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Idarucizumab reverses dabigatran’s anticoagulant effects
TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.
Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).
“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.
In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.
Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.
“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.
Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.
“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”
In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”
“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.
Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.
Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.
“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.
“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.
Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.
Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.
TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.
Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).
“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.
In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.
Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.
“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.
Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.
“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”
In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”
“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.
Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.
Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.
“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.
“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.
Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.
Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.
TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.
Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).
“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.
In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.
Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.
“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.
Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.
“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”
In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”
“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.
Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.
Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.
“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.
“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.
Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.
Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.
AT 2015 ISTH CONGRESS
Key clinical point: The investigational monoclonal antibody idarucizumab reversed the anticoagulant effects of dabigatran.
Major finding: Idarucizumab provided a median maximum dabigatran reversal of 100% (95% CI, 100-100) of the anticoagulation effect within 4 hours in an interim analysis.
Data source: RE-VERSE AD, a prospective cohort study in which 90 patients treated with dabigatran who had uncontrolled bleeding or required emergency surgery or procedures were given 5.0 g idarucizumab.
Disclosures: Boehringer Ingelheim sponsored RE-VERSE AD. Dr. Pollack reported receiving personal fees from Boehringer Ingelheim, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.
Promacta approved for pediatric treatment of chronic ITP
The Food and Drug Administration has approved Promacta for the treatment of chronic immune thrombocytopenia in children 6 years and older, Novartis, the drug’s manufacturer, announced in a statement.
Promacta (eltrombopag) is an oral thrombopoietin receptor agonist that increases platelet production by inducing stimulation and differentiation of megakaryocytes from bone marrow stem cells. Chronic immune thrombocytopenia (ITP) patients often have low platelet counts and are at risk for significant bleeding.
Promacta was approved for adult use in 2008; the drug was evaluated for pediatric use in PETIT and PETIT2, two multiphase, double-blind placebo-controlled trials designed to evaluate the drug’s safety profile. Both studies found Promacta’s safety to be consistent with the known safety profile of Promacta in chronic ITP in adults.
Promacta’s manufacturers say the drug can be useful for chronic ITP patients who have had an insufficient response to the most commonly available and used therapies for chronic ITP, such as corticosteroids, intravenous immunoglobulin, or splenectomy. ITP affects as many as 5 in 100,000 children each year.
The most common adverse reactions to Promacta in pediatric chronic ITP patients were upper respiratory tract infection, nasopharyngitis, and rhinitis. In adults, Promacta has been associated with nausea, diarrhea, upper respiratory tract infection, and vomiting; rarer but more serious side effects include liver problems, high platelet counts, a higher risk for blood clots, and new or worsened cataracts.
The Food and Drug Administration has approved Promacta for the treatment of chronic immune thrombocytopenia in children 6 years and older, Novartis, the drug’s manufacturer, announced in a statement.
Promacta (eltrombopag) is an oral thrombopoietin receptor agonist that increases platelet production by inducing stimulation and differentiation of megakaryocytes from bone marrow stem cells. Chronic immune thrombocytopenia (ITP) patients often have low platelet counts and are at risk for significant bleeding.
Promacta was approved for adult use in 2008; the drug was evaluated for pediatric use in PETIT and PETIT2, two multiphase, double-blind placebo-controlled trials designed to evaluate the drug’s safety profile. Both studies found Promacta’s safety to be consistent with the known safety profile of Promacta in chronic ITP in adults.
Promacta’s manufacturers say the drug can be useful for chronic ITP patients who have had an insufficient response to the most commonly available and used therapies for chronic ITP, such as corticosteroids, intravenous immunoglobulin, or splenectomy. ITP affects as many as 5 in 100,000 children each year.
The most common adverse reactions to Promacta in pediatric chronic ITP patients were upper respiratory tract infection, nasopharyngitis, and rhinitis. In adults, Promacta has been associated with nausea, diarrhea, upper respiratory tract infection, and vomiting; rarer but more serious side effects include liver problems, high platelet counts, a higher risk for blood clots, and new or worsened cataracts.
The Food and Drug Administration has approved Promacta for the treatment of chronic immune thrombocytopenia in children 6 years and older, Novartis, the drug’s manufacturer, announced in a statement.
Promacta (eltrombopag) is an oral thrombopoietin receptor agonist that increases platelet production by inducing stimulation and differentiation of megakaryocytes from bone marrow stem cells. Chronic immune thrombocytopenia (ITP) patients often have low platelet counts and are at risk for significant bleeding.
Promacta was approved for adult use in 2008; the drug was evaluated for pediatric use in PETIT and PETIT2, two multiphase, double-blind placebo-controlled trials designed to evaluate the drug’s safety profile. Both studies found Promacta’s safety to be consistent with the known safety profile of Promacta in chronic ITP in adults.
