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NICE rejects obinutuzumab for CLL
Credit: Linda Bartlett
In a new draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend obinutuzumab (Gazyvaro) to treat chronic lymphocytic leukemia (CLL).
NICE CEO Sir Andrew Dillon said that although data suggest obinutuzumab is effective, there were too many “uncertainties” in the information submitted by Roche, the company developing the drug.
So NICE cannot be sure obinutuzumab would be an effective use of the National Health Service’s resources.
This is despite the fact that Roche offered to discount the drug’s list price of £26,496 per treatment course.
NICE is accepting comments on the draft guidance until 5 pm on October 23.
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells. The drug induces antibody-dependent cellular cytotoxicity and caspase-independent apoptosis.
The European Commission approved obinutuzumab in July for use in combination with chlorambucil to treat patients with previously untreated CLL who have comorbidities that make them ineligible to receive fludarabine-based therapy.
Obinutuzumab was approved for this indication in the US in November 2013.
Obinutuzumab is marketed as Gazyvaro in the European Union and Switzerland but as Gazyva in the US and the rest of the world. 
Credit: Linda Bartlett
In a new draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend obinutuzumab (Gazyvaro) to treat chronic lymphocytic leukemia (CLL).
NICE CEO Sir Andrew Dillon said that although data suggest obinutuzumab is effective, there were too many “uncertainties” in the information submitted by Roche, the company developing the drug.
So NICE cannot be sure obinutuzumab would be an effective use of the National Health Service’s resources.
This is despite the fact that Roche offered to discount the drug’s list price of £26,496 per treatment course.
NICE is accepting comments on the draft guidance until 5 pm on October 23.
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells. The drug induces antibody-dependent cellular cytotoxicity and caspase-independent apoptosis.
The European Commission approved obinutuzumab in July for use in combination with chlorambucil to treat patients with previously untreated CLL who have comorbidities that make them ineligible to receive fludarabine-based therapy.
Obinutuzumab was approved for this indication in the US in November 2013.
Obinutuzumab is marketed as Gazyvaro in the European Union and Switzerland but as Gazyva in the US and the rest of the world.
Credit: Linda Bartlett
In a new draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend obinutuzumab (Gazyvaro) to treat chronic lymphocytic leukemia (CLL).
NICE CEO Sir Andrew Dillon said that although data suggest obinutuzumab is effective, there were too many “uncertainties” in the information submitted by Roche, the company developing the drug.
So NICE cannot be sure obinutuzumab would be an effective use of the National Health Service’s resources.
This is despite the fact that Roche offered to discount the drug’s list price of £26,496 per treatment course.
NICE is accepting comments on the draft guidance until 5 pm on October 23.
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells. The drug induces antibody-dependent cellular cytotoxicity and caspase-independent apoptosis.
The European Commission approved obinutuzumab in July for use in combination with chlorambucil to treat patients with previously untreated CLL who have comorbidities that make them ineligible to receive fludarabine-based therapy.
Obinutuzumab was approved for this indication in the US in November 2013.
Obinutuzumab is marketed as Gazyvaro in the European Union and Switzerland but as Gazyva in the US and the rest of the world.
FDA approves cancer drugs faster, study shows
MADRID—The US Food and Drug Administration (FDA) tends to approve cancer drugs faster than Health Canada and the European Medicines Agency (EMA),
according to a study presented at the ESMO 2014 Congress.
On average, the FDA approved antineoplastic agents about 6 to 8 months faster than the EMA and Health Canada, researchers found.
One of the drugs studied had been FDA-approved for more than 4.5 years before the EMA and Health Canada authorized its use.
The researchers said these results suggest a need for a coordinated international approach to reduce the disparity in approval times.
“There needs to be a dialogue amongst industry, regulatory agencies, patient bodies, [the] research community, and oncology professionals on how best we can reduce the time to approval while ensuring safety for approved drugs,” said study investigator Sunil Verma, MD, of Sunnybrook Odette Cancer Center in Toronto, Canada.
A previous study, published in NEJM in 2012, showed that, between 2001 and 2010, the FDA tended to approve all types of drugs faster than the EMA and Health Canada.
Dr Verma and Nardin Samuel, an MD/PhD student at the University of Toronto, focused their study on cancer drugs and presented their findings at ESMO as abstract 1036O_PR.
The pair analyzed approval data for 41 antineoplastic agents and found the average time to FDA approval for these drugs was 6 months shorter than for the EMA and 7.6 months shorter than for Health Canada.
Azacitidine, which is approved to treat hematologic malignancies, had the greatest delay between FDA and Health Canada approval, at 66.1 months. The EMA approved azacitidine 10.3 months earlier than Health Canada but 55.8 months after the FDA.
The fastest approval time among the drugs studied was for cabazitaxel, which was approved for metastatic prostate cancer by the FDA just 17 days after the drug’s manufacturer filed for approval. In Canada and the European Union, the times to approval for cabazitaxel were 11.63 months and 11.03 months, respectively.
“It is not clear why there were these differences, but they are of some concern . . . ,” said David Cameron, MD, of the Edinburgh Cancer Research Centre in the UK, who was not involved in this research.
“[T]hey suggest that, in the absence of data to the contrary, there may be bureaucratic rather than medical/scientific reasons for differential geographical approval timelines, which, of course, will lead to differential geographical benefits from new agents.”
Dr Cameron added that more work is needed to understand the reasons for these differences, as well as assess any potential impact on patients.
MADRID—The US Food and Drug Administration (FDA) tends to approve cancer drugs faster than Health Canada and the European Medicines Agency (EMA),
according to a study presented at the ESMO 2014 Congress.
On average, the FDA approved antineoplastic agents about 6 to 8 months faster than the EMA and Health Canada, researchers found.
One of the drugs studied had been FDA-approved for more than 4.5 years before the EMA and Health Canada authorized its use.
The researchers said these results suggest a need for a coordinated international approach to reduce the disparity in approval times.
“There needs to be a dialogue amongst industry, regulatory agencies, patient bodies, [the] research community, and oncology professionals on how best we can reduce the time to approval while ensuring safety for approved drugs,” said study investigator Sunil Verma, MD, of Sunnybrook Odette Cancer Center in Toronto, Canada.
A previous study, published in NEJM in 2012, showed that, between 2001 and 2010, the FDA tended to approve all types of drugs faster than the EMA and Health Canada.
Dr Verma and Nardin Samuel, an MD/PhD student at the University of Toronto, focused their study on cancer drugs and presented their findings at ESMO as abstract 1036O_PR.
The pair analyzed approval data for 41 antineoplastic agents and found the average time to FDA approval for these drugs was 6 months shorter than for the EMA and 7.6 months shorter than for Health Canada.
Azacitidine, which is approved to treat hematologic malignancies, had the greatest delay between FDA and Health Canada approval, at 66.1 months. The EMA approved azacitidine 10.3 months earlier than Health Canada but 55.8 months after the FDA.
The fastest approval time among the drugs studied was for cabazitaxel, which was approved for metastatic prostate cancer by the FDA just 17 days after the drug’s manufacturer filed for approval. In Canada and the European Union, the times to approval for cabazitaxel were 11.63 months and 11.03 months, respectively.
“It is not clear why there were these differences, but they are of some concern . . . ,” said David Cameron, MD, of the Edinburgh Cancer Research Centre in the UK, who was not involved in this research.
“[T]hey suggest that, in the absence of data to the contrary, there may be bureaucratic rather than medical/scientific reasons for differential geographical approval timelines, which, of course, will lead to differential geographical benefits from new agents.”
Dr Cameron added that more work is needed to understand the reasons for these differences, as well as assess any potential impact on patients.
