relapsed at least twice, or relapsed after an allogeneic hematopoietic stem cell transplant.

Treatment in this study has been completed, and subjects are being monitored for long-term efficacy. The data is being submitted for publication.

Preliminary data were presented at the 2014 ASH Annual Meeting (abstract 3703).

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application for blinatumomab (Blincyto) as a treatment for pediatric and adolescent patients with Philadelphia chromosome negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.

The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.

The Prescription Drug User Fee Act target action date for the supplemental biologics license application for blinatumomab is September 1, 2016.

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

Blinatumomab was previously granted breakthrough therapy and priority review designations by the FDA and is now approved in the US for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.

This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is marketed by Amgen as Blincyto. The full US prescribing information is available at www.BLINCYTO.com.

‘205 trial

The supplemental biologics license application for blinatumomab in pediatric and adolescent patients is based on data from the phase 1/2 '205 trial.

In this study, researchers evaluated blinatumomab in patients younger than 18 years of age. The patients had B-cell precursor ALL that was refractory, had relapsed at least twice, or relapsed after an allogeneic hematopoietic stem cell transplant.

Treatment in this study has been completed, and subjects are being monitored for long-term efficacy. The data is being submitted for publication.

Preliminary data were presented at the 2014 ASH Annual Meeting (abstract 3703).

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application for blinatumomab (Blincyto) as a treatment for pediatric and adolescent patients with Philadelphia chromosome negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.

The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.

The Prescription Drug User Fee Act target action date for the supplemental biologics license application for blinatumomab is September 1, 2016.

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

Blinatumomab was previously granted breakthrough therapy and priority review designations by the FDA and is now approved in the US for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.

This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is marketed by Amgen as Blincyto. The full US prescribing information is available at www.BLINCYTO.com.

‘205 trial

The supplemental biologics license application for blinatumomab in pediatric and adolescent patients is based on data from the phase 1/2 '205 trial.

In this study, researchers evaluated blinatumomab in patients younger than 18 years of age. The patients had B-cell precursor ALL that was refractory, had relapsed at least twice, or relapsed after an allogeneic hematopoietic stem cell transplant.

Treatment in this study has been completed, and subjects are being monitored for long-term efficacy. The data is being submitted for publication.

Preliminary data were presented at the 2014 ASH Annual Meeting (abstract 3703).

Micrograph showing MCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for several hematologic malignancies.

This includes primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).

KTE-C19 previously received orphan designation from the FDA for the treatment of diffuse large B-cell lymphoma (DLBCL).

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity.

KTE-C19 also has breakthrough therapy designation from the FDA as a treatment for DLBCL, PMBCL, and transformed FL.

About KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target CD19. The product is being developed by Kite Pharma, Inc.

In a study published in the Journal of Clinical Oncology, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Thirteen patients were evaluable for response. The overall response rate was 92%. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).

Of the 7 patients with DLBCL, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Three of the CRs were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

Of the 4 patients with CLL, 3 had a CR, and 1 had a PR. All 3 CRs were ongoing at the time of publication, with the duration ranging from 14 months to 23 months.

Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR. The duration of the CR was 11 months at the time of publication.

KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

KTE-C19 is currently under investigation in a phase 2 trial of refractory DLBCL, PMBCL, and transformed FL (ZUMA-1), a phase 2 trial of relapsed/refractory MCL (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult ALL (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric ALL (ZUMA-4).

Results from ZUMA-1 were recently presented at the 2016 AACR Annual Meeting (abstract CT135).

Micrograph showing MCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for several hematologic malignancies.

This includes primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).

KTE-C19 previously received orphan designation from the FDA for the treatment of diffuse large B-cell lymphoma (DLBCL).

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity.

KTE-C19 also has breakthrough therapy designation from the FDA as a treatment for DLBCL, PMBCL, and transformed FL.

About KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target CD19. The product is being developed by Kite Pharma, Inc.

In a study published in the Journal of Clinical Oncology, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Thirteen patients were evaluable for response. The overall response rate was 92%. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).

Of the 7 patients with DLBCL, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Three of the CRs were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

Of the 4 patients with CLL, 3 had a CR, and 1 had a PR. All 3 CRs were ongoing at the time of publication, with the duration ranging from 14 months to 23 months.

Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR. The duration of the CR was 11 months at the time of publication.

KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

KTE-C19 is currently under investigation in a phase 2 trial of refractory DLBCL, PMBCL, and transformed FL (ZUMA-1), a phase 2 trial of relapsed/refractory MCL (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult ALL (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric ALL (ZUMA-4).