Promacta’s manufacturers say the drug can be useful for chronic ITP patients who have had an insufficient response to the most commonly available and used therapies for chronic ITP, such as corticosteroids, intravenous immunoglobulin, or splenectomy. ITP affects as many as 5 in 100,000 children each year.
The most common adverse reactions to Promacta in pediatric chronic ITP patients were upper respiratory tract infection, nasopharyngitis, and rhinitis. In adults, Promacta has been associated with nausea, diarrhea, upper respiratory tract infection, and vomiting; rarer but more serious side effects include liver problems, high platelet counts, a higher risk for blood clots, and new or worsened cataracts.
DDW: VIDEO: What we don’t know in the management of liver disease and coagulopathy
WASHINGTON – Your patient has cirrhosis, platelets 60,000 mm3, an INR of 2.0, serum creatinine of 1.2 mg/dL, and requires an endoscopic retrograde cholangiopancreatography with sphincterotomy.
What do you do next?
Management of a patient such as this is challenging, but not just because of the long-perceived risk for bleeding, Dr. Patrick S. Kamath of the Mayo Clinic in Rochester, Minn., said during a clinical symposium at the annual Digestive Disease Week.
Several other factors must be considered, including the clotting risk in patients with liver disease and the fact that procedure-related bleeding risk cannot be adequately determined preprocedure. Transfusions also carry their own dangers in this patient population and should be approached with caution, he said.
To hear more from this world-renowned liver expert, check out our interview as we sat down with Dr. Kamath at this year’s DDW.
Dr. Kamath reported no relevant financial conflicts.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @pwendl
WASHINGTON – Your patient has cirrhosis, platelets 60,000 mm3, an INR of 2.0, serum creatinine of 1.2 mg/dL, and requires an endoscopic retrograde cholangiopancreatography with sphincterotomy.
What do you do next?
Management of a patient such as this is challenging, but not just because of the long-perceived risk for bleeding, Dr. Patrick S. Kamath of the Mayo Clinic in Rochester, Minn., said during a clinical symposium at the annual Digestive Disease Week.
Several other factors must be considered, including the clotting risk in patients with liver disease and the fact that procedure-related bleeding risk cannot be adequately determined preprocedure. Transfusions also carry their own dangers in this patient population and should be approached with caution, he said.
To hear more from this world-renowned liver expert, check out our interview as we sat down with Dr. Kamath at this year’s DDW.
Dr. Kamath reported no relevant financial conflicts.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @pwendl
WASHINGTON – Your patient has cirrhosis, platelets 60,000 mm3, an INR of 2.0, serum creatinine of 1.2 mg/dL, and requires an endoscopic retrograde cholangiopancreatography with sphincterotomy.
What do you do next?
Management of a patient such as this is challenging, but not just because of the long-perceived risk for bleeding, Dr. Patrick S. Kamath of the Mayo Clinic in Rochester, Minn., said during a clinical symposium at the annual Digestive Disease Week.
Several other factors must be considered, including the clotting risk in patients with liver disease and the fact that procedure-related bleeding risk cannot be adequately determined preprocedure. Transfusions also carry their own dangers in this patient population and should be approached with caution, he said.
To hear more from this world-renowned liver expert, check out our interview as we sat down with Dr. Kamath at this year’s DDW.
Dr. Kamath reported no relevant financial conflicts.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @pwendl
AT DDW 2015
FDA approves new formulation of deferasirox for iron chelation
The Food and Drug Administration approved a new formulation of deferasirox as a once-daily oral tablet for iron chelation, Novartis announced.
The product, to be marketed as Jadenu, is indicated for chronic iron overload due to blood transfusions in patients 2 years of age and older, and chronic iron overload in non–transfusion-dependent thalassemia in patients 10 years of age or older. Novartis said it is the only once-daily oral iron chelator that can be swallowed whole, with or without food.
Jadenu is a reformulation of Exjade, a dispersible tablet that must be mixed in liquid and taken on an empty stomach.
The new product received its green light under the FDA’s accelerated approval process based on a reduction of liver iron concentrations and serum ferritin levels. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials, Novartis said.
Nausea, vomiting, diarrhea, stomach pain, increases in kidney laboratory values, and skin rash were the most common side effects reported in deferasirox clinical trials. Novartis warned that the drug may cause serious kidney problems, liver problems, and bleeding in the stomach or intestines, and in some cases, death from these complications. The company added that it is not known if Jadenu is safe or effective when taken with other iron chelation therapy, and controlled clinical trials of deferasirox for patients with myelodysplastic syndromes and chronic iron overload due to blood transfusions have not been performed.
Full prescribing information is available at http://tinyurl.com/nspjlek.
The Food and Drug Administration approved a new formulation of deferasirox as a once-daily oral tablet for iron chelation, Novartis announced.
The product, to be marketed as Jadenu, is indicated for chronic iron overload due to blood transfusions in patients 2 years of age and older, and chronic iron overload in non–transfusion-dependent thalassemia in patients 10 years of age or older. Novartis said it is the only once-daily oral iron chelator that can be swallowed whole, with or without food.
