HT Staff

Photo from Penn Medicine

The US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) has unanimously recommended approval for the chimeric antigen receptor (CAR) T-cell therapy CTL019 (tisagenlecleucel).

The committee voted 10 to 0 in favor of approving CTL019 for the treatment of pediatric and young adult patients (ages 3 to 25) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

The FDA will consider this vote as it reviews the biologics license application (BLA) for CTL019, but the agency is not obligated to follow the ODAC’s recommendation.

The BLA for CTL019 is supported by results from 3 trials.

This includes a pilot study, which was presented at the 2015 ASH Annual Meeting; the phase 2 ENSIGN trial, which was presented at the 2016 ASH Annual Meeting; and the phase 2 ELIANA study, which was recently presented at the 22nd Congress of the European Hematology Association (EHA).

ELIANA enrolled 88 patients with relapsed/refractory B-cell ALL, and 68 of them received CTL019.

Nine patients did not receive CTL019 due to death or adverse events, 7 patients were affected by manufacturing failures, and 4 patients were pending infusion at last follow-up.

Most of the infused patients (n=65) received lymphodepleting chemotherapy prior to CTL019 (single dose). The median dose was 3.0 × 10⁶ (range, 0.2-5.4 × 10⁶) transduced CTL019 cells/kg.

Sixty-three patients were evaluable for efficacy.

The overall response rate—complete response (CR) plus CR with incomplete hematologic recovery (CRi)—was 83% (52/63). All patients with CR/CRis were minimal residual disease-negative in the bone marrow.

Sixty-eight patients were evaluated for safety.

Serious adverse events occurred in 69% of patients. These included life-threatening cytokine release syndrome (CRS) and hemophagocytic lymphohistiocytosis, neurological events that occurred with CRS or after CRS was resolved, coagulopathies with CRS, and life-threatening infections.

Seventy-eight percent of patients had CRS—21% with grade 3 and 27% with grade 4 CRS. There were no deaths from CRS.

Forty-four percent of patients had neurological toxicities—15% grade 3 or higher. These included encephalopathy, delirium, hallucinations, somnolence, cognitive disorder, seizure, depressed level of consciousness, mental status changes, dysphagia, muscular weakness, and dysarthria.

Severe infectious complications occurred in 26% of patients, and 3 patients died of such complications.

Eleven patients died after receiving CTL019—7 due to ALL, 1 from cerebral hemorrhage, 1 from encephalitis, 1 from a respiratory tract infection, and 1 from systemic mycosis.

Photo from Penn Medicine

The US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) has unanimously recommended approval for the chimeric antigen receptor (CAR) T-cell therapy CTL019 (tisagenlecleucel).

The committee voted 10 to 0 in favor of approving CTL019 for the treatment of pediatric and young adult patients (ages 3 to 25) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

The FDA will consider this vote as it reviews the biologics license application (BLA) for CTL019, but the agency is not obligated to follow the ODAC’s recommendation.

The BLA for CTL019 is supported by results from 3 trials.

This includes a pilot study, which was presented at the 2015 ASH Annual Meeting; the phase 2 ENSIGN trial, which was presented at the 2016 ASH Annual Meeting; and the phase 2 ELIANA study, which was recently presented at the 22nd Congress of the European Hematology Association (EHA).

ELIANA enrolled 88 patients with relapsed/refractory B-cell ALL, and 68 of them received CTL019.

Nine patients did not receive CTL019 due to death or adverse events, 7 patients were affected by manufacturing failures, and 4 patients were pending infusion at last follow-up.

Most of the infused patients (n=65) received lymphodepleting chemotherapy prior to CTL019 (single dose). The median dose was 3.0 × 10⁶ (range, 0.2-5.4 × 10⁶) transduced CTL019 cells/kg.

Sixty-three patients were evaluable for efficacy.

The overall response rate—complete response (CR) plus CR with incomplete hematologic recovery (CRi)—was 83% (52/63). All patients with CR/CRis were minimal residual disease-negative in the bone marrow.

Sixty-eight patients were evaluated for safety.

Serious adverse events occurred in 69% of patients. These included life-threatening cytokine release syndrome (CRS) and hemophagocytic lymphohistiocytosis, neurological events that occurred with CRS or after CRS was resolved, coagulopathies with CRS, and life-threatening infections.

Seventy-eight percent of patients had CRS—21% with grade 3 and 27% with grade 4 CRS. There were no deaths from CRS.

Forty-four percent of patients had neurological toxicities—15% grade 3 or higher. These included encephalopathy, delirium, hallucinations, somnolence, cognitive disorder, seizure, depressed level of consciousness, mental status changes, dysphagia, muscular weakness, and dysarthria.

Severe infectious complications occurred in 26% of patients, and 3 patients died of such complications.

Eleven patients died after receiving CTL019—7 due to ALL, 1 from cerebral hemorrhage, 1 from encephalitis, 1 from a respiratory tract infection, and 1 from systemic mycosis.

Photo from Penn Medicine

The US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) has unanimously recommended approval for the chimeric antigen receptor (CAR) T-cell therapy CTL019 (tisagenlecleucel).

The committee voted 10 to 0 in favor of approving CTL019 for the treatment of pediatric and young adult patients (ages 3 to 25) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

The FDA will consider this vote as it reviews the biologics license application (BLA) for CTL019, but the agency is not obligated to follow the ODAC’s recommendation.

The BLA for CTL019 is supported by results from 3 trials.

This includes a pilot study, which was presented at the 2015 ASH Annual Meeting; the phase 2 ENSIGN trial, which was presented at the 2016 ASH Annual Meeting; and the phase 2 ELIANA study, which was recently presented at the 22nd Congress of the European Hematology Association (EHA).

ELIANA enrolled 88 patients with relapsed/refractory B-cell ALL, and 68 of them received CTL019.

Nine patients did not receive CTL019 due to death or adverse events, 7 patients were affected by manufacturing failures, and 4 patients were pending infusion at last follow-up.

