Pharmacy

Photo from Shire

The European Commission (EC) has granted marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The EC approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults (age 18 and older) with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.

The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials—one in a surgical setting and one in a non-surgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.

Phase 1 trial

This trial (NCT00816660, 070701) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII)—referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII to plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).

The safety analysis included 32 patients who received rVWF-rFVIII. There were no thrombotic events, serious adverse events, or new cases of inhibitors to VWF or FVIII in these patients.

The pharmacokinetic analysis included 19 patients. The researchers said the pharmacokinetics of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar with rVWF-rFVIII and pdVWF-pdFVIII.

FVIII levels were higher after infusion with rVWF-rFVIII than with pdVWF-pdFVIII, even after 72 hours. The researchers said this suggests that rVWF alone “could maintain sufficient FVIII activity to treat a bleeding episode once the initial FVIII level has reached a therapeutic threshold.”

These results were published in Blood in 2013.

Phase 3: Non-surgical

This study (NCT01410227, 071001) included 49 patients with VWD who received vonicog alfa with or without rFVIII.

All participants had successful treatment of bleeding episodes. Most (96.9%) treated bleeds (192 bleeds in 22 patients) were given an “excellent” efficacy rating (as good as or better than expected).

Most bleeds (81.8%) were resolved with a single infusion of vonicog alfa, and the treatment had a mean half-life of 21.9 hours.

There were 8 adverse events considered related to vonicog alfa, and 2 were serious. One patient experienced 2 simultaneous serious events—chest discomfort and increased heart rate—but these were resolved.

There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII.

These results were published in Blood in 2015.

Phase 3: Surgical setting

This trial (NCT02283268, 071101) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).

Patients received vonicog alfa at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s FVIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.

Within an hour of surgery, patients received a dose of vonicog alfa, with or without rFVIII, depending on the target FVIII:C levels at the 3-hour assessment.

Ten patients received rVWF alone, 12 did not receive any preoperative FVIII, and 2 did not receive rVWF postoperatively.

Vonicog alfa demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.

Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.

One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.

One patient tested positive for binding antibodies to VWF. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.

These results were presented at the WFH 2018 World Congress.

Photo from Shire

The European Commission (EC) has granted marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The EC approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults (age 18 and older) with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.

The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials—one in a surgical setting and one in a non-surgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.

Phase 1 trial

This trial (NCT00816660, 070701) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII)—referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII to plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).

The safety analysis included 32 patients who received rVWF-rFVIII. There were no thrombotic events, serious adverse events, or new cases of inhibitors to VWF or FVIII in these patients.

The pharmacokinetic analysis included 19 patients. The researchers said the pharmacokinetics of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar with rVWF-rFVIII and pdVWF-pdFVIII.

FVIII levels were higher after infusion with rVWF-rFVIII than with pdVWF-pdFVIII, even after 72 hours. The researchers said this suggests that rVWF alone “could maintain sufficient FVIII activity to treat a bleeding episode once the initial FVIII level has reached a therapeutic threshold.”

These results were published in Blood in 2013.

Phase 3: Non-surgical

This study (NCT01410227, 071001) included 49 patients with VWD who received vonicog alfa with or without rFVIII.

All participants had successful treatment of bleeding episodes. Most (96.9%) treated bleeds (192 bleeds in 22 patients) were given an “excellent” efficacy rating (as good as or better than expected).

Most bleeds (81.8%) were resolved with a single infusion of vonicog alfa, and the treatment had a mean half-life of 21.9 hours.

There were 8 adverse events considered related to vonicog alfa, and 2 were serious. One patient experienced 2 simultaneous serious events—chest discomfort and increased heart rate—but these were resolved.

There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII.

These results were published in Blood in 2015.

Phase 3: Surgical setting

This trial (NCT02283268, 071101) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).

Patients received vonicog alfa at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s FVIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.

Within an hour of surgery, patients received a dose of vonicog alfa, with or without rFVIII, depending on the target FVIII:C levels at the 3-hour assessment.

Ten patients received rVWF alone, 12 did not receive any preoperative FVIII, and 2 did not receive rVWF postoperatively.

Vonicog alfa demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.

Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.

One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.

One patient tested positive for binding antibodies to VWF. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.

These results were presented at the WFH 2018 World Congress.

Photo from Shire

The European Commission (EC) has granted marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The EC approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults (age 18 and older) with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.

The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials—one in a surgical setting and one in a non-surgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.

Phase 1 trial

This trial (NCT00816660, 070701) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII)—referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII to plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).

The safety analysis included 32 patients who received rVWF-rFVIII. There were no thrombotic events, serious adverse events, or new cases of inhibitors to VWF or FVIII in these patients.

The pharmacokinetic analysis included 19 patients. The researchers said the pharmacokinetics of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar with rVWF-rFVIII and pdVWF-pdFVIII.

FVIII levels were higher after infusion with rVWF-rFVIII than with pdVWF-pdFVIII, even after 72 hours. The researchers said this suggests that rVWF alone “could maintain sufficient FVIII activity to treat a bleeding episode once the initial FVIII level has reached a therapeutic threshold.”

These results were published in Blood in 2013.

Phase 3: Non-surgical

This study (NCT01410227, 071001) included 49 patients with VWD who received vonicog alfa with or without rFVIII.

All participants had successful treatment of bleeding episodes. Most (96.9%) treated bleeds (192 bleeds in 22 patients) were given an “excellent” efficacy rating (as good as or better than expected).

Most bleeds (81.8%) were resolved with a single infusion of vonicog alfa, and the treatment had a mean half-life of 21.9 hours.

There were 8 adverse events considered related to vonicog alfa, and 2 were serious. One patient experienced 2 simultaneous serious events—chest discomfort and increased heart rate—but these were resolved.

There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII.

These results were published in Blood in 2015.

Phase 3: Surgical setting

This trial (NCT02283268, 071101) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).

Patients received vonicog alfa at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s FVIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.

Within an hour of surgery, patients received a dose of vonicog alfa, with or without rFVIII, depending on the target FVIII:C levels at the 3-hour assessment.

