Pharmacy

 

 

Micrograph showing DLBCL

 

ProNAi Therapeutics recently announced its decision to stop development of PNT2258, a drug designed to treat cancers characterized by overexpression of BCL2.

In June, the company suspended development of PNT2258, closing enrollment in a phase 2 trial of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and a phase 2 trial of patients with Richter’s transformation.

Now, ProNAi has said it does not plan to resume development of the drug.

“[N]o further investment in PNT2258 or the underlying DNAi platform by ProNAi is contemplated, and the company subsequently has closed its research facility based in Plymouth, Michigan, which supported these programs,” the company said in a statement.

About PNT2258

PNT2258 consists of a single-stranded, 24-base DNAi oligonucleotide known as PNT100 that is encapsulated in lipid nanoparticles.

The DNAi technology platform is based on a discovery that single-stranded DNA oligonucleotides can interact with genomic DNA to interfere with oncogenes. PNT100 DNAi is designed to target a genetic regulatory region associated with BCL2.

Last March, PNT2258 was granted orphan drug designation from the US Food and Drug Administration for the treatment of DLBCL.

ProNAi initially suspended the development of PNT2258 in June, following a review of interim data from the phase 2 Wolverine trial. The company said the drug produced “modest efficacy” in this trial, but it seemed the data were not “robust enough” to justify continued development of PNT2258.

“We have decided to suspend development of PNT2258 pending further review of these data in order to determine next steps for both this asset and the DNAi platform,” Nick Glover, president and CEO of ProNAi, said at the time.

The Wolverine trial was designed to evaluate the safety and efficacy of PNT2258 monotherapy in 61 patients with relapsed/refractory DLBCL.

ProNAi reported interim safety and efficacy data as of April 25, 2016, for the first 37 subjects enrolled. The response rate was 8.1% overall (n=37) and 15.8% in the response-evaluable subgroup (n=19).

Subjects were considered response-evaluable if they met the amended eligibility criteria—a performance status of 0 to 1, 1 to 3 prior systemic treatment regimens, and receipt of at least 8 doses of PNT2258 within 35 days of starting therapy.

PNT2258 was also being evaluated in patients with Richter’s transformation in the phase 2 Brighton study. In June, ProNAi said it had enrolled 5 subjects in this study, and 4 had discontinued. No responses were observed.

“On the basis of these interim assessments, we have decided to close the Wolverine and Brighton studies to further enrollment of new subjects,” Barbara Klencke, chief development officer of ProNAi, said at the time.

PNT2258 was evaluated in 2 prior studies as well. In a phase 1 study (NCT01191775), PNT2258 was given to 22 subjects with advanced solid tumors. The drug was considered well tolerated at doses ranging from 1 mg/m² through 150 mg/m².

A pilot study of PNT2258 (NCT01733238) enrolled 13 subjects with relapsed/refractory B-cell non-Hodgkin lymphoma. Responses were observed in subjects with DLBCL and those with follicular lymphoma.

Six subjects were progression-free at 12 months, and progression-free survival extended to 2 years and beyond in 4 subjects. The majority of the adverse events were grade 1 or 2.

 

 

Micrograph showing DLBCL

 

ProNAi Therapeutics recently announced its decision to stop development of PNT2258, a drug designed to treat cancers characterized by overexpression of BCL2.

In June, the company suspended development of PNT2258, closing enrollment in a phase 2 trial of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and a phase 2 trial of patients with Richter’s transformation.

Now, ProNAi has said it does not plan to resume development of the drug.

“[N]o further investment in PNT2258 or the underlying DNAi platform by ProNAi is contemplated, and the company subsequently has closed its research facility based in Plymouth, Michigan, which supported these programs,” the company said in a statement.

About PNT2258

PNT2258 consists of a single-stranded, 24-base DNAi oligonucleotide known as PNT100 that is encapsulated in lipid nanoparticles.

The DNAi technology platform is based on a discovery that single-stranded DNA oligonucleotides can interact with genomic DNA to interfere with oncogenes. PNT100 DNAi is designed to target a genetic regulatory region associated with BCL2.

