HT Staff

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel^®).

The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.

This approval was granted under priority review, and the drug received orphan designation for this indication.

The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.

The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.

For more details, see the full prescribing information.

Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.

Pediatric studies

The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.

There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.

Ninety-one patients received dasatinib at 60 mg/m² once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.

The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.

The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).

At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.

At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.

The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.

Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel^®).

The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.

This approval was granted under priority review, and the drug received orphan designation for this indication.

The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.

The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.

For more details, see the full prescribing information.

Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.

Pediatric studies

The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.

There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.

Ninety-one patients received dasatinib at 60 mg/m² once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.

The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.

The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).

At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.

At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.

The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.

Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel^®).

The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.

This approval was granted under priority review, and the drug received orphan designation for this indication.

The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.

The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.

For more details, see the full prescribing information.

Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.

Pediatric studies

The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.

There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.

Ninety-one patients received dasatinib at 60 mg/m² once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.

The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.

The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).

At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.

At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.

The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.

Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).

CMV infection

The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).

Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.

“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.

Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)

The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.

Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.

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

Trial results

The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Results from this trial were presented at the 2017 BMT Tandem Meetings.

CMV infection

The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).

Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.

“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.

Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)

The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.

Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.

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

Trial results

The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Results from this trial were presented at the 2017 BMT Tandem Meetings.

CMV infection

The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).

Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.

“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.

Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)

The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.

Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.

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

Trial results

The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Results from this trial were presented at the 2017 BMT Tandem Meetings.

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Warfarin tablets

New research suggests warfarin use may reduce the risk of cancer among people over the age of 50.

An observational study of more than 1 million people in Norway revealed that individuals who took warfarin had a lower incidence of cancers overall, as well as certain types of cancers, than people who did not take warfarin.

James B. Lorens, PhD, of the University of Bergen in Norway, and his colleagues reported these findings in JAMA Internal Medicine.

The researchers analyzed data from the Norwegian National Registry, the Norwegian Prescription Database, and the Cancer Registry of Norway.

This included data for all individuals ages 52 to 82 who were living in Norway from January 1, 2006, through December 31, 2012, (n=1,256,725).

The researchers looked for cancer diagnoses in this group during the 7-year observation period. They compared the incidence of any new cancer (including certain cancer types) between warfarin users and non-users.

People were considered warfarin users if they had taken at least 6 months of a warfarin prescription and at least 2 years had elapsed from their first prescription to any cancer diagnosis.

Most study subjects were non-users (92.6%, n=1,163,783), but 7.4% (n=92,942) were warfarin users.

The researchers noted that warfarin users were older than non-users, with mean ages of 70.2 and 63.9, respectively. Warfarin users were also more likely to be male (61.7%; n=57,370) and non-users female (52.7%; n=613,803).

The incidence of cancer was 10.6% (n=132,687) in the entire study cohort, 9.4% (n=8754) among warfarin users, and 10.6% (n=123,933) among non-users. The most common cancer types were prostate, lung, colon, and breast.

The researchers found a significantly lower age- and sex-adjusted incidence rate ratio (IRR) for all cancers among warfarin users than nonusers. The IRR was 0.84 (95% CI, 0.82-0.86).

The IRR was also significantly lower among users than non-users for 3 of the 4 most common cancers. The IRR was 0.69 (95% CI, 0.65-0.72) for prostate cancer, 0.80 (95% CI, 0.75-0.86) for lung cancer, and 0.90 (95% CI, 0.82-1.00) for female breast cancer.

The researchers said there was no significant difference between users and non-users for colon cancer. The IRR was 0.99 (95% CI, 0.93-1.06).

The team also assessed hematologic malignancies. The IRRs, for users compared to non-users, were as follows:

• 0.99 (95% CI, 0.89-1.11) for leukemia
• 0.89 (95% CI, 0.71-1.11) for chronic lymphocytic leukemia
• 0.70 (95% CI, 0.51-0.98) for acute myeloid leukemia
• 0.92 (95% CI, 0.82-1.04) for lymphoma
• 0.66 (95% CI, 0.34-1.26) for Hodgkin lymphoma
• 0.92 (95% CI, 0.81-1.04) for non-Hodgkin lymphoma.

The researchers noted that they did not collect information on other medications subjects were taking or risk factors that might influence cancer development, and new cancers may have been cancer recurrences.

In addition, the team said the prescription of warfarin may be a marker for other healthcare factors that lead to cancer prevention.

Still, the researchers said warfarin appeared to be associated with reduced cancer risk in this study.

They therefore believe this finding could have implications for choosing anticoagulants, although additional research is needed.