Ten patients received rVWF alone, 12 did not receive any preoperative FVIII, and 2 did not receive rVWF postoperatively.

Vonicog alfa demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.

Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.

One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.

One patient tested positive for binding antibodies to VWF. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.

These results were presented at the WFH 2018 World Congress.

Antihemophilic factor

CSL Behring has announced that Idelvion (Coagulation Factor IX [Recombinant], Albumin Fusion Protein) is now available in a 3500 IU vial size.

Idelvion is also available in 250 IU, 500 IU, 1000 IU, and 2000 IU vial sizes.

For some patients requiring high doses of Idelvion, the new 3500 IU vial size will reduce the reconstitution time needed to prepare multiple vials for a similar dose.

Idelvion is a fusion protein linking recombinant coagulation factor IX with recombinant albumin, and it is approved by the U.S. Food and Drug Administration to treat children and adults with hemophilia B.

Idelvion can be used as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand control and prevention of bleeding episodes, and for the perioperative management of bleeding.

Idelvion is approved for up to 14-day dosing in appropriate patients.

For more details on Idelvion, see the prescribing information.

Antihemophilic factor

CSL Behring has announced that Idelvion (Coagulation Factor IX [Recombinant], Albumin Fusion Protein) is now available in a 3500 IU vial size.

Idelvion is also available in 250 IU, 500 IU, 1000 IU, and 2000 IU vial sizes.

For some patients requiring high doses of Idelvion, the new 3500 IU vial size will reduce the reconstitution time needed to prepare multiple vials for a similar dose.

Idelvion is a fusion protein linking recombinant coagulation factor IX with recombinant albumin, and it is approved by the U.S. Food and Drug Administration to treat children and adults with hemophilia B.

Idelvion can be used as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand control and prevention of bleeding episodes, and for the perioperative management of bleeding.

Idelvion is approved for up to 14-day dosing in appropriate patients.

For more details on Idelvion, see the prescribing information.

Antihemophilic factor

CSL Behring has announced that Idelvion (Coagulation Factor IX [Recombinant], Albumin Fusion Protein) is now available in a 3500 IU vial size.

Idelvion is also available in 250 IU, 500 IU, 1000 IU, and 2000 IU vial sizes.

For some patients requiring high doses of Idelvion, the new 3500 IU vial size will reduce the reconstitution time needed to prepare multiple vials for a similar dose.

Idelvion is a fusion protein linking recombinant coagulation factor IX with recombinant albumin, and it is approved by the U.S. Food and Drug Administration to treat children and adults with hemophilia B.

Idelvion can be used as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand control and prevention of bleeding episodes, and for the perioperative management of bleeding.

Idelvion is approved for up to 14-day dosing in appropriate patients.

For more details on Idelvion, see the prescribing information.

Micrograph showing ALL

Health Canada has authorized use of tisagenlecleucel (Kymriah™), making it the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.

Tisagenlecleucel (formerly CTL019) is approved to treat patients ages 3 to 25 with B-cell acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.

Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.

Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers, and Novartis is enhancing manufacturing capacity to meet patient needs.

Tisagenlecleucel has been studied in a pair of phase 2 trials—ELIANA and JULIET.

JULIET trial

JULIET enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.

The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.

The 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).

These results were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).

ELIANA trial

ELIANA included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).

All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.

The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi. All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

Ninety-five percent of patients had AEs thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 AEs was 73%.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

These results were published in The New England Journal of Medicine in February.

Micrograph showing ALL

Health Canada has authorized use of tisagenlecleucel (Kymriah™), making it the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.

Tisagenlecleucel (formerly CTL019) is approved to treat patients ages 3 to 25 with B-cell acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.

Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.

Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers, and Novartis is enhancing manufacturing capacity to meet patient needs.

Tisagenlecleucel has been studied in a pair of phase 2 trials—ELIANA and JULIET.

JULIET trial

JULIET enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.

The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.

The 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).

These results were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).

ELIANA trial

ELIANA included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).

All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.

The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi. All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

Ninety-five percent of patients had AEs thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 AEs was 73%.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

These results were published in The New England Journal of Medicine in February.

Micrograph showing ALL

Health Canada has authorized use of tisagenlecleucel (Kymriah™), making it the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.

Tisagenlecleucel (formerly CTL019) is approved to treat patients ages 3 to 25 with B-cell acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.

Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.

Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers, and Novartis is enhancing manufacturing capacity to meet patient needs.

Tisagenlecleucel has been studied in a pair of phase 2 trials—ELIANA and JULIET.

JULIET trial

JULIET enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.

The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.

The 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).

These results were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).

ELIANA trial

ELIANA included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).

All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.

The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi. All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

Ninety-five percent of patients had AEs thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 AEs was 73%.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

These results were published in The New England Journal of Medicine in February.

Photo from Novartis

The National Health Service (NHS) of England has announced that tisagenlecleucel (Kymriah^®), a chimeric antigen receptor (CAR) T-cell therapy, will soon be available for certain leukemia patients.

Tisagenlecleucel will be made available through the Cancer Drugs Fund, and patients could potentially begin receiving the treatment within weeks.

NHS England struck a deal with Novartis to lower the price of tisagenlecleucel, which costs around £282,000 per patient at its full list price. The discount offered to the NHS is confidential.

Tisagenlecleucel was recently approved by the European Commission (EC) to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

The EC also approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

However, tisagenlecleucel will only be available for ALL patients in England, at least initially. A decision has not been made regarding funding for tisagenlecleucel in DLBCL, and Novartis previously decided to launch tisagenlecleucel in ALL first.

“It’s fantastic news for children and young people with this form of leukemia that CAR T-cell therapy will be made available on the NHS, making them the first in Europe to have routine access to this exciting new type of immunotherapy,” said Charles Swanton, Cancer Research UK’s chief clinician.

The first three NHS hospitals to go through the international accreditation process for the provision of tisagenlecleucel are in London, Manchester, and Newcastle. Subject to passing accreditation requirements, the first treatments could begin in a matter of weeks.

