Pharmacy

Micrograph showing primary MF

The US Food and Drug Administration (FDA) has placed a partial clinical hold on trials conducted under the investigational new drug

(IND) application for pacritinib.

Pacritinib is a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The partial clinical hold impacts part of the clinical work currently being conducted under the pacritinib IND and will also affect planned clinical trials.

The FDA said the reasons for the partial clinical hold are excess mortality and other adverse events in pacritinib-treated patients (compared to the control arm) in the PERSIST-1 trial.

The excess mortality was most evident during the non-randomized crossover period following the initial 24 weeks of randomized treatment, during which patients in the control arm could switch to pacritinib treatment.

Under the partial clinical hold, investigators may not enroll new patients or start pacritinib as initial or crossover treatment, and patients not deriving benefit after 30 weeks of pacritinib treatment must stop using pacritinib.

In addition, the FDA has recommended that CTI BioPharma make certain modifications to protocols, provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, and take certain other actions.

CTI BioPharma said it intends to implement the FDA’s recommendations, and all clinical investigators worldwide have been notified of the partial clinical hold.

Just before the FDA notified CTI BioPharma of the partial clinical hold, the company completed enrollment in the phase 3 PERSIST-2 trial.

In PERSIST-2, researchers are comparing the efficacy and safety of pacritinib and best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

Under the partial clinical hold, patients on this trial who are currently receiving pacritinib may continue to do so unless they are not deriving benefit after 30 weeks of pacritinib treatment, and crossover of patients from the control arm to the pacritinib arm will not be allowed.

Micrograph showing primary MF

The US Food and Drug Administration (FDA) has placed a partial clinical hold on trials conducted under the investigational new drug

(IND) application for pacritinib.

Pacritinib is a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The partial clinical hold impacts part of the clinical work currently being conducted under the pacritinib IND and will also affect planned clinical trials.

The FDA said the reasons for the partial clinical hold are excess mortality and other adverse events in pacritinib-treated patients (compared to the control arm) in the PERSIST-1 trial.

The excess mortality was most evident during the non-randomized crossover period following the initial 24 weeks of randomized treatment, during which patients in the control arm could switch to pacritinib treatment.

Under the partial clinical hold, investigators may not enroll new patients or start pacritinib as initial or crossover treatment, and patients not deriving benefit after 30 weeks of pacritinib treatment must stop using pacritinib.

In addition, the FDA has recommended that CTI BioPharma make certain modifications to protocols, provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, and take certain other actions.

CTI BioPharma said it intends to implement the FDA’s recommendations, and all clinical investigators worldwide have been notified of the partial clinical hold.

Just before the FDA notified CTI BioPharma of the partial clinical hold, the company completed enrollment in the phase 3 PERSIST-2 trial.

In PERSIST-2, researchers are comparing the efficacy and safety of pacritinib and best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

Under the partial clinical hold, patients on this trial who are currently receiving pacritinib may continue to do so unless they are not deriving benefit after 30 weeks of pacritinib treatment, and crossover of patients from the control arm to the pacritinib arm will not be allowed.

Micrograph showing primary MF

The US Food and Drug Administration (FDA) has placed a partial clinical hold on trials conducted under the investigational new drug

(IND) application for pacritinib.

Pacritinib is a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The partial clinical hold impacts part of the clinical work currently being conducted under the pacritinib IND and will also affect planned clinical trials.

The FDA said the reasons for the partial clinical hold are excess mortality and other adverse events in pacritinib-treated patients (compared to the control arm) in the PERSIST-1 trial.

The excess mortality was most evident during the non-randomized crossover period following the initial 24 weeks of randomized treatment, during which patients in the control arm could switch to pacritinib treatment.

Under the partial clinical hold, investigators may not enroll new patients or start pacritinib as initial or crossover treatment, and patients not deriving benefit after 30 weeks of pacritinib treatment must stop using pacritinib.

In addition, the FDA has recommended that CTI BioPharma make certain modifications to protocols, provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, and take certain other actions.

CTI BioPharma said it intends to implement the FDA’s recommendations, and all clinical investigators worldwide have been notified of the partial clinical hold.

Just before the FDA notified CTI BioPharma of the partial clinical hold, the company completed enrollment in the phase 3 PERSIST-2 trial.

In PERSIST-2, researchers are comparing the efficacy and safety of pacritinib and best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

Under the partial clinical hold, patients on this trial who are currently receiving pacritinib may continue to do so unless they are not deriving benefit after 30 weeks of pacritinib treatment, and crossover of patients from the control arm to the pacritinib arm will not be allowed.

Drug vials and a syringe

The European Medicines Agency (EMA) has recommended marketing authorization for Coagadex to treat hereditary factor X deficiency, a rare bleeding disorder.

The active substance in Coagadex is coagulation factor X, a protein derived from human plasma.