Jadenu is a reformulation of Exjade, a dispersible tablet that must be mixed in liquid and taken on an empty stomach.
The new product received its green light under the FDA’s accelerated approval process based on a reduction of liver iron concentrations and serum ferritin levels. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials, Novartis said.
Nausea, vomiting, diarrhea, stomach pain, increases in kidney laboratory values, and skin rash were the most common side effects reported in deferasirox clinical trials. Novartis warned that the drug may cause serious kidney problems, liver problems, and bleeding in the stomach or intestines, and in some cases, death from these complications. The company added that it is not known if Jadenu is safe or effective when taken with other iron chelation therapy, and controlled clinical trials of deferasirox for patients with myelodysplastic syndromes and chronic iron overload due to blood transfusions have not been performed.
Full prescribing information is available at http://tinyurl.com/nspjlek.
The Food and Drug Administration approved a new formulation of deferasirox as a once-daily oral tablet for iron chelation, Novartis announced.
The product, to be marketed as Jadenu, is indicated for chronic iron overload due to blood transfusions in patients 2 years of age and older, and chronic iron overload in non–transfusion-dependent thalassemia in patients 10 years of age or older. Novartis said it is the only once-daily oral iron chelator that can be swallowed whole, with or without food.
Jadenu is a reformulation of Exjade, a dispersible tablet that must be mixed in liquid and taken on an empty stomach.
The new product received its green light under the FDA’s accelerated approval process based on a reduction of liver iron concentrations and serum ferritin levels. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials, Novartis said.
Nausea, vomiting, diarrhea, stomach pain, increases in kidney laboratory values, and skin rash were the most common side effects reported in deferasirox clinical trials. Novartis warned that the drug may cause serious kidney problems, liver problems, and bleeding in the stomach or intestines, and in some cases, death from these complications. The company added that it is not known if Jadenu is safe or effective when taken with other iron chelation therapy, and controlled clinical trials of deferasirox for patients with myelodysplastic syndromes and chronic iron overload due to blood transfusions have not been performed.
Full prescribing information is available at http://tinyurl.com/nspjlek.
Lentiviral gene therapy could prove useful for adults with hemophilia
Liver-directed lentiviral gene therapy is an effective treatment for hemophilia B in dogs, according to Alessio Cantore, Ph.D., and his associates.
The investigators found that all of the dogs administered the treatment were still alive 5 years after the therapy. Spontaneous bleeding was cut down significantly from before the therapy began. No significant side effects were seen in any of the dogs, and no lentiviral vector DNA was found in blood samples, proving long-term effectiveness of vector-transduced cells.
“If we extrapolate the observed dose response in dogs to humans, the current lentiviral vector–manufacturing capacity could support the treatment of adult patients with hemophilia” if a hyperfunctional IX transgene factor were used, Dr. Cantore and his associates wrote. “Lentiviral vectors may complement other available vectors to address some of the outstanding challenges posed by liver gene therapy for the treatment of hemophilia and conceivably other diseases.”
Read the full study in Science Translational Medicine (doi: 10.1126/scitranslmed.aaa1405).
Liver-directed lentiviral gene therapy is an effective treatment for hemophilia B in dogs, according to Alessio Cantore, Ph.D., and his associates.
The investigators found that all of the dogs administered the treatment were still alive 5 years after the therapy. Spontaneous bleeding was cut down significantly from before the therapy began. No significant side effects were seen in any of the dogs, and no lentiviral vector DNA was found in blood samples, proving long-term effectiveness of vector-transduced cells.
“If we extrapolate the observed dose response in dogs to humans, the current lentiviral vector–manufacturing capacity could support the treatment of adult patients with hemophilia” if a hyperfunctional IX transgene factor were used, Dr. Cantore and his associates wrote. “Lentiviral vectors may complement other available vectors to address some of the outstanding challenges posed by liver gene therapy for the treatment of hemophilia and conceivably other diseases.”
Read the full study in Science Translational Medicine (doi: 10.1126/scitranslmed.aaa1405).
Liver-directed lentiviral gene therapy is an effective treatment for hemophilia B in dogs, according to Alessio Cantore, Ph.D., and his associates.
The investigators found that all of the dogs administered the treatment were still alive 5 years after the therapy. Spontaneous bleeding was cut down significantly from before the therapy began. No significant side effects were seen in any of the dogs, and no lentiviral vector DNA was found in blood samples, proving long-term effectiveness of vector-transduced cells.
“If we extrapolate the observed dose response in dogs to humans, the current lentiviral vector–manufacturing capacity could support the treatment of adult patients with hemophilia” if a hyperfunctional IX transgene factor were used, Dr. Cantore and his associates wrote. “Lentiviral vectors may complement other available vectors to address some of the outstanding challenges posed by liver gene therapy for the treatment of hemophilia and conceivably other diseases.”
