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Compound could treat leukemia, other cancers
and Patrick Harran with
a model of DZ-2384
Photo courtesy of
Reed Hutchinson/UCLA
A new compound holds promise for treating leukemia and other cancers, according to researchers.
The compound, DZ-2384, is a synthetic version of diazonamide A, a toxin isolated from a marine animal.
DZ-2384 is a microtubule-targeting agent (MTA). It binds to and alters the stability of microtubules, disrupting the normal function of the mitotic spindle and arresting cell-cycle progression at mitosis, ultimately leading to cell death.
However, researchers found that DZ-2384 behaves somewhat differently from other MTAs.
They reported these findings in Science Translational Medicine. The research was supported, in part, by Diazon Pharmaceuticals Inc.
The researchers tested DZ-2384 in mouse models of various cancers, including adult Philadelphia chromosome–negative acute lymphocytic leukemia.
In animals receiving DZ-2384, tumors shrank as much as or more than when a conventional MTA was used, but with much less toxicity at effective doses.
In particular, animals receiving DZ-2384 had markedly less peripheral neuropathy than those that received docetaxel, a conventional MTA. Peripheral neuropathy is one of the chief side effects of MTAs and can prompt treatment discontinuation.
“We have good reason to expect that human clinical trials of DZ-2384 will show that, at doses effective for treating a person’s cancer, there will be much less risk of the peripheral neuropathy that can force clinicians to stop treatment,” said study author Patrick Harran, PhD, of the University of California, Los Angeles.
Dr Harran believes clinical trials of DZ-2384 could begin within 2 years.
How this study began
Dr Harran began his work with diazonamides as a fundamental chemistry research problem.
In 1991, a group of researchers described diazonamides A and B, which they had isolated from the marine animal Diazona chinensis.
But Dr Harran and his colleagues found the described structure of diazonamide A was incorrect. In 2001, the team published a study that corrected the chemical structure of diazonamide A, and, 2 years later, they had synthesized the true structure in their lab.
Next, they began studying what the molecule might be doing to stop cells from dividing. In 2007, they discovered that the synthetic diazonamides they had produced minimized undesirable toxic effects that are commonly associated with chemotherapy.
Specifically, the compounds had an unusually large therapeutic window. In experiment after experiment, Dr Harran said, the researchers found that synthetic diazonamides’ therapeutic window was at least 10 times larger than that of traditional MTAs.
A key finding
In 2015, researchers prepared a form of DZ-2384 that was engineered with a molecular-scale “tracking device” so they could monitor its activity and better understand how it worked.
That helped the team confirm what they had come to suspect: that the compound binds to tubulin, which is a building block of mitotic spindles and a common target of MTAs.
Armed with this information, the researchers used X-ray crystallography to determine the structure of DZ-2384 bound to tubulin.
Their work offers a possible explanation for how DZ-2384 could disrupt dynamic tubulin polymers during cell division but spare those polymers in resting cells like neurons in the peripheral nervous system.
And that is what appears to allow the compound to attack growing cancer cells while minimizing damage to healthy cells. 
and Patrick Harran with
a model of DZ-2384
Photo courtesy of
Reed Hutchinson/UCLA
A new compound holds promise for treating leukemia and other cancers, according to researchers.
The compound, DZ-2384, is a synthetic version of diazonamide A, a toxin isolated from a marine animal.
DZ-2384 is a microtubule-targeting agent (MTA). It binds to and alters the stability of microtubules, disrupting the normal function of the mitotic spindle and arresting cell-cycle progression at mitosis, ultimately leading to cell death.
However, researchers found that DZ-2384 behaves somewhat differently from other MTAs.
They reported these findings in Science Translational Medicine. The research was supported, in part, by Diazon Pharmaceuticals Inc.
The researchers tested DZ-2384 in mouse models of various cancers, including adult Philadelphia chromosome–negative acute lymphocytic leukemia.
In animals receiving DZ-2384, tumors shrank as much as or more than when a conventional MTA was used, but with much less toxicity at effective doses.
In particular, animals receiving DZ-2384 had markedly less peripheral neuropathy than those that received docetaxel, a conventional MTA. Peripheral neuropathy is one of the chief side effects of MTAs and can prompt treatment discontinuation.