MADRID—The US Food and Drug Administration (FDA) tends to approve cancer drugs faster than Health Canada and the European Medicines Agency (EMA),
according to a study presented at the ESMO 2014 Congress.
On average, the FDA approved antineoplastic agents about 6 to 8 months faster than the EMA and Health Canada, researchers found.
One of the drugs studied had been FDA-approved for more than 4.5 years before the EMA and Health Canada authorized its use.
The researchers said these results suggest a need for a coordinated international approach to reduce the disparity in approval times.
“There needs to be a dialogue amongst industry, regulatory agencies, patient bodies, [the] research community, and oncology professionals on how best we can reduce the time to approval while ensuring safety for approved drugs,” said study investigator Sunil Verma, MD, of Sunnybrook Odette Cancer Center in Toronto, Canada.
A previous study, published in NEJM in 2012, showed that, between 2001 and 2010, the FDA tended to approve all types of drugs faster than the EMA and Health Canada.
Dr Verma and Nardin Samuel, an MD/PhD student at the University of Toronto, focused their study on cancer drugs and presented their findings at ESMO as abstract 1036O_PR.
The pair analyzed approval data for 41 antineoplastic agents and found the average time to FDA approval for these drugs was 6 months shorter than for the EMA and 7.6 months shorter than for Health Canada.
Azacitidine, which is approved to treat hematologic malignancies, had the greatest delay between FDA and Health Canada approval, at 66.1 months. The EMA approved azacitidine 10.3 months earlier than Health Canada but 55.8 months after the FDA.
The fastest approval time among the drugs studied was for cabazitaxel, which was approved for metastatic prostate cancer by the FDA just 17 days after the drug’s manufacturer filed for approval. In Canada and the European Union, the times to approval for cabazitaxel were 11.63 months and 11.03 months, respectively.
“It is not clear why there were these differences, but they are of some concern . . . ,” said David Cameron, MD, of the Edinburgh Cancer Research Centre in the UK, who was not involved in this research.
“[T]hey suggest that, in the absence of data to the contrary, there may be bureaucratic rather than medical/scientific reasons for differential geographical approval timelines, which, of course, will lead to differential geographical benefits from new agents.”
Dr Cameron added that more work is needed to understand the reasons for these differences, as well as assess any potential impact on patients.
Blood testing system wins marketing authorization in US
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted marketing authorization for the T2Candida® Panel and the T2Dx® Instrument, a system that provides direct detection of 5 yeast pathogens in whole blood samples.
The system can detect Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei in patients with symptoms of, or medical conditions predisposing them to, invasive fungal infections.
It can take up to 6 days to detect yeast pathogens using blood culture, and even more time to identify the specific type of yeast present.
The T2Candida system can identify specific Candida pathogens from a single blood sample within 3 to 5 hours.
However, false positive results are possible with this system, so physicians should perform blood cultures to confirm T2Candida results, according to the FDA. Still, a negative test result may provide timely data that allows physicians to avoid or suspend unnecessary antifungal treatment.
“By testing 1 blood sample for 5 yeast pathogens—and getting results within a few hours—physicians can initiate appropriate antifungal treatment earlier and potentially reduce patient illness and decrease the risk of dying from these infections,” said Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health.
How the system works
The T2Candida panel and T2Dx instrument are powered by T2MR, a miniaturized, magnetic-resonance-based diagnostic approach that measures how water molecules react in the presence of magnetic fields.
The system uses blood-compatible polymerase chain reaction to amplify Candida DNA, which then binds to superparamagnetic nanoparticles coated with a complementary DNA strand. The binding event causes the nanoparticles to cluster, which changes the sample’s T2 magnetic resonance signal.
If the system detects yeast DNA, it can then determine the species category to which the DNA belongs, which helps point healthcare providers to the appropriate treatment.
T2Dx is a fully automated, bench-top instrument. To perform a test, the patient sample is snapped onto a disposable test cartridge, which is preloaded with the necessary reagents. The cartridge is then inserted into T2Dx, which processes the sample and delivers a diagnostic test result.
Studies and FDA review
The FDA reviewed the T2Candida panel and the T2Dx instrument through the agency’s de novo classification process, a regulatory pathway for certain novel, low- to moderate-risk medical devices.
The FDA based its review on a clinical study of 1500 patients, in which the T2Candida system correctly categorized nearly 100% of the negative specimens as negative for the presence of yeast.
In a separate study of 300 blood samples with specific concentrations of yeast, the system correctly identified the organism in 84% to 96% of the positive specimens.
The T2Candida panel and T2Dx instrument are manufactured by T2 Biosystems, Inc.
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted marketing authorization for the T2Candida® Panel and the T2Dx® Instrument, a system that provides direct detection of 5 yeast pathogens in whole blood samples.
The system can detect Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei in patients with symptoms of, or medical conditions predisposing them to, invasive fungal infections.
It can take up to 6 days to detect yeast pathogens using blood culture, and even more time to identify the specific type of yeast present.
The T2Candida system can identify specific Candida pathogens from a single blood sample within 3 to 5 hours.
However, false positive results are possible with this system, so physicians should perform blood cultures to confirm T2Candida results, according to the FDA. Still, a negative test result may provide timely data that allows physicians to avoid or suspend unnecessary antifungal treatment.
“By testing 1 blood sample for 5 yeast pathogens—and getting results within a few hours—physicians can initiate appropriate antifungal treatment earlier and potentially reduce patient illness and decrease the risk of dying from these infections,” said Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health.
How the system works
The T2Candida panel and T2Dx instrument are powered by T2MR, a miniaturized, magnetic-resonance-based diagnostic approach that measures how water molecules react in the presence of magnetic fields.
The system uses blood-compatible polymerase chain reaction to amplify Candida DNA, which then binds to superparamagnetic nanoparticles coated with a complementary DNA strand. The binding event causes the nanoparticles to cluster, which changes the sample’s T2 magnetic resonance signal.
If the system detects yeast DNA, it can then determine the species category to which the DNA belongs, which helps point healthcare providers to the appropriate treatment.
T2Dx is a fully automated, bench-top instrument. To perform a test, the patient sample is snapped onto a disposable test cartridge, which is preloaded with the necessary reagents. The cartridge is then inserted into T2Dx, which processes the sample and delivers a diagnostic test result.
Studies and FDA review
The FDA reviewed the T2Candida panel and the T2Dx instrument through the agency’s de novo classification process, a regulatory pathway for certain novel, low- to moderate-risk medical devices.
The FDA based its review on a clinical study of 1500 patients, in which the T2Candida system correctly categorized nearly 100% of the negative specimens as negative for the presence of yeast.
In a separate study of 300 blood samples with specific concentrations of yeast, the system correctly identified the organism in 84% to 96% of the positive specimens.
The T2Candida panel and T2Dx instrument are manufactured by T2 Biosystems, Inc.
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted marketing authorization for the T2Candida® Panel and the T2Dx® Instrument, a system that provides direct detection of 5 yeast pathogens in whole blood samples.
The system can detect Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei in patients with symptoms of, or medical conditions predisposing them to, invasive fungal infections.
It can take up to 6 days to detect yeast pathogens using blood culture, and even more time to identify the specific type of yeast present.
The T2Candida system can identify specific Candida pathogens from a single blood sample within 3 to 5 hours.
However, false positive results are possible with this system, so physicians should perform blood cultures to confirm T2Candida results, according to the FDA. Still, a negative test result may provide timely data that allows physicians to avoid or suspend unnecessary antifungal treatment.
“By testing 1 blood sample for 5 yeast pathogens—and getting results within a few hours—physicians can initiate appropriate antifungal treatment earlier and potentially reduce patient illness and decrease the risk of dying from these infections,” said Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health.