Read the full study in Science Translational Medicine (doi: 10.1126/scitranslmed.aaa1405).
JAK inhibitor more effective than standard therapy for polycythemia vera
Treatment with ruxolitinib, an oral inhibitor of Janus kinase 1 and 2, was associated with significantly better responses and improvement in symptoms in patients with polycythemia vera who had not responded to or had experienced unacceptable side effects with hydroxyurea, compared with those who received standard therapy, in a phase III, open-label study, Dr. Alessandro Vannucchi of the University of Florence (Italy) and his associates reported.
In the RESPONSE study, patients with splenomegaly who required phlebotomy for control of hematocrit and had an inadequate response or had experienced unacceptable side effects with hydroxyurea were randomized to treatment with the kinase inhibitor (110 patients) or to interferon and other standard treatments (112). After 32 weeks, 21% of those treated with ruxolitinib had met the primary endpoint, which was control of hematocrit and at least a 35% reduction in spleen volume (measured by MRI or CT), compared with 1% of those on standard treatment, a statistically significant difference with a P value less than .001. A significantly greater proportion of those in the ruxolitinib-treated group also met the two individual components of the primary endpoint.
“Response rates with ruxolitinib were similar among patients who had unacceptable side effects from hydroxyurea and those who had an inadequate response to hydroxyurea. ... and there was no relationship between response and age, sex, or baseline spleen volume,” the authors wrote. The study is the basis of the recent Food and Drug Administration approval of ruxolitinib for this indication (N. Engl. J. Med. 2015 Jan. 28. [doi:10.1056/NEJMoa1409002])Other endpoints included complete hematologic remission, achieved by 24% of those treated with ruxolitinib vs. 9% on standard therapy. At week 32, almost half of those on ruxolitinib had at least a 50% reduction in the total symptom score that assessed disease-related symptoms vs. 5% of those on standard therapy.
Some hematologic adverse events were more common among those on ruxolitinib: 2% developed grade 3 or 4 anemia, and 5% developed grade 3 or 4 thrombocytopenia, compared with 0% and 4% of those on standard treatment. In addition, 6% of those on ruxolitinib developed herpes zoster infections, compared with none of those on standard therapy. One patient on ruxolitinib and six patients on standard therapy had thromboembolic events. Three patients treated with ruxolitinib developed myelofibrosis 120-469 days after being randomized to treatment (about 5-9 years after they had been diagnosed with polycythemia vera) and one patient was diagnosed with acute myeloid leukemia after 56 days of treatment. Among those on standard therapy, one patient developed myelofibrosis after 101 days of treatment and two were diagnosed with myelofibrosis more than 300 days after they crossed over to treatment with ruxolitinib, including one patient who progressed to acute myelogenous leukemia.
While many patients with polycythemia vera respond adequately to hydroxyurea, the most commonly used cytoreductive agent used to treat polycythemia vera, about 25% do not have a satisfactory response or experience unacceptable side effects, “and alternative treatment options are needed for these patients,” the authors said.
The mean age of the patients in the study was 60-62 years, and they had been diagnosed with polycythemia vera a median of 8-9 years previously; 60% of those in the ruxolitinib group and 71% in the standard therapy group were men. The investigators chose the standard therapy, which included hydroxyurea at a dose that did not result in unacceptable side effects (59%), interferon (12%), anagrelide (7%), immunomodulators (4.5%), and pipobroman (2%); and in about 15% of patients, no medication was given.
Ruxolitinib was approved by the Food and Drug Administration in December 2014 for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. It was initially approved by the FDA in 2011, for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post essential thrombocythemia myelofibrosis.
Ruxolitinib inhibits Janus kinase (JAK) 1 and JAK2, which “mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function,” according to the prescribing information. It is marketed as Jakafi by Incyte.
Most of the patients on ruxolitinib are continuing treatment in the RESPONSE study, which is ongoing but is not recruiting any more patients, according to the authors.
The study was sponsored by Incyte and Novartis, which has licensed ruxolitinib from Incyte for development and commercialization outside the United States. Dr. Vannucchi disclosed having received grant support and serving as an adviser for Novartis; three authors are employees of Incyte; three are employees of Novartis in the United States or Switzerland, six authors had no disclosures, and one author received grants from Incyte during the study. The remaining three authors reported serving on the advisory board, serving as speakers or lecturers, and/or receiving grant support from Novartis.
Treatment with ruxolitinib, an oral inhibitor of Janus kinase 1 and 2, was associated with significantly better responses and improvement in symptoms in patients with polycythemia vera who had not responded to or had experienced unacceptable side effects with hydroxyurea, compared with those who received standard therapy, in a phase III, open-label study, Dr. Alessandro Vannucchi of the University of Florence (Italy) and his associates reported.