Results from ZUMA-1 were recently presented at the 2016 AACR Annual Meeting (abstract CT135).

Micrograph showing MCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for several hematologic malignancies.

This includes primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).

KTE-C19 previously received orphan designation from the FDA for the treatment of diffuse large B-cell lymphoma (DLBCL).

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity.

KTE-C19 also has breakthrough therapy designation from the FDA as a treatment for DLBCL, PMBCL, and transformed FL.

About KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target CD19. The product is being developed by Kite Pharma, Inc.

In a study published in the Journal of Clinical Oncology, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Thirteen patients were evaluable for response. The overall response rate was 92%. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).

Of the 7 patients with DLBCL, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Three of the CRs were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

Of the 4 patients with CLL, 3 had a CR, and 1 had a PR. All 3 CRs were ongoing at the time of publication, with the duration ranging from 14 months to 23 months.

Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR. The duration of the CR was 11 months at the time of publication.

KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

KTE-C19 is currently under investigation in a phase 2 trial of refractory DLBCL, PMBCL, and transformed FL (ZUMA-1), a phase 2 trial of relapsed/refractory MCL (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult ALL (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric ALL (ZUMA-4).

Results from ZUMA-1 were recently presented at the 2016 AACR Annual Meeting (abstract CT135).

 

 

Micrograph showing FL

 

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody, be approved for use in patients with follicular lymphoma (FL).

The recommended indication is for obinutuzumab to be given first in combination with bendamustine and then as maintenance therapy in FL patients who did not respond to, progressed during, or progressed up to 6 months after treatment with rituximab or a rituximab-containing regimen.

Based on the CHMP’s recommendation, a final decision regarding the approval of obinutuzumab in FL is expected from the European Commission in the coming months.

Obinutuzumab is already approved in the European Union for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.

Obinutuzumab is being developed by Roche.

GADOLIN trial

The CHMP’s recommendation to approve obinutuzumab in FL is based on results from the phase 3 GADOLIN trial. The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.

The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.

Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).

The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.

The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.

The median overall survival has not yet been reached in either study arm.

The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).

The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).

 

 

Micrograph showing FL

 

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody, be approved for use in patients with follicular lymphoma (FL).

The recommended indication is for obinutuzumab to be given first in combination with bendamustine and then as maintenance therapy in FL patients who did not respond to, progressed during, or progressed up to 6 months after treatment with rituximab or a rituximab-containing regimen.

Based on the CHMP’s recommendation, a final decision regarding the approval of obinutuzumab in FL is expected from the European Commission in the coming months.

Obinutuzumab is already approved in the European Union for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.

Obinutuzumab is being developed by Roche.

GADOLIN trial

The CHMP’s recommendation to approve obinutuzumab in FL is based on results from the phase 3 GADOLIN trial. The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.

The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.

Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).

The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.

The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.

The median overall survival has not yet been reached in either study arm.

The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).

The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).

 

 

Micrograph showing FL

 

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody, be approved for use in patients with follicular lymphoma (FL).

The recommended indication is for obinutuzumab to be given first in combination with bendamustine and then as maintenance therapy in FL patients who did not respond to, progressed during, or progressed up to 6 months after treatment with rituximab or a rituximab-containing regimen.

Based on the CHMP’s recommendation, a final decision regarding the approval of obinutuzumab in FL is expected from the European Commission in the coming months.

Obinutuzumab is already approved in the European Union for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.

Obinutuzumab is being developed by Roche.

GADOLIN trial

The CHMP’s recommendation to approve obinutuzumab in FL is based on results from the phase 3 GADOLIN trial. The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.

The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.

Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).

The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.

The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.

The median overall survival has not yet been reached in either study arm.

The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).

The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).

Prescription medications

Photo courtesy of the CDC

New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.

The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.

In addition, most existing therapies had substantial price increases from the time they were launched to 2014.

“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.

The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.

When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.

The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).

However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).

Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.

“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.

She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.

Prescription medications

Photo courtesy of the CDC

New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.

The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.

In addition, most existing therapies had substantial price increases from the time they were launched to 2014.

“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.

The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.

When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.

The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).

However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).

Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.

“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.

She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.

Prescription medications

Photo courtesy of the CDC

New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.

The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.

In addition, most existing therapies had substantial price increases from the time they were launched to 2014.

“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.

The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.

When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.

The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).

However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).

Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.