How the system works
The T2Candida panel and T2Dx instrument are powered by T2MR, a miniaturized, magnetic-resonance-based diagnostic approach that measures how water molecules react in the presence of magnetic fields.
The system uses blood-compatible polymerase chain reaction to amplify Candida DNA, which then binds to superparamagnetic nanoparticles coated with a complementary DNA strand. The binding event causes the nanoparticles to cluster, which changes the sample’s T2 magnetic resonance signal.
If the system detects yeast DNA, it can then determine the species category to which the DNA belongs, which helps point healthcare providers to the appropriate treatment.
T2Dx is a fully automated, bench-top instrument. To perform a test, the patient sample is snapped onto a disposable test cartridge, which is preloaded with the necessary reagents. The cartridge is then inserted into T2Dx, which processes the sample and delivers a diagnostic test result.
Studies and FDA review
The FDA reviewed the T2Candida panel and the T2Dx instrument through the agency’s de novo classification process, a regulatory pathway for certain novel, low- to moderate-risk medical devices.
The FDA based its review on a clinical study of 1500 patients, in which the T2Candida system correctly categorized nearly 100% of the negative specimens as negative for the presence of yeast.
In a separate study of 300 blood samples with specific concentrations of yeast, the system correctly identified the organism in 84% to 96% of the positive specimens.
The T2Candida panel and T2Dx instrument are manufactured by T2 Biosystems, Inc.
FDA approves 30-day pack of anticoagulant
Credit: NHS
The US Food and Drug Administration (FDA) has approved the Xarelto Starter Pack™ for the treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE).
The pack provides a 30-day supply of Xarelto (rivaroxaban), which gives patients time to follow up with their primary care physician after leaving the hospital, without missing treatment.
Patients have the greatest risk of recurrence in the first 30 days after a DVT or PE.
“The starter pack will make a difference for patients impacted by blood clots by offering a 30-day supply of the drug in a new, convenient package, which may help support patients as they transition from the hospital to outpatient care,” said Paul Burton, MD, PhD, Vice President of Medical Affairs at Janssen, the company developing Xarelto.
The Xarelto Starter Pack™ will be available at pharmacies in October.
Xarelto is a factor Xa inhibitor that is FDA-approved to treat and prevent the recurrence of DVT/PE, as thromboprophylaxis in patients who have undergone knee or hip replacement surgery, and to reduce the risk of stroke in patients with non-valvular atrial fibrillation.
For DVT/PE patients, Xarelto is given twice daily at 15 mg with food for the first 21 days. On day 22, patients transition to a once-daily dose of 20 mg with food for the remainder of treatment.
Xarelto has a boxed warning stating that premature discontinuation of the drug increases the risk of thrombotic events, and epidural or spinal hematomas have occurred in Xarelto-treated patients who are receiving neuraxial anesthesia or undergoing spinal puncture.
For more details on Xarelto, see the full prescribing information.
Credit: NHS
The US Food and Drug Administration (FDA) has approved the Xarelto Starter Pack™ for the treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE).
The pack provides a 30-day supply of Xarelto (rivaroxaban), which gives patients time to follow up with their primary care physician after leaving the hospital, without missing treatment.
Patients have the greatest risk of recurrence in the first 30 days after a DVT or PE.
“The starter pack will make a difference for patients impacted by blood clots by offering a 30-day supply of the drug in a new, convenient package, which may help support patients as they transition from the hospital to outpatient care,” said Paul Burton, MD, PhD, Vice President of Medical Affairs at Janssen, the company developing Xarelto.
The Xarelto Starter Pack™ will be available at pharmacies in October.
Xarelto is a factor Xa inhibitor that is FDA-approved to treat and prevent the recurrence of DVT/PE, as thromboprophylaxis in patients who have undergone knee or hip replacement surgery, and to reduce the risk of stroke in patients with non-valvular atrial fibrillation.
For DVT/PE patients, Xarelto is given twice daily at 15 mg with food for the first 21 days. On day 22, patients transition to a once-daily dose of 20 mg with food for the remainder of treatment.
Xarelto has a boxed warning stating that premature discontinuation of the drug increases the risk of thrombotic events, and epidural or spinal hematomas have occurred in Xarelto-treated patients who are receiving neuraxial anesthesia or undergoing spinal puncture.
For more details on Xarelto, see the full prescribing information.
Credit: NHS
The US Food and Drug Administration (FDA) has approved the Xarelto Starter Pack™ for the treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE).
The pack provides a 30-day supply of Xarelto (rivaroxaban), which gives patients time to follow up with their primary care physician after leaving the hospital, without missing treatment.
Patients have the greatest risk of recurrence in the first 30 days after a DVT or PE.
“The starter pack will make a difference for patients impacted by blood clots by offering a 30-day supply of the drug in a new, convenient package, which may help support patients as they transition from the hospital to outpatient care,” said Paul Burton, MD, PhD, Vice President of Medical Affairs at Janssen, the company developing Xarelto.
The Xarelto Starter Pack™ will be available at pharmacies in October.
Xarelto is a factor Xa inhibitor that is FDA-approved to treat and prevent the recurrence of DVT/PE, as thromboprophylaxis in patients who have undergone knee or hip replacement surgery, and to reduce the risk of stroke in patients with non-valvular atrial fibrillation.
For DVT/PE patients, Xarelto is given twice daily at 15 mg with food for the first 21 days. On day 22, patients transition to a once-daily dose of 20 mg with food for the remainder of treatment.
Xarelto has a boxed warning stating that premature discontinuation of the drug increases the risk of thrombotic events, and epidural or spinal hematomas have occurred in Xarelto-treated patients who are receiving neuraxial anesthesia or undergoing spinal puncture.
For more details on Xarelto, see the full prescribing information.
Idelalisib approved to treat CLL, FL in EU
The European Commission has granted marketing authorization for the PI3K delta inhibitor idelalisib (Zydelig) to treat chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) in the European Union.
The drug is now approved for use in combination with rituximab for CLL patients who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and are not eligible for chemo-immunotherapy.
Idelalisib is also approved as monotherapy for FL patients who were refractory to 2 prior lines of treatment.
These approvals are based on data from 2 clinical trials—Study 116 and Study 101-09.
Study 116: Idelalisib in CLL
This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.
The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.
Patients in the rituximab-idelalisib arm had a much higher overall response rate than patients in the rituximab-placebo arm—81% and 13%, respectively (P<0.001). There were no complete responses.
At 24 weeks, the rate of progression-free survival was 93% in the rituximab-idelalisib arm and 46% in the rituximab-placebo arm (P<0.001). The median progression-free survival was 5.5 months in the rituximab-placebo arm and not reached in the rituximab-idelalisib arm (P<0.001).
At 12 months, the overall survival rate was 92% in the rituximab-idelalisib arm and 80% in the rituximab-placebo arm (P=0.02).
Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the rituximab-idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the rituximab-placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.
There were more serious adverse events in the rituximab-idelalisib arm than in the rituximab-placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).
Study 101-09: Idelalisib in FL
This phase 2 trial enrolled 125 patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent. Patients received idelalisib monotherapy.
Of the 72 subjects with FL, 54% achieved a response, and 8% had a complete response. The median duration of response was not reached (range, 0-14.8 months).
Improvements in survival or disease-related symptoms have not been established.
In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).
Idelalisib is under development by Gilead Sciences. The drug is already approved in the US for the aforementioned indications, as well as to treat small lymphocytic lymphoma.
The European Commission has granted marketing authorization for the PI3K delta inhibitor idelalisib (Zydelig) to treat chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) in the European Union.
The drug is now approved for use in combination with rituximab for CLL patients who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and are not eligible for chemo-immunotherapy.
Idelalisib is also approved as monotherapy for FL patients who were refractory to 2 prior lines of treatment.