Another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta^®), has not fared as well as tisagenlecleucel. The National Institute for Health and Care Excellence (NICE) recently issued a draft guidance recommending against the use of axicabtagene ciloleucel in England.

Axicabtagene ciloleucel was approved by the EC to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. NICE also said the price of axicabtagene ciloleucel is too high for the therapy to be considered a cost-effective use of NHS resources, and axicabtagene ciloleucel does not meet the criteria for inclusion in the Cancer Drugs Fund.

Photo from Novartis

The National Health Service (NHS) of England has announced that tisagenlecleucel (Kymriah^®), a chimeric antigen receptor (CAR) T-cell therapy, will soon be available for certain leukemia patients.

Tisagenlecleucel will be made available through the Cancer Drugs Fund, and patients could potentially begin receiving the treatment within weeks.

NHS England struck a deal with Novartis to lower the price of tisagenlecleucel, which costs around £282,000 per patient at its full list price. The discount offered to the NHS is confidential.

Tisagenlecleucel was recently approved by the European Commission (EC) to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

The EC also approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

However, tisagenlecleucel will only be available for ALL patients in England, at least initially. A decision has not been made regarding funding for tisagenlecleucel in DLBCL, and Novartis previously decided to launch tisagenlecleucel in ALL first.

“It’s fantastic news for children and young people with this form of leukemia that CAR T-cell therapy will be made available on the NHS, making them the first in Europe to have routine access to this exciting new type of immunotherapy,” said Charles Swanton, Cancer Research UK’s chief clinician.

The first three NHS hospitals to go through the international accreditation process for the provision of tisagenlecleucel are in London, Manchester, and Newcastle. Subject to passing accreditation requirements, the first treatments could begin in a matter of weeks.

Another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta^®), has not fared as well as tisagenlecleucel. The National Institute for Health and Care Excellence (NICE) recently issued a draft guidance recommending against the use of axicabtagene ciloleucel in England.

Axicabtagene ciloleucel was approved by the EC to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. NICE also said the price of axicabtagene ciloleucel is too high for the therapy to be considered a cost-effective use of NHS resources, and axicabtagene ciloleucel does not meet the criteria for inclusion in the Cancer Drugs Fund.

Photo from Novartis

The National Health Service (NHS) of England has announced that tisagenlecleucel (Kymriah^®), a chimeric antigen receptor (CAR) T-cell therapy, will soon be available for certain leukemia patients.

Tisagenlecleucel will be made available through the Cancer Drugs Fund, and patients could potentially begin receiving the treatment within weeks.

NHS England struck a deal with Novartis to lower the price of tisagenlecleucel, which costs around £282,000 per patient at its full list price. The discount offered to the NHS is confidential.

Tisagenlecleucel was recently approved by the European Commission (EC) to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

The EC also approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

However, tisagenlecleucel will only be available for ALL patients in England, at least initially. A decision has not been made regarding funding for tisagenlecleucel in DLBCL, and Novartis previously decided to launch tisagenlecleucel in ALL first.

“It’s fantastic news for children and young people with this form of leukemia that CAR T-cell therapy will be made available on the NHS, making them the first in Europe to have routine access to this exciting new type of immunotherapy,” said Charles Swanton, Cancer Research UK’s chief clinician.

The first three NHS hospitals to go through the international accreditation process for the provision of tisagenlecleucel are in London, Manchester, and Newcastle. Subject to passing accreditation requirements, the first treatments could begin in a matter of weeks.

Another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta^®), has not fared as well as tisagenlecleucel. The National Institute for Health and Care Excellence (NICE) recently issued a draft guidance recommending against the use of axicabtagene ciloleucel in England.

Axicabtagene ciloleucel was approved by the EC to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. NICE also said the price of axicabtagene ciloleucel is too high for the therapy to be considered a cost-effective use of NHS resources, and axicabtagene ciloleucel does not meet the criteria for inclusion in the Cancer Drugs Fund.

Vials and a syringe

The European Commission has granted marketing authorization for caplacizumab (Cablivi™), a humanized bivalent nanobody that inhibits the interaction between von Willebrand factor and platelets.

Caplacizumab is now approved to treat adults with acquired thrombotic thrombocytopenic purpura (aTTP) in all member countries of the European Union as well as Norway, Iceland, and Liechtenstein.

Sanofi Genzyme said it will work with relevant local authorities to make caplacizumab available in countries across Europe.

“The approval of Cablivi provides an important addition to the standard-of-care treatment for patients with aTTP in Europe because it can significantly reduce time to platelet count normalization and induce a clinically meaningful reduction in recurrences,” said Marie Scully, MD, of University College Hospital in London, UK.

The European Commission’s approval of caplacizumab is supported by data from the phase 2 TITAN study and the phase 3 HERCULES study.

TITAN

Results from the TITAN trial were published in The New England Journal of Medicine in 2016.

The study included 75 aTTP patients who were randomized to caplacizumab (n=36) or placebo (n=39), with all patients receiving the current standard of care—daily plasma exchange and immunosuppressive therapy.

The study’s primary endpoint was time to response, which was defined as platelet count normalization (150,000/mm³ or higher).

Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).

Among the 69 patients who had not undergone a plasma exchange session before enrollment, the median time to response was 3.0 days in the caplacizumab arm and 4.9 days in the placebo arm.

Among the 6 patients who did undergo a plasma exchange session before enrollment, the median time to a response was 2.4 days in the caplacizumab arm and 4.3 days in the placebo arm.

The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.

There were 541 adverse events (AEs) in 34 of the 35 evaluable patients receiving caplacizumab (97%) and 522 AEs in all 37 evaluable patients receiving placebo (100%). TTP exacerbations and relapses were not included as AEs.

The rate of AEs thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of AEs that were possibly related was 54% and 8%, respectively. The rate of serious AEs was 37% and 32%, respectively.

There were no deaths in the caplacizumab arm and two in the placebo arm. One death was due to severe, refractory TTP, and the other was due to cerebral hemorrhage.

HERCULES

Results from the HERCULES trial were presented at the 2017 ASH Annual Meeting.