Warfarin tablets

New research suggests warfarin use may reduce the risk of cancer among people over the age of 50.

An observational study of more than 1 million people in Norway revealed that individuals who took warfarin had a lower incidence of cancers overall, as well as certain types of cancers, than people who did not take warfarin.

James B. Lorens, PhD, of the University of Bergen in Norway, and his colleagues reported these findings in JAMA Internal Medicine.

The researchers analyzed data from the Norwegian National Registry, the Norwegian Prescription Database, and the Cancer Registry of Norway.

This included data for all individuals ages 52 to 82 who were living in Norway from January 1, 2006, through December 31, 2012, (n=1,256,725).

The researchers looked for cancer diagnoses in this group during the 7-year observation period. They compared the incidence of any new cancer (including certain cancer types) between warfarin users and non-users.

People were considered warfarin users if they had taken at least 6 months of a warfarin prescription and at least 2 years had elapsed from their first prescription to any cancer diagnosis.

Most study subjects were non-users (92.6%, n=1,163,783), but 7.4% (n=92,942) were warfarin users.

The researchers noted that warfarin users were older than non-users, with mean ages of 70.2 and 63.9, respectively. Warfarin users were also more likely to be male (61.7%; n=57,370) and non-users female (52.7%; n=613,803).

The incidence of cancer was 10.6% (n=132,687) in the entire study cohort, 9.4% (n=8754) among warfarin users, and 10.6% (n=123,933) among non-users. The most common cancer types were prostate, lung, colon, and breast.

The researchers found a significantly lower age- and sex-adjusted incidence rate ratio (IRR) for all cancers among warfarin users than nonusers. The IRR was 0.84 (95% CI, 0.82-0.86).

The IRR was also significantly lower among users than non-users for 3 of the 4 most common cancers. The IRR was 0.69 (95% CI, 0.65-0.72) for prostate cancer, 0.80 (95% CI, 0.75-0.86) for lung cancer, and 0.90 (95% CI, 0.82-1.00) for female breast cancer.

The researchers said there was no significant difference between users and non-users for colon cancer. The IRR was 0.99 (95% CI, 0.93-1.06).

The team also assessed hematologic malignancies. The IRRs, for users compared to non-users, were as follows:

• 0.99 (95% CI, 0.89-1.11) for leukemia
• 0.89 (95% CI, 0.71-1.11) for chronic lymphocytic leukemia
• 0.70 (95% CI, 0.51-0.98) for acute myeloid leukemia
• 0.92 (95% CI, 0.82-1.04) for lymphoma
• 0.66 (95% CI, 0.34-1.26) for Hodgkin lymphoma
• 0.92 (95% CI, 0.81-1.04) for non-Hodgkin lymphoma.

The researchers noted that they did not collect information on other medications subjects were taking or risk factors that might influence cancer development, and new cancers may have been cancer recurrences.

In addition, the team said the prescription of warfarin may be a marker for other healthcare factors that lead to cancer prevention.

Still, the researchers said warfarin appeared to be associated with reduced cancer risk in this study.

They therefore believe this finding could have implications for choosing anticoagulants, although additional research is needed.

Warfarin tablets

New research suggests warfarin use may reduce the risk of cancer among people over the age of 50.

An observational study of more than 1 million people in Norway revealed that individuals who took warfarin had a lower incidence of cancers overall, as well as certain types of cancers, than people who did not take warfarin.

James B. Lorens, PhD, of the University of Bergen in Norway, and his colleagues reported these findings in JAMA Internal Medicine.

The researchers analyzed data from the Norwegian National Registry, the Norwegian Prescription Database, and the Cancer Registry of Norway.

This included data for all individuals ages 52 to 82 who were living in Norway from January 1, 2006, through December 31, 2012, (n=1,256,725).

The researchers looked for cancer diagnoses in this group during the 7-year observation period. They compared the incidence of any new cancer (including certain cancer types) between warfarin users and non-users.

People were considered warfarin users if they had taken at least 6 months of a warfarin prescription and at least 2 years had elapsed from their first prescription to any cancer diagnosis.

Most study subjects were non-users (92.6%, n=1,163,783), but 7.4% (n=92,942) were warfarin users.

The researchers noted that warfarin users were older than non-users, with mean ages of 70.2 and 63.9, respectively. Warfarin users were also more likely to be male (61.7%; n=57,370) and non-users female (52.7%; n=613,803).

The incidence of cancer was 10.6% (n=132,687) in the entire study cohort, 9.4% (n=8754) among warfarin users, and 10.6% (n=123,933) among non-users. The most common cancer types were prostate, lung, colon, and breast.