Coagadex is intended to treat and prevent bleeding episodes and control bleeding during surgical procedures in patients with hereditary factor X deficiency.

If the European Commission follows the EMA’s recommendation, Coagadex will be the first specific replacement therapy approved in the European Union (EU) to treat patients with this disorder.

Current treatment for factor X deficiency in the EU includes replacement therapies that contain a mix of coagulation factors. These are associated with dosing problems and the risk of elevating other clotting factors, which may result in complications.

Due to the lack of specific treatment options for factor X deficiency, the EMA’s Committee for Medicinal Products for Human Use (CHMP) decided to speed up the evaluation of Coagadex and recommended marketing authorization following an accelerated assessment. This is one of the agency’s tools to speed up patient access to new medicines if they address an unmet medical need.

The CHMP based its recommendation for authorization of Coagadex on the results of 2 non-randomized studies.

The first trial included 16 patients who received Coagadex for pharmacokinetic evaluation, on-demand treatment and control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures.

Coagadex was used to treat 208 bleeding episodes, and 187 of these episodes (in 15 patients) were evaluated for efficacy. Ninety-eight episodes were major bleeds, 88 were minor bleeds, and 1 was not assessed.

One hundred and fifty-five bleeds (83%) were treated with a single infusion of Coagadex, 28 (15%) were treated with 2 infusions, 3 bleeds (2%) required 3 infusions, and 1 bleed (0.5%) required 4 infusions. Four bleeding episodes in 2 patients were considered treatment failures.

The mean dose of Coagadex per infusion was 25.4 IU/kg, and the mean total dose was 30.4 IU/kg. The recommended dose of 25 IU/kg to treat a bleed was maintained for 14 of the 16 patients. The other 2 patients used doses of up to 30 IU/kg and 33 IU/kg.

There were 176 adverse events in this trial, but only 6 events in 2 patients were considered possibly related to Coagadex. This included 2 reports of infusion site erythema in 1 patient, 2 reports of fatigue in 1 patient, 1 report of back pain, and 1 report of infusion site pain.

The second trial included patients who received Coagadex for perioperative management. Five patients received Coagadex for 7 surgical procedures.

For major surgeries, a median of 13 infusions (range, 2-15) and a median cumulative dose of 181 IU/kg (range, 45-210 IU/kg) were required to maintain hemostasis.

For minor surgeries, a median of 2.5 infusions (range, 1-4) and a median cumulative dose of 89 IU/kg (range, 51-127 IU/kg) were required to maintain hemostasis.

There were no adverse events related to Coagadex in this trial.

The company developing Coagadex, Bio Products Laboratory, received scientific advice on the design of the trials from the CHMP. Scientific advice is one of the agency’s main tools to facilitate and stimulate research and development within the EU.

Because factor X deficiency is rare, Coagadex was designated as an orphan medicine by the EMA’s Committee for Orphan Medicinal Products. Orphan designation gives pharmaceutical companies access to incentives that encourage the development of medicines for patients with rare diseases.

The CHMP’s recommendation to approve Coagadex for use in the EU is an intermediary step on Coagadex’s path to patient access. The CHMP’s opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Once a marketing authorization has been granted, decisions about price and reimbursement will take place at the level of each member state, taking into account the potential role/use of this medicine in the context of the national health system of that country.

Drug vials and a syringe

The European Medicines Agency (EMA) has recommended marketing authorization for Coagadex to treat hereditary factor X deficiency, a rare bleeding disorder.

The active substance in Coagadex is coagulation factor X, a protein derived from human plasma.

Coagadex is intended to treat and prevent bleeding episodes and control bleeding during surgical procedures in patients with hereditary factor X deficiency.

If the European Commission follows the EMA’s recommendation, Coagadex will be the first specific replacement therapy approved in the European Union (EU) to treat patients with this disorder.

Current treatment for factor X deficiency in the EU includes replacement therapies that contain a mix of coagulation factors. These are associated with dosing problems and the risk of elevating other clotting factors, which may result in complications.

Due to the lack of specific treatment options for factor X deficiency, the EMA’s Committee for Medicinal Products for Human Use (CHMP) decided to speed up the evaluation of Coagadex and recommended marketing authorization following an accelerated assessment. This is one of the agency’s tools to speed up patient access to new medicines if they address an unmet medical need.

The CHMP based its recommendation for authorization of Coagadex on the results of 2 non-randomized studies.

The first trial included 16 patients who received Coagadex for pharmacokinetic evaluation, on-demand treatment and control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures.

Coagadex was used to treat 208 bleeding episodes, and 187 of these episodes (in 15 patients) were evaluated for efficacy. Ninety-eight episodes were major bleeds, 88 were minor bleeds, and 1 was not assessed.