“We have good reason to expect that human clinical trials of DZ-2384 will show that, at doses effective for treating a person’s cancer, there will be much less risk of the peripheral neuropathy that can force clinicians to stop treatment,” said study author Patrick Harran, PhD, of the University of California, Los Angeles.
Dr Harran believes clinical trials of DZ-2384 could begin within 2 years.
How this study began
Dr Harran began his work with diazonamides as a fundamental chemistry research problem.
In 1991, a group of researchers described diazonamides A and B, which they had isolated from the marine animal Diazona chinensis.
But Dr Harran and his colleagues found the described structure of diazonamide A was incorrect. In 2001, the team published a study that corrected the chemical structure of diazonamide A, and, 2 years later, they had synthesized the true structure in their lab.
Next, they began studying what the molecule might be doing to stop cells from dividing. In 2007, they discovered that the synthetic diazonamides they had produced minimized undesirable toxic effects that are commonly associated with chemotherapy.
Specifically, the compounds had an unusually large therapeutic window. In experiment after experiment, Dr Harran said, the researchers found that synthetic diazonamides’ therapeutic window was at least 10 times larger than that of traditional MTAs.
A key finding
In 2015, researchers prepared a form of DZ-2384 that was engineered with a molecular-scale “tracking device” so they could monitor its activity and better understand how it worked.
That helped the team confirm what they had come to suspect: that the compound binds to tubulin, which is a building block of mitotic spindles and a common target of MTAs.
Armed with this information, the researchers used X-ray crystallography to determine the structure of DZ-2384 bound to tubulin.
Their work offers a possible explanation for how DZ-2384 could disrupt dynamic tubulin polymers during cell division but spare those polymers in resting cells like neurons in the peripheral nervous system.
And that is what appears to allow the compound to attack growing cancer cells while minimizing damage to healthy cells.
and Patrick Harran with
a model of DZ-2384
Photo courtesy of
Reed Hutchinson/UCLA
A new compound holds promise for treating leukemia and other cancers, according to researchers.
The compound, DZ-2384, is a synthetic version of diazonamide A, a toxin isolated from a marine animal.
DZ-2384 is a microtubule-targeting agent (MTA). It binds to and alters the stability of microtubules, disrupting the normal function of the mitotic spindle and arresting cell-cycle progression at mitosis, ultimately leading to cell death.
However, researchers found that DZ-2384 behaves somewhat differently from other MTAs.
They reported these findings in Science Translational Medicine. The research was supported, in part, by Diazon Pharmaceuticals Inc.
The researchers tested DZ-2384 in mouse models of various cancers, including adult Philadelphia chromosome–negative acute lymphocytic leukemia.
In animals receiving DZ-2384, tumors shrank as much as or more than when a conventional MTA was used, but with much less toxicity at effective doses.
In particular, animals receiving DZ-2384 had markedly less peripheral neuropathy than those that received docetaxel, a conventional MTA. Peripheral neuropathy is one of the chief side effects of MTAs and can prompt treatment discontinuation.
“We have good reason to expect that human clinical trials of DZ-2384 will show that, at doses effective for treating a person’s cancer, there will be much less risk of the peripheral neuropathy that can force clinicians to stop treatment,” said study author Patrick Harran, PhD, of the University of California, Los Angeles.
Dr Harran believes clinical trials of DZ-2384 could begin within 2 years.
How this study began
Dr Harran began his work with diazonamides as a fundamental chemistry research problem.
In 1991, a group of researchers described diazonamides A and B, which they had isolated from the marine animal Diazona chinensis.
But Dr Harran and his colleagues found the described structure of diazonamide A was incorrect. In 2001, the team published a study that corrected the chemical structure of diazonamide A, and, 2 years later, they had synthesized the true structure in their lab.
Next, they began studying what the molecule might be doing to stop cells from dividing. In 2007, they discovered that the synthetic diazonamides they had produced minimized undesirable toxic effects that are commonly associated with chemotherapy.