“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.

She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has approved the use of a powder formulation of ferric pyrophosphate citrate (Triferic powder packet) to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease.

The FDA previously approved ferric pyrophosphate citrate solution (Triferic) in ampule form. It is an iron-replacement drug intended to treat anemia in chronic kidney disease patients receiving hemodialysis.

Triferic is delivered to hemodialysis patients via dialysate, replacing the ongoing iron loss that occurs during their dialysis treatment. The drug is added to the bicarbonate concentrate on-site at the dialysis clinic.

Once in dialysate, Triferic crosses the dialyzer membrane and enters the blood, where it immediately binds to transferrin and is transported to the erythroid precursor cells to be incorporated into hemoglobin.

Triferic is designed to deliver sufficient iron to the bone marrow and maintain hemoglobin without increasing iron stores.

“We are pleased to obtain this FDA approval for the Triferic powder packet,” said Robert L. Chioini, founder, chairman, and chief executive officer of Rockwell Medical, Inc., makers of Triferic.

“The Triferic powder packet is similar to the size of a packet of sugar. It is much smaller and lighter than the current Triferic liquid ampule, and it enables us to place 3-times greater the number of units in an even smaller carton.”

“This presentation is much more convenient for customers, as it reduces storage space and requires fewer reorders to maintain inventory. We expect it to be commercially available shortly.”

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has approved the use of a powder formulation of ferric pyrophosphate citrate (Triferic powder packet) to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease.

The FDA previously approved ferric pyrophosphate citrate solution (Triferic) in ampule form. It is an iron-replacement drug intended to treat anemia in chronic kidney disease patients receiving hemodialysis.

Triferic is delivered to hemodialysis patients via dialysate, replacing the ongoing iron loss that occurs during their dialysis treatment. The drug is added to the bicarbonate concentrate on-site at the dialysis clinic.

Once in dialysate, Triferic crosses the dialyzer membrane and enters the blood, where it immediately binds to transferrin and is transported to the erythroid precursor cells to be incorporated into hemoglobin.

Triferic is designed to deliver sufficient iron to the bone marrow and maintain hemoglobin without increasing iron stores.

“We are pleased to obtain this FDA approval for the Triferic powder packet,” said Robert L. Chioini, founder, chairman, and chief executive officer of Rockwell Medical, Inc., makers of Triferic.

“The Triferic powder packet is similar to the size of a packet of sugar. It is much smaller and lighter than the current Triferic liquid ampule, and it enables us to place 3-times greater the number of units in an even smaller carton.”

“This presentation is much more convenient for customers, as it reduces storage space and requires fewer reorders to maintain inventory. We expect it to be commercially available shortly.”

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has approved the use of a powder formulation of ferric pyrophosphate citrate (Triferic powder packet) to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease.

The FDA previously approved ferric pyrophosphate citrate solution (Triferic) in ampule form. It is an iron-replacement drug intended to treat anemia in chronic kidney disease patients receiving hemodialysis.

Triferic is delivered to hemodialysis patients via dialysate, replacing the ongoing iron loss that occurs during their dialysis treatment. The drug is added to the bicarbonate concentrate on-site at the dialysis clinic.

Once in dialysate, Triferic crosses the dialyzer membrane and enters the blood, where it immediately binds to transferrin and is transported to the erythroid precursor cells to be incorporated into hemoglobin.

Triferic is designed to deliver sufficient iron to the bone marrow and maintain hemoglobin without increasing iron stores.

“We are pleased to obtain this FDA approval for the Triferic powder packet,” said Robert L. Chioini, founder, chairman, and chief executive officer of Rockwell Medical, Inc., makers of Triferic.

“The Triferic powder packet is similar to the size of a packet of sugar. It is much smaller and lighter than the current Triferic liquid ampule, and it enables us to place 3-times greater the number of units in an even smaller carton.”

“This presentation is much more convenient for customers, as it reduces storage space and requires fewer reorders to maintain inventory. We expect it to be commercially available shortly.”

Red blood cells

Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).

This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.

The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.

Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.

The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.

“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.

“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”

To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.

Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.

When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.

In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.

“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”

“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.

“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”

The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.”

Red blood cells

Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).

This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.

The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.

Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.

The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.

“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.

“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”

To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.

Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.

When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.

In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.

“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”

“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.

“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”

The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.”

Red blood cells

Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).

This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.

The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.

Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.

The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.

“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.

“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”

To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.

Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.

When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.

In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.

“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”

“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.

“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”

The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.”