One hundred and fifty-five bleeds (83%) were treated with a single infusion of Coagadex, 28 (15%) were treated with 2 infusions, 3 bleeds (2%) required 3 infusions, and 1 bleed (0.5%) required 4 infusions. Four bleeding episodes in 2 patients were considered treatment failures.

The mean dose of Coagadex per infusion was 25.4 IU/kg, and the mean total dose was 30.4 IU/kg. The recommended dose of 25 IU/kg to treat a bleed was maintained for 14 of the 16 patients. The other 2 patients used doses of up to 30 IU/kg and 33 IU/kg.

There were 176 adverse events in this trial, but only 6 events in 2 patients were considered possibly related to Coagadex. This included 2 reports of infusion site erythema in 1 patient, 2 reports of fatigue in 1 patient, 1 report of back pain, and 1 report of infusion site pain.

The second trial included patients who received Coagadex for perioperative management. Five patients received Coagadex for 7 surgical procedures.

For major surgeries, a median of 13 infusions (range, 2-15) and a median cumulative dose of 181 IU/kg (range, 45-210 IU/kg) were required to maintain hemostasis.

For minor surgeries, a median of 2.5 infusions (range, 1-4) and a median cumulative dose of 89 IU/kg (range, 51-127 IU/kg) were required to maintain hemostasis.

There were no adverse events related to Coagadex in this trial.

The company developing Coagadex, Bio Products Laboratory, received scientific advice on the design of the trials from the CHMP. Scientific advice is one of the agency’s main tools to facilitate and stimulate research and development within the EU.

Because factor X deficiency is rare, Coagadex was designated as an orphan medicine by the EMA’s Committee for Orphan Medicinal Products. Orphan designation gives pharmaceutical companies access to incentives that encourage the development of medicines for patients with rare diseases.

The CHMP’s recommendation to approve Coagadex for use in the EU is an intermediary step on Coagadex’s path to patient access. The CHMP’s opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Once a marketing authorization has been granted, decisions about price and reimbursement will take place at the level of each member state, taking into account the potential role/use of this medicine in the context of the national health system of that country.

Drug vials and a syringe

The European Medicines Agency (EMA) has recommended marketing authorization for Coagadex to treat hereditary factor X deficiency, a rare bleeding disorder.

The active substance in Coagadex is coagulation factor X, a protein derived from human plasma.

Coagadex is intended to treat and prevent bleeding episodes and control bleeding during surgical procedures in patients with hereditary factor X deficiency.

If the European Commission follows the EMA’s recommendation, Coagadex will be the first specific replacement therapy approved in the European Union (EU) to treat patients with this disorder.

Current treatment for factor X deficiency in the EU includes replacement therapies that contain a mix of coagulation factors. These are associated with dosing problems and the risk of elevating other clotting factors, which may result in complications.

Due to the lack of specific treatment options for factor X deficiency, the EMA’s Committee for Medicinal Products for Human Use (CHMP) decided to speed up the evaluation of Coagadex and recommended marketing authorization following an accelerated assessment. This is one of the agency’s tools to speed up patient access to new medicines if they address an unmet medical need.

The CHMP based its recommendation for authorization of Coagadex on the results of 2 non-randomized studies.

The first trial included 16 patients who received Coagadex for pharmacokinetic evaluation, on-demand treatment and control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures.

Coagadex was used to treat 208 bleeding episodes, and 187 of these episodes (in 15 patients) were evaluated for efficacy. Ninety-eight episodes were major bleeds, 88 were minor bleeds, and 1 was not assessed.

One hundred and fifty-five bleeds (83%) were treated with a single infusion of Coagadex, 28 (15%) were treated with 2 infusions, 3 bleeds (2%) required 3 infusions, and 1 bleed (0.5%) required 4 infusions. Four bleeding episodes in 2 patients were considered treatment failures.

The mean dose of Coagadex per infusion was 25.4 IU/kg, and the mean total dose was 30.4 IU/kg. The recommended dose of 25 IU/kg to treat a bleed was maintained for 14 of the 16 patients. The other 2 patients used doses of up to 30 IU/kg and 33 IU/kg.

There were 176 adverse events in this trial, but only 6 events in 2 patients were considered possibly related to Coagadex. This included 2 reports of infusion site erythema in 1 patient, 2 reports of fatigue in 1 patient, 1 report of back pain, and 1 report of infusion site pain.

The second trial included patients who received Coagadex for perioperative management. Five patients received Coagadex for 7 surgical procedures.

For major surgeries, a median of 13 infusions (range, 2-15) and a median cumulative dose of 181 IU/kg (range, 45-210 IU/kg) were required to maintain hemostasis.

For minor surgeries, a median of 2.5 infusions (range, 1-4) and a median cumulative dose of 89 IU/kg (range, 51-127 IU/kg) were required to maintain hemostasis.

There were no adverse events related to Coagadex in this trial.