The study enrolled patients with an acute episode of aTTP. They were randomized to receive caplacizumab (n=72) or placebo (n=73) in addition to standard care—plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization), which was defined as an initial platelet count of at least 150 x 10⁹/L with subsequent stop of daily plasma exchange within 5 days.

There was a significant reduction in time to platelet count response in the caplacizumab arm compared to the placebo arm. The platelet normalization rate ratio was 1.55 (P<0.01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12.7% (n=9) in the caplacizumab arm and 49.3% (n=36) in the placebo arm (P<0.0001).

The incidence of aTTP-related death was 0% (n=0) in the caplacizumab arm and 4.1% (n=3) in the placebo arm. The incidence of aTTP recurrence was 4.2% (n=3) and 38.4% (n=28), respectively. The incidence of at least one major thromboembolic event was 8.5% (n=6) and 8.2% (n=6), respectively.

The proportion of patients with at least one study-drug-related AE was 57.7% in the caplacizumab arm and 43.8% in the placebo arm. The proportion of patients with at least one study-drug-related serious AE was 14.1% (n=10) and 5.5% (n=4), respectively. The rate of discontinuation due to at least one AE was 7.0% and 12.3%, respectively.

During the treatment period, there were no deaths in the caplacizumab arm and three deaths in the placebo arm. There was one death in the caplacizumab arm during the follow-up period, but it was considered unrelated to caplacizumab.

Vials and a syringe

The European Commission has granted marketing authorization for caplacizumab (Cablivi™), a humanized bivalent nanobody that inhibits the interaction between von Willebrand factor and platelets.

Caplacizumab is now approved to treat adults with acquired thrombotic thrombocytopenic purpura (aTTP) in all member countries of the European Union as well as Norway, Iceland, and Liechtenstein.

Sanofi Genzyme said it will work with relevant local authorities to make caplacizumab available in countries across Europe.

“The approval of Cablivi provides an important addition to the standard-of-care treatment for patients with aTTP in Europe because it can significantly reduce time to platelet count normalization and induce a clinically meaningful reduction in recurrences,” said Marie Scully, MD, of University College Hospital in London, UK.

The European Commission’s approval of caplacizumab is supported by data from the phase 2 TITAN study and the phase 3 HERCULES study.

TITAN

Results from the TITAN trial were published in The New England Journal of Medicine in 2016.

The study included 75 aTTP patients who were randomized to caplacizumab (n=36) or placebo (n=39), with all patients receiving the current standard of care—daily plasma exchange and immunosuppressive therapy.

The study’s primary endpoint was time to response, which was defined as platelet count normalization (150,000/mm³ or higher).

Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).

Among the 69 patients who had not undergone a plasma exchange session before enrollment, the median time to response was 3.0 days in the caplacizumab arm and 4.9 days in the placebo arm.

Among the 6 patients who did undergo a plasma exchange session before enrollment, the median time to a response was 2.4 days in the caplacizumab arm and 4.3 days in the placebo arm.

The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.

There were 541 adverse events (AEs) in 34 of the 35 evaluable patients receiving caplacizumab (97%) and 522 AEs in all 37 evaluable patients receiving placebo (100%). TTP exacerbations and relapses were not included as AEs.

The rate of AEs thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of AEs that were possibly related was 54% and 8%, respectively. The rate of serious AEs was 37% and 32%, respectively.

There were no deaths in the caplacizumab arm and two in the placebo arm. One death was due to severe, refractory TTP, and the other was due to cerebral hemorrhage.

HERCULES

Results from the HERCULES trial were presented at the 2017 ASH Annual Meeting.

The study enrolled patients with an acute episode of aTTP. They were randomized to receive caplacizumab (n=72) or placebo (n=73) in addition to standard care—plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization), which was defined as an initial platelet count of at least 150 x 10⁹/L with subsequent stop of daily plasma exchange within 5 days.

There was a significant reduction in time to platelet count response in the caplacizumab arm compared to the placebo arm. The platelet normalization rate ratio was 1.55 (P<0.01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12.7% (n=9) in the caplacizumab arm and 49.3% (n=36) in the placebo arm (P<0.0001).

The incidence of aTTP-related death was 0% (n=0) in the caplacizumab arm and 4.1% (n=3) in the placebo arm. The incidence of aTTP recurrence was 4.2% (n=3) and 38.4% (n=28), respectively. The incidence of at least one major thromboembolic event was 8.5% (n=6) and 8.2% (n=6), respectively.

The proportion of patients with at least one study-drug-related AE was 57.7% in the caplacizumab arm and 43.8% in the placebo arm. The proportion of patients with at least one study-drug-related serious AE was 14.1% (n=10) and 5.5% (n=4), respectively. The rate of discontinuation due to at least one AE was 7.0% and 12.3%, respectively.

During the treatment period, there were no deaths in the caplacizumab arm and three deaths in the placebo arm. There was one death in the caplacizumab arm during the follow-up period, but it was considered unrelated to caplacizumab.

Vials and a syringe

The European Commission has granted marketing authorization for caplacizumab (Cablivi™), a humanized bivalent nanobody that inhibits the interaction between von Willebrand factor and platelets.

Caplacizumab is now approved to treat adults with acquired thrombotic thrombocytopenic purpura (aTTP) in all member countries of the European Union as well as Norway, Iceland, and Liechtenstein.

Sanofi Genzyme said it will work with relevant local authorities to make caplacizumab available in countries across Europe.

“The approval of Cablivi provides an important addition to the standard-of-care treatment for patients with aTTP in Europe because it can significantly reduce time to platelet count normalization and induce a clinically meaningful reduction in recurrences,” said Marie Scully, MD, of University College Hospital in London, UK.

The European Commission’s approval of caplacizumab is supported by data from the phase 2 TITAN study and the phase 3 HERCULES study.

TITAN

Results from the TITAN trial were published in The New England Journal of Medicine in 2016.

The study included 75 aTTP patients who were randomized to caplacizumab (n=36) or placebo (n=39), with all patients receiving the current standard of care—daily plasma exchange and immunosuppressive therapy.