These approvals are based on data from 2 clinical trials—Study 116 and Study 101-09.
Study 116: Idelalisib in CLL
This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.
The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.
Patients in the rituximab-idelalisib arm had a much higher overall response rate than patients in the rituximab-placebo arm—81% and 13%, respectively (P<0.001). There were no complete responses.
At 24 weeks, the rate of progression-free survival was 93% in the rituximab-idelalisib arm and 46% in the rituximab-placebo arm (P<0.001). The median progression-free survival was 5.5 months in the rituximab-placebo arm and not reached in the rituximab-idelalisib arm (P<0.001).
At 12 months, the overall survival rate was 92% in the rituximab-idelalisib arm and 80% in the rituximab-placebo arm (P=0.02).
Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the rituximab-idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the rituximab-placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.
There were more serious adverse events in the rituximab-idelalisib arm than in the rituximab-placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).
Study 101-09: Idelalisib in FL
This phase 2 trial enrolled 125 patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent. Patients received idelalisib monotherapy.
Of the 72 subjects with FL, 54% achieved a response, and 8% had a complete response. The median duration of response was not reached (range, 0-14.8 months).
Improvements in survival or disease-related symptoms have not been established.
In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).
Idelalisib is under development by Gilead Sciences. The drug is already approved in the US for the aforementioned indications, as well as to treat small lymphocytic lymphoma.
The European Commission has granted marketing authorization for the PI3K delta inhibitor idelalisib (Zydelig) to treat chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) in the European Union.
The drug is now approved for use in combination with rituximab for CLL patients who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and are not eligible for chemo-immunotherapy.
Idelalisib is also approved as monotherapy for FL patients who were refractory to 2 prior lines of treatment.
These approvals are based on data from 2 clinical trials—Study 116 and Study 101-09.
Study 116: Idelalisib in CLL
This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.
The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.
Patients in the rituximab-idelalisib arm had a much higher overall response rate than patients in the rituximab-placebo arm—81% and 13%, respectively (P<0.001). There were no complete responses.
At 24 weeks, the rate of progression-free survival was 93% in the rituximab-idelalisib arm and 46% in the rituximab-placebo arm (P<0.001). The median progression-free survival was 5.5 months in the rituximab-placebo arm and not reached in the rituximab-idelalisib arm (P<0.001).
At 12 months, the overall survival rate was 92% in the rituximab-idelalisib arm and 80% in the rituximab-placebo arm (P=0.02).
Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the rituximab-idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the rituximab-placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.
There were more serious adverse events in the rituximab-idelalisib arm than in the rituximab-placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).
Study 101-09: Idelalisib in FL
This phase 2 trial enrolled 125 patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent. Patients received idelalisib monotherapy.
Of the 72 subjects with FL, 54% achieved a response, and 8% had a complete response. The median duration of response was not reached (range, 0-14.8 months).
Improvements in survival or disease-related symptoms have not been established.
In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).
Idelalisib is under development by Gilead Sciences. The drug is already approved in the US for the aforementioned indications, as well as to treat small lymphocytic lymphoma.
FDA approves treatment for kids with hemophilia B
The US Food and Drug Administration (FDA) has approved a recombinant factor IX product (Rixubis) for use in children with hemophilia B.
Rixubis is indicated for routine prophylactic treatment, control and prevention of bleeding episodes, and perioperative management in these patients.
Rixubis was the first recombinant factor IX product to gain FDA approval for routine prophylaxis and control of bleeding episodes in adults with hemophilia B.
The latest FDA approval is based on results of a trial investigating the efficacy and safety of Rixubis in 23 previously treated male patients younger than 12 years of age who had severe or moderately severe hemophilia B.
The patients received a twice-weekly Rixubis prophylaxis regimen (mean dose 56 IU/kg) for a mean treatment duration of 6 months and a mean of 54 exposure days.
The median annualized bleeding rate was 2.0 (0.0 for spontaneous bleeds and joint bleeds). Nine patients (39.1%) experienced no bleeds, and 23 bleeding episodes (88.5%) were treated with 1 to 2 infusions.
There were no reports of inhibitor development, severe allergic reactions, thrombotic events, or treatment-related adverse events.
These data were presented at the 2013 ASH Annual Meeting (abstract 1118).
Common adverse reactions observed in more than 1% of subjects in clinical studies of Rixubis were dysgeusia, pain in an extremity, and a positive test for furin antibody. Rixubis may pose a risk of hypersensitivity reactions, inhibitor development, nephrotic syndrome, and thromboembolic complications.
Rixubis is contraindicated in patients who have known hypersensitivity to the product or its excipients (including hamster protein), patients with disseminated intravascular coagulation, and those with signs of fibrinolysis.
For more details on Rixubis, see the full prescribing information. Rixubis is under development by Baxter International Inc.
The US Food and Drug Administration (FDA) has approved a recombinant factor IX product (Rixubis) for use in children with hemophilia B.
Rixubis is indicated for routine prophylactic treatment, control and prevention of bleeding episodes, and perioperative management in these patients.
Rixubis was the first recombinant factor IX product to gain FDA approval for routine prophylaxis and control of bleeding episodes in adults with hemophilia B.
The latest FDA approval is based on results of a trial investigating the efficacy and safety of Rixubis in 23 previously treated male patients younger than 12 years of age who had severe or moderately severe hemophilia B.
The patients received a twice-weekly Rixubis prophylaxis regimen (mean dose 56 IU/kg) for a mean treatment duration of 6 months and a mean of 54 exposure days.
The median annualized bleeding rate was 2.0 (0.0 for spontaneous bleeds and joint bleeds). Nine patients (39.1%) experienced no bleeds, and 23 bleeding episodes (88.5%) were treated with 1 to 2 infusions.
There were no reports of inhibitor development, severe allergic reactions, thrombotic events, or treatment-related adverse events.
These data were presented at the 2013 ASH Annual Meeting (abstract 1118).
Common adverse reactions observed in more than 1% of subjects in clinical studies of Rixubis were dysgeusia, pain in an extremity, and a positive test for furin antibody. Rixubis may pose a risk of hypersensitivity reactions, inhibitor development, nephrotic syndrome, and thromboembolic complications.
Rixubis is contraindicated in patients who have known hypersensitivity to the product or its excipients (including hamster protein), patients with disseminated intravascular coagulation, and those with signs of fibrinolysis.
For more details on Rixubis, see the full prescribing information. Rixubis is under development by Baxter International Inc.
The US Food and Drug Administration (FDA) has approved a recombinant factor IX product (Rixubis) for use in children with hemophilia B.
Rixubis is indicated for routine prophylactic treatment, control and prevention of bleeding episodes, and perioperative management in these patients.
Rixubis was the first recombinant factor IX product to gain FDA approval for routine prophylaxis and control of bleeding episodes in adults with hemophilia B.
The latest FDA approval is based on results of a trial investigating the efficacy and safety of Rixubis in 23 previously treated male patients younger than 12 years of age who had severe or moderately severe hemophilia B.
The patients received a twice-weekly Rixubis prophylaxis regimen (mean dose 56 IU/kg) for a mean treatment duration of 6 months and a mean of 54 exposure days.
The median annualized bleeding rate was 2.0 (0.0 for spontaneous bleeds and joint bleeds). Nine patients (39.1%) experienced no bleeds, and 23 bleeding episodes (88.5%) were treated with 1 to 2 infusions.
There were no reports of inhibitor development, severe allergic reactions, thrombotic events, or treatment-related adverse events.
These data were presented at the 2013 ASH Annual Meeting (abstract 1118).
Common adverse reactions observed in more than 1% of subjects in clinical studies of Rixubis were dysgeusia, pain in an extremity, and a positive test for furin antibody. Rixubis may pose a risk of hypersensitivity reactions, inhibitor development, nephrotic syndrome, and thromboembolic complications.