Specifically, the compounds had an unusually large therapeutic window. In experiment after experiment, Dr Harran said, the researchers found that synthetic diazonamides’ therapeutic window was at least 10 times larger than that of traditional MTAs.
A key finding
In 2015, researchers prepared a form of DZ-2384 that was engineered with a molecular-scale “tracking device” so they could monitor its activity and better understand how it worked.
That helped the team confirm what they had come to suspect: that the compound binds to tubulin, which is a building block of mitotic spindles and a common target of MTAs.
Armed with this information, the researchers used X-ray crystallography to determine the structure of DZ-2384 bound to tubulin.
Their work offers a possible explanation for how DZ-2384 could disrupt dynamic tubulin polymers during cell division but spare those polymers in resting cells like neurons in the peripheral nervous system.
And that is what appears to allow the compound to attack growing cancer cells while minimizing damage to healthy cells.
Anticoagulant therapies appear comparable
Photo from Business Wire
NEW ORLEANS—Two types of anticoagulant therapy produce comparable outcomes for patients undergoing percutaneous coronary intervention (PCI), according to a new study.
The study was designed to determine which of 2 treatment methods—heparin combined with a short-term (less than 6 hours) infusion of tirofiban, or short-term periprocedural bivalirudin—was more effective.
Results showed that the 1-year risk of death, myocardial infarction, and urgent target vessel revascularization (UTVR) was not significantly different between the 2 treatment methods.
The incidence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding at 30 days was also similar between the treatment groups.
Results of this study were presented at the American Heart Association Scientific Sessions (abstract 15074). The study was funded by an unrestricted grant from the Medicure Corporation.
“Bivalirudin has been considered the gold standard for reducing bleeding during percutaneous coronary intervention, but our study shows heparin plus short-term tirofiban is just as good and possibly better,” said study investigator J. Brent Muhlestein, MD, of Intermountain Medical Center Heart Institute in Salt Lake City, Utah.
“The results certainly justify a randomized clinical trial to explore identified trends.”
Dr Muhlestein and his colleagues studied data on patients who underwent PCI between January 2013 and December 2015.
Of the 857 patients enrolled in the study, 402 received heparin plus short-term tirofiban treatment, and 455 received bivalirudin. The patients were between the ages of 51 and 78.
Results
At 30 days, the incidence of TIMI major bleeding was 1.2% for patients treated with heparin and tirofiban and 3.1% for bivalirudin-treated patients (P=0.10).
Also at 30 days, the incidence of death was 0.7% in the heparin/tirofiban group and 1.9% in the bivalirudin group (P=0.23). The incidence of myocardial infarction was 0.5% and 0.7%, respectively (P=1.00). And the incidence of UTVR was 0% and 0.7%, respectively (P=0.25).
At 1 year, the incidence of death was 3.4% for patients treated with heparin and tirofiban and 5.5% for bivalirudin-treated patients (P=0.42).
The incidence of myocardial infarction at 1 year was 2.9% and 3.0%, respectively (P=1.00). And the incidence of UTVR was 2.0% and 1.5%, respectively (P=0.67).
In multivariable analysis, the odds ratio (OR) for 30-day TIMI major bleeding (heparin/tirofiban vs bivalirudin) was 0.41 (P=0.11).
The OR for death at 1 year was 0.50 (P=0.33). The OR for non-fatal myocardial infarction at 1 year was 1.09 (P=0.91). And the OR for UTVR at 1 year was 1.23 (P=0.84).
Photo from Business Wire
NEW ORLEANS—Two types of anticoagulant therapy produce comparable outcomes for patients undergoing percutaneous coronary intervention (PCI), according to a new study.
The study was designed to determine which of 2 treatment methods—heparin combined with a short-term (less than 6 hours) infusion of tirofiban, or short-term periprocedural bivalirudin—was more effective.
Results showed that the 1-year risk of death, myocardial infarction, and urgent target vessel revascularization (UTVR) was not significantly different between the 2 treatment methods.
The incidence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding at 30 days was also similar between the treatment groups.
Results of this study were presented at the American Heart Association Scientific Sessions (abstract 15074). The study was funded by an unrestricted grant from the Medicure Corporation.