Most of the infused patients (n=65) received lymphodepleting chemotherapy prior to CTL019 (single dose). The median dose was 3.0 × 10⁶ (range, 0.2-5.4 × 10⁶) transduced CTL019 cells/kg.

Sixty-three patients were evaluable for efficacy.

The overall response rate—complete response (CR) plus CR with incomplete hematologic recovery (CRi)—was 83% (52/63). All patients with CR/CRis were minimal residual disease-negative in the bone marrow.

Sixty-eight patients were evaluated for safety.

Serious adverse events occurred in 69% of patients. These included life-threatening cytokine release syndrome (CRS) and hemophagocytic lymphohistiocytosis, neurological events that occurred with CRS or after CRS was resolved, coagulopathies with CRS, and life-threatening infections.

Seventy-eight percent of patients had CRS—21% with grade 3 and 27% with grade 4 CRS. There were no deaths from CRS.

Forty-four percent of patients had neurological toxicities—15% grade 3 or higher. These included encephalopathy, delirium, hallucinations, somnolence, cognitive disorder, seizure, depressed level of consciousness, mental status changes, dysphagia, muscular weakness, and dysarthria.

Severe infectious complications occurred in 26% of patients, and 3 patients died of such complications.

Eleven patients died after receiving CTL019—7 due to ALL, 1 from cerebral hemorrhage, 1 from encephalitis, 1 from a respiratory tract infection, and 1 from systemic mycosis.

Photo by Bill Branson

The US Food and Drug Administration’s (FDA) Oncologic Drug Advisory Committee (ODAC) has announced a positive opinion of gemtuzumab ozogamicin (GO, Mylotarg), a drug that was withdrawn from the US market in 2010.

In a vote of 6 to 1, the ODAC concluded that trial results suggest a favorable risk-benefit profile for low-dose GO given in combination with standard chemotherapy to patients with newly diagnosed, CD33-positive acute myeloid leukemia (AML).

The ODAC’s role is to provide recommendations to the FDA. The FDA is expected to make a decision on the biologics license application (BLA) for GO by September 2017.

With this BLA, Pfizer is seeking approval for GO in 2 indications.

One is for GO in combination with standard chemotherapy (daunorubicin and cytarabine) for the treatment of previously untreated, de novo, CD33-positive AML.

The other is for GO monotherapy for CD33-positive AML patients in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy.

GO is an investigational antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

However, results of subsequent trials suggested that a lower dose of GO was safer.

The current BLA for GO includes data from such a study, known as ALFA-0701.

The ODAC voted that results from ALFA-0701 demonstrated a favorable risk-benefit profile for GO when the drug was given at 3 mg/m² on days 1, 4, and 7 in combination with daunorubicin and cytarabine.

The BLA for GO also includes Pfizer-sponsored studies from the original new drug application for GO and a meta-analysis of patients in 5 randomized, phase 3 studies (including ALFA-0701). These studies span 10 years of research and include more than 4300 patients.

Photo by Bill Branson

The US Food and Drug Administration’s (FDA) Oncologic Drug Advisory Committee (ODAC) has announced a positive opinion of gemtuzumab ozogamicin (GO, Mylotarg), a drug that was withdrawn from the US market in 2010.

In a vote of 6 to 1, the ODAC concluded that trial results suggest a favorable risk-benefit profile for low-dose GO given in combination with standard chemotherapy to patients with newly diagnosed, CD33-positive acute myeloid leukemia (AML).

The ODAC’s role is to provide recommendations to the FDA. The FDA is expected to make a decision on the biologics license application (BLA) for GO by September 2017.

With this BLA, Pfizer is seeking approval for GO in 2 indications.

One is for GO in combination with standard chemotherapy (daunorubicin and cytarabine) for the treatment of previously untreated, de novo, CD33-positive AML.

The other is for GO monotherapy for CD33-positive AML patients in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy.

GO is an investigational antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

However, results of subsequent trials suggested that a lower dose of GO was safer.

The current BLA for GO includes data from such a study, known as ALFA-0701.

The ODAC voted that results from ALFA-0701 demonstrated a favorable risk-benefit profile for GO when the drug was given at 3 mg/m² on days 1, 4, and 7 in combination with daunorubicin and cytarabine.

The BLA for GO also includes Pfizer-sponsored studies from the original new drug application for GO and a meta-analysis of patients in 5 randomized, phase 3 studies (including ALFA-0701). These studies span 10 years of research and include more than 4300 patients.

Photo by Bill Branson

The US Food and Drug Administration’s (FDA) Oncologic Drug Advisory Committee (ODAC) has announced a positive opinion of gemtuzumab ozogamicin (GO, Mylotarg), a drug that was withdrawn from the US market in 2010.

In a vote of 6 to 1, the ODAC concluded that trial results suggest a favorable risk-benefit profile for low-dose GO given in combination with standard chemotherapy to patients with newly diagnosed, CD33-positive acute myeloid leukemia (AML).

The ODAC’s role is to provide recommendations to the FDA. The FDA is expected to make a decision on the biologics license application (BLA) for GO by September 2017.

With this BLA, Pfizer is seeking approval for GO in 2 indications.

One is for GO in combination with standard chemotherapy (daunorubicin and cytarabine) for the treatment of previously untreated, de novo, CD33-positive AML.

The other is for GO monotherapy for CD33-positive AML patients in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy.

GO is an investigational antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

However, results of subsequent trials suggested that a lower dose of GO was safer.

The current BLA for GO includes data from such a study, known as ALFA-0701.

The ODAC voted that results from ALFA-0701 demonstrated a favorable risk-benefit profile for GO when the drug was given at 3 mg/m² on days 1, 4, and 7 in combination with daunorubicin and cytarabine.

The BLA for GO also includes Pfizer-sponsored studies from the original new drug application for GO and a meta-analysis of patients in 5 randomized, phase 3 studies (including ALFA-0701). These studies span 10 years of research and include more than 4300 patients.