Rixubis is contraindicated in patients who have known hypersensitivity to the product or its excipients (including hamster protein), patients with disseminated intravascular coagulation, and those with signs of fibrinolysis.
For more details on Rixubis, see the full prescribing information. Rixubis is under development by Baxter International Inc.
FDA approves new treatment for PI
Credit: Baxter
The US Food and Drug Administration (FDA) has approved a subcutaneous immune globulin product for use in adults with primary immunodeficiency (PI).
The product, HyQvia, is an immune globulin with a recombinant human hyaluronidase. It requires a single infusion every 3 to 4 weeks and 1 injection site per infusion to deliver a full therapeutic dose of immune globulin.
Current therapies require weekly or bi-weekly treatment with multiple infusion sites per treatment.
Baxter International Inc. expects to launch HyQvia in the US in the coming weeks. The product has been FDA-approved with a black-box warning detailing the risk of thrombosis associated with immune globulin products.
The immune globulin component of HyQvia is a 10% solution prepared from large pools of human plasma consisting of at least 98% IgG. The recombinant human hyaluronidase increases the dispersion and absorption of the immune globulin.
In a phase 3 trial, HyQvia compared well with intravenous human immune globulin 10% (IVIG).
Researchers compared the treatments at different time periods in a cohort of PI patients with a median age of 35 (range, 4-78 years). All 87 patients studied received IVIG, and 83 of the patients received at least 1 dose of HyQvia.
Patients received HyQvia for a median of 366 days and IVIG for a median of 91 days. The median ratio (HyQvia:IVIG) for the IgG dosage administered was 1.088 (range, 0.986–1.382).
Trough IgG concentrations, the incidence of infection, and rates of adverse events were generally similar during the HyQvia treatment period and the IVIG treatment period.
For patients aged 12 years and older, the median IgG Ctrough values with HyQvia were approximately the same as with IVIG. The median trough ratio (HyQvia:IVIG) was 0.985.
For patients younger than 12 (n=11), the median IgG Ctrough values were 10.0 and 9.6 g/L after HyQvia and IVIG, respectively, with a median trough ratio of 1.038.
The overall infection rates were 2.97 per patient-year with HyQvia and 4.51 per patient-year with IVIG.
During the HyQvia treatment period, the rate of acute serious bacterial infection (SBI) was 0.025 per patient-year. The rate of acute SBIs occurring during IVIG treatment was not reported.
In patients age 18 and older (n=59), the rate of acute SBIs was 0.00 per patient-year, and the overall infection rate was 3.20 per patient-year.
For this same patient group, the local adverse reaction rate was 0.286 per infusion.
The rate of systemic adverse events temporally related to an infusion was 0.20 per infusion with HyQvia and 0.33 per infusion with IVIG. There were no serious adverse events reported in these patients with either treatment.
HyQvia was approved in Europe in 2013 for adults with PI syndromes and myeloma or chronic lymphocytic leukemia with severe secondary hypogammaglobulinemia and recurrent infections.
For more details on HyQvia, see the prescribing information.
Credit: Baxter
The US Food and Drug Administration (FDA) has approved a subcutaneous immune globulin product for use in adults with primary immunodeficiency (PI).
The product, HyQvia, is an immune globulin with a recombinant human hyaluronidase. It requires a single infusion every 3 to 4 weeks and 1 injection site per infusion to deliver a full therapeutic dose of immune globulin.
Current therapies require weekly or bi-weekly treatment with multiple infusion sites per treatment.
Baxter International Inc. expects to launch HyQvia in the US in the coming weeks. The product has been FDA-approved with a black-box warning detailing the risk of thrombosis associated with immune globulin products.
The immune globulin component of HyQvia is a 10% solution prepared from large pools of human plasma consisting of at least 98% IgG. The recombinant human hyaluronidase increases the dispersion and absorption of the immune globulin.
In a phase 3 trial, HyQvia compared well with intravenous human immune globulin 10% (IVIG).
Researchers compared the treatments at different time periods in a cohort of PI patients with a median age of 35 (range, 4-78 years). All 87 patients studied received IVIG, and 83 of the patients received at least 1 dose of HyQvia.
Patients received HyQvia for a median of 366 days and IVIG for a median of 91 days. The median ratio (HyQvia:IVIG) for the IgG dosage administered was 1.088 (range, 0.986–1.382).
Trough IgG concentrations, the incidence of infection, and rates of adverse events were generally similar during the HyQvia treatment period and the IVIG treatment period.
For patients aged 12 years and older, the median IgG Ctrough values with HyQvia were approximately the same as with IVIG. The median trough ratio (HyQvia:IVIG) was 0.985.
For patients younger than 12 (n=11), the median IgG Ctrough values were 10.0 and 9.6 g/L after HyQvia and IVIG, respectively, with a median trough ratio of 1.038.
The overall infection rates were 2.97 per patient-year with HyQvia and 4.51 per patient-year with IVIG.
During the HyQvia treatment period, the rate of acute serious bacterial infection (SBI) was 0.025 per patient-year. The rate of acute SBIs occurring during IVIG treatment was not reported.
In patients age 18 and older (n=59), the rate of acute SBIs was 0.00 per patient-year, and the overall infection rate was 3.20 per patient-year.
For this same patient group, the local adverse reaction rate was 0.286 per infusion.
The rate of systemic adverse events temporally related to an infusion was 0.20 per infusion with HyQvia and 0.33 per infusion with IVIG. There were no serious adverse events reported in these patients with either treatment.
HyQvia was approved in Europe in 2013 for adults with PI syndromes and myeloma or chronic lymphocytic leukemia with severe secondary hypogammaglobulinemia and recurrent infections.
For more details on HyQvia, see the prescribing information.
Credit: Baxter
The US Food and Drug Administration (FDA) has approved a subcutaneous immune globulin product for use in adults with primary immunodeficiency (PI).
The product, HyQvia, is an immune globulin with a recombinant human hyaluronidase. It requires a single infusion every 3 to 4 weeks and 1 injection site per infusion to deliver a full therapeutic dose of immune globulin.
Current therapies require weekly or bi-weekly treatment with multiple infusion sites per treatment.
Baxter International Inc. expects to launch HyQvia in the US in the coming weeks. The product has been FDA-approved with a black-box warning detailing the risk of thrombosis associated with immune globulin products.
The immune globulin component of HyQvia is a 10% solution prepared from large pools of human plasma consisting of at least 98% IgG. The recombinant human hyaluronidase increases the dispersion and absorption of the immune globulin.
In a phase 3 trial, HyQvia compared well with intravenous human immune globulin 10% (IVIG).
Researchers compared the treatments at different time periods in a cohort of PI patients with a median age of 35 (range, 4-78 years). All 87 patients studied received IVIG, and 83 of the patients received at least 1 dose of HyQvia.
Patients received HyQvia for a median of 366 days and IVIG for a median of 91 days. The median ratio (HyQvia:IVIG) for the IgG dosage administered was 1.088 (range, 0.986–1.382).
Trough IgG concentrations, the incidence of infection, and rates of adverse events were generally similar during the HyQvia treatment period and the IVIG treatment period.
For patients aged 12 years and older, the median IgG Ctrough values with HyQvia were approximately the same as with IVIG. The median trough ratio (HyQvia:IVIG) was 0.985.
For patients younger than 12 (n=11), the median IgG Ctrough values were 10.0 and 9.6 g/L after HyQvia and IVIG, respectively, with a median trough ratio of 1.038.
The overall infection rates were 2.97 per patient-year with HyQvia and 4.51 per patient-year with IVIG.