The company developing Coagadex, Bio Products Laboratory, received scientific advice on the design of the trials from the CHMP. Scientific advice is one of the agency’s main tools to facilitate and stimulate research and development within the EU.

Because factor X deficiency is rare, Coagadex was designated as an orphan medicine by the EMA’s Committee for Orphan Medicinal Products. Orphan designation gives pharmaceutical companies access to incentives that encourage the development of medicines for patients with rare diseases.

The CHMP’s recommendation to approve Coagadex for use in the EU is an intermediary step on Coagadex’s path to patient access. The CHMP’s opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Once a marketing authorization has been granted, decisions about price and reimbursement will take place at the level of each member state, taking into account the potential role/use of this medicine in the context of the national health system of that country.

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved a supplemental new drug application for single-dose fosaprepitant dimeglumine (Emend) for injection.

The agency approved the substance P/neurokinin-1 (NK1) receptor antagonist for use in combination with other anti-emetic medicines to prevent delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC).

This makes fosaprepitant dimeglumine the first intravenous NK1 receptor antagonist approved in the US for patients receiving either highly emetogenic chemotherapy or MEC.

Fosaprepitant dimeglumine has not been studied for the treatment of established nausea and vomiting.

The FDA’s latest approval of fosaprepitant dimeglumine is supported by data from a phase 3 study published in the Annals of Oncology.

Patients receiving MEC were given ondansetron and dexamethasone (n=498) or ondansetron and dexamethasone plus a single intravenous infusion of fosaprepitant dimeglumine (n=502).

The primary endpoint was complete response (CR)—defined as no vomiting and no use of rescue therapy—in the delayed phase of chemotherapy-induced nausea and vomiting, which is 25 to 120 hours after the initiation of chemotherapy.

Secondary endpoints included CR in the overall and acute phases—0 to 120 and 0 to 24 hours after MEC initiation, respectively—and no vomiting in the overall phase.

The fosaprepitant regimen improved CR significantly in the delayed and overall phases but not in the acute phase.

In the delayed phase, the CR rate was 78.9% with the fosaprepitant regimen and 68.5% with the control regimen (P<0.001). In the acute phase, the CR rate was 93.2% and 91.0%, respectively (P=0.184). Overall, the CR rate was 77.1% and 66.9%, respectively (P<0.001).

In the overall phase, the proportion of subjects with no vomiting was 82.7% with the fosaprepitant regimen and 72.9% with the control regimen (P<0.001). The proportion of patients with no significant nausea was 83.2% and 77.9%, respectively (P=0.030).

The most common adverse events reported in the fosaprepitant and control arms, respectively, were fatigue (15% vs 13%), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremity (2% vs 1%).

Fosaprepitant dimeglumine is a product of Merck. For more details on the drug, see the prescribing information.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved a supplemental new drug application for single-dose fosaprepitant dimeglumine (Emend) for injection.

The agency approved the substance P/neurokinin-1 (NK1) receptor antagonist for use in combination with other anti-emetic medicines to prevent delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC).

This makes fosaprepitant dimeglumine the first intravenous NK1 receptor antagonist approved in the US for patients receiving either highly emetogenic chemotherapy or MEC.

Fosaprepitant dimeglumine has not been studied for the treatment of established nausea and vomiting.

The FDA’s latest approval of fosaprepitant dimeglumine is supported by data from a phase 3 study published in the Annals of Oncology.

Patients receiving MEC were given ondansetron and dexamethasone (n=498) or ondansetron and dexamethasone plus a single intravenous infusion of fosaprepitant dimeglumine (n=502).

The primary endpoint was complete response (CR)—defined as no vomiting and no use of rescue therapy—in the delayed phase of chemotherapy-induced nausea and vomiting, which is 25 to 120 hours after the initiation of chemotherapy.

Secondary endpoints included CR in the overall and acute phases—0 to 120 and 0 to 24 hours after MEC initiation, respectively—and no vomiting in the overall phase.

The fosaprepitant regimen improved CR significantly in the delayed and overall phases but not in the acute phase.

In the delayed phase, the CR rate was 78.9% with the fosaprepitant regimen and 68.5% with the control regimen (P<0.001). In the acute phase, the CR rate was 93.2% and 91.0%, respectively (P=0.184). Overall, the CR rate was 77.1% and 66.9%, respectively (P<0.001).

In the overall phase, the proportion of subjects with no vomiting was 82.7% with the fosaprepitant regimen and 72.9% with the control regimen (P<0.001). The proportion of patients with no significant nausea was 83.2% and 77.9%, respectively (P=0.030).

The most common adverse events reported in the fosaprepitant and control arms, respectively, were fatigue (15% vs 13%), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremity (2% vs 1%).

Fosaprepitant dimeglumine is a product of Merck. For more details on the drug, see the prescribing information.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved a supplemental new drug application for single-dose fosaprepitant dimeglumine (Emend) for injection.