The study’s primary endpoint was time to response, which was defined as platelet count normalization (150,000/mm³ or higher).

Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).

Among the 69 patients who had not undergone a plasma exchange session before enrollment, the median time to response was 3.0 days in the caplacizumab arm and 4.9 days in the placebo arm.

Among the 6 patients who did undergo a plasma exchange session before enrollment, the median time to a response was 2.4 days in the caplacizumab arm and 4.3 days in the placebo arm.

The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.

There were 541 adverse events (AEs) in 34 of the 35 evaluable patients receiving caplacizumab (97%) and 522 AEs in all 37 evaluable patients receiving placebo (100%). TTP exacerbations and relapses were not included as AEs.

The rate of AEs thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of AEs that were possibly related was 54% and 8%, respectively. The rate of serious AEs was 37% and 32%, respectively.

There were no deaths in the caplacizumab arm and two in the placebo arm. One death was due to severe, refractory TTP, and the other was due to cerebral hemorrhage.

HERCULES

Results from the HERCULES trial were presented at the 2017 ASH Annual Meeting.

The study enrolled patients with an acute episode of aTTP. They were randomized to receive caplacizumab (n=72) or placebo (n=73) in addition to standard care—plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization), which was defined as an initial platelet count of at least 150 x 10⁹/L with subsequent stop of daily plasma exchange within 5 days.

There was a significant reduction in time to platelet count response in the caplacizumab arm compared to the placebo arm. The platelet normalization rate ratio was 1.55 (P<0.01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12.7% (n=9) in the caplacizumab arm and 49.3% (n=36) in the placebo arm (P<0.0001).

The incidence of aTTP-related death was 0% (n=0) in the caplacizumab arm and 4.1% (n=3) in the placebo arm. The incidence of aTTP recurrence was 4.2% (n=3) and 38.4% (n=28), respectively. The incidence of at least one major thromboembolic event was 8.5% (n=6) and 8.2% (n=6), respectively.

The proportion of patients with at least one study-drug-related AE was 57.7% in the caplacizumab arm and 43.8% in the placebo arm. The proportion of patients with at least one study-drug-related serious AE was 14.1% (n=10) and 5.5% (n=4), respectively. The rate of discontinuation due to at least one AE was 7.0% and 12.3%, respectively.

During the treatment period, there were no deaths in the caplacizumab arm and three deaths in the placebo arm. There was one death in the caplacizumab arm during the follow-up period, but it was considered unrelated to caplacizumab.

Photo courtesy of Janssen

The European Commission (EC) has approved a new indication for daratumumab (Darzalex®).

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was previously approved by the EC for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is EC-approved as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

Photo courtesy of Janssen

The European Commission (EC) has approved a new indication for daratumumab (Darzalex®).

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was previously approved by the EC for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is EC-approved as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

Photo courtesy of Janssen

The European Commission (EC) has approved a new indication for daratumumab (Darzalex®).

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was previously approved by the EC for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is EC-approved as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

Photo from Bayer

The US Food and Drug Administration (FDA) has approved Jivi® (antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate approved for use in previously treated adults and adolescents (age 12 and older) with hemophilia A.

The product is approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.

The initial recommended prophylactic regimen is dosing twice weekly (30-40 IU/kg) with the ability to dose every 5 days (45-60 IU/kg) and further individually adjust to less or more frequent dosing based on bleeding episodes.

The FDA’s approval of Jivi is based on results from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated Jivi for perioperative management.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

The US Food and Drug Administration (FDA) has approved Jivi® (antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate approved for use in previously treated adults and adolescents (age 12 and older) with hemophilia A.

The product is approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.

The initial recommended prophylactic regimen is dosing twice weekly (30-40 IU/kg) with the ability to dose every 5 days (45-60 IU/kg) and further individually adjust to less or more frequent dosing based on bleeding episodes.

The FDA’s approval of Jivi is based on results from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated Jivi for perioperative management.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

The US Food and Drug Administration (FDA) has approved Jivi® (antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate approved for use in previously treated adults and adolescents (age 12 and older) with hemophilia A.

The product is approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.

The initial recommended prophylactic regimen is dosing twice weekly (30-40 IU/kg) with the ability to dose every 5 days (45-60 IU/kg) and further individually adjust to less or more frequent dosing based on bleeding episodes.

The FDA’s approval of Jivi is based on results from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated Jivi for perioperative management.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo courtesy of Amgen

The European Commission (EC) has expanded the approved indication for blinatumomab (Blincyto®), a bispecific, CD19-directed, CD3 T-cell engager immunotherapy.

Blinatumomab is now approved as monotherapy for pediatric patients age 1 year or older who have relapsed/refractory, Philadelphia chromosome-negative, CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL).

The patients must have received at least two prior therapies, or they must have relapsed after allogeneic hematopoietic stem cell transplant.

This approval of blinatumomab extends to all countries in the European Union, as well as Norway, Iceland, and Liechtenstein.

The EC previously approved blinatumomab to treat adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor ALL.

’205 study

The EC’s approval of blinatumomab in pediatric patients is based on results from the phase 1/2 ’205 study, which were published in the Journal of Clinical Oncology in 2016.

The study included 93 pediatric patients with relapsed/refractory B-cell precursor ALL. Patients received blinatumomab as a continuous intravenous infusion—49 patients in the phase 1 portion of the trial and 44 in phase 2. The patients were followed for 2 years.

There were 4 dose-limiting toxicities (DLTs) during the phase 1 portion of the trial, and 2 DLTs were fatal. Three patients had grade 4 cytokine release syndrome (CRS), one had grade 5 cardiac failure (as well as grade 4 CRS), and one had grade 5 respiratory failure.

Recommended dose

Based on the DLTs, the maximum-tolerated dose of blinatumomab was 15 µg/m²/day, but a step-wise dosage was recommended to reduce the risk of CRS. The recommended dose was 5 μg/m²/day on days 1-7 and 15 μg/m²/day on days 8-28 for cycle 1, and 15 μg/m²/day on days 1-28 for subsequent cycles.