During the HyQvia treatment period, the rate of acute serious bacterial infection (SBI) was 0.025 per patient-year. The rate of acute SBIs occurring during IVIG treatment was not reported.
In patients age 18 and older (n=59), the rate of acute SBIs was 0.00 per patient-year, and the overall infection rate was 3.20 per patient-year.
For this same patient group, the local adverse reaction rate was 0.286 per infusion.
The rate of systemic adverse events temporally related to an infusion was 0.20 per infusion with HyQvia and 0.33 per infusion with IVIG. There were no serious adverse events reported in these patients with either treatment.
HyQvia was approved in Europe in 2013 for adults with PI syndromes and myeloma or chronic lymphocytic leukemia with severe secondary hypogammaglobulinemia and recurrent infections.
For more details on HyQvia, see the prescribing information.
Heparin lot recalled due to particulate
Hospira Inc. has initiated a US-wide recall of 1 lot of heparin sodium, following a customer report of particulate in a single unit.
The recall affects lot 41-046-JT of 1000 USP Heparin Units/500 mL (2 USP Heparin Units/mL), in 0.9% Sodium Chloride Injection, 500 mL (NDC 0409-7620-03; expiration date November 1, 2015).
The foreign particle found in a unit from this lot was a human hair sealed between the tube and the film at the round seal of the unused administrative port on the non-print side of the container.
To date, Hospira has not received reports of any adverse events associated with this issue. The root cause has not been determined and is under investigation.
Heparin sodium injection is indicated as an anticoagulant to maintain catheter patency. In the event that a particulate breaks and pieces are able to pass through the intravenous catheter, injected particulate material may result in local inflammation, phlebitis, and/or low-level allergic response.
Capillaries may become occluded. Patients with a pre-existing condition of trauma or another medical condition that adversely affects the microvascular blood supply are at an increased risk.
The lot of heparin affected by this recall was distributed nationwide between June 2014 and August 2014 to wholesalers/distributors, hospitals, and pharmacies.
Anyone with existing inventory should stop use and distribution and quarantine the product immediately. Customers should also inform potential users of this product about the recall.
Hospira will be notifying its direct distributors/customers via a recall letter and will arrange for the impacted product to be returned to Stericycle. For additional assistance, call Stericycle at 1-855-201-4337 between the hours of 8 am and 5pm ET, Monday through Friday.
For clinical inquiries, contact Hospira. To report adverse events or product complaints, call 1-800-441-4100 (8 am to 5 pm CT, Monday through Friday) or email ProductComplaintsPP@hospira.com.
For medical inquiries, call 1-800-615-0187 (available 24 hours a day, 7 days per week) or email medcom@hospira.com.
Adverse reactions or quality problems associated with this product can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.
Hospira Inc. has initiated a US-wide recall of 1 lot of heparin sodium, following a customer report of particulate in a single unit.
The recall affects lot 41-046-JT of 1000 USP Heparin Units/500 mL (2 USP Heparin Units/mL), in 0.9% Sodium Chloride Injection, 500 mL (NDC 0409-7620-03; expiration date November 1, 2015).
The foreign particle found in a unit from this lot was a human hair sealed between the tube and the film at the round seal of the unused administrative port on the non-print side of the container.
To date, Hospira has not received reports of any adverse events associated with this issue. The root cause has not been determined and is under investigation.
Heparin sodium injection is indicated as an anticoagulant to maintain catheter patency. In the event that a particulate breaks and pieces are able to pass through the intravenous catheter, injected particulate material may result in local inflammation, phlebitis, and/or low-level allergic response.
Capillaries may become occluded. Patients with a pre-existing condition of trauma or another medical condition that adversely affects the microvascular blood supply are at an increased risk.
The lot of heparin affected by this recall was distributed nationwide between June 2014 and August 2014 to wholesalers/distributors, hospitals, and pharmacies.
Anyone with existing inventory should stop use and distribution and quarantine the product immediately. Customers should also inform potential users of this product about the recall.
Hospira will be notifying its direct distributors/customers via a recall letter and will arrange for the impacted product to be returned to Stericycle. For additional assistance, call Stericycle at 1-855-201-4337 between the hours of 8 am and 5pm ET, Monday through Friday.
For clinical inquiries, contact Hospira. To report adverse events or product complaints, call 1-800-441-4100 (8 am to 5 pm CT, Monday through Friday) or email ProductComplaintsPP@hospira.com.
For medical inquiries, call 1-800-615-0187 (available 24 hours a day, 7 days per week) or email medcom@hospira.com.
Adverse reactions or quality problems associated with this product can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.
Hospira Inc. has initiated a US-wide recall of 1 lot of heparin sodium, following a customer report of particulate in a single unit.
The recall affects lot 41-046-JT of 1000 USP Heparin Units/500 mL (2 USP Heparin Units/mL), in 0.9% Sodium Chloride Injection, 500 mL (NDC 0409-7620-03; expiration date November 1, 2015).
The foreign particle found in a unit from this lot was a human hair sealed between the tube and the film at the round seal of the unused administrative port on the non-print side of the container.
To date, Hospira has not received reports of any adverse events associated with this issue. The root cause has not been determined and is under investigation.
Heparin sodium injection is indicated as an anticoagulant to maintain catheter patency. In the event that a particulate breaks and pieces are able to pass through the intravenous catheter, injected particulate material may result in local inflammation, phlebitis, and/or low-level allergic response.
Capillaries may become occluded. Patients with a pre-existing condition of trauma or another medical condition that adversely affects the microvascular blood supply are at an increased risk.
The lot of heparin affected by this recall was distributed nationwide between June 2014 and August 2014 to wholesalers/distributors, hospitals, and pharmacies.
Anyone with existing inventory should stop use and distribution and quarantine the product immediately. Customers should also inform potential users of this product about the recall.
Hospira will be notifying its direct distributors/customers via a recall letter and will arrange for the impacted product to be returned to Stericycle. For additional assistance, call Stericycle at 1-855-201-4337 between the hours of 8 am and 5pm ET, Monday through Friday.
For clinical inquiries, contact Hospira. To report adverse events or product complaints, call 1-800-441-4100 (8 am to 5 pm CT, Monday through Friday) or email ProductComplaintsPP@hospira.com.
For medical inquiries, call 1-800-615-0187 (available 24 hours a day, 7 days per week) or email medcom@hospira.com.
Adverse reactions or quality problems associated with this product can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.
Discovery could lead to better proteasome inhibitors
showing multiple myeloma
A newly discovered mechanism has paved the way for the next generation of proteasome inhibitors, according to a paper published in Chemistry & Biology.
Investigators developed a series of molecules that employ this mechanism, inhibiting the proteasome in 2 ways.
They are now planning to synthesize related compounds that may offer improved proteasome inhibition, target cancer cells more selectivity, and eliminate the resistance problems that occur with current drugs.
The group’s research began with epoxyketone, a molecule isolated from a cyanobacterium called carmaphycin, whose reactive group is the same as that of the proteasome inhibitor carfilzomib.
“Epoxyketones are very potent, selective inhibitors of the proteasome because they interact with this enzyme in 2 stages—the first reversible, and the second irreversible,” noted study author Daniela Trivella, PhD, of the Brazilian Biosciences National Laboratory at the Brazilian Center for Research in Energy and Materials in Campinas.
To optimize epoxyketone’s effects and find new reactive groups, the investigators developed and tested a series of synthetic analogs with slight structural modifications.
One of the molecules had an enone as a reactive group and had characteristics of carmaphycin and another natural molecule called syringolin, which was isolated from plant pathogens.
By investigating the reaction mechanisms of the new molecule, called carmaphycin-syringolin enone, the team verified that the enone interacts with the proteasome in 2 stages, with the second stage being irreversible.