Photo by Piotr Bodzek

BERLIN—Final results from the RE-VERSE AD trial suggest idarucizumab can reverse the anticoagulant effect of dabigatran etexilate mesylate in emergency situations.

Patients who required dabigatran reversal because they needed urgent surgery were able to have their procedure a median of 1.6 hours from idarucizumab administration.

In patients who required dabigatran reversal due to uncontrollable bleeding, the median time to bleeding cessation was 2.5 hours. However, the time to bleeding cessation could not be assessed in all patients.

“RE-VERSE AD has shown that idarucizumab reverses the anticoagulant effect of dabigatran within minutes so that treating physicians can fully focus on dealing with the emergency at hand,” said study investigator Charles Pollack, MD, of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania.

“Prior to idarucizumab, there was no rapid, reliable, and effective method for reversing dabigatran and other orally administered blood thinners, which otherwise may take at least 12 to 24 hours to clear from the body.”

The rate of thrombotic events in RE-VERSE AD was low (6% to 7%), and researchers said there were no serious adverse safety signals related to idarucizumab.

These results were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress and published in NEJM. The research was funded by Boehringer Ingelheim Pharmaceuticals.

The phase 3 trial enrolled 503 patients who required dabigatran reversal. They were divided into 2 groups.

Group A included 301 patients with uncontrolled or life-threatening bleeding complications (eg, intracranial hemorrhage or severe trauma after a car accident).

Group B included 202 patients requiring an invasive procedure or an emergency surgery or intervention (eg, surgery for an open fracture after a fall).

Results

The study’s primary endpoint was the degree of reversal of the anticoagulant effect of dabigatran achieved by idarucizumab within 4 hours. This was measured by diluted thrombin time or ecarin clotting time.

The median maximum percentage of dabigatran reversal was 100%. Dabigatran reversal occurred independently of patients’ age, sex, renal function, and dabigatran concentration at baseline.

Group A

Roughly 68% of evaluable patients in Group A (134/203) had confirmed bleeding cessation within 24 hours of idarucizumab administration.

Bleeding cessation was not confirmed in 67 patients, bleeding stopped before treatment in 2 patients, and the time to bleeding cessation could not be assessed in the 98 patients with intracranial bleeding.

Among the 134 patients in who had confirmed bleeding cessation, the median time to hemostasis after idarucizumab administration was 2.5 hours.

Sixty-seven percent (n=201) of patients in Group A received hemostatic treatment, 62% (n=185) received whole blood/blood components, 7% (n=20) received plasma derivatives, and 23% (n=69) received volume expanders, pro-hemostatic agents, albumin, and other treatments.

At 90 days, thrombotic events had occurred in 6.3% of the patients in Group A, and the mortality rate was 18.8%.

Group B

For patients in Group B, their required procedures began a median of 1.6 hours from idarucizumab administration.

Hemostasis during the procedure was described as normal for 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%.

Thirty-nine percent (n=79) of patients in Group B received hemostatic treatment, 26% (n=53) received whole blood/blood components, 4% (n=8) received plasma derivatives, and 21% (n=42) received volume expanders, pro-hemostatic agents, albumin, and other treatments.

At 90 days, thrombotic events had occurred in 7.4% of patients in Group B, and the mortality rate was 18.9%.

Photo by Piotr Bodzek

BERLIN—Final results from the RE-VERSE AD trial suggest idarucizumab can reverse the anticoagulant effect of dabigatran etexilate mesylate in emergency situations.

Patients who required dabigatran reversal because they needed urgent surgery were able to have their procedure a median of 1.6 hours from idarucizumab administration.

In patients who required dabigatran reversal due to uncontrollable bleeding, the median time to bleeding cessation was 2.5 hours. However, the time to bleeding cessation could not be assessed in all patients.

“RE-VERSE AD has shown that idarucizumab reverses the anticoagulant effect of dabigatran within minutes so that treating physicians can fully focus on dealing with the emergency at hand,” said study investigator Charles Pollack, MD, of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania.

“Prior to idarucizumab, there was no rapid, reliable, and effective method for reversing dabigatran and other orally administered blood thinners, which otherwise may take at least 12 to 24 hours to clear from the body.”

The rate of thrombotic events in RE-VERSE AD was low (6% to 7%), and researchers said there were no serious adverse safety signals related to idarucizumab.

These results were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress and published in NEJM. The research was funded by Boehringer Ingelheim Pharmaceuticals.

The phase 3 trial enrolled 503 patients who required dabigatran reversal. They were divided into 2 groups.

Group A included 301 patients with uncontrolled or life-threatening bleeding complications (eg, intracranial hemorrhage or severe trauma after a car accident).

Group B included 202 patients requiring an invasive procedure or an emergency surgery or intervention (eg, surgery for an open fracture after a fall).

Results

The study’s primary endpoint was the degree of reversal of the anticoagulant effect of dabigatran achieved by idarucizumab within 4 hours. This was measured by diluted thrombin time or ecarin clotting time.

The median maximum percentage of dabigatran reversal was 100%. Dabigatran reversal occurred independently of patients’ age, sex, renal function, and dabigatran concentration at baseline.

Group A

Roughly 68% of evaluable patients in Group A (134/203) had confirmed bleeding cessation within 24 hours of idarucizumab administration.

Bleeding cessation was not confirmed in 67 patients, bleeding stopped before treatment in 2 patients, and the time to bleeding cessation could not be assessed in the 98 patients with intracranial bleeding.

Among the 134 patients in who had confirmed bleeding cessation, the median time to hemostasis after idarucizumab administration was 2.5 hours.

Sixty-seven percent (n=201) of patients in Group A received hemostatic treatment, 62% (n=185) received whole blood/blood components, 7% (n=20) received plasma derivatives, and 23% (n=69) received volume expanders, pro-hemostatic agents, albumin, and other treatments.

At 90 days, thrombotic events had occurred in 6.3% of the patients in Group A, and the mortality rate was 18.8%.

Group B

For patients in Group B, their required procedures began a median of 1.6 hours from idarucizumab administration.