Last March, PNT2258 was granted orphan drug designation from the US Food and Drug Administration for the treatment of DLBCL.

ProNAi initially suspended the development of PNT2258 in June, following a review of interim data from the phase 2 Wolverine trial. The company said the drug produced “modest efficacy” in this trial, but it seemed the data were not “robust enough” to justify continued development of PNT2258.

“We have decided to suspend development of PNT2258 pending further review of these data in order to determine next steps for both this asset and the DNAi platform,” Nick Glover, president and CEO of ProNAi, said at the time.

The Wolverine trial was designed to evaluate the safety and efficacy of PNT2258 monotherapy in 61 patients with relapsed/refractory DLBCL.

ProNAi reported interim safety and efficacy data as of April 25, 2016, for the first 37 subjects enrolled. The response rate was 8.1% overall (n=37) and 15.8% in the response-evaluable subgroup (n=19).

Subjects were considered response-evaluable if they met the amended eligibility criteria—a performance status of 0 to 1, 1 to 3 prior systemic treatment regimens, and receipt of at least 8 doses of PNT2258 within 35 days of starting therapy.

PNT2258 was also being evaluated in patients with Richter’s transformation in the phase 2 Brighton study. In June, ProNAi said it had enrolled 5 subjects in this study, and 4 had discontinued. No responses were observed.

“On the basis of these interim assessments, we have decided to close the Wolverine and Brighton studies to further enrollment of new subjects,” Barbara Klencke, chief development officer of ProNAi, said at the time.

PNT2258 was evaluated in 2 prior studies as well. In a phase 1 study (NCT01191775), PNT2258 was given to 22 subjects with advanced solid tumors. The drug was considered well tolerated at doses ranging from 1 mg/m² through 150 mg/m².

A pilot study of PNT2258 (NCT01733238) enrolled 13 subjects with relapsed/refractory B-cell non-Hodgkin lymphoma. Responses were observed in subjects with DLBCL and those with follicular lymphoma.

Six subjects were progression-free at 12 months, and progression-free survival extended to 2 years and beyond in 4 subjects. The majority of the adverse events were grade 1 or 2.

 

 

Micrograph showing DLBCL

 

ProNAi Therapeutics recently announced its decision to stop development of PNT2258, a drug designed to treat cancers characterized by overexpression of BCL2.

In June, the company suspended development of PNT2258, closing enrollment in a phase 2 trial of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and a phase 2 trial of patients with Richter’s transformation.

Now, ProNAi has said it does not plan to resume development of the drug.

“[N]o further investment in PNT2258 or the underlying DNAi platform by ProNAi is contemplated, and the company subsequently has closed its research facility based in Plymouth, Michigan, which supported these programs,” the company said in a statement.

About PNT2258

PNT2258 consists of a single-stranded, 24-base DNAi oligonucleotide known as PNT100 that is encapsulated in lipid nanoparticles.

The DNAi technology platform is based on a discovery that single-stranded DNA oligonucleotides can interact with genomic DNA to interfere with oncogenes. PNT100 DNAi is designed to target a genetic regulatory region associated with BCL2.

Last March, PNT2258 was granted orphan drug designation from the US Food and Drug Administration for the treatment of DLBCL.

ProNAi initially suspended the development of PNT2258 in June, following a review of interim data from the phase 2 Wolverine trial. The company said the drug produced “modest efficacy” in this trial, but it seemed the data were not “robust enough” to justify continued development of PNT2258.

“We have decided to suspend development of PNT2258 pending further review of these data in order to determine next steps for both this asset and the DNAi platform,” Nick Glover, president and CEO of ProNAi, said at the time.

The Wolverine trial was designed to evaluate the safety and efficacy of PNT2258 monotherapy in 61 patients with relapsed/refractory DLBCL.

ProNAi reported interim safety and efficacy data as of April 25, 2016, for the first 37 subjects enrolled. The response rate was 8.1% overall (n=37) and 15.8% in the response-evaluable subgroup (n=19).