The investigators also observed that, in the case of the enone, the second reaction occurs more slowly, increasing the duration of the reversible phase of carmaphycin-syringolin enone inhibition.
“Because the irreversible inactivation of the proteasome has toxic effects, the best window of reversibility observed for the carmaphycin-syringolin enone will potentially reduce the toxicity of this new class of proteasome inhibitors,” Dr Trivella said. “The compound would therefore present a balance between selectivity and potency.”
Toxicity tests are still underway. But the investigators have already conducted studies to determine exactly how the interaction between the enzyme target and the carmaphycin-syringolin enone target occurs.
“We discovered that a chemical reaction called hydroamination occurs, which had never before [been] seen under physiological conditions,” Dr Trivella said.
“This type of reaction is frequently used by synthetic chemists in preparing substances, but, normally, it requires very specific temperature and pH conditions and the use of catalysts to occur. It has never been reported as a mechanism of enzyme inhibition.”
Inspired by this new mechanism for proteasome inhibition, the investigators plan to synthesize and test a new series of carmaphycin-syringolin enone analogs to determine their effects on the therapeutic window and assess whether they are also capable of reacting with proteasomes that are resistant to traditional inhibitors.
showing multiple myeloma
A newly discovered mechanism has paved the way for the next generation of proteasome inhibitors, according to a paper published in Chemistry & Biology.
Investigators developed a series of molecules that employ this mechanism, inhibiting the proteasome in 2 ways.
They are now planning to synthesize related compounds that may offer improved proteasome inhibition, target cancer cells more selectivity, and eliminate the resistance problems that occur with current drugs.
The group’s research began with epoxyketone, a molecule isolated from a cyanobacterium called carmaphycin, whose reactive group is the same as that of the proteasome inhibitor carfilzomib.
“Epoxyketones are very potent, selective inhibitors of the proteasome because they interact with this enzyme in 2 stages—the first reversible, and the second irreversible,” noted study author Daniela Trivella, PhD, of the Brazilian Biosciences National Laboratory at the Brazilian Center for Research in Energy and Materials in Campinas.
To optimize epoxyketone’s effects and find new reactive groups, the investigators developed and tested a series of synthetic analogs with slight structural modifications.
One of the molecules had an enone as a reactive group and had characteristics of carmaphycin and another natural molecule called syringolin, which was isolated from plant pathogens.
By investigating the reaction mechanisms of the new molecule, called carmaphycin-syringolin enone, the team verified that the enone interacts with the proteasome in 2 stages, with the second stage being irreversible.
The investigators also observed that, in the case of the enone, the second reaction occurs more slowly, increasing the duration of the reversible phase of carmaphycin-syringolin enone inhibition.
“Because the irreversible inactivation of the proteasome has toxic effects, the best window of reversibility observed for the carmaphycin-syringolin enone will potentially reduce the toxicity of this new class of proteasome inhibitors,” Dr Trivella said. “The compound would therefore present a balance between selectivity and potency.”
Toxicity tests are still underway. But the investigators have already conducted studies to determine exactly how the interaction between the enzyme target and the carmaphycin-syringolin enone target occurs.
“We discovered that a chemical reaction called hydroamination occurs, which had never before [been] seen under physiological conditions,” Dr Trivella said.
“This type of reaction is frequently used by synthetic chemists in preparing substances, but, normally, it requires very specific temperature and pH conditions and the use of catalysts to occur. It has never been reported as a mechanism of enzyme inhibition.”
Inspired by this new mechanism for proteasome inhibition, the investigators plan to synthesize and test a new series of carmaphycin-syringolin enone analogs to determine their effects on the therapeutic window and assess whether they are also capable of reacting with proteasomes that are resistant to traditional inhibitors.
showing multiple myeloma
A newly discovered mechanism has paved the way for the next generation of proteasome inhibitors, according to a paper published in Chemistry & Biology.
Investigators developed a series of molecules that employ this mechanism, inhibiting the proteasome in 2 ways.
They are now planning to synthesize related compounds that may offer improved proteasome inhibition, target cancer cells more selectivity, and eliminate the resistance problems that occur with current drugs.
The group’s research began with epoxyketone, a molecule isolated from a cyanobacterium called carmaphycin, whose reactive group is the same as that of the proteasome inhibitor carfilzomib.
“Epoxyketones are very potent, selective inhibitors of the proteasome because they interact with this enzyme in 2 stages—the first reversible, and the second irreversible,” noted study author Daniela Trivella, PhD, of the Brazilian Biosciences National Laboratory at the Brazilian Center for Research in Energy and Materials in Campinas.
To optimize epoxyketone’s effects and find new reactive groups, the investigators developed and tested a series of synthetic analogs with slight structural modifications.
One of the molecules had an enone as a reactive group and had characteristics of carmaphycin and another natural molecule called syringolin, which was isolated from plant pathogens.
By investigating the reaction mechanisms of the new molecule, called carmaphycin-syringolin enone, the team verified that the enone interacts with the proteasome in 2 stages, with the second stage being irreversible.
The investigators also observed that, in the case of the enone, the second reaction occurs more slowly, increasing the duration of the reversible phase of carmaphycin-syringolin enone inhibition.
“Because the irreversible inactivation of the proteasome has toxic effects, the best window of reversibility observed for the carmaphycin-syringolin enone will potentially reduce the toxicity of this new class of proteasome inhibitors,” Dr Trivella said. “The compound would therefore present a balance between selectivity and potency.”
Toxicity tests are still underway. But the investigators have already conducted studies to determine exactly how the interaction between the enzyme target and the carmaphycin-syringolin enone target occurs.
“We discovered that a chemical reaction called hydroamination occurs, which had never before [been] seen under physiological conditions,” Dr Trivella said.
“This type of reaction is frequently used by synthetic chemists in preparing substances, but, normally, it requires very specific temperature and pH conditions and the use of catalysts to occur. It has never been reported as a mechanism of enzyme inhibition.”
Inspired by this new mechanism for proteasome inhibition, the investigators plan to synthesize and test a new series of carmaphycin-syringolin enone analogs to determine their effects on the therapeutic window and assess whether they are also capable of reacting with proteasomes that are resistant to traditional inhibitors.
NICE recommends eculizumab for aHUS despite cost
Credit: Globovision
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending eculizumab (Soliris) to treat atypical hemolytic uremic syndrome (aHUS), despite the drug’s high cost.
NICE estimates that eculizumab will cost the National Health Service (NHS) up to £58 million in the first year, rising to £82 million after 5 years.
The drug is currently funded by NHS England through interim specialized commissioning arrangements.
Eculizumab is ‘breakthrough’ for aHUS
aHUS is an extremely rare but life-threatening disease that causes inflammation of blood vessels and the formation of blood clots throughout the body. Patients with aHUS are at constant risk of sudden and progressive damage to, and failure of, vital organs.
Roughly 10% to 15% of patients die in the initial, acute phase of aHUS. The majority of patients—up to 70%—develop end-stage kidney failure requiring dialysis. And 1 in 5 patients has aHUS affecting organs other than the kidneys, most commonly the brain or heart.
Eculizumab inhibits the disease by blocking pro-thrombotic and pro-inflammatory processes, which can lead to cellular damage in small blood vessels throughout the body, renal failure, and damage to other organs.
“Eculizumab radically improves the quality of life of the small number of people with aHUS,” said NICE Chief Executive Sir Andrew Dillon.
“From the available evidence and from the testimony of clinicians and patients, families, and carers, it is clear that eculizumab is a significant breakthrough in the management of aHUS. The drug offers people with the disease the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”
Breakthrough comes with considerable cost
Eculizumab costs £3150 per 30 mL vial (excluding value-added tax). The net budget impact of eculizumab based on the developer’s predicted rate of uptake over a 5-year period is confidential.