The agency approved the substance P/neurokinin-1 (NK1) receptor antagonist for use in combination with other anti-emetic medicines to prevent delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC).

This makes fosaprepitant dimeglumine the first intravenous NK1 receptor antagonist approved in the US for patients receiving either highly emetogenic chemotherapy or MEC.

Fosaprepitant dimeglumine has not been studied for the treatment of established nausea and vomiting.

The FDA’s latest approval of fosaprepitant dimeglumine is supported by data from a phase 3 study published in the Annals of Oncology.

Patients receiving MEC were given ondansetron and dexamethasone (n=498) or ondansetron and dexamethasone plus a single intravenous infusion of fosaprepitant dimeglumine (n=502).

The primary endpoint was complete response (CR)—defined as no vomiting and no use of rescue therapy—in the delayed phase of chemotherapy-induced nausea and vomiting, which is 25 to 120 hours after the initiation of chemotherapy.

Secondary endpoints included CR in the overall and acute phases—0 to 120 and 0 to 24 hours after MEC initiation, respectively—and no vomiting in the overall phase.

The fosaprepitant regimen improved CR significantly in the delayed and overall phases but not in the acute phase.

In the delayed phase, the CR rate was 78.9% with the fosaprepitant regimen and 68.5% with the control regimen (P<0.001). In the acute phase, the CR rate was 93.2% and 91.0%, respectively (P=0.184). Overall, the CR rate was 77.1% and 66.9%, respectively (P<0.001).

In the overall phase, the proportion of subjects with no vomiting was 82.7% with the fosaprepitant regimen and 72.9% with the control regimen (P<0.001). The proportion of patients with no significant nausea was 83.2% and 77.9%, respectively (P=0.030).

The most common adverse events reported in the fosaprepitant and control arms, respectively, were fatigue (15% vs 13%), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremity (2% vs 1%).

Fosaprepitant dimeglumine is a product of Merck. For more details on the drug, see the prescribing information.

Patient consults pharmacist

Photo by Rhoda Baer

Sun Pharma has announced the US launch of imatinib mesylate tablets, which are a generic version of Novartis’s Gleevec, for indications approved by the US Food and Drug Administration (FDA).

As part of this launch, Sun Pharma has rolled out a savings card program. The goal is to provide greater access to imatinib mesylate tablets for patients who have commercial insurance, but their out-of-pocket cost may exceed an affordable amount.

Sun Pharma’s Imatinib Mesylate Savings Card will reduce patient’s co-payment to $10. The card will also offer patients an additional savings benefit of up to $700 for a 30-day fill to offset any additional out-of-pocket cost should they be required to meet their deductible or co-insurance.

Participating pharmacies across the US can use the patient’s card as part of this program.

Eligible patients can participate in Sun Pharma’s Imatinib Mesylate Savings Card program by registering at www.imatinibrx.com or by requesting a savings card from their oncologist. Sun Pharma will be supplying its Imatinib Mesylate Savings Cards to more than 4500 oncologists.

Sun Pharma has established a Hub service so patients can call and speak with a trained healthcare professional about imatinib mesylate. The number is 1-844-502-5950.

In addition, qualifying patients can receive Sun Pharma’s imatinib mesylate at no cost. Based on qualifications for applying and including a doctor’s prescription, the Hub service will determine if a patient is qualified to receive imatinib mesylate for free. Upon acceptance, the prescription will be processed and delivered to the qualifying patient at no cost.

Sun Pharma’s imatinib mesylate was approved by the FDA in December 2015 and was granted 180 days of marketing exclusivity from the time of its launch. The drug is available in 100 mg and 400 mg tablets.

It is approved to treat:

• Newly diagnosed adult and pediatric patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adults with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adults with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
• Adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia, including those who have the FIP1L1-PDGFRα fusion kinase
• Adult patients with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Sun Pharma’s imatinib mesylate is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Patient consults pharmacist

Photo by Rhoda Baer

Sun Pharma has announced the US launch of imatinib mesylate tablets, which are a generic version of Novartis’s Gleevec, for indications approved by the US Food and Drug Administration (FDA).

As part of this launch, Sun Pharma has rolled out a savings card program. The goal is to provide greater access to imatinib mesylate tablets for patients who have commercial insurance, but their out-of-pocket cost may exceed an affordable amount.

Sun Pharma’s Imatinib Mesylate Savings Card will reduce patient’s co-payment to $10. The card will also offer patients an additional savings benefit of up to $700 for a 30-day fill to offset any additional out-of-pocket cost should they be required to meet their deductible or co-insurance.

Participating pharmacies across the US can use the patient’s card as part of this program.