Subjects were considered response-evaluable if they met the amended eligibility criteria—a performance status of 0 to 1, 1 to 3 prior systemic treatment regimens, and receipt of at least 8 doses of PNT2258 within 35 days of starting therapy.

PNT2258 was also being evaluated in patients with Richter’s transformation in the phase 2 Brighton study. In June, ProNAi said it had enrolled 5 subjects in this study, and 4 had discontinued. No responses were observed.

“On the basis of these interim assessments, we have decided to close the Wolverine and Brighton studies to further enrollment of new subjects,” Barbara Klencke, chief development officer of ProNAi, said at the time.

PNT2258 was evaluated in 2 prior studies as well. In a phase 1 study (NCT01191775), PNT2258 was given to 22 subjects with advanced solid tumors. The drug was considered well tolerated at doses ranging from 1 mg/m² through 150 mg/m².

A pilot study of PNT2258 (NCT01733238) enrolled 13 subjects with relapsed/refractory B-cell non-Hodgkin lymphoma. Responses were observed in subjects with DLBCL and those with follicular lymphoma.

Six subjects were progression-free at 12 months, and progression-free survival extended to 2 years and beyond in 4 subjects. The majority of the adverse events were grade 1 or 2.

Ticagrelor tablets

Photo from AstraZeneca

The National Institute for Health and Care Excellence (NICE) has published a draft guidance recommending the antiplatelet agent ticagrelor (Brilique, AstraZeneca) be made available on the National Health Service (NHS) at a lower dose that can be used for a longer duration.

NICE previously decided ticagrelor should be available on the NHS as a treatment option for certain patients with acute coronary syndromes.

For these patients, the drug could be given at a dose of 90 mg, in combination with low-dose aspirin, for up to a year to prevent atherothrombotic events.

Now, NICE is recommending an additional option.

The agency’s new draft guidance recommends ticagrelor at 60 mg, to be given twice a day in combination with aspirin at 75 mg to 150 mg daily, as a continuation therapy for the prevention of atherothrombotic events in certain patients with a history of myocardial infarction and a high risk of developing atherothrombotic events.

Patients must have had a myocardial infarction at least a year ago and have already taken ticagrelor at 90 mg (or another adenosine diphosphate receptor inhibitor therapy), in combination with aspirin, for 1 year.

Ticagrelor at 60 mg, plus aspirin, must be continued without interruption. And the treatment must be stopped when clinically indicated or after a maximum of 3 years.

“The evidence shows that ticagrelor, in combination with aspirin, is effective at reducing the risk of further heart attacks and strokes in people who have already had a heart attack,” said Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“In provisionally recommending ticagrelor, we are pleased to be able to increase the treatment options available to the many thousands of people who stand to benefit from it.”

NICE’s new draft guidance is not intended to affect the position of patients whose treatment with ticagrelor at 60 mg, in combination with aspirin, as a continuation therapy was started within the NHS before this guidance was published.

Treatment of those patients may continue without change to whatever funding arrangements were in place for them before this guidance was published until they and their NHS clinician consider it appropriate to stop.

NICE’s draft guidance is open for comments until 5 pm (GMT) on September 5, 2016.

Ticagrelor tablets

Photo from AstraZeneca

The National Institute for Health and Care Excellence (NICE) has published a draft guidance recommending the antiplatelet agent ticagrelor (Brilique, AstraZeneca) be made available on the National Health Service (NHS) at a lower dose that can be used for a longer duration.

NICE previously decided ticagrelor should be available on the NHS as a treatment option for certain patients with acute coronary syndromes.

For these patients, the drug could be given at a dose of 90 mg, in combination with low-dose aspirin, for up to a year to prevent atherothrombotic events.

Now, NICE is recommending an additional option.

The agency’s new draft guidance recommends ticagrelor at 60 mg, to be given twice a day in combination with aspirin at 75 mg to 150 mg daily, as a continuation therapy for the prevention of atherothrombotic events in certain patients with a history of myocardial infarction and a high risk of developing atherothrombotic events.

Patients must have had a myocardial infarction at least a year ago and have already taken ticagrelor at 90 mg (or another adenosine diphosphate receptor inhibitor therapy), in combination with aspirin, for 1 year.