However, to allow consultees and commentators to properly engage in the consultation process, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information available in the public domain.
This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult), and assumes a patient cohort of 170, as estimated by NHS England in its interim commissioning policy.
If all of these adult patients with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.
If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2. That assumes all new patients are treated, and all existing patients continue to be treated at the maintenance cost of £327,600 per year.
Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).
Conditions of the recommendation
The expert committee advising NICE on eculizumab believes the budget impact of recommending the drug for aHUS in relation to the benefits it offers would be lower if the potential for dose adjustment and treatment discontinuation was taken into account, according to Sir Dillon.
“Therefore, the draft guidance recommends that eculizumab is funded only if important conditions are met,” he said. “These include coordinating the use of eculizumab through an expert center and putting in place systems for monitoring how many people are diagnosed with aHUS, how many receive the drug, at what dose, and for how long.”
“The program also needs to develop protocols for starting and stopping treatment with eculizumab for clinical reasons and introduce a research program to collect data to evaluate when stopping treatment or adjusting the dose of the drug might occur.”
Given that the budget impact of eculizumab for treating aHUS will be considerable, the draft guidance also recommends that NHS England and the drug’s developer, Alexion, should consider what opportunities might exist to reduce the overall cost of eculizumab to the NHS.
NICE has not yet issued final guidance to the NHS. These decisions may change after consultation. The public can comment on the preliminary recommendations, which will be available until midday on September 25.
Comments received during this consultation period will be considered by the advisory committee at its meeting in October and, following this meeting, the next draft guidance will be issued.
Credit: Globovision
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending eculizumab (Soliris) to treat atypical hemolytic uremic syndrome (aHUS), despite the drug’s high cost.
NICE estimates that eculizumab will cost the National Health Service (NHS) up to £58 million in the first year, rising to £82 million after 5 years.
The drug is currently funded by NHS England through interim specialized commissioning arrangements.
Eculizumab is ‘breakthrough’ for aHUS
aHUS is an extremely rare but life-threatening disease that causes inflammation of blood vessels and the formation of blood clots throughout the body. Patients with aHUS are at constant risk of sudden and progressive damage to, and failure of, vital organs.
Roughly 10% to 15% of patients die in the initial, acute phase of aHUS. The majority of patients—up to 70%—develop end-stage kidney failure requiring dialysis. And 1 in 5 patients has aHUS affecting organs other than the kidneys, most commonly the brain or heart.
Eculizumab inhibits the disease by blocking pro-thrombotic and pro-inflammatory processes, which can lead to cellular damage in small blood vessels throughout the body, renal failure, and damage to other organs.
“Eculizumab radically improves the quality of life of the small number of people with aHUS,” said NICE Chief Executive Sir Andrew Dillon.
“From the available evidence and from the testimony of clinicians and patients, families, and carers, it is clear that eculizumab is a significant breakthrough in the management of aHUS. The drug offers people with the disease the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”
Breakthrough comes with considerable cost
Eculizumab costs £3150 per 30 mL vial (excluding value-added tax). The net budget impact of eculizumab based on the developer’s predicted rate of uptake over a 5-year period is confidential.
However, to allow consultees and commentators to properly engage in the consultation process, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information available in the public domain.
This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult), and assumes a patient cohort of 170, as estimated by NHS England in its interim commissioning policy.
If all of these adult patients with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.
If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2. That assumes all new patients are treated, and all existing patients continue to be treated at the maintenance cost of £327,600 per year.
Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).
Conditions of the recommendation
The expert committee advising NICE on eculizumab believes the budget impact of recommending the drug for aHUS in relation to the benefits it offers would be lower if the potential for dose adjustment and treatment discontinuation was taken into account, according to Sir Dillon.
“Therefore, the draft guidance recommends that eculizumab is funded only if important conditions are met,” he said. “These include coordinating the use of eculizumab through an expert center and putting in place systems for monitoring how many people are diagnosed with aHUS, how many receive the drug, at what dose, and for how long.”
“The program also needs to develop protocols for starting and stopping treatment with eculizumab for clinical reasons and introduce a research program to collect data to evaluate when stopping treatment or adjusting the dose of the drug might occur.”
Given that the budget impact of eculizumab for treating aHUS will be considerable, the draft guidance also recommends that NHS England and the drug’s developer, Alexion, should consider what opportunities might exist to reduce the overall cost of eculizumab to the NHS.
NICE has not yet issued final guidance to the NHS. These decisions may change after consultation. The public can comment on the preliminary recommendations, which will be available until midday on September 25.
Comments received during this consultation period will be considered by the advisory committee at its meeting in October and, following this meeting, the next draft guidance will be issued.
Credit: Globovision
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending eculizumab (Soliris) to treat atypical hemolytic uremic syndrome (aHUS), despite the drug’s high cost.
NICE estimates that eculizumab will cost the National Health Service (NHS) up to £58 million in the first year, rising to £82 million after 5 years.
The drug is currently funded by NHS England through interim specialized commissioning arrangements.
Eculizumab is ‘breakthrough’ for aHUS
aHUS is an extremely rare but life-threatening disease that causes inflammation of blood vessels and the formation of blood clots throughout the body. Patients with aHUS are at constant risk of sudden and progressive damage to, and failure of, vital organs.
Roughly 10% to 15% of patients die in the initial, acute phase of aHUS. The majority of patients—up to 70%—develop end-stage kidney failure requiring dialysis. And 1 in 5 patients has aHUS affecting organs other than the kidneys, most commonly the brain or heart.
Eculizumab inhibits the disease by blocking pro-thrombotic and pro-inflammatory processes, which can lead to cellular damage in small blood vessels throughout the body, renal failure, and damage to other organs.
“Eculizumab radically improves the quality of life of the small number of people with aHUS,” said NICE Chief Executive Sir Andrew Dillon.
“From the available evidence and from the testimony of clinicians and patients, families, and carers, it is clear that eculizumab is a significant breakthrough in the management of aHUS. The drug offers people with the disease the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”
Breakthrough comes with considerable cost
Eculizumab costs £3150 per 30 mL vial (excluding value-added tax). The net budget impact of eculizumab based on the developer’s predicted rate of uptake over a 5-year period is confidential.
However, to allow consultees and commentators to properly engage in the consultation process, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information available in the public domain.
This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult), and assumes a patient cohort of 170, as estimated by NHS England in its interim commissioning policy.
If all of these adult patients with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.
If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2. That assumes all new patients are treated, and all existing patients continue to be treated at the maintenance cost of £327,600 per year.
Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).
Conditions of the recommendation
The expert committee advising NICE on eculizumab believes the budget impact of recommending the drug for aHUS in relation to the benefits it offers would be lower if the potential for dose adjustment and treatment discontinuation was taken into account, according to Sir Dillon.
“Therefore, the draft guidance recommends that eculizumab is funded only if important conditions are met,” he said. “These include coordinating the use of eculizumab through an expert center and putting in place systems for monitoring how many people are diagnosed with aHUS, how many receive the drug, at what dose, and for how long.”
“The program also needs to develop protocols for starting and stopping treatment with eculizumab for clinical reasons and introduce a research program to collect data to evaluate when stopping treatment or adjusting the dose of the drug might occur.”
Given that the budget impact of eculizumab for treating aHUS will be considerable, the draft guidance also recommends that NHS England and the drug’s developer, Alexion, should consider what opportunities might exist to reduce the overall cost of eculizumab to the NHS.
NICE has not yet issued final guidance to the NHS. These decisions may change after consultation. The public can comment on the preliminary recommendations, which will be available until midday on September 25.
Comments received during this consultation period will be considered by the advisory committee at its meeting in October and, following this meeting, the next draft guidance will be issued.