Hemostasis during the procedure was described as normal for 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%.

Thirty-nine percent (n=79) of patients in Group B received hemostatic treatment, 26% (n=53) received whole blood/blood components, 4% (n=8) received plasma derivatives, and 21% (n=42) received volume expanders, pro-hemostatic agents, albumin, and other treatments.

At 90 days, thrombotic events had occurred in 7.4% of patients in Group B, and the mortality rate was 18.9%.

Photo by Piotr Bodzek

BERLIN—Final results from the RE-VERSE AD trial suggest idarucizumab can reverse the anticoagulant effect of dabigatran etexilate mesylate in emergency situations.

Patients who required dabigatran reversal because they needed urgent surgery were able to have their procedure a median of 1.6 hours from idarucizumab administration.

In patients who required dabigatran reversal due to uncontrollable bleeding, the median time to bleeding cessation was 2.5 hours. However, the time to bleeding cessation could not be assessed in all patients.

“RE-VERSE AD has shown that idarucizumab reverses the anticoagulant effect of dabigatran within minutes so that treating physicians can fully focus on dealing with the emergency at hand,” said study investigator Charles Pollack, MD, of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania.

“Prior to idarucizumab, there was no rapid, reliable, and effective method for reversing dabigatran and other orally administered blood thinners, which otherwise may take at least 12 to 24 hours to clear from the body.”

The rate of thrombotic events in RE-VERSE AD was low (6% to 7%), and researchers said there were no serious adverse safety signals related to idarucizumab.

These results were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress and published in NEJM. The research was funded by Boehringer Ingelheim Pharmaceuticals.

The phase 3 trial enrolled 503 patients who required dabigatran reversal. They were divided into 2 groups.

Group A included 301 patients with uncontrolled or life-threatening bleeding complications (eg, intracranial hemorrhage or severe trauma after a car accident).

Group B included 202 patients requiring an invasive procedure or an emergency surgery or intervention (eg, surgery for an open fracture after a fall).

Results

The study’s primary endpoint was the degree of reversal of the anticoagulant effect of dabigatran achieved by idarucizumab within 4 hours. This was measured by diluted thrombin time or ecarin clotting time.

The median maximum percentage of dabigatran reversal was 100%. Dabigatran reversal occurred independently of patients’ age, sex, renal function, and dabigatran concentration at baseline.

Group A

Roughly 68% of evaluable patients in Group A (134/203) had confirmed bleeding cessation within 24 hours of idarucizumab administration.

Bleeding cessation was not confirmed in 67 patients, bleeding stopped before treatment in 2 patients, and the time to bleeding cessation could not be assessed in the 98 patients with intracranial bleeding.

Among the 134 patients in who had confirmed bleeding cessation, the median time to hemostasis after idarucizumab administration was 2.5 hours.

Sixty-seven percent (n=201) of patients in Group A received hemostatic treatment, 62% (n=185) received whole blood/blood components, 7% (n=20) received plasma derivatives, and 23% (n=69) received volume expanders, pro-hemostatic agents, albumin, and other treatments.

At 90 days, thrombotic events had occurred in 6.3% of the patients in Group A, and the mortality rate was 18.8%.

Group B

For patients in Group B, their required procedures began a median of 1.6 hours from idarucizumab administration.

Hemostasis during the procedure was described as normal for 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%.

Thirty-nine percent (n=79) of patients in Group B received hemostatic treatment, 26% (n=53) received whole blood/blood components, 4% (n=8) received plasma derivatives, and 21% (n=42) received volume expanders, pro-hemostatic agents, albumin, and other treatments.

At 90 days, thrombotic events had occurred in 7.4% of patients in Group B, and the mortality rate was 18.9%.

Image by Difu Wu

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for dasatinib (Sprycel).

Bristol Myers Squibb is seeking approval for dasatinib as a treatment for children with Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML), as well as approval for a powder formulation of dasatinib for oral suspension.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the dasatinib sNDA by November 9, 2017.

The sNDA includes data from CA180-226 (NCT00777036), an ongoing, phase 2 trial of dasatinib in pediatric patients with CP-CML who are resistant to or cannot tolerate imatinib and pediatric patients newly diagnosed with CP-CML.

The trial enrolled patients aged 18 and younger with newly diagnosed CML or Ph+ leukemias resistant to or intolerant of imatinib.

Cohort 1 included 29 CP-CML patients resistant to or intolerant of imatinib. Cohort 2 included patients with accelerated/blast phase CML or Ph+ acute lymphoblastic leukemia. Cohort 3 included 84 patients with newly diagnosed CP-CML.

Data from Cohorts 1 and 3 were recently presented at the 2017 ASCO Annual Meeting.

Three months into treatment with dasatinib, patients with CP-CML who were resistant to or intolerant of imatinib (Cohort 1) had a cumulative major cytogenetic response rate of 55.2%. This response rate increased over time to exceed 90% at 24 months.

Newly diagnosed patients with CP-CML (Cohort 3) received dasatinib orally or as powder for oral suspension once daily. They achieved a cumulative complete cytogenetic response rate of 64% as early as 6 months into treatment. This response rate increased to 94% at 24 months.

The median duration of response was not estimable or not yet reached in each cohort at the time of follow-up.

The estimated progression-free survival at 48 months was greater than 75% for patients in Cohort 1 and greater than 90% for patients in Cohort 3.

The safety profile of dasatinib in this study was deemed comparable to that reported in adults with CP-CML. In this study, there were no reported events of pleural/pericardial effusion, pulmonary edema/hypertension, or pulmonary arterial hypertension related to dasatinib.

Dasatinib first received FDA approval in 2006. The drug is currently approved to treat adults with:

• Newly diagnosed Ph+ CP-CML
• Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
  

Image by Difu Wu

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for dasatinib (Sprycel).

Bristol Myers Squibb is seeking approval for dasatinib as a treatment for children with Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML), as well as approval for a powder formulation of dasatinib for oral suspension.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the dasatinib sNDA by November 9, 2017.