Eligible patients can participate in Sun Pharma’s Imatinib Mesylate Savings Card program by registering at www.imatinibrx.com or by requesting a savings card from their oncologist. Sun Pharma will be supplying its Imatinib Mesylate Savings Cards to more than 4500 oncologists.

Sun Pharma has established a Hub service so patients can call and speak with a trained healthcare professional about imatinib mesylate. The number is 1-844-502-5950.

In addition, qualifying patients can receive Sun Pharma’s imatinib mesylate at no cost. Based on qualifications for applying and including a doctor’s prescription, the Hub service will determine if a patient is qualified to receive imatinib mesylate for free. Upon acceptance, the prescription will be processed and delivered to the qualifying patient at no cost.

Sun Pharma’s imatinib mesylate was approved by the FDA in December 2015 and was granted 180 days of marketing exclusivity from the time of its launch. The drug is available in 100 mg and 400 mg tablets.

It is approved to treat:

• Newly diagnosed adult and pediatric patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adults with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adults with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
• Adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia, including those who have the FIP1L1-PDGFRα fusion kinase
• Adult patients with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Sun Pharma’s imatinib mesylate is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Patient consults pharmacist

Photo by Rhoda Baer

Sun Pharma has announced the US launch of imatinib mesylate tablets, which are a generic version of Novartis’s Gleevec, for indications approved by the US Food and Drug Administration (FDA).

As part of this launch, Sun Pharma has rolled out a savings card program. The goal is to provide greater access to imatinib mesylate tablets for patients who have commercial insurance, but their out-of-pocket cost may exceed an affordable amount.

Sun Pharma’s Imatinib Mesylate Savings Card will reduce patient’s co-payment to $10. The card will also offer patients an additional savings benefit of up to $700 for a 30-day fill to offset any additional out-of-pocket cost should they be required to meet their deductible or co-insurance.

Participating pharmacies across the US can use the patient’s card as part of this program.

Eligible patients can participate in Sun Pharma’s Imatinib Mesylate Savings Card program by registering at www.imatinibrx.com or by requesting a savings card from their oncologist. Sun Pharma will be supplying its Imatinib Mesylate Savings Cards to more than 4500 oncologists.

Sun Pharma has established a Hub service so patients can call and speak with a trained healthcare professional about imatinib mesylate. The number is 1-844-502-5950.

In addition, qualifying patients can receive Sun Pharma’s imatinib mesylate at no cost. Based on qualifications for applying and including a doctor’s prescription, the Hub service will determine if a patient is qualified to receive imatinib mesylate for free. Upon acceptance, the prescription will be processed and delivered to the qualifying patient at no cost.

Sun Pharma’s imatinib mesylate was approved by the FDA in December 2015 and was granted 180 days of marketing exclusivity from the time of its launch. The drug is available in 100 mg and 400 mg tablets.

It is approved to treat:

• Newly diagnosed adult and pediatric patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adults with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adults with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
• Adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia, including those who have the FIP1L1-PDGFRα fusion kinase
• Adult patients with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Sun Pharma’s imatinib mesylate is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Researcher in the lab

Photo by Daniel Sone

The European Hematology Association (EHA) has created a “roadmap” for hematology research in Europe.

This guidance document summarizes the current status of basic, translational, and clinical hematology research and identifies areas of unmet scientific and medical need in Europe.

It is intended to help European and national policy makers, funding agencies, charities, research institutes, and researchers make decisions on initiating, funding, or developing research.

The guidance, “The European Hematology Association Roadmap for European Hematology Research: A Consensus Document,” is published in this month’s issue of haematologica.

“For the first time, hematologists in Europe came together to develop a roadmap to guide hematology research in Europe” said Andreas Engert, MD, chair of the EHA Research Roadmap Task Force.

“Hematology in Europe has achieved a lot, but the discipline must focus and collaborate to be efficient and remain successful in improving patient outcomes. The roadmap does just that and will determine the research agenda in Europe in the coming years.”

Roughly 300 experts from more than 20 countries—including clinicians, basic researchers, and patients—contributed to the roadmap. Stakeholders such as national hematology societies, patient organizations, hematology trial groups, and other European organizations were consulted to comment on the final draft version.

The final roadmap has 9 sections: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation.

The roadmap lists priorities and needs in these areas, including the need for targeted therapies based on genomic profiling and chemical biology, the need to eradicate minimal residual disease, and the need for treatments that are better tolerated by elderly patients.

“Now’s the time for Europe to pay attention,” said Ulrich Jäger, MD, chair of the EHA European Affairs Committee.

“With an aging population, the slow recovery from the financial and Euro crises, costly medical breakthroughs and innovations—quite a few of which involve hematology researchers—Europe faces increased health expenditures while budgets are limited.”