“Bivalirudin has been considered the gold standard for reducing bleeding during percutaneous coronary intervention, but our study shows heparin plus short-term tirofiban is just as good and possibly better,” said study investigator J. Brent Muhlestein, MD, of Intermountain Medical Center Heart Institute in Salt Lake City, Utah.
“The results certainly justify a randomized clinical trial to explore identified trends.”
Dr Muhlestein and his colleagues studied data on patients who underwent PCI between January 2013 and December 2015.
Of the 857 patients enrolled in the study, 402 received heparin plus short-term tirofiban treatment, and 455 received bivalirudin. The patients were between the ages of 51 and 78.
Results
At 30 days, the incidence of TIMI major bleeding was 1.2% for patients treated with heparin and tirofiban and 3.1% for bivalirudin-treated patients (P=0.10).
Also at 30 days, the incidence of death was 0.7% in the heparin/tirofiban group and 1.9% in the bivalirudin group (P=0.23). The incidence of myocardial infarction was 0.5% and 0.7%, respectively (P=1.00). And the incidence of UTVR was 0% and 0.7%, respectively (P=0.25).
At 1 year, the incidence of death was 3.4% for patients treated with heparin and tirofiban and 5.5% for bivalirudin-treated patients (P=0.42).
The incidence of myocardial infarction at 1 year was 2.9% and 3.0%, respectively (P=1.00). And the incidence of UTVR was 2.0% and 1.5%, respectively (P=0.67).
In multivariable analysis, the odds ratio (OR) for 30-day TIMI major bleeding (heparin/tirofiban vs bivalirudin) was 0.41 (P=0.11).
The OR for death at 1 year was 0.50 (P=0.33). The OR for non-fatal myocardial infarction at 1 year was 1.09 (P=0.91). And the OR for UTVR at 1 year was 1.23 (P=0.84).
Photo from Business Wire
NEW ORLEANS—Two types of anticoagulant therapy produce comparable outcomes for patients undergoing percutaneous coronary intervention (PCI), according to a new study.
The study was designed to determine which of 2 treatment methods—heparin combined with a short-term (less than 6 hours) infusion of tirofiban, or short-term periprocedural bivalirudin—was more effective.
Results showed that the 1-year risk of death, myocardial infarction, and urgent target vessel revascularization (UTVR) was not significantly different between the 2 treatment methods.
The incidence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding at 30 days was also similar between the treatment groups.
Results of this study were presented at the American Heart Association Scientific Sessions (abstract 15074). The study was funded by an unrestricted grant from the Medicure Corporation.
“Bivalirudin has been considered the gold standard for reducing bleeding during percutaneous coronary intervention, but our study shows heparin plus short-term tirofiban is just as good and possibly better,” said study investigator J. Brent Muhlestein, MD, of Intermountain Medical Center Heart Institute in Salt Lake City, Utah.
“The results certainly justify a randomized clinical trial to explore identified trends.”
Dr Muhlestein and his colleagues studied data on patients who underwent PCI between January 2013 and December 2015.
Of the 857 patients enrolled in the study, 402 received heparin plus short-term tirofiban treatment, and 455 received bivalirudin. The patients were between the ages of 51 and 78.
Results
At 30 days, the incidence of TIMI major bleeding was 1.2% for patients treated with heparin and tirofiban and 3.1% for bivalirudin-treated patients (P=0.10).
Also at 30 days, the incidence of death was 0.7% in the heparin/tirofiban group and 1.9% in the bivalirudin group (P=0.23). The incidence of myocardial infarction was 0.5% and 0.7%, respectively (P=1.00). And the incidence of UTVR was 0% and 0.7%, respectively (P=0.25).
At 1 year, the incidence of death was 3.4% for patients treated with heparin and tirofiban and 5.5% for bivalirudin-treated patients (P=0.42).
The incidence of myocardial infarction at 1 year was 2.9% and 3.0%, respectively (P=1.00). And the incidence of UTVR was 2.0% and 1.5%, respectively (P=0.67).
In multivariable analysis, the odds ratio (OR) for 30-day TIMI major bleeding (heparin/tirofiban vs bivalirudin) was 0.41 (P=0.11).