Dose adjustment was possible in case of adverse events (AEs). Patients who responded to blinatumomab but later relapsed had the option to be retreated with blinatumomab.

Seventy patients received at least one infusion of blinatumomab at the recommended dose. The median number of treatment cycles was 1 (range, 1 to 5).

The patients’ median age was 8 years (range, 7 months to 17 years). Forty patients (57%) had undergone allogeneic transplant prior to receiving blinatumomab, and 39 (56%) had refractory disease.

Safety

The most common AEs among patients who received the recommended dose of blinatumomab were pyrexia (80%), anemia (41%), nausea (33%), and headache (30%).

The most frequent grade 3 or higher AEs were anemia (36%), thrombocytopenia (21%), febrile neutropenia (17%), hypokalemia (17%), and neutropenia (17%).

Eight patients developed CRS. Three had grade 3 and one had grade 4 CRS.

Ten patients (14%) had treatment interruptions due to AEs, and 4 (6%) discontinued treatment permanently because of AEs.

Six patients had fatal AEs. Three died after they went on to allogeneic transplant—one of multiorgan failure, one of sepsis, and one of respiratory failure. The three other deaths were due to fungal infection, multiorgan failure, and thrombocytopenia.

Response and follow-up

Among the 70 patients who received the recommended dose of blinatumomab, 27 (39%) achieved a complete response (CR) within the first 2 cycles. Fourteen of these patients (52%) achieved minimal residual disease negativity.

Thirteen of the 27 patients (48%) who achieved a CR went on to receive an allogeneic transplant.

At the end of the 2-year follow-up, 4 of the 27 complete responders were still in remission.

Two of the patients had relapsed but were still alive, three had withdrawn consent (one in CR and two after relapse), three had died in CR after transplant, and 15 had relapsed and died.

Of the 43 patients who did not achieve a CR within the first two treatment cycles, 8 were still alive at the end of the 2-year follow-up.

Photo courtesy of Amgen

The European Commission (EC) has expanded the approved indication for blinatumomab (Blincyto®), a bispecific, CD19-directed, CD3 T-cell engager immunotherapy.

Blinatumomab is now approved as monotherapy for pediatric patients age 1 year or older who have relapsed/refractory, Philadelphia chromosome-negative, CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL).

The patients must have received at least two prior therapies, or they must have relapsed after allogeneic hematopoietic stem cell transplant.

This approval of blinatumomab extends to all countries in the European Union, as well as Norway, Iceland, and Liechtenstein.

The EC previously approved blinatumomab to treat adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor ALL.

’205 study

The EC’s approval of blinatumomab in pediatric patients is based on results from the phase 1/2 ’205 study, which were published in the Journal of Clinical Oncology in 2016.

The study included 93 pediatric patients with relapsed/refractory B-cell precursor ALL. Patients received blinatumomab as a continuous intravenous infusion—49 patients in the phase 1 portion of the trial and 44 in phase 2. The patients were followed for 2 years.

There were 4 dose-limiting toxicities (DLTs) during the phase 1 portion of the trial, and 2 DLTs were fatal. Three patients had grade 4 cytokine release syndrome (CRS), one had grade 5 cardiac failure (as well as grade 4 CRS), and one had grade 5 respiratory failure.

Recommended dose

Based on the DLTs, the maximum-tolerated dose of blinatumomab was 15 µg/m²/day, but a step-wise dosage was recommended to reduce the risk of CRS. The recommended dose was 5 μg/m²/day on days 1-7 and 15 μg/m²/day on days 8-28 for cycle 1, and 15 μg/m²/day on days 1-28 for subsequent cycles.

Dose adjustment was possible in case of adverse events (AEs). Patients who responded to blinatumomab but later relapsed had the option to be retreated with blinatumomab.

Seventy patients received at least one infusion of blinatumomab at the recommended dose. The median number of treatment cycles was 1 (range, 1 to 5).

The patients’ median age was 8 years (range, 7 months to 17 years). Forty patients (57%) had undergone allogeneic transplant prior to receiving blinatumomab, and 39 (56%) had refractory disease.

Safety

The most common AEs among patients who received the recommended dose of blinatumomab were pyrexia (80%), anemia (41%), nausea (33%), and headache (30%).

The most frequent grade 3 or higher AEs were anemia (36%), thrombocytopenia (21%), febrile neutropenia (17%), hypokalemia (17%), and neutropenia (17%).

Eight patients developed CRS. Three had grade 3 and one had grade 4 CRS.

Ten patients (14%) had treatment interruptions due to AEs, and 4 (6%) discontinued treatment permanently because of AEs.

Six patients had fatal AEs. Three died after they went on to allogeneic transplant—one of multiorgan failure, one of sepsis, and one of respiratory failure. The three other deaths were due to fungal infection, multiorgan failure, and thrombocytopenia.

Response and follow-up

Among the 70 patients who received the recommended dose of blinatumomab, 27 (39%) achieved a complete response (CR) within the first 2 cycles. Fourteen of these patients (52%) achieved minimal residual disease negativity.

Thirteen of the 27 patients (48%) who achieved a CR went on to receive an allogeneic transplant.

At the end of the 2-year follow-up, 4 of the 27 complete responders were still in remission.

Two of the patients had relapsed but were still alive, three had withdrawn consent (one in CR and two after relapse), three had died in CR after transplant, and 15 had relapsed and died.

Of the 43 patients who did not achieve a CR within the first two treatment cycles, 8 were still alive at the end of the 2-year follow-up.

Photo courtesy of Amgen

The European Commission (EC) has expanded the approved indication for blinatumomab (Blincyto®), a bispecific, CD19-directed, CD3 T-cell engager immunotherapy.

Blinatumomab is now approved as monotherapy for pediatric patients age 1 year or older who have relapsed/refractory, Philadelphia chromosome-negative, CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL).

The patients must have received at least two prior therapies, or they must have relapsed after allogeneic hematopoietic stem cell transplant.

This approval of blinatumomab extends to all countries in the European Union, as well as Norway, Iceland, and Liechtenstein.