In the RESPONSE study, patients with splenomegaly who required phlebotomy for control of hematocrit and had an inadequate response or had experienced unacceptable side effects with hydroxyurea were randomized to treatment with the kinase inhibitor (110 patients) or to interferon and other standard treatments (112). After 32 weeks, 21% of those treated with ruxolitinib had met the primary endpoint, which was control of hematocrit and at least a 35% reduction in spleen volume (measured by MRI or CT), compared with 1% of those on standard treatment, a statistically significant difference with a P value less than .001. A significantly greater proportion of those in the ruxolitinib-treated group also met the two individual components of the primary endpoint.
“Response rates with ruxolitinib were similar among patients who had unacceptable side effects from hydroxyurea and those who had an inadequate response to hydroxyurea. ... and there was no relationship between response and age, sex, or baseline spleen volume,” the authors wrote. The study is the basis of the recent Food and Drug Administration approval of ruxolitinib for this indication (N. Engl. J. Med. 2015 Jan. 28. [doi:10.1056/NEJMoa1409002])Other endpoints included complete hematologic remission, achieved by 24% of those treated with ruxolitinib vs. 9% on standard therapy. At week 32, almost half of those on ruxolitinib had at least a 50% reduction in the total symptom score that assessed disease-related symptoms vs. 5% of those on standard therapy.
Some hematologic adverse events were more common among those on ruxolitinib: 2% developed grade 3 or 4 anemia, and 5% developed grade 3 or 4 thrombocytopenia, compared with 0% and 4% of those on standard treatment. In addition, 6% of those on ruxolitinib developed herpes zoster infections, compared with none of those on standard therapy. One patient on ruxolitinib and six patients on standard therapy had thromboembolic events. Three patients treated with ruxolitinib developed myelofibrosis 120-469 days after being randomized to treatment (about 5-9 years after they had been diagnosed with polycythemia vera) and one patient was diagnosed with acute myeloid leukemia after 56 days of treatment. Among those on standard therapy, one patient developed myelofibrosis after 101 days of treatment and two were diagnosed with myelofibrosis more than 300 days after they crossed over to treatment with ruxolitinib, including one patient who progressed to acute myelogenous leukemia.
While many patients with polycythemia vera respond adequately to hydroxyurea, the most commonly used cytoreductive agent used to treat polycythemia vera, about 25% do not have a satisfactory response or experience unacceptable side effects, “and alternative treatment options are needed for these patients,” the authors said.
The mean age of the patients in the study was 60-62 years, and they had been diagnosed with polycythemia vera a median of 8-9 years previously; 60% of those in the ruxolitinib group and 71% in the standard therapy group were men. The investigators chose the standard therapy, which included hydroxyurea at a dose that did not result in unacceptable side effects (59%), interferon (12%), anagrelide (7%), immunomodulators (4.5%), and pipobroman (2%); and in about 15% of patients, no medication was given.
Ruxolitinib was approved by the Food and Drug Administration in December 2014 for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. It was initially approved by the FDA in 2011, for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post essential thrombocythemia myelofibrosis.
Ruxolitinib inhibits Janus kinase (JAK) 1 and JAK2, which “mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function,” according to the prescribing information. It is marketed as Jakafi by Incyte.
Most of the patients on ruxolitinib are continuing treatment in the RESPONSE study, which is ongoing but is not recruiting any more patients, according to the authors.
The study was sponsored by Incyte and Novartis, which has licensed ruxolitinib from Incyte for development and commercialization outside the United States. Dr. Vannucchi disclosed having received grant support and serving as an adviser for Novartis; three authors are employees of Incyte; three are employees of Novartis in the United States or Switzerland, six authors had no disclosures, and one author received grants from Incyte during the study. The remaining three authors reported serving on the advisory board, serving as speakers or lecturers, and/or receiving grant support from Novartis.
Treatment with ruxolitinib, an oral inhibitor of Janus kinase 1 and 2, was associated with significantly better responses and improvement in symptoms in patients with polycythemia vera who had not responded to or had experienced unacceptable side effects with hydroxyurea, compared with those who received standard therapy, in a phase III, open-label study, Dr. Alessandro Vannucchi of the University of Florence (Italy) and his associates reported.
In the RESPONSE study, patients with splenomegaly who required phlebotomy for control of hematocrit and had an inadequate response or had experienced unacceptable side effects with hydroxyurea were randomized to treatment with the kinase inhibitor (110 patients) or to interferon and other standard treatments (112). After 32 weeks, 21% of those treated with ruxolitinib had met the primary endpoint, which was control of hematocrit and at least a 35% reduction in spleen volume (measured by MRI or CT), compared with 1% of those on standard treatment, a statistically significant difference with a P value less than .001. A significantly greater proportion of those in the ruxolitinib-treated group also met the two individual components of the primary endpoint.