The OR for death at 1 year was 0.50 (P=0.33). The OR for non-fatal myocardial infarction at 1 year was 1.09 (P=0.91). And the OR for UTVR at 1 year was 1.23 (P=0.84).
Team develops model of common infant ALL
Photo by Petr Kratochvil
After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic
leukemia (ALL).
The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.
This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).
“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.
“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”
That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.
However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.
The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.
“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”
That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.
So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.
The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.
The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.
Photo by Petr Kratochvil
After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic
leukemia (ALL).
The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.
This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).
“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.
“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”
That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.
However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.
The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.
“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”
That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.
So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.
The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.
The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.
Photo by Petr Kratochvil
After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic
leukemia (ALL).
The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.
This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).
“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.
“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”
That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.
However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.
The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.
“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”
That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.
So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.
The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.
The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.
Study shows lower bleeding risk with rivaroxaban
NEW ORLEANS—Results of the PIONEER AF-PCI trial suggest certain patients may have a lower risk of bleeding if they receive rivaroxaban rather than a vitamin K antagonist (VKA).
The study showed that patients with nonvalvular atrial fibrillation (NVAF) who underwent percutaneous coronary intervention (PCI) with stenting had a lower risk of clinically significant bleeding if they received rivaroxaban plus antiplatelet therapy rather than a VKA plus antiplatelet therapy.
However, the trial showed no significant difference between the treatment groups when it came to the risk of cardiovascular events.
These results were presented at the American Heart Association’s Scientific Sessions 2016 and simultaneously published in NEJM.
The trial was supported by Janssen Scientific Affairs LLC, and Bayer Health Care Pharmaceuticals.
“In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications,” said study investigator C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.
“This trial, which tested 2 entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with antiplatelet therapy is successful in minimizing bleeding while preventing clotting.”
The trial included 2124 patients with NVAF who had undergone PCI with stenting. They were randomized to receive, in a 1:1:1 ratio:
- Low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1)
- Very-low-dose rivaroxaban (2.5 mg twice daily) plus dual antiplatelet therapy (DAPT) for 1, 6, or 12 months (group 2)
- Standard therapy with a dose-adjusted VKA (once daily) plus DAPT for 1, 6, or 12 months (group 3).
Key endpoints
The study’s primary safety endpoint was clinically significant bleeding, which was a composite of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria, minor bleeding according to TIMI criteria, and bleeding requiring medical attention.
At 1 year, the rate of clinically significant bleeding was significantly lower in the 2 rivaroxaban groups than in the VKA group—16.8% in group 1, 18.0% in group 2, and 26.7% in group 3.
The hazard ratio for group 1 compared to group 3 was 0.59 (P<0.001). And the hazard ratio for group 2 compared to group 3 was 0.63 (P<0.001).
The researchers said this reduction in bleeding for the 2 rivaroxaban groups was consistent across multiple subgroups of patients.
The study’s key efficacy endpoint was major adverse cardiovascular events, which was a composite of death from cardiovascular causes, myocardial infarction, and stroke.
There was no significant difference between the groups with regard to this endpoint. It occurred in 6.5% of the patients in group 1, 5.6% in group 2, and 6.0% in group 3 (P>0.05 for both comparisons).
“For the first time in this population, a treatment regimen resulted in less bleeding than the current standard of care,” Dr Gibson said.
“Pairing rivaroxaban with single or dual antiplatelet therapy has the potential to transform current practice, as demonstrated in this study, with significantly less bleeding and numerically similar efficacy when compared to warfarin [VKA] with dual antiplatelet therapy.”
NEW ORLEANS—Results of the PIONEER AF-PCI trial suggest certain patients may have a lower risk of bleeding if they receive rivaroxaban rather than a vitamin K antagonist (VKA).
The study showed that patients with nonvalvular atrial fibrillation (NVAF) who underwent percutaneous coronary intervention (PCI) with stenting had a lower risk of clinically significant bleeding if they received rivaroxaban plus antiplatelet therapy rather than a VKA plus antiplatelet therapy.
However, the trial showed no significant difference between the treatment groups when it came to the risk of cardiovascular events.