The sNDA includes data from CA180-226 (NCT00777036), an ongoing, phase 2 trial of dasatinib in pediatric patients with CP-CML who are resistant to or cannot tolerate imatinib and pediatric patients newly diagnosed with CP-CML.

The trial enrolled patients aged 18 and younger with newly diagnosed CML or Ph+ leukemias resistant to or intolerant of imatinib.

Cohort 1 included 29 CP-CML patients resistant to or intolerant of imatinib. Cohort 2 included patients with accelerated/blast phase CML or Ph+ acute lymphoblastic leukemia. Cohort 3 included 84 patients with newly diagnosed CP-CML.

Data from Cohorts 1 and 3 were recently presented at the 2017 ASCO Annual Meeting.

Three months into treatment with dasatinib, patients with CP-CML who were resistant to or intolerant of imatinib (Cohort 1) had a cumulative major cytogenetic response rate of 55.2%. This response rate increased over time to exceed 90% at 24 months.

Newly diagnosed patients with CP-CML (Cohort 3) received dasatinib orally or as powder for oral suspension once daily. They achieved a cumulative complete cytogenetic response rate of 64% as early as 6 months into treatment. This response rate increased to 94% at 24 months.

The median duration of response was not estimable or not yet reached in each cohort at the time of follow-up.

The estimated progression-free survival at 48 months was greater than 75% for patients in Cohort 1 and greater than 90% for patients in Cohort 3.

The safety profile of dasatinib in this study was deemed comparable to that reported in adults with CP-CML. In this study, there were no reported events of pleural/pericardial effusion, pulmonary edema/hypertension, or pulmonary arterial hypertension related to dasatinib.

Dasatinib first received FDA approval in 2006. The drug is currently approved to treat adults with:

• Newly diagnosed Ph+ CP-CML
• Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
  

Image by Difu Wu

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for dasatinib (Sprycel).

Bristol Myers Squibb is seeking approval for dasatinib as a treatment for children with Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML), as well as approval for a powder formulation of dasatinib for oral suspension.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the dasatinib sNDA by November 9, 2017.

The sNDA includes data from CA180-226 (NCT00777036), an ongoing, phase 2 trial of dasatinib in pediatric patients with CP-CML who are resistant to or cannot tolerate imatinib and pediatric patients newly diagnosed with CP-CML.

The trial enrolled patients aged 18 and younger with newly diagnosed CML or Ph+ leukemias resistant to or intolerant of imatinib.

Cohort 1 included 29 CP-CML patients resistant to or intolerant of imatinib. Cohort 2 included patients with accelerated/blast phase CML or Ph+ acute lymphoblastic leukemia. Cohort 3 included 84 patients with newly diagnosed CP-CML.

Data from Cohorts 1 and 3 were recently presented at the 2017 ASCO Annual Meeting.

Three months into treatment with dasatinib, patients with CP-CML who were resistant to or intolerant of imatinib (Cohort 1) had a cumulative major cytogenetic response rate of 55.2%. This response rate increased over time to exceed 90% at 24 months.

Newly diagnosed patients with CP-CML (Cohort 3) received dasatinib orally or as powder for oral suspension once daily. They achieved a cumulative complete cytogenetic response rate of 64% as early as 6 months into treatment. This response rate increased to 94% at 24 months.

The median duration of response was not estimable or not yet reached in each cohort at the time of follow-up.

The estimated progression-free survival at 48 months was greater than 75% for patients in Cohort 1 and greater than 90% for patients in Cohort 3.

The safety profile of dasatinib in this study was deemed comparable to that reported in adults with CP-CML. In this study, there were no reported events of pleural/pericardial effusion, pulmonary edema/hypertension, or pulmonary arterial hypertension related to dasatinib.

Dasatinib first received FDA approval in 2006. The drug is currently approved to treat adults with:

• Newly diagnosed Ph+ CP-CML
• Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
  

Hematology Analyzers

Sysmex America, Inc. has launched its XN-L™ automated hematology analyzers in the US.

The company says this new, smaller XN-L line delivers the same clinical and operational value as its XN-Series™ to lower-volume hematology laboratories.

“The XN-Series has been our flagship hematology analyzer line, and, today, we expand our offering by introducing the XN-L Series to meet the demands of lower-volume facilities,” said Andy Hay, chief operating officer of Sysmex America.

“With an XN-L analyzer, clinicians can rely upon the same expanded complete blood count (CBC) featured in our XN-Series analyzers to assess and monitor patients.  This expanded CBC goes well beyond the 3-part differential that is currently available to most of the low-volume segment today and can aid in the assessment of sepsis and other hematological disorders.”

The XN-L automated hematology analyzers offer a 6-part differential, including immature granulocyte analysis on each sample.

In addition, the XN-L Series offers optional software licenses for (1) a reticulocyte channel to aid in anemia management and (2) body fluid cell counts.

The XN-L analyzers will also be the first to feature BeyondCare Quality Monitor, a new approach to quality assurance.

“BeyondCare Quality Monitor, a Sysmex proprietary innovation, is a leading-edge, evidence-based QC and calibration verification management program that partners Sysmex with the laboratory to proactively monitor quality assurance metrics,” Hay said.  “It will be standard on all XN-L hematology analyzers.

Additional information on XN-L analyzers is available on the Sysmex website at www.sysmex.com/XNL.

The XN-L analyzers will be available both directly through the company and through its distribution partners. Interested parties should contact their Sysmex representative or Sysmex distributor for complete details. 

Hematology Analyzers

Sysmex America, Inc. has launched its XN-L™ automated hematology analyzers in the US.

The company says this new, smaller XN-L line delivers the same clinical and operational value as its XN-Series™ to lower-volume hematology laboratories.

“The XN-Series has been our flagship hematology analyzer line, and, today, we expand our offering by introducing the XN-L Series to meet the demands of lower-volume facilities,” said Andy Hay, chief operating officer of Sysmex America.