“Response rates with ruxolitinib were similar among patients who had unacceptable side effects from hydroxyurea and those who had an inadequate response to hydroxyurea. ... and there was no relationship between response and age, sex, or baseline spleen volume,” the authors wrote. The study is the basis of the recent Food and Drug Administration approval of ruxolitinib for this indication (N. Engl. J. Med. 2015 Jan. 28. [doi:10.1056/NEJMoa1409002])Other endpoints included complete hematologic remission, achieved by 24% of those treated with ruxolitinib vs. 9% on standard therapy. At week 32, almost half of those on ruxolitinib had at least a 50% reduction in the total symptom score that assessed disease-related symptoms vs. 5% of those on standard therapy.
Some hematologic adverse events were more common among those on ruxolitinib: 2% developed grade 3 or 4 anemia, and 5% developed grade 3 or 4 thrombocytopenia, compared with 0% and 4% of those on standard treatment. In addition, 6% of those on ruxolitinib developed herpes zoster infections, compared with none of those on standard therapy. One patient on ruxolitinib and six patients on standard therapy had thromboembolic events. Three patients treated with ruxolitinib developed myelofibrosis 120-469 days after being randomized to treatment (about 5-9 years after they had been diagnosed with polycythemia vera) and one patient was diagnosed with acute myeloid leukemia after 56 days of treatment. Among those on standard therapy, one patient developed myelofibrosis after 101 days of treatment and two were diagnosed with myelofibrosis more than 300 days after they crossed over to treatment with ruxolitinib, including one patient who progressed to acute myelogenous leukemia.
While many patients with polycythemia vera respond adequately to hydroxyurea, the most commonly used cytoreductive agent used to treat polycythemia vera, about 25% do not have a satisfactory response or experience unacceptable side effects, “and alternative treatment options are needed for these patients,” the authors said.
The mean age of the patients in the study was 60-62 years, and they had been diagnosed with polycythemia vera a median of 8-9 years previously; 60% of those in the ruxolitinib group and 71% in the standard therapy group were men. The investigators chose the standard therapy, which included hydroxyurea at a dose that did not result in unacceptable side effects (59%), interferon (12%), anagrelide (7%), immunomodulators (4.5%), and pipobroman (2%); and in about 15% of patients, no medication was given.
Ruxolitinib was approved by the Food and Drug Administration in December 2014 for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. It was initially approved by the FDA in 2011, for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post essential thrombocythemia myelofibrosis.
Ruxolitinib inhibits Janus kinase (JAK) 1 and JAK2, which “mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function,” according to the prescribing information. It is marketed as Jakafi by Incyte.
Most of the patients on ruxolitinib are continuing treatment in the RESPONSE study, which is ongoing but is not recruiting any more patients, according to the authors.
The study was sponsored by Incyte and Novartis, which has licensed ruxolitinib from Incyte for development and commercialization outside the United States. Dr. Vannucchi disclosed having received grant support and serving as an adviser for Novartis; three authors are employees of Incyte; three are employees of Novartis in the United States or Switzerland, six authors had no disclosures, and one author received grants from Incyte during the study. The remaining three authors reported serving on the advisory board, serving as speakers or lecturers, and/or receiving grant support from Novartis.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Ruxolitinib, now approved for treatment of polycythemia vera in the United States, is an alternative to hydroxyurea in patients who have failed treatment with or cannot tolerate hydroxyurea.
Major finding: After 8 months, treatment with ruxolitinib resulted in significantly better responses than standard therapy in patients with polycythemia vera who had an unsatisfactory response or unacceptable side effects with hydroxyurea, as measured by control of hematocrit and at least a 35% reduction in spleen volume (21% vs. 1%).
Data source: A phase III, international, open-label, randomized trial of 222 patients with polycythemia vera who had unacceptable side effects or did not respond adequately to hydroxyurea or standard therapy.
Disclosures: The study was sponsored by Incyte and Novartis. Four authors reported serving on the advisory board, serving as speakers or lecturers, and/or receiving grant support from Novartis; one author received grants from Incyte during the study; six are employees of Incyte or Novartis; and six authors had no disclosures.
FDA expands ruxolitinib approval to include polycythemia vera
Ruxolitinib has been approved for the treatment of polycythemia vera in patients who have an inadequate response to hydroxyurea or are unable to tolerate that drug.
The Food and Drug Administration approved the drug, a Janus-associated kinase (JAK) inhibitor marketed as Jakafi, on Dec. 4. Ruxolitinib received a priority, expedited review at the agency.
“The approval of Jakafi for polycythemia vera underscores the importance of developing drugs matched to our increasing knowledge of the mechanisms of diseases,” said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement.
Ruxolitinib “represents an important advance for patients with uncontrolled PV,” said Dr. Srdan Verstovsek, a professor in the leukemia department at the University of Texas MD Anderson Cancer Center, Houston, in a statement issued by ruxolitinib maker Incyte Corp. “For the first time, we are able to provide these patients a treatment that has been shown to provide effective and consistent control of their blood counts and reduce spleen volume.”