These results were presented at the American Heart Association’s Scientific Sessions 2016 and simultaneously published in NEJM.
The trial was supported by Janssen Scientific Affairs LLC, and Bayer Health Care Pharmaceuticals.
“In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications,” said study investigator C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.
“This trial, which tested 2 entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with antiplatelet therapy is successful in minimizing bleeding while preventing clotting.”
The trial included 2124 patients with NVAF who had undergone PCI with stenting. They were randomized to receive, in a 1:1:1 ratio:
- Low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1)
- Very-low-dose rivaroxaban (2.5 mg twice daily) plus dual antiplatelet therapy (DAPT) for 1, 6, or 12 months (group 2)
- Standard therapy with a dose-adjusted VKA (once daily) plus DAPT for 1, 6, or 12 months (group 3).
Key endpoints
The study’s primary safety endpoint was clinically significant bleeding, which was a composite of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria, minor bleeding according to TIMI criteria, and bleeding requiring medical attention.
At 1 year, the rate of clinically significant bleeding was significantly lower in the 2 rivaroxaban groups than in the VKA group—16.8% in group 1, 18.0% in group 2, and 26.7% in group 3.
The hazard ratio for group 1 compared to group 3 was 0.59 (P<0.001). And the hazard ratio for group 2 compared to group 3 was 0.63 (P<0.001).
The researchers said this reduction in bleeding for the 2 rivaroxaban groups was consistent across multiple subgroups of patients.
The study’s key efficacy endpoint was major adverse cardiovascular events, which was a composite of death from cardiovascular causes, myocardial infarction, and stroke.
There was no significant difference between the groups with regard to this endpoint. It occurred in 6.5% of the patients in group 1, 5.6% in group 2, and 6.0% in group 3 (P>0.05 for both comparisons).
“For the first time in this population, a treatment regimen resulted in less bleeding than the current standard of care,” Dr Gibson said.
“Pairing rivaroxaban with single or dual antiplatelet therapy has the potential to transform current practice, as demonstrated in this study, with significantly less bleeding and numerically similar efficacy when compared to warfarin [VKA] with dual antiplatelet therapy.”
NEW ORLEANS—Results of the PIONEER AF-PCI trial suggest certain patients may have a lower risk of bleeding if they receive rivaroxaban rather than a vitamin K antagonist (VKA).
The study showed that patients with nonvalvular atrial fibrillation (NVAF) who underwent percutaneous coronary intervention (PCI) with stenting had a lower risk of clinically significant bleeding if they received rivaroxaban plus antiplatelet therapy rather than a VKA plus antiplatelet therapy.
However, the trial showed no significant difference between the treatment groups when it came to the risk of cardiovascular events.
These results were presented at the American Heart Association’s Scientific Sessions 2016 and simultaneously published in NEJM.
The trial was supported by Janssen Scientific Affairs LLC, and Bayer Health Care Pharmaceuticals.
“In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications,” said study investigator C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.
“This trial, which tested 2 entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with antiplatelet therapy is successful in minimizing bleeding while preventing clotting.”
The trial included 2124 patients with NVAF who had undergone PCI with stenting. They were randomized to receive, in a 1:1:1 ratio:
- Low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1)
- Very-low-dose rivaroxaban (2.5 mg twice daily) plus dual antiplatelet therapy (DAPT) for 1, 6, or 12 months (group 2)
- Standard therapy with a dose-adjusted VKA (once daily) plus DAPT for 1, 6, or 12 months (group 3).
Key endpoints
The study’s primary safety endpoint was clinically significant bleeding, which was a composite of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria, minor bleeding according to TIMI criteria, and bleeding requiring medical attention.
At 1 year, the rate of clinically significant bleeding was significantly lower in the 2 rivaroxaban groups than in the VKA group—16.8% in group 1, 18.0% in group 2, and 26.7% in group 3.
The hazard ratio for group 1 compared to group 3 was 0.59 (P<0.001). And the hazard ratio for group 2 compared to group 3 was 0.63 (P<0.001).
The researchers said this reduction in bleeding for the 2 rivaroxaban groups was consistent across multiple subgroups of patients.