“Policy makers are rightfully cautious when spending the taxpayers’ money. So it is our responsibility to provide the policy makers with the information and evidence they need to decide where their support impacts knowledge and health most efficiently, to the benefit of patients and society. The Research Roadmap delivers on that. Now, it is up to the policy makers in the EU to deliver too.”

Researcher in the lab

Photo by Daniel Sone

The European Hematology Association (EHA) has created a “roadmap” for hematology research in Europe.

This guidance document summarizes the current status of basic, translational, and clinical hematology research and identifies areas of unmet scientific and medical need in Europe.

It is intended to help European and national policy makers, funding agencies, charities, research institutes, and researchers make decisions on initiating, funding, or developing research.

The guidance, “The European Hematology Association Roadmap for European Hematology Research: A Consensus Document,” is published in this month’s issue of haematologica.

“For the first time, hematologists in Europe came together to develop a roadmap to guide hematology research in Europe” said Andreas Engert, MD, chair of the EHA Research Roadmap Task Force.

“Hematology in Europe has achieved a lot, but the discipline must focus and collaborate to be efficient and remain successful in improving patient outcomes. The roadmap does just that and will determine the research agenda in Europe in the coming years.”

Roughly 300 experts from more than 20 countries—including clinicians, basic researchers, and patients—contributed to the roadmap. Stakeholders such as national hematology societies, patient organizations, hematology trial groups, and other European organizations were consulted to comment on the final draft version.

The final roadmap has 9 sections: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation.

The roadmap lists priorities and needs in these areas, including the need for targeted therapies based on genomic profiling and chemical biology, the need to eradicate minimal residual disease, and the need for treatments that are better tolerated by elderly patients.

“Now’s the time for Europe to pay attention,” said Ulrich Jäger, MD, chair of the EHA European Affairs Committee.

“With an aging population, the slow recovery from the financial and Euro crises, costly medical breakthroughs and innovations—quite a few of which involve hematology researchers—Europe faces increased health expenditures while budgets are limited.”

“Policy makers are rightfully cautious when spending the taxpayers’ money. So it is our responsibility to provide the policy makers with the information and evidence they need to decide where their support impacts knowledge and health most efficiently, to the benefit of patients and society. The Research Roadmap delivers on that. Now, it is up to the policy makers in the EU to deliver too.”

Researcher in the lab

Photo by Daniel Sone

The European Hematology Association (EHA) has created a “roadmap” for hematology research in Europe.

This guidance document summarizes the current status of basic, translational, and clinical hematology research and identifies areas of unmet scientific and medical need in Europe.

It is intended to help European and national policy makers, funding agencies, charities, research institutes, and researchers make decisions on initiating, funding, or developing research.

The guidance, “The European Hematology Association Roadmap for European Hematology Research: A Consensus Document,” is published in this month’s issue of haematologica.

“For the first time, hematologists in Europe came together to develop a roadmap to guide hematology research in Europe” said Andreas Engert, MD, chair of the EHA Research Roadmap Task Force.

“Hematology in Europe has achieved a lot, but the discipline must focus and collaborate to be efficient and remain successful in improving patient outcomes. The roadmap does just that and will determine the research agenda in Europe in the coming years.”

Roughly 300 experts from more than 20 countries—including clinicians, basic researchers, and patients—contributed to the roadmap. Stakeholders such as national hematology societies, patient organizations, hematology trial groups, and other European organizations were consulted to comment on the final draft version.

The final roadmap has 9 sections: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation.

The roadmap lists priorities and needs in these areas, including the need for targeted therapies based on genomic profiling and chemical biology, the need to eradicate minimal residual disease, and the need for treatments that are better tolerated by elderly patients.

“Now’s the time for Europe to pay attention,” said Ulrich Jäger, MD, chair of the EHA European Affairs Committee.

“With an aging population, the slow recovery from the financial and Euro crises, costly medical breakthroughs and innovations—quite a few of which involve hematology researchers—Europe faces increased health expenditures while budgets are limited.”

“Policy makers are rightfully cautious when spending the taxpayers’ money. So it is our responsibility to provide the policy makers with the information and evidence they need to decide where their support impacts knowledge and health most efficiently, to the benefit of patients and society. The Research Roadmap delivers on that. Now, it is up to the policy makers in the EU to deliver too.”

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of the immunostimulatory antibody elotuzumab (Empliciti).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice and is expected to deliver its final decision on elotuzumab within 3 months.

The CHMP’s positive opinion of elotuzumab is 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. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

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.

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.

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

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of the immunostimulatory antibody elotuzumab (Empliciti).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice and is expected to deliver its final decision on elotuzumab within 3 months.

The CHMP’s positive opinion of elotuzumab is 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. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

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.

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.

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

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of the immunostimulatory antibody elotuzumab (Empliciti).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice and is expected to deliver its final decision on elotuzumab within 3 months.

The CHMP’s positive opinion of elotuzumab is 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. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

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.