“With an XN-L analyzer, clinicians can rely upon the same expanded complete blood count (CBC) featured in our XN-Series analyzers to assess and monitor patients.  This expanded CBC goes well beyond the 3-part differential that is currently available to most of the low-volume segment today and can aid in the assessment of sepsis and other hematological disorders.”

The XN-L automated hematology analyzers offer a 6-part differential, including immature granulocyte analysis on each sample.

In addition, the XN-L Series offers optional software licenses for (1) a reticulocyte channel to aid in anemia management and (2) body fluid cell counts.

The XN-L analyzers will also be the first to feature BeyondCare Quality Monitor, a new approach to quality assurance.

“BeyondCare Quality Monitor, a Sysmex proprietary innovation, is a leading-edge, evidence-based QC and calibration verification management program that partners Sysmex with the laboratory to proactively monitor quality assurance metrics,” Hay said.  “It will be standard on all XN-L hematology analyzers.

Additional information on XN-L analyzers is available on the Sysmex website at www.sysmex.com/XNL.

The XN-L analyzers will be available both directly through the company and through its distribution partners. Interested parties should contact their Sysmex representative or Sysmex distributor for complete details. 

Hematology Analyzers

Sysmex America, Inc. has launched its XN-L™ automated hematology analyzers in the US.

The company says this new, smaller XN-L line delivers the same clinical and operational value as its XN-Series™ to lower-volume hematology laboratories.

“The XN-Series has been our flagship hematology analyzer line, and, today, we expand our offering by introducing the XN-L Series to meet the demands of lower-volume facilities,” said Andy Hay, chief operating officer of Sysmex America.

“With an XN-L analyzer, clinicians can rely upon the same expanded complete blood count (CBC) featured in our XN-Series analyzers to assess and monitor patients.  This expanded CBC goes well beyond the 3-part differential that is currently available to most of the low-volume segment today and can aid in the assessment of sepsis and other hematological disorders.”

The XN-L automated hematology analyzers offer a 6-part differential, including immature granulocyte analysis on each sample.

In addition, the XN-L Series offers optional software licenses for (1) a reticulocyte channel to aid in anemia management and (2) body fluid cell counts.

The XN-L analyzers will also be the first to feature BeyondCare Quality Monitor, a new approach to quality assurance.

“BeyondCare Quality Monitor, a Sysmex proprietary innovation, is a leading-edge, evidence-based QC and calibration verification management program that partners Sysmex with the laboratory to proactively monitor quality assurance metrics,” Hay said.  “It will be standard on all XN-L hematology analyzers.

Additional information on XN-L analyzers is available on the Sysmex website at www.sysmex.com/XNL.

The XN-L analyzers will be available both directly through the company and through its distribution partners. Interested parties should contact their Sysmex representative or Sysmex distributor for complete details. 

Photo by Linda Bartlett

BERLIN—Emicizumab can reduce bleeding in adults and adolescents with hemophilia A and inhibitors to factor VIII, according to a phase 3 trial.

In the HAVEN 1 trial, prophylaxis with emicizumab reduced the treated bleed rate by 87% when compared to no prophylaxis.

Emicizumab reduced the treated bleed rate by 79% when compared to prior prophylaxis with bypassing agents (BPAs).

The incidence of adverse events (AEs) related to emicizumab was 22%, and the incidence of serious AEs was 9%.

There were 3 cases of thrombotic microangiopathy, 2 serious thromboembolic events, and 1 death (from hemorrhage).

These results were presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Congress and published in NEJM.

The study was funded by F. Hoffmann–La Roche and Chugai Pharmaceutical.

“The HAVEN 1 study is one of the most robust clinical studies conducted to date in people with hemophilia A with inhibitors to factor VIII, including a first-ever intra-patient comparison to prior prophylaxis with bypassing agents,” said study author Johannes Oldenburg, MD, PhD, of the University of Bonn in Bonn, Germany.

“The reduction in bleeding events across all measures seen with emicizumab compared to either on-demand or prophylactic bypassing agents supports that it may be one of the most significant scientific innovations in the treatment of hemophilia A in over 30 years.”

Emicizumab is a bispecific monoclonal antibody designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process.

HAVEN 1 is a randomized, phase 3 study of emicizumab that enrolled 109 patients (12 years of age or older) with hemophilia A and inhibitors to factor VIII. The patients were previously treated with BPAs on-demand or as prophylaxis.

Patients previously treated with on-demand BPAs were randomized in a 2:1 fashion to receive emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B).

Patients previously treated with prophylactic BPAs received emicizumab prophylaxis (Arm C). Additional patients previously on BPAs (on-demand or prophylaxis) were also enrolled in a separate arm (Arm D).

On-demand treatment of breakthrough bleeds with BPAs was allowed per protocol in all arms.

Efficacy

The primary endpoint of this study was the number of treated bleeds over time with emicizumab prophylaxis (Arm A) compared with no prophylaxis (Arm B).

There was a significant reduction in treated bleeds of 87% (risk rate [RR]=0.13, P<0.0001) with emicizumab compared with no prophylaxis.

The researchers also performed an intra-patient comparison of bleed rate with emicizumab prophylaxis to bleed rate with prior prophylaxis (with BPAs) for patients in Arm C. A subset of patients in this arm had previously participated in a non-interventional study (NIS), which allowed for the comparison.

The analysis showed a 79% (RR=0.21, P=0.0003) reduction in treated bleeds in patients receiving emicizumab compared with their prior prophylaxis during the NIS.

Additional data on bleeds in Arms A, B, and C are included in the following table.

*Negative binomial regression model

Safety

Safety results in patients who received emicizumab prophylaxis (n=103) are as follows.

*The third thrombotic microangiopathy event occurred after the primary data cut-off. This patient also experienced fatal rectal hemorrhage.

**Serious thromboembolic events consisted of skin necrosis/superficial thrombophlebitis in 1 patient and cavernous sinus thrombosis in a second patient.

None of the patients tested positive for anti-drug antibodies. 