The EC previously approved blinatumomab to treat adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor ALL.

’205 study

The EC’s approval of blinatumomab in pediatric patients is based on results from the phase 1/2 ’205 study, which were published in the Journal of Clinical Oncology in 2016.

The study included 93 pediatric patients with relapsed/refractory B-cell precursor ALL. Patients received blinatumomab as a continuous intravenous infusion—49 patients in the phase 1 portion of the trial and 44 in phase 2. The patients were followed for 2 years.

There were 4 dose-limiting toxicities (DLTs) during the phase 1 portion of the trial, and 2 DLTs were fatal. Three patients had grade 4 cytokine release syndrome (CRS), one had grade 5 cardiac failure (as well as grade 4 CRS), and one had grade 5 respiratory failure.

Recommended dose

Based on the DLTs, the maximum-tolerated dose of blinatumomab was 15 µg/m²/day, but a step-wise dosage was recommended to reduce the risk of CRS. The recommended dose was 5 μg/m²/day on days 1-7 and 15 μg/m²/day on days 8-28 for cycle 1, and 15 μg/m²/day on days 1-28 for subsequent cycles.

Dose adjustment was possible in case of adverse events (AEs). Patients who responded to blinatumomab but later relapsed had the option to be retreated with blinatumomab.

Seventy patients received at least one infusion of blinatumomab at the recommended dose. The median number of treatment cycles was 1 (range, 1 to 5).

The patients’ median age was 8 years (range, 7 months to 17 years). Forty patients (57%) had undergone allogeneic transplant prior to receiving blinatumomab, and 39 (56%) had refractory disease.

Safety

The most common AEs among patients who received the recommended dose of blinatumomab were pyrexia (80%), anemia (41%), nausea (33%), and headache (30%).

The most frequent grade 3 or higher AEs were anemia (36%), thrombocytopenia (21%), febrile neutropenia (17%), hypokalemia (17%), and neutropenia (17%).

Eight patients developed CRS. Three had grade 3 and one had grade 4 CRS.

Ten patients (14%) had treatment interruptions due to AEs, and 4 (6%) discontinued treatment permanently because of AEs.

Six patients had fatal AEs. Three died after they went on to allogeneic transplant—one of multiorgan failure, one of sepsis, and one of respiratory failure. The three other deaths were due to fungal infection, multiorgan failure, and thrombocytopenia.

Response and follow-up

Among the 70 patients who received the recommended dose of blinatumomab, 27 (39%) achieved a complete response (CR) within the first 2 cycles. Fourteen of these patients (52%) achieved minimal residual disease negativity.

Thirteen of the 27 patients (48%) who achieved a CR went on to receive an allogeneic transplant.

At the end of the 2-year follow-up, 4 of the 27 complete responders were still in remission.

Two of the patients had relapsed but were still alive, three had withdrawn consent (one in CR and two after relapse), three had died in CR after transplant, and 15 had relapsed and died.

Of the 43 patients who did not achieve a CR within the first two treatment cycles, 8 were still alive at the end of the 2-year follow-up.

Photo by Bill Branson

The European Commission (EC) has approved CPX-351 (Vyxeos), a liposomal formulation that delivers a fixed ratio of daunorubicin and cytarabine (44 mg/100 mg).

CPX-351 is approved to treat adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.

The approval extends to all European Union member states as well as Iceland, Norway, and Liechtenstein.

The EC’s approval is supported by data from 5 studies, including a phase 3 trial.

Data from the phase 3 trial were published in the Journal of Clinical Oncology in July.

The trial enrolled 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

Patients received CPX-351 (n=153) or cytarabine and daunorubicin (7+3; n=156).

The overall remission rate—the rate of complete response (CR) plus CR with incomplete count recovery—was 47.7% in the CPX-351 arm and 33.3% in the 7+3 arm (P=0.016). The CR rate was 37.3% and 25.6%, respectively (P=0.040).

About 30% of patients went on to allogeneic hematopoietic stem cell transplant—34% in the CPX-351 arm and 25% in the 7+3 arm (P=0.098).

The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (P=0.003). The median event-free survival was 2.53 months and 1.31 months, respectively (P=0.021).

Adverse events (AEs) that led to treatment discontinuation in the CPX-351 arm were cardiac failure (n=1), cardiomyopathy (n=1), and acute renal failure (n=1). AEs that led to treatment discontinuation in the 7+3 arm were decreased ejection fraction in 2 patients.

The most common grade 3 to 5 AEs (in the CPX-351 and 7+3 arms, respectively) were infection-related events (83.7% and 86.1%), febrile neutropenia (68.0% and 70.9%), pneumonia (19.6% and 14.6%), hypoxia (13.1% and 15.2%), and bleeding events (11.8% and 8.6%).

Ultimately, 69.3% of patients in the CPX-351 arm and 84.8% of those in the 7+3 arm died.

Deaths (in the CPX-351 and 7+3 cohorts, respectively) were due to progressive disease (n=65 and 67), AEs (n=15 and 19), cancer-related organ failure in the absence of progressive disease (n=0 and 5), and unknown/other causes (n=26 and 37).

Photo by Bill Branson

The European Commission (EC) has approved CPX-351 (Vyxeos), a liposomal formulation that delivers a fixed ratio of daunorubicin and cytarabine (44 mg/100 mg).

CPX-351 is approved to treat adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.

The approval extends to all European Union member states as well as Iceland, Norway, and Liechtenstein.

The EC’s approval is supported by data from 5 studies, including a phase 3 trial.

Data from the phase 3 trial were published in the Journal of Clinical Oncology in July.

The trial enrolled 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

Patients received CPX-351 (n=153) or cytarabine and daunorubicin (7+3; n=156).

The overall remission rate—the rate of complete response (CR) plus CR with incomplete count recovery—was 47.7% in the CPX-351 arm and 33.3% in the 7+3 arm (P=0.016). The CR rate was 37.3% and 25.6%, respectively (P=0.040).

About 30% of patients went on to allogeneic hematopoietic stem cell transplant—34% in the CPX-351 arm and 25% in the 7+3 arm (P=0.098).