Ticagrelor at 60 mg, plus aspirin, must be continued without interruption. And the treatment must be stopped when clinically indicated or after a maximum of 3 years.

“The evidence shows that ticagrelor, in combination with aspirin, is effective at reducing the risk of further heart attacks and strokes in people who have already had a heart attack,” said Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“In provisionally recommending ticagrelor, we are pleased to be able to increase the treatment options available to the many thousands of people who stand to benefit from it.”

NICE’s new draft guidance is not intended to affect the position of patients whose treatment with ticagrelor at 60 mg, in combination with aspirin, as a continuation therapy was started within the NHS before this guidance was published.

Treatment of those patients may continue without change to whatever funding arrangements were in place for them before this guidance was published until they and their NHS clinician consider it appropriate to stop.

NICE’s draft guidance is open for comments until 5 pm (GMT) on September 5, 2016.

Ticagrelor tablets

Photo from AstraZeneca

The National Institute for Health and Care Excellence (NICE) has published a draft guidance recommending the antiplatelet agent ticagrelor (Brilique, AstraZeneca) be made available on the National Health Service (NHS) at a lower dose that can be used for a longer duration.

NICE previously decided ticagrelor should be available on the NHS as a treatment option for certain patients with acute coronary syndromes.

For these patients, the drug could be given at a dose of 90 mg, in combination with low-dose aspirin, for up to a year to prevent atherothrombotic events.

Now, NICE is recommending an additional option.

The agency’s new draft guidance recommends ticagrelor at 60 mg, to be given twice a day in combination with aspirin at 75 mg to 150 mg daily, as a continuation therapy for the prevention of atherothrombotic events in certain patients with a history of myocardial infarction and a high risk of developing atherothrombotic events.

Patients must have had a myocardial infarction at least a year ago and have already taken ticagrelor at 90 mg (or another adenosine diphosphate receptor inhibitor therapy), in combination with aspirin, for 1 year.

Ticagrelor at 60 mg, plus aspirin, must be continued without interruption. And the treatment must be stopped when clinically indicated or after a maximum of 3 years.

“The evidence shows that ticagrelor, in combination with aspirin, is effective at reducing the risk of further heart attacks and strokes in people who have already had a heart attack,” said Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“In provisionally recommending ticagrelor, we are pleased to be able to increase the treatment options available to the many thousands of people who stand to benefit from it.”

NICE’s new draft guidance is not intended to affect the position of patients whose treatment with ticagrelor at 60 mg, in combination with aspirin, as a continuation therapy was started within the NHS before this guidance was published.

Treatment of those patients may continue without change to whatever funding arrangements were in place for them before this guidance was published until they and their NHS clinician consider it appropriate to stop.

NICE’s draft guidance is open for comments until 5 pm (GMT) on September 5, 2016.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.

Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.

The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.

“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”

Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.

Phase 3 trials

The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.

In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).

Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.

In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.

A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.

“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.

“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”

For more details on the drug, access the full prescribing information at www.SUSTOL.com.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.

Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.

The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.

“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”

Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.

Phase 3 trials

The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.

In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).

Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.

In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.

A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.

“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.

“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”

For more details on the drug, access the full prescribing information at www.SUSTOL.com.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.

Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.

The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.

“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”

Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.

Phase 3 trials

The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.

In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).

Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.

In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.

A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.

“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.

“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”

For more details on the drug, access the full prescribing information at www.SUSTOL.com.

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Prescription medications

Photo by Steven Harbour

Teva Pharmaceutical Industries Ltd. has announced the US launch of imatinib mesylate, the generic equivalent of Novartis’s Gleevec®, in 100 mg and 400 mg tablets.

In the US, imatinib is approved to treat newly diagnosed Philadelphia-chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase, blast crisis, and accelerated phase, as well as Ph+

chronic myeloid leukemia in chronic phase after failure of interferon-alpha therapy.

Imatinib is also approved to treat adults with relapsed or refractory Ph+ acute lymphoblastic leukemia, adults with myelodysplastic syndromes or myeloproliferative neoplasms associated with platelet-derived growth factor receptor gene re-arrangements, and adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with unknown c-Kit mutational status.