Polycythemia vera, a chronic disease, causes a hyperproliferation of red blood cells. Patients may also experience an increase in white blood cells and platelets, and splenomegaly, and are at higher risk for heart attack and stroke.
“The trial used to evaluate Jakafi confirmed clinically meaningful reductions in spleen size and the need for phlebotomies to control the disease,” said Dr. Pazdur.
Ruxolitinib was first approved in 2011 for myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis, and post–essential thrombocythemia myelofibrosis.
The new indication is for polycythemia vera patients who do not respond to or cannot tolerate hydroxyurea.
The drug’s safety and effectiveness were evaluated in a study of 222 patients who received either ruxolitinib or the best available therapy, and who had the disease for at least 24 weeks, had an inadequate response to or could not tolerate hydroxyurea, had undergone a phlebotomy procedure and exhibited an enlarged spleen.
Of patients receiving ruxolitinib, 21% experienced a reduction in the need for a phlebotomy and a reduction in spleen volume by the end of the 32-week study, compared with 1% of participants who received best available therapy.
The most common side effects were anemia and thrombocytopenia, dizziness, constipation, and shingles.
On Twitter @aliciaault
Ruxolitinib has been approved for the treatment of polycythemia vera in patients who have an inadequate response to hydroxyurea or are unable to tolerate that drug.
The Food and Drug Administration approved the drug, a Janus-associated kinase (JAK) inhibitor marketed as Jakafi, on Dec. 4. Ruxolitinib received a priority, expedited review at the agency.
“The approval of Jakafi for polycythemia vera underscores the importance of developing drugs matched to our increasing knowledge of the mechanisms of diseases,” said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement.
Ruxolitinib “represents an important advance for patients with uncontrolled PV,” said Dr. Srdan Verstovsek, a professor in the leukemia department at the University of Texas MD Anderson Cancer Center, Houston, in a statement issued by ruxolitinib maker Incyte Corp. “For the first time, we are able to provide these patients a treatment that has been shown to provide effective and consistent control of their blood counts and reduce spleen volume.”
Polycythemia vera, a chronic disease, causes a hyperproliferation of red blood cells. Patients may also experience an increase in white blood cells and platelets, and splenomegaly, and are at higher risk for heart attack and stroke.
“The trial used to evaluate Jakafi confirmed clinically meaningful reductions in spleen size and the need for phlebotomies to control the disease,” said Dr. Pazdur.
Ruxolitinib was first approved in 2011 for myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis, and post–essential thrombocythemia myelofibrosis.
The new indication is for polycythemia vera patients who do not respond to or cannot tolerate hydroxyurea.
The drug’s safety and effectiveness were evaluated in a study of 222 patients who received either ruxolitinib or the best available therapy, and who had the disease for at least 24 weeks, had an inadequate response to or could not tolerate hydroxyurea, had undergone a phlebotomy procedure and exhibited an enlarged spleen.
Of patients receiving ruxolitinib, 21% experienced a reduction in the need for a phlebotomy and a reduction in spleen volume by the end of the 32-week study, compared with 1% of participants who received best available therapy.
The most common side effects were anemia and thrombocytopenia, dizziness, constipation, and shingles.
On Twitter @aliciaault
Ruxolitinib has been approved for the treatment of polycythemia vera in patients who have an inadequate response to hydroxyurea or are unable to tolerate that drug.
The Food and Drug Administration approved the drug, a Janus-associated kinase (JAK) inhibitor marketed as Jakafi, on Dec. 4. Ruxolitinib received a priority, expedited review at the agency.
“The approval of Jakafi for polycythemia vera underscores the importance of developing drugs matched to our increasing knowledge of the mechanisms of diseases,” said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement.
Ruxolitinib “represents an important advance for patients with uncontrolled PV,” said Dr. Srdan Verstovsek, a professor in the leukemia department at the University of Texas MD Anderson Cancer Center, Houston, in a statement issued by ruxolitinib maker Incyte Corp. “For the first time, we are able to provide these patients a treatment that has been shown to provide effective and consistent control of their blood counts and reduce spleen volume.”
Polycythemia vera, a chronic disease, causes a hyperproliferation of red blood cells. Patients may also experience an increase in white blood cells and platelets, and splenomegaly, and are at higher risk for heart attack and stroke.
“The trial used to evaluate Jakafi confirmed clinically meaningful reductions in spleen size and the need for phlebotomies to control the disease,” said Dr. Pazdur.
Ruxolitinib was first approved in 2011 for myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis, and post–essential thrombocythemia myelofibrosis.
The new indication is for polycythemia vera patients who do not respond to or cannot tolerate hydroxyurea.