The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (P=0.003). The median event-free survival was 2.53 months and 1.31 months, respectively (P=0.021).

Adverse events (AEs) that led to treatment discontinuation in the CPX-351 arm were cardiac failure (n=1), cardiomyopathy (n=1), and acute renal failure (n=1). AEs that led to treatment discontinuation in the 7+3 arm were decreased ejection fraction in 2 patients.

The most common grade 3 to 5 AEs (in the CPX-351 and 7+3 arms, respectively) were infection-related events (83.7% and 86.1%), febrile neutropenia (68.0% and 70.9%), pneumonia (19.6% and 14.6%), hypoxia (13.1% and 15.2%), and bleeding events (11.8% and 8.6%).

Ultimately, 69.3% of patients in the CPX-351 arm and 84.8% of those in the 7+3 arm died.

Deaths (in the CPX-351 and 7+3 cohorts, respectively) were due to progressive disease (n=65 and 67), AEs (n=15 and 19), cancer-related organ failure in the absence of progressive disease (n=0 and 5), and unknown/other causes (n=26 and 37).

Photo by Bill Branson

The European Commission (EC) has approved CPX-351 (Vyxeos), a liposomal formulation that delivers a fixed ratio of daunorubicin and cytarabine (44 mg/100 mg).

CPX-351 is approved to treat adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.

The approval extends to all European Union member states as well as Iceland, Norway, and Liechtenstein.

The EC’s approval is supported by data from 5 studies, including a phase 3 trial.

Data from the phase 3 trial were published in the Journal of Clinical Oncology in July.

The trial enrolled 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

Patients received CPX-351 (n=153) or cytarabine and daunorubicin (7+3; n=156).

The overall remission rate—the rate of complete response (CR) plus CR with incomplete count recovery—was 47.7% in the CPX-351 arm and 33.3% in the 7+3 arm (P=0.016). The CR rate was 37.3% and 25.6%, respectively (P=0.040).

About 30% of patients went on to allogeneic hematopoietic stem cell transplant—34% in the CPX-351 arm and 25% in the 7+3 arm (P=0.098).

The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (P=0.003). The median event-free survival was 2.53 months and 1.31 months, respectively (P=0.021).

Adverse events (AEs) that led to treatment discontinuation in the CPX-351 arm were cardiac failure (n=1), cardiomyopathy (n=1), and acute renal failure (n=1). AEs that led to treatment discontinuation in the 7+3 arm were decreased ejection fraction in 2 patients.

The most common grade 3 to 5 AEs (in the CPX-351 and 7+3 arms, respectively) were infection-related events (83.7% and 86.1%), febrile neutropenia (68.0% and 70.9%), pneumonia (19.6% and 14.6%), hypoxia (13.1% and 15.2%), and bleeding events (11.8% and 8.6%).

Ultimately, 69.3% of patients in the CPX-351 arm and 84.8% of those in the 7+3 arm died.

Deaths (in the CPX-351 and 7+3 cohorts, respectively) were due to progressive disease (n=65 and 67), AEs (n=15 and 19), cancer-related organ failure in the absence of progressive disease (n=0 and 5), and unknown/other causes (n=26 and 37).

Photo from Novartis

The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy targeting CD19.

Tisagenlecleucel (formerly CTL019) is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

The EC’s approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.

Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.

The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.

JULIET trial

Updated results from JULIET were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).

The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so due to disease progression or clinical deterioration. The patients’ median age at baseline was 56 (range, 22-76).

Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.

The median time from infusion to data cutoff was 13.9 months.

The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached.

At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.

For all infused patients (n=111), the 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Fifteen percent of patients received tocilizumab for CRS, including 3% of patients with grade 2 CRS and 50% of patients with grade 3 CRS.

Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).

ELIANA trial

Updated results from ELIANA were published in NEJM in February.

The trial included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).

All 75 patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.

The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to transplant while in remission. At last follow-up, 4 were still in remission, and 4 had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

All patients experienced at least one AE, and 95% had AEs thought to be related to tisagenlecleucel. The rate of grade 3/4 AEs was 88%, and the rate of related grade 3/4 AEs was 73%.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

Photo from Novartis

The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy targeting CD19.

Tisagenlecleucel (formerly CTL019) is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

The EC’s approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.

Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.

The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.

JULIET trial

Updated results from JULIET were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).

The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so due to disease progression or clinical deterioration. The patients’ median age at baseline was 56 (range, 22-76).

Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.

The median time from infusion to data cutoff was 13.9 months.

The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached.

At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.

For all infused patients (n=111), the 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Fifteen percent of patients received tocilizumab for CRS, including 3% of patients with grade 2 CRS and 50% of patients with grade 3 CRS.

Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).

ELIANA trial

Updated results from ELIANA were published in NEJM in February.

The trial included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).

All 75 patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.

The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to transplant while in remission. At last follow-up, 4 were still in remission, and 4 had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

All patients experienced at least one AE, and 95% had AEs thought to be related to tisagenlecleucel. The rate of grade 3/4 AEs was 88%, and the rate of related grade 3/4 AEs was 73%.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

Photo from Novartis

The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy targeting CD19.

Tisagenlecleucel (formerly CTL019) is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

The EC’s approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.

Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.

The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.

JULIET trial

Updated results from JULIET were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).

The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so due to disease progression or clinical deterioration. The patients’ median age at baseline was 56 (range, 22-76).

Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.

The median time from infusion to data cutoff was 13.9 months.

The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached.

At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.

For all infused patients (n=111), the 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Fifteen percent of patients received tocilizumab for CRS, including 3% of patients with grade 2 CRS and 50% of patients with grade 3 CRS.

Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).

ELIANA trial

Updated results from ELIANA were published in NEJM in February.

The trial included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).

All 75 patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.

The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to transplant while in remission. At last follow-up, 4 were still in remission, and 4 had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

All patients experienced at least one AE, and 95% had AEs thought to be related to tisagenlecleucel. The rate of grade 3/4 AEs was 88%, and the rate of related grade 3/4 AEs was 73%.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).