Photo by Linda Bartlett

BERLIN—Emicizumab can reduce bleeding in adults and adolescents with hemophilia A and inhibitors to factor VIII, according to a phase 3 trial.

In the HAVEN 1 trial, prophylaxis with emicizumab reduced the treated bleed rate by 87% when compared to no prophylaxis.

Emicizumab reduced the treated bleed rate by 79% when compared to prior prophylaxis with bypassing agents (BPAs).

The incidence of adverse events (AEs) related to emicizumab was 22%, and the incidence of serious AEs was 9%.

There were 3 cases of thrombotic microangiopathy, 2 serious thromboembolic events, and 1 death (from hemorrhage).

These results were presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Congress and published in NEJM.

The study was funded by F. Hoffmann–La Roche and Chugai Pharmaceutical.

“The HAVEN 1 study is one of the most robust clinical studies conducted to date in people with hemophilia A with inhibitors to factor VIII, including a first-ever intra-patient comparison to prior prophylaxis with bypassing agents,” said study author Johannes Oldenburg, MD, PhD, of the University of Bonn in Bonn, Germany.

“The reduction in bleeding events across all measures seen with emicizumab compared to either on-demand or prophylactic bypassing agents supports that it may be one of the most significant scientific innovations in the treatment of hemophilia A in over 30 years.”

Emicizumab is a bispecific monoclonal antibody designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process.

HAVEN 1 is a randomized, phase 3 study of emicizumab that enrolled 109 patients (12 years of age or older) with hemophilia A and inhibitors to factor VIII. The patients were previously treated with BPAs on-demand or as prophylaxis.

Patients previously treated with on-demand BPAs were randomized in a 2:1 fashion to receive emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B).

Patients previously treated with prophylactic BPAs received emicizumab prophylaxis (Arm C). Additional patients previously on BPAs (on-demand or prophylaxis) were also enrolled in a separate arm (Arm D).

On-demand treatment of breakthrough bleeds with BPAs was allowed per protocol in all arms.

Efficacy

The primary endpoint of this study was the number of treated bleeds over time with emicizumab prophylaxis (Arm A) compared with no prophylaxis (Arm B).

There was a significant reduction in treated bleeds of 87% (risk rate [RR]=0.13, P<0.0001) with emicizumab compared with no prophylaxis.

The researchers also performed an intra-patient comparison of bleed rate with emicizumab prophylaxis to bleed rate with prior prophylaxis (with BPAs) for patients in Arm C. A subset of patients in this arm had previously participated in a non-interventional study (NIS), which allowed for the comparison.

The analysis showed a 79% (RR=0.21, P=0.0003) reduction in treated bleeds in patients receiving emicizumab compared with their prior prophylaxis during the NIS.

Additional data on bleeds in Arms A, B, and C are included in the following table.

*Negative binomial regression model

Safety

Safety results in patients who received emicizumab prophylaxis (n=103) are as follows.

*The third thrombotic microangiopathy event occurred after the primary data cut-off. This patient also experienced fatal rectal hemorrhage.

**Serious thromboembolic events consisted of skin necrosis/superficial thrombophlebitis in 1 patient and cavernous sinus thrombosis in a second patient.

None of the patients tested positive for anti-drug antibodies. 

Photo by Linda Bartlett

BERLIN—Emicizumab can reduce bleeding in adults and adolescents with hemophilia A and inhibitors to factor VIII, according to a phase 3 trial.

In the HAVEN 1 trial, prophylaxis with emicizumab reduced the treated bleed rate by 87% when compared to no prophylaxis.

Emicizumab reduced the treated bleed rate by 79% when compared to prior prophylaxis with bypassing agents (BPAs).

The incidence of adverse events (AEs) related to emicizumab was 22%, and the incidence of serious AEs was 9%.

There were 3 cases of thrombotic microangiopathy, 2 serious thromboembolic events, and 1 death (from hemorrhage).

These results were presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Congress and published in NEJM.

The study was funded by F. Hoffmann–La Roche and Chugai Pharmaceutical.

“The HAVEN 1 study is one of the most robust clinical studies conducted to date in people with hemophilia A with inhibitors to factor VIII, including a first-ever intra-patient comparison to prior prophylaxis with bypassing agents,” said study author Johannes Oldenburg, MD, PhD, of the University of Bonn in Bonn, Germany.

“The reduction in bleeding events across all measures seen with emicizumab compared to either on-demand or prophylactic bypassing agents supports that it may be one of the most significant scientific innovations in the treatment of hemophilia A in over 30 years.”

Emicizumab is a bispecific monoclonal antibody designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process.

HAVEN 1 is a randomized, phase 3 study of emicizumab that enrolled 109 patients (12 years of age or older) with hemophilia A and inhibitors to factor VIII. The patients were previously treated with BPAs on-demand or as prophylaxis.

Patients previously treated with on-demand BPAs were randomized in a 2:1 fashion to receive emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B).

Patients previously treated with prophylactic BPAs received emicizumab prophylaxis (Arm C). Additional patients previously on BPAs (on-demand or prophylaxis) were also enrolled in a separate arm (Arm D).

On-demand treatment of breakthrough bleeds with BPAs was allowed per protocol in all arms.

Efficacy

The primary endpoint of this study was the number of treated bleeds over time with emicizumab prophylaxis (Arm A) compared with no prophylaxis (Arm B).

There was a significant reduction in treated bleeds of 87% (risk rate [RR]=0.13, P<0.0001) with emicizumab compared with no prophylaxis.

The researchers also performed an intra-patient comparison of bleed rate with emicizumab prophylaxis to bleed rate with prior prophylaxis (with BPAs) for patients in Arm C. A subset of patients in this arm had previously participated in a non-interventional study (NIS), which allowed for the comparison.

The analysis showed a 79% (RR=0.21, P=0.0003) reduction in treated bleeds in patients receiving emicizumab compared with their prior prophylaxis during the NIS.

Additional data on bleeds in Arms A, B, and C are included in the following table.