The researchers found a significantly lower age- and sex-adjusted incidence rate ratio (IRR) for all cancers among warfarin users than nonusers. The IRR was 0.84 (95% CI, 0.82-0.86).

The IRR was also significantly lower among users than non-users for 3 of the 4 most common cancers. The IRR was 0.69 (95% CI, 0.65-0.72) for prostate cancer, 0.80 (95% CI, 0.75-0.86) for lung cancer, and 0.90 (95% CI, 0.82-1.00) for female breast cancer.

The researchers said there was no significant difference between users and non-users for colon cancer. The IRR was 0.99 (95% CI, 0.93-1.06).

The team also assessed hematologic malignancies. The IRRs, for users compared to non-users, were as follows:

• 0.99 (95% CI, 0.89-1.11) for leukemia
• 0.89 (95% CI, 0.71-1.11) for chronic lymphocytic leukemia
• 0.70 (95% CI, 0.51-0.98) for acute myeloid leukemia
• 0.92 (95% CI, 0.82-1.04) for lymphoma
• 0.66 (95% CI, 0.34-1.26) for Hodgkin lymphoma
• 0.92 (95% CI, 0.81-1.04) for non-Hodgkin lymphoma.

The researchers noted that they did not collect information on other medications subjects were taking or risk factors that might influence cancer development, and new cancers may have been cancer recurrences.

In addition, the team said the prescription of warfarin may be a marker for other healthcare factors that lead to cancer prevention.

Still, the researchers said warfarin appeared to be associated with reduced cancer risk in this study.

They therefore believe this finding could have implications for choosing anticoagulants, although additional research is needed.

Photo by Jorge Ferreira

The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.

Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.

The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.

Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).

At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.

Artemis Therapeutics, Inc. has not yet released safety data from this trial.

Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.

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.

Photo by Jorge Ferreira

The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.

Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.

The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.

Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).

At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.

Artemis Therapeutics, Inc. has not yet released safety data from this trial.

Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.

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.

Photo by Jorge Ferreira

The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.

Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.

The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.

Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).

At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.

Artemis Therapeutics, Inc. has not yet released safety data from this trial.

Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.

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.

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted accelerated assessment to a marketing authorization application (MAA) for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

The MAA is for CPX-351 to treat adults with high-risk acute myeloid leukemia (AML), defined as therapy-related AML or AML with myelodysplasia-related changes.

Accelerated assessment is designed to reduce the review timeline for products of major interest for public health and therapeutic innovation.

“If approved, Vyxeos will become the first new chemotherapy treatment option specifically for European patients with therapy-related AML or AML with myelodysplasia-related changes,” said Karen Smith, MD, PhD, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, the company developing and marketing CPX-351.

The MAA for CPX-351 is supported by clinical data from 5 studies, including a phase 3 study. Results from this study were presented at the 2016 ASCO Annual Meeting.

In this study, researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted accelerated assessment to a marketing authorization application (MAA) for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

The MAA is for CPX-351 to treat adults with high-risk acute myeloid leukemia (AML), defined as therapy-related AML or AML with myelodysplasia-related changes.

Accelerated assessment is designed to reduce the review timeline for products of major interest for public health and therapeutic innovation.

“If approved, Vyxeos will become the first new chemotherapy treatment option specifically for European patients with therapy-related AML or AML with myelodysplasia-related changes,” said Karen Smith, MD, PhD, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, the company developing and marketing CPX-351.

The MAA for CPX-351 is supported by clinical data from 5 studies, including a phase 3 study. Results from this study were presented at the 2016 ASCO Annual Meeting.

In this study, researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted accelerated assessment to a marketing authorization application (MAA) for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

The MAA is for CPX-351 to treat adults with high-risk acute myeloid leukemia (AML), defined as therapy-related AML or AML with myelodysplasia-related changes.

Accelerated assessment is designed to reduce the review timeline for products of major interest for public health and therapeutic innovation.

“If approved, Vyxeos will become the first new chemotherapy treatment option specifically for European patients with therapy-related AML or AML with myelodysplasia-related changes,” said Karen Smith, MD, PhD, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, the company developing and marketing CPX-351.

The MAA for CPX-351 is supported by clinical data from 5 studies, including a phase 3 study. Results from this study were presented at the 2016 ASCO Annual Meeting.

In this study, researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to ACH-4471 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

And the European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products has recommended the drug receive orphan status for the same indication in the European Economic Area.

ACH-4471 is a factor D inhibitor being developed by Achillion Pharmaceuticals, Inc.

In April, the company announced the initiation of a phase 2, three-month, dose-ranging trial with ACH-4471 for patients with untreated PNH (NCT03053102).