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.

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

Carfilzomib (Kyprolis)

Photo courtesy of Amgen

Health Canada has approved the proteasome inhibitor carfilzomib (Kyprolis) for use in combination with lenalidomide and dexamethasone to treat patients with relapsed multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.

Carfilzomib, a product of Amgen Canada, is also approved for use in the US, the European Union, Argentina, Israel, Kuwait, Mexico, Thailand, and Colombia.

Health Canada’s approval is based on results of the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. The median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Carfilzomib (Kyprolis)

Photo courtesy of Amgen

Health Canada has approved the proteasome inhibitor carfilzomib (Kyprolis) for use in combination with lenalidomide and dexamethasone to treat patients with relapsed multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.

Carfilzomib, a product of Amgen Canada, is also approved for use in the US, the European Union, Argentina, Israel, Kuwait, Mexico, Thailand, and Colombia.

Health Canada’s approval is based on results of the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. The median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Carfilzomib (Kyprolis)

Photo courtesy of Amgen

Health Canada has approved the proteasome inhibitor carfilzomib (Kyprolis) for use in combination with lenalidomide and dexamethasone to treat patients with relapsed multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.

Carfilzomib, a product of Amgen Canada, is also approved for use in the US, the European Union, Argentina, Israel, Kuwait, Mexico, Thailand, and Colombia.

Health Canada’s approval is based on results of the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. The median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Micrograph showing AML

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted a third breakthrough therapy designation for the BCL-2 inhibitor venetoclax (ABT-199).

This time, the designation is for venetoclax in combination with hypomethylating agents to treat patients with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.

Venetoclax previously received breakthrough designation as a single agent for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and in combination with rituximab to treat patients with relapsed or refractory CLL and 17p deletion.

Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.

Venetoclax is currently under investigation in a phase 1/2 trial in combination with low-dose cytarabine for treatment-naïve patients with AML and in a phase 1b study in combination with decitabine or azacitidine for treatment-naïve AML patients.

A phase 2 study of single-agent venetoclax in AML has been completed. The results were presented at ASH 2014.

At that time, the trial had enrolled 32 patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.

The overall response rate was 15.5%, with 1 patient achieving a complete response (CR) and 4 patients achieving a CR with incomplete count recovery (CRi).

The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.

The median bone marrow blast count in evaluable patients decreased 36% after treatment, and 6 patients (19%) had at least a 50% reduction in bone marrow blasts.

Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting.

Grade 3 and 4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia. No patient died as a result of treatment-related adverse events.

Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.

Micrograph showing AML

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted a third breakthrough therapy designation for the BCL-2 inhibitor venetoclax (ABT-199).

This time, the designation is for venetoclax in combination with hypomethylating agents to treat patients with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.

Venetoclax previously received breakthrough designation as a single agent for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and in combination with rituximab to treat patients with relapsed or refractory CLL and 17p deletion.

Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.

Venetoclax is currently under investigation in a phase 1/2 trial in combination with low-dose cytarabine for treatment-naïve patients with AML and in a phase 1b study in combination with decitabine or azacitidine for treatment-naïve AML patients.

A phase 2 study of single-agent venetoclax in AML has been completed. The results were presented at ASH 2014.

At that time, the trial had enrolled 32 patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.

The overall response rate was 15.5%, with 1 patient achieving a complete response (CR) and 4 patients achieving a CR with incomplete count recovery (CRi).

The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.

The median bone marrow blast count in evaluable patients decreased 36% after treatment, and 6 patients (19%) had at least a 50% reduction in bone marrow blasts.

Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting.

Grade 3 and 4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia. No patient died as a result of treatment-related adverse events.

Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.

Micrograph showing AML

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted a third breakthrough therapy designation for the BCL-2 inhibitor venetoclax (ABT-199).

This time, the designation is for venetoclax in combination with hypomethylating agents to treat patients with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.

Venetoclax previously received breakthrough designation as a single agent for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and in combination with rituximab to treat patients with relapsed or refractory CLL and 17p deletion.

Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.

Venetoclax is currently under investigation in a phase 1/2 trial in combination with low-dose cytarabine for treatment-naïve patients with AML and in a phase 1b study in combination with decitabine or azacitidine for treatment-naïve AML patients.

A phase 2 study of single-agent venetoclax in AML has been completed. The results were presented at ASH 2014.

At that time, the trial had enrolled 32 patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.

The overall response rate was 15.5%, with 1 patient achieving a complete response (CR) and 4 patients achieving a CR with incomplete count recovery (CRi).

The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.

The median bone marrow blast count in evaluable patients decreased 36% after treatment, and 6 patients (19%) had at least a 50% reduction in bone marrow blasts.

Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting.

Grade 3 and 4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia. No patient died as a result of treatment-related adverse events.

Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each. 

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each. 

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each.