The drug’s safety and effectiveness were evaluated in a study of 222 patients who received either ruxolitinib or the best available therapy, and who had the disease for at least 24 weeks, had an inadequate response to or could not tolerate hydroxyurea, had undergone a phlebotomy procedure and exhibited an enlarged spleen.
Of patients receiving ruxolitinib, 21% experienced a reduction in the need for a phlebotomy and a reduction in spleen volume by the end of the 32-week study, compared with 1% of participants who received best available therapy.
The most common side effects were anemia and thrombocytopenia, dizziness, constipation, and shingles.
On Twitter @aliciaault
Management of Bleeding Complications in Patients with Cancer
Patients with cancer can have many hematologic complications. One of the most serious is bleeding, which can range in severity from laboratory abnormalities to life-threatening hemorrhage. The bleeding can be due to complications of the cancer, its therapy, or treatment for complications of cancer such as thrombosis. This manual discusses an approach to the cancer patient with bleeding, with a specific focus on issues such as coagulation defects, thrombocytopenia, and platelet dysfunction. Bleeding complications of specific cancers and their treatment will be discussed as well.
To read the full article in PDF:
Patients with cancer can have many hematologic complications. One of the most serious is bleeding, which can range in severity from laboratory abnormalities to life-threatening hemorrhage. The bleeding can be due to complications of the cancer, its therapy, or treatment for complications of cancer such as thrombosis. This manual discusses an approach to the cancer patient with bleeding, with a specific focus on issues such as coagulation defects, thrombocytopenia, and platelet dysfunction. Bleeding complications of specific cancers and their treatment will be discussed as well.
To read the full article in PDF:
Patients with cancer can have many hematologic complications. One of the most serious is bleeding, which can range in severity from laboratory abnormalities to life-threatening hemorrhage. The bleeding can be due to complications of the cancer, its therapy, or treatment for complications of cancer such as thrombosis. This manual discusses an approach to the cancer patient with bleeding, with a specific focus on issues such as coagulation defects, thrombocytopenia, and platelet dysfunction. Bleeding complications of specific cancers and their treatment will be discussed as well.
To read the full article in PDF:
Drug gets orphan status for PNH in US
The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal
hemoglobinuria (PNH).
Roughly 2 months ago, the European Medicines Agency (EMA) did the same.
Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is
planning to move the drug into clinical trials in 2015.
If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.
“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.
Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.
About AMY-101 and PNH
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH. 
The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal
hemoglobinuria (PNH).
Roughly 2 months ago, the European Medicines Agency (EMA) did the same.
Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is
planning to move the drug into clinical trials in 2015.
If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.
“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.
Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.
About AMY-101 and PNH
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.
The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal
hemoglobinuria (PNH).
Roughly 2 months ago, the European Medicines Agency (EMA) did the same.
Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is
planning to move the drug into clinical trials in 2015.
If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.
“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.
Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.
About AMY-101 and PNH
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.
Drug granted orphan status for PNH in EU
A novel compound has received orphan status in the Europe Union to treat paroxysmal nocturnal hemoglobinuria (PNH), a life-threatening disease that causes severe anemia and confers a high risk of thrombosis.
The compound, AMY-101, works by inhibiting C3, a central component of the complement immune system.
AMY-101 was developed by John Lambris, PhD, of the University of Pennsylvania, and subsequently licensed to Amyndas Pharmaceuticals.
AMY-101’s orphan status provides Amyndas with benefits such as tax incentives, market exclusivity for 10 years, possibilities for additional research funding, and additional guidance from the European Medicines Agency during clinical development.
How AMY-101 works
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit the complement cascade, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.
A novel compound has received orphan status in the Europe Union to treat paroxysmal nocturnal hemoglobinuria (PNH), a life-threatening disease that causes severe anemia and confers a high risk of thrombosis.
The compound, AMY-101, works by inhibiting C3, a central component of the complement immune system.
AMY-101 was developed by John Lambris, PhD, of the University of Pennsylvania, and subsequently licensed to Amyndas Pharmaceuticals.
AMY-101’s orphan status provides Amyndas with benefits such as tax incentives, market exclusivity for 10 years, possibilities for additional research funding, and additional guidance from the European Medicines Agency during clinical development.
How AMY-101 works
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit the complement cascade, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.
A novel compound has received orphan status in the Europe Union to treat paroxysmal nocturnal hemoglobinuria (PNH), a life-threatening disease that causes severe anemia and confers a high risk of thrombosis.
The compound, AMY-101, works by inhibiting C3, a central component of the complement immune system.
AMY-101 was developed by John Lambris, PhD, of the University of Pennsylvania, and subsequently licensed to Amyndas Pharmaceuticals.
AMY-101’s orphan status provides Amyndas with benefits such as tax incentives, market exclusivity for 10 years, possibilities for additional research funding, and additional guidance from the European Medicines Agency during clinical development.
How AMY-101 works
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit the complement cascade, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.