The primary objective of the trial is to assess the change from baseline in serum lactate dehydrogenase (LDH) levels. Secondary endpoints include changes in hemoglobin, PNH red blood cells, fatigue score (FACIT scale), changes in levels of complement pathway biomarkers such as Bb and factor D, pharmacokinetics, and safety.

The protocol allows for intra-patient dose-escalation. Patients initially receive 100 mg or 150 mg of ACH-4471 three times daily, and doses may be increased during the treatment period.

After patients complete 3 months of treatment and investigators have assessed safety and clinical benefit, patients may be enrolled in the long-term extension trial (NCT03181633).

To date, 200 mg three times daily has been the highest dose of ACH-4471 administered. And Achillion has collected data on 4 patients.

Two of the patients have completed the 3-month trial and entered the long-term extension trial. One patient continues to receive dosing in the 3-month trial, and the fourth patient voluntarily withdrew from the trial on day 41 for reasons unrelated to safety.

Thus far, ACH-4471 has produced clinically meaningful complement inhibition and demonstrated a favorable tolerability profile, with no reports of clinically meaningful increases in liver enzymes. ACH-4471 has improved LDH, hemoglobin, fatigue score, and other measures of response, including PNH clone size.

FDA’s 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.

EMA’s orphan designation

The EMA’s orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. It also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to ACH-4471 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

And the European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products has recommended the drug receive orphan status for the same indication in the European Economic Area.

ACH-4471 is a factor D inhibitor being developed by Achillion Pharmaceuticals, Inc.

In April, the company announced the initiation of a phase 2, three-month, dose-ranging trial with ACH-4471 for patients with untreated PNH (NCT03053102).

The primary objective of the trial is to assess the change from baseline in serum lactate dehydrogenase (LDH) levels. Secondary endpoints include changes in hemoglobin, PNH red blood cells, fatigue score (FACIT scale), changes in levels of complement pathway biomarkers such as Bb and factor D, pharmacokinetics, and safety.

The protocol allows for intra-patient dose-escalation. Patients initially receive 100 mg or 150 mg of ACH-4471 three times daily, and doses may be increased during the treatment period.

After patients complete 3 months of treatment and investigators have assessed safety and clinical benefit, patients may be enrolled in the long-term extension trial (NCT03181633).

To date, 200 mg three times daily has been the highest dose of ACH-4471 administered. And Achillion has collected data on 4 patients.

Two of the patients have completed the 3-month trial and entered the long-term extension trial. One patient continues to receive dosing in the 3-month trial, and the fourth patient voluntarily withdrew from the trial on day 41 for reasons unrelated to safety.

Thus far, ACH-4471 has produced clinically meaningful complement inhibition and demonstrated a favorable tolerability profile, with no reports of clinically meaningful increases in liver enzymes. ACH-4471 has improved LDH, hemoglobin, fatigue score, and other measures of response, including PNH clone size.

FDA’s 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.

EMA’s orphan designation

The EMA’s orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. It also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to ACH-4471 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

And the European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products has recommended the drug receive orphan status for the same indication in the European Economic Area.

ACH-4471 is a factor D inhibitor being developed by Achillion Pharmaceuticals, Inc.

In April, the company announced the initiation of a phase 2, three-month, dose-ranging trial with ACH-4471 for patients with untreated PNH (NCT03053102).

The primary objective of the trial is to assess the change from baseline in serum lactate dehydrogenase (LDH) levels. Secondary endpoints include changes in hemoglobin, PNH red blood cells, fatigue score (FACIT scale), changes in levels of complement pathway biomarkers such as Bb and factor D, pharmacokinetics, and safety.

The protocol allows for intra-patient dose-escalation. Patients initially receive 100 mg or 150 mg of ACH-4471 three times daily, and doses may be increased during the treatment period.

After patients complete 3 months of treatment and investigators have assessed safety and clinical benefit, patients may be enrolled in the long-term extension trial (NCT03181633).

To date, 200 mg three times daily has been the highest dose of ACH-4471 administered. And Achillion has collected data on 4 patients.

Two of the patients have completed the 3-month trial and entered the long-term extension trial. One patient continues to receive dosing in the 3-month trial, and the fourth patient voluntarily withdrew from the trial on day 41 for reasons unrelated to safety.

Thus far, ACH-4471 has produced clinically meaningful complement inhibition and demonstrated a favorable tolerability profile, with no reports of clinically meaningful increases in liver enzymes. ACH-4471 has improved LDH, hemoglobin, fatigue score, and other measures of response, including PNH clone size.

FDA’s 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.

EMA’s orphan designation

The EMA’s orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. It also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission.

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.