In addition, imatinib is approved to treat adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia (regardless of whether they have the FIP1L1-PDGFRα fusion kinase) and adults with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Finally, the drug is approved as an adjuvant treatment following complete gross resection of Kit (CD117)-positive gastrointestinal stromal tumors in adults.

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

Prescription medications

Photo by Steven Harbour

Teva Pharmaceutical Industries Ltd. has announced the US launch of imatinib mesylate, the generic equivalent of Novartis’s Gleevec®, in 100 mg and 400 mg tablets.

In the US, imatinib is approved to treat newly diagnosed Philadelphia-chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase, blast crisis, and accelerated phase, as well as Ph+

chronic myeloid leukemia in chronic phase after failure of interferon-alpha therapy.

Imatinib is also approved to treat adults with relapsed or refractory Ph+ acute lymphoblastic leukemia, adults with myelodysplastic syndromes or myeloproliferative neoplasms associated with platelet-derived growth factor receptor gene re-arrangements, and adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with unknown c-Kit mutational status.

In addition, imatinib is approved to treat adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia (regardless of whether they have the FIP1L1-PDGFRα fusion kinase) and adults with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Finally, the drug is approved as an adjuvant treatment following complete gross resection of Kit (CD117)-positive gastrointestinal stromal tumors in adults.

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

Prescription medications

Photo by Steven Harbour

Teva Pharmaceutical Industries Ltd. has announced the US launch of imatinib mesylate, the generic equivalent of Novartis’s Gleevec®, in 100 mg and 400 mg tablets.

In the US, imatinib is approved to treat newly diagnosed Philadelphia-chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase, blast crisis, and accelerated phase, as well as Ph+

chronic myeloid leukemia in chronic phase after failure of interferon-alpha therapy.

Imatinib is also approved to treat adults with relapsed or refractory Ph+ acute lymphoblastic leukemia, adults with myelodysplastic syndromes or myeloproliferative neoplasms associated with platelet-derived growth factor receptor gene re-arrangements, and adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with unknown c-Kit mutational status.

In addition, imatinib is approved to treat adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia (regardless of whether they have the FIP1L1-PDGFRα fusion kinase) and adults with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Finally, the drug is approved as an adjuvant treatment following complete gross resection of Kit (CD117)-positive gastrointestinal stromal tumors in adults.

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

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

Patient consults pharmacist

Photo by Rhoda Baer

Physicians may still prescribe a controversial drug combination despite safety concerns, according to a study published in Pharmacology Research & Perspectives.

Regulatory agencies have warned against prescribing the antiplatelet agent clopidogrel with the proton pump inhibitors (PPIs) omeprazole and esomeprazole.

A PPI may be prescribed with clopidogrel to reduce the risk of gastrointestinal bleeding associated with antiplatelet therapy.

However, concomitant use of clopidogrel and esomeprazole/omeprazole is thought by some to reduce the pharmacological activity of clopidogrel.

In 2009 and 2010, regulatory agencies in Europe and the US published statements advising against concomitant use of clopidogrel and the aforementioned PPIs.

Willemien J. Kruik-Kolloffel, PharmD, of Medisch Spectrum Twente in Enschede, The Netherlands, and his colleagues wanted to determine if this recommendation was followed in The Netherlands.

The researchers studied data spanning the period from 2008 to 2011 and encompassing 39,496 patients. Forty percent of the patients did not use gastroprotective drugs at all during the study period.

Twenty-seven percent of patients were taking gastroprotective drugs before starting clopidogrel, 23% started gastroprotective drugs and clopidogrel concomitantly, and 10% started gastroprotective drugs at least 4 weeks after starting clopidogrel.

Among the patients who started a gastroprotective drug and clopidogrel concomitantly, an average of 40% started on esomeprazole/omeprazole before the first statement from a regulatory agency was released in January 2009.

This percentage decreased to around 20% after the statements were released. The percentage of patients starting on other PPIs rose from 60% to about 80%.