*Negative binomial regression model

Safety

Safety results in patients who received emicizumab prophylaxis (n=103) are as follows.

*The third thrombotic microangiopathy event occurred after the primary data cut-off. This patient also experienced fatal rectal hemorrhage.

**Serious thromboembolic events consisted of skin necrosis/superficial thrombophlebitis in 1 patient and cavernous sinus thrombosis in a second patient.

None of the patients tested positive for anti-drug antibodies. 

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

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

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

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

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

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

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

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

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

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.” 

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.” 

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.” 

Photo by Rhoda Baer

Narrow insurance plan coverage may prevent US cancer patients from receiving care at “high-quality” cancer centers, according to research published in the Journal of Clinical Oncology.

Researchers found that “narrow network” insurance plans—lower-premium plans with reduced access to certain providers—are more likely to exclude doctors associated with National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN) cancer centers.

These centers are recognized for their scientific and research leadership, quality and safety initiatives, and access to expert physicians and clinical trials.

NCCN member institutions are particularly recognized for higher-quality care, and treatment at NCI-designated cancer centers is associated with lower mortality than other hospitals, particularly among more severely ill patients and those with more advanced disease.

For this study, researchers examined cancer provider networks offered on the 2014 individual health insurance exchanges and then determined which oncologists were affiliated with NCI-designated and NCCN cancer centers.

The researchers found that narrower networks were less likely to include physicians associated with NCI-designated and NCCN member institutions.

“To see such a robust result was surprising,” said study author Laura Yasaitis, PhD, of the University of Pennsylvania in Philadelphia.

“The finding that narrower networks were more likely to exclude NCI and NCCN oncologists was consistent no matter how we looked at it. This is not just a few networks. It’s a clear trend.”

The researchers said the results point to 2 major problems—transparency and access.

“Patients should be able to easily figure out whether the physicians they might need will be covered under a given plan,” said study author Justin E. Bekelman, MD, of the University of Pennsylvania.

The researchers suggested that insurers report doctor’s affiliations with NCI and NCCN cancer centers so that consumers can make more informed choices.

The team also suggested that insurers offer mechanisms that would allow patients to seek care out of network without incurring penalties in exceptional circumstances.

“If patients have narrow network plans and absolutely need the kind of complex cancer care that they can only receive from one of these providers, there should be a standard exception process to allow patients to access the care they need,” Dr Bekelman said. 

Photo by Rhoda Baer

Narrow insurance plan coverage may prevent US cancer patients from receiving care at “high-quality” cancer centers, according to research published in the Journal of Clinical Oncology.

Researchers found that “narrow network” insurance plans—lower-premium plans with reduced access to certain providers—are more likely to exclude doctors associated with National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN) cancer centers.

These centers are recognized for their scientific and research leadership, quality and safety initiatives, and access to expert physicians and clinical trials.

NCCN member institutions are particularly recognized for higher-quality care, and treatment at NCI-designated cancer centers is associated with lower mortality than other hospitals, particularly among more severely ill patients and those with more advanced disease.

For this study, researchers examined cancer provider networks offered on the 2014 individual health insurance exchanges and then determined which oncologists were affiliated with NCI-designated and NCCN cancer centers.

The researchers found that narrower networks were less likely to include physicians associated with NCI-designated and NCCN member institutions.

“To see such a robust result was surprising,” said study author Laura Yasaitis, PhD, of the University of Pennsylvania in Philadelphia.

“The finding that narrower networks were more likely to exclude NCI and NCCN oncologists was consistent no matter how we looked at it. This is not just a few networks. It’s a clear trend.”

The researchers said the results point to 2 major problems—transparency and access.

“Patients should be able to easily figure out whether the physicians they might need will be covered under a given plan,” said study author Justin E. Bekelman, MD, of the University of Pennsylvania.

The researchers suggested that insurers report doctor’s affiliations with NCI and NCCN cancer centers so that consumers can make more informed choices.

The team also suggested that insurers offer mechanisms that would allow patients to seek care out of network without incurring penalties in exceptional circumstances.

“If patients have narrow network plans and absolutely need the kind of complex cancer care that they can only receive from one of these providers, there should be a standard exception process to allow patients to access the care they need,” Dr Bekelman said. 

Photo by Rhoda Baer

Narrow insurance plan coverage may prevent US cancer patients from receiving care at “high-quality” cancer centers, according to research published in the Journal of Clinical Oncology.

Researchers found that “narrow network” insurance plans—lower-premium plans with reduced access to certain providers—are more likely to exclude doctors associated with National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN) cancer centers.

These centers are recognized for their scientific and research leadership, quality and safety initiatives, and access to expert physicians and clinical trials.

NCCN member institutions are particularly recognized for higher-quality care, and treatment at NCI-designated cancer centers is associated with lower mortality than other hospitals, particularly among more severely ill patients and those with more advanced disease.

For this study, researchers examined cancer provider networks offered on the 2014 individual health insurance exchanges and then determined which oncologists were affiliated with NCI-designated and NCCN cancer centers.

The researchers found that narrower networks were less likely to include physicians associated with NCI-designated and NCCN member institutions.

“To see such a robust result was surprising,” said study author Laura Yasaitis, PhD, of the University of Pennsylvania in Philadelphia.

“The finding that narrower networks were more likely to exclude NCI and NCCN oncologists was consistent no matter how we looked at it. This is not just a few networks. It’s a clear trend.”

The researchers said the results point to 2 major problems—transparency and access.

“Patients should be able to easily figure out whether the physicians they might need will be covered under a given plan,” said study author Justin E. Bekelman, MD, of the University of Pennsylvania.

The researchers suggested that insurers report doctor’s affiliations with NCI and NCCN cancer centers so that consumers can make more informed choices.

The team also suggested that insurers offer mechanisms that would allow patients to seek care out of network without incurring penalties in exceptional circumstances.

“If patients have narrow network plans and absolutely need the kind of complex cancer care that they can only receive from one of these providers, there should be a standard exception process to allow patients to access the care they need,” Dr Bekelman said. 

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).