After the last statement was released in February 2010, there was an 11.9% decrease in dispensation of omeprazole and esomeprazole and an increase of 16.0% for other PPIs.

Results were similar among the patients who started taking a gastroprotective drug at least 4 weeks after starting clopidogrel.

These data suggest the regulatory agencies’ advice was followed, though not fully. The researchers said this may be, in part, because physicians doubt the suggested interaction between clopidogrel and esomeprazole/omeprazole.

“Regulatory agencies should base their advice on sound scientific data to convince prescribers,” Dr Kruik-Kolloffel said. “We, the authors, doubt the interaction, as do a lot of professionals all around the world.”

Patient consults pharmacist

Photo by Rhoda Baer

Physicians may still prescribe a controversial drug combination despite safety concerns, according to a study published in Pharmacology Research & Perspectives.

Regulatory agencies have warned against prescribing the antiplatelet agent clopidogrel with the proton pump inhibitors (PPIs) omeprazole and esomeprazole.

A PPI may be prescribed with clopidogrel to reduce the risk of gastrointestinal bleeding associated with antiplatelet therapy.

However, concomitant use of clopidogrel and esomeprazole/omeprazole is thought by some to reduce the pharmacological activity of clopidogrel.

In 2009 and 2010, regulatory agencies in Europe and the US published statements advising against concomitant use of clopidogrel and the aforementioned PPIs.

Willemien J. Kruik-Kolloffel, PharmD, of Medisch Spectrum Twente in Enschede, The Netherlands, and his colleagues wanted to determine if this recommendation was followed in The Netherlands.

The researchers studied data spanning the period from 2008 to 2011 and encompassing 39,496 patients. Forty percent of the patients did not use gastroprotective drugs at all during the study period.

Twenty-seven percent of patients were taking gastroprotective drugs before starting clopidogrel, 23% started gastroprotective drugs and clopidogrel concomitantly, and 10% started gastroprotective drugs at least 4 weeks after starting clopidogrel.

Among the patients who started a gastroprotective drug and clopidogrel concomitantly, an average of 40% started on esomeprazole/omeprazole before the first statement from a regulatory agency was released in January 2009.

This percentage decreased to around 20% after the statements were released. The percentage of patients starting on other PPIs rose from 60% to about 80%.

After the last statement was released in February 2010, there was an 11.9% decrease in dispensation of omeprazole and esomeprazole and an increase of 16.0% for other PPIs.

Results were similar among the patients who started taking a gastroprotective drug at least 4 weeks after starting clopidogrel.

These data suggest the regulatory agencies’ advice was followed, though not fully. The researchers said this may be, in part, because physicians doubt the suggested interaction between clopidogrel and esomeprazole/omeprazole.

“Regulatory agencies should base their advice on sound scientific data to convince prescribers,” Dr Kruik-Kolloffel said. “We, the authors, doubt the interaction, as do a lot of professionals all around the world.”

Patient consults pharmacist

Photo by Rhoda Baer

Physicians may still prescribe a controversial drug combination despite safety concerns, according to a study published in Pharmacology Research & Perspectives.

Regulatory agencies have warned against prescribing the antiplatelet agent clopidogrel with the proton pump inhibitors (PPIs) omeprazole and esomeprazole.

A PPI may be prescribed with clopidogrel to reduce the risk of gastrointestinal bleeding associated with antiplatelet therapy.

However, concomitant use of clopidogrel and esomeprazole/omeprazole is thought by some to reduce the pharmacological activity of clopidogrel.

In 2009 and 2010, regulatory agencies in Europe and the US published statements advising against concomitant use of clopidogrel and the aforementioned PPIs.

Willemien J. Kruik-Kolloffel, PharmD, of Medisch Spectrum Twente in Enschede, The Netherlands, and his colleagues wanted to determine if this recommendation was followed in The Netherlands.

The researchers studied data spanning the period from 2008 to 2011 and encompassing 39,496 patients. Forty percent of the patients did not use gastroprotective drugs at all during the study period.

Twenty-seven percent of patients were taking gastroprotective drugs before starting clopidogrel, 23% started gastroprotective drugs and clopidogrel concomitantly, and 10% started gastroprotective drugs at least 4 weeks after starting clopidogrel.

Among the patients who started a gastroprotective drug and clopidogrel concomitantly, an average of 40% started on esomeprazole/omeprazole before the first statement from a regulatory agency was released in January 2009.

This percentage decreased to around 20% after the statements were released. The percentage of patients starting on other PPIs rose from 60% to about 80%.

After the last statement was released in February 2010, there was an 11.9% decrease in dispensation of omeprazole and esomeprazole and an increase of 16.0% for other PPIs.

Results were similar among the patients who started taking a gastroprotective drug at least 4 weeks after starting clopidogrel.

These data suggest the regulatory agencies’ advice was followed, though not fully. The researchers said this may be, in part, because physicians doubt the suggested interaction between clopidogrel and esomeprazole/omeprazole.

“Regulatory agencies should base their advice on sound scientific data to convince prescribers,” Dr Kruik-Kolloffel said. “We, the authors, doubt the interaction, as do a lot of professionals all around the world.”

Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has approved the Baxject III reconstitution system for Adynovate, a pegylated recombinant factor VIII (FVIII) product.

The system is designed to mix a FVIII product with a diluent prior to infusion.

The Baxject III reconstitution system was previously FDA-approved for use with Advate, a recombinant FVIII product.

The latest FDA approval means the system will be available with Adynovate as well.

Adynovate and the diluent will come pre-packaged in the reconstitution system.

The Baxject III reconstitution system with Adynovate will be available to most customers in the fourth quarter of 2016, with a 2 mL diluent for the 250, 500, and 1000 IU potencies; and a 5 mL diluent for the 2000 IU potency.

Adynovate was approved by the FDA in 2015 for use in hemophilia A patients age 12 and older for on-demand treatment and control of bleeding and for prophylaxis to reduce the frequency of bleeding episodes. Full prescribing information is available here.

Advate was first approved by the FDA in 2003. The product is indicated for use in children and adults with hemophilia A for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes. Full prescribing information is available here.

The Baxject III reconstitution system, Adynovate, and Advate are all products of Baxalta, which is now a part of Shire.

Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has approved the Baxject III reconstitution system for Adynovate, a pegylated recombinant factor VIII (FVIII) product.

The system is designed to mix a FVIII product with a diluent prior to infusion.

The Baxject III reconstitution system was previously FDA-approved for use with Advate, a recombinant FVIII product.

The latest FDA approval means the system will be available with Adynovate as well.

Adynovate and the diluent will come pre-packaged in the reconstitution system.

The Baxject III reconstitution system with Adynovate will be available to most customers in the fourth quarter of 2016, with a 2 mL diluent for the 250, 500, and 1000 IU potencies; and a 5 mL diluent for the 2000 IU potency.

Adynovate was approved by the FDA in 2015 for use in hemophilia A patients age 12 and older for on-demand treatment and control of bleeding and for prophylaxis to reduce the frequency of bleeding episodes. Full prescribing information is available here.

Advate was first approved by the FDA in 2003. The product is indicated for use in children and adults with hemophilia A for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes. Full prescribing information is available here.

The Baxject III reconstitution system, Adynovate, and Advate are all products of Baxalta, which is now a part of Shire.

Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has approved the Baxject III reconstitution system for Adynovate, a pegylated recombinant factor VIII (FVIII) product.

The system is designed to mix a FVIII product with a diluent prior to infusion.

The Baxject III reconstitution system was previously FDA-approved for use with Advate, a recombinant FVIII product.

The latest FDA approval means the system will be available with Adynovate as well.

Adynovate and the diluent will come pre-packaged in the reconstitution system.

The Baxject III reconstitution system with Adynovate will be available to most customers in the fourth quarter of 2016, with a 2 mL diluent for the 250, 500, and 1000 IU potencies; and a 5 mL diluent for the 2000 IU potency.

Adynovate was approved by the FDA in 2015 for use in hemophilia A patients age 12 and older for on-demand treatment and control of bleeding and for prophylaxis to reduce the frequency of bleeding episodes. Full prescribing information is available here.

Advate was first approved by the FDA in 2003. The product is indicated for use in children and adults with hemophilia A for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes. Full prescribing information is available here.

The Baxject III reconstitution system, Adynovate, and Advate are all products of Baxalta, which is now a part of Shire.

DNA coiled around histones

Image by Eric Smith

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the histone deacetylase (HDAC) inhibitor pracinostat to be used in combination with azacitidine to treat newly diagnosed acute myeloid leukemia (AML) patients who are 75 and older or unfit for intensive chemotherapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough therapy designation for pracinostat is supported by data from a phase 2 study of the HDAC inhibitor in combination with azacitidine in elderly patients with newly diagnosed AML who were not candidates for induction chemotherapy.

Detailed results from this trial were presented at the 20th Congress of the European Hematology Association last year. The research was sponsored by MEI Pharma, the company developing pracinostat.

The study included 50 AML patients who had a median age of 75 (range, 66-84).

The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.

According to updated data from MEI Pharma, the complete response rate was 42% (n=21), and the median overall survival was 19.1 months.

The company said these data compare favorably to a phase 3 study of azacitidine (AZA-AML-0011), which showed a median overall survival of 10.4 months with azacitidine alone and a complete response rate of 19.5% in a similar patient population.

The combination of pracinostat and azacitidine was thought to be well tolerated overall, with no unexpected toxicities. The most common grade 3-4 treatment-emergent adverse events included febrile neutropenia, thrombocytopenia, anemia, and fatigue.

DNA coiled around histones

Image by Eric Smith

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the histone deacetylase (HDAC) inhibitor pracinostat to be used in combination with azacitidine to treat newly diagnosed acute myeloid leukemia (AML) patients who are 75 and older or unfit for intensive chemotherapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough therapy designation for pracinostat is supported by data from a phase 2 study of the HDAC inhibitor in combination with azacitidine in elderly patients with newly diagnosed AML who were not candidates for induction chemotherapy.

Detailed results from this trial were presented at the 20th Congress of the European Hematology Association last year. The research was sponsored by MEI Pharma, the company developing pracinostat.

The study included 50 AML patients who had a median age of 75 (range, 66-84).

The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.

According to updated data from MEI Pharma, the complete response rate was 42% (n=21), and the median overall survival was 19.1 months.

The company said these data compare favorably to a phase 3 study of azacitidine (AZA-AML-0011), which showed a median overall survival of 10.4 months with azacitidine alone and a complete response rate of 19.5% in a similar patient population.

The combination of pracinostat and azacitidine was thought to be well tolerated overall, with no unexpected toxicities. The most common grade 3-4 treatment-emergent adverse events included febrile neutropenia, thrombocytopenia, anemia, and fatigue.

DNA coiled around histones

Image by Eric Smith

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the histone deacetylase (HDAC) inhibitor pracinostat to be used in combination with azacitidine to treat newly diagnosed acute myeloid leukemia (AML) patients who are 75 and older or unfit for intensive chemotherapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough therapy designation for pracinostat is supported by data from a phase 2 study of the HDAC inhibitor in combination with azacitidine in elderly patients with newly diagnosed AML who were not candidates for induction chemotherapy.

Detailed results from this trial were presented at the 20th Congress of the European Hematology Association last year. The research was sponsored by MEI Pharma, the company developing pracinostat.

The study included 50 AML patients who had a median age of 75 (range, 66-84).

The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.

According to updated data from MEI Pharma, the complete response rate was 42% (n=21), and the median overall survival was 19.1 months.

The company said these data compare favorably to a phase 3 study of azacitidine (AZA-AML-0011), which showed a median overall survival of 10.4 months with azacitidine alone and a complete response rate of 19.5% in a similar patient population.

The combination of pracinostat and azacitidine was thought to be well tolerated overall, with no unexpected toxicities. The most common grade 3-4 treatment-emergent adverse events included febrile neutropenia, thrombocytopenia, anemia, and fatigue.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.