The study’s key efficacy endpoint was major adverse cardiovascular events, which was a composite of death from cardiovascular causes, myocardial infarction, and stroke.
There was no significant difference between the groups with regard to this endpoint. It occurred in 6.5% of the patients in group 1, 5.6% in group 2, and 6.0% in group 3 (P>0.05 for both comparisons).
“For the first time in this population, a treatment regimen resulted in less bleeding than the current standard of care,” Dr Gibson said.
“Pairing rivaroxaban with single or dual antiplatelet therapy has the potential to transform current practice, as demonstrated in this study, with significantly less bleeding and numerically similar efficacy when compared to warfarin [VKA] with dual antiplatelet therapy.”
Hemophilia treatment falling short, study suggests
Results of a real-world, retrospective study suggest there may be a need to improve the standard of care for hemophilia A and B in some European countries.
Hemophilia treatment practices varied widely among the 7 countries studied, as did annual bleeding rates (ABRs).
Some countries had low median ABRs in hemophilia A and B patients receiving prophylaxis—in the range of 1.0 to 2.0.
However, the median ABR was as high as 8.0 for some patients, despite receiving prophylaxis. And these were patients with moderate disease.
The study, which was sponsored by Sobi, was published in Haemophilia.
“The overall results indicate that there is a significant need to advance standard of care within hemophilia,” said Stefan Lethagen, vice president medical & clinical sciences, haemophilia at Sobi.
“Even when prophylaxis is the norm, it appears that prophylactic treatment is driven to the minimal acceptable level or even lower, which increases the risk of joint injury and limits the ability to live a full and active life.”
The study was designed to provide insight into current hemophilia treatment practice and outcomes in 7 European countries—Belgium, France, Germany, Italy, Spain, Sweden, and the UK.
The researchers analyzed data on 1346 patients with hemophilia A and 312 with hemophilia B treated in these countries.
Treatment type, dosing
Prophylaxis was, overall, the most dominating treatment for patients with severe hemophilia A. It was the most common treatment regimen among children and decreased with increasing age.
On-demand treatment was reported to be most common in moderate hemophilia A, and there was no trend across age groups.
For patients with hemophilia B, prophylaxis was the most common treatment in 4 out of the 7 countries (France, Germany, Sweden, and UK).
Overall, a majority of patients received a recombinant antihemophilic factor product as opposed to a plasma-derived product. The one exception was patients with hemophilia B in Germany. A majority of these patients (66%) received a plasma-derived product.
The mean prescribed prophylactic treatment ranged from 67.9 IU kg-1 per week (Belgium) to 108.4 IU kg-1 per week (Germany) for hemophilia A and 32.3 IU kg-1 per week (Belgium) to 97.7 IU kg-1 per week (France) for hemophilia B.
Most patients on prophylaxis were treated 3 or more times a week if they had hemophilia A and 2 times a week if they had hemophilia B.
ABRs across countries
For hemophilia A patients on prophylaxis, the median ABR ranged from 1.0 (Belgium, Italy, Sweden) to 4.0 (France, UK) for patients with severe disease and from 2.0 (Sweden) to 8.0 (Belgium) for patients with moderate disease.
The researchers pointed out that ABRs were higher for patients with moderate hemophilia A, but low patient numbers should be taken into account when interpreting these data.
The median ABRs for hemophilia A patients who received on-demand treatment ranged from 4.5 (Sweden) to 18.0 (UK, Belgium) for patients with severe disease and from 1.0 (Spain, Sweden) to 12.0 (UK) for patients with moderate disease.
For hemophilia B patients on prophylaxis, the median ABRs ranged from 1.0 (Germany, Sweden) to 6.0 (Belgium) for patients with severe disease and from 1.5 (Sweden) to 8.0 (Belgium) for patients with moderate disease. Again, ABRs were higher for patients with moderate disease.
The median ABRs for hemophilia B patients who received on-demand treatment ranged from 1.5 (Germany) to 14.0 (UK) for patients with severe disease and from 1.0 (Belgium, France, Germany, Italy) to 6.5 (UK) for patients with moderate disease.
The researchers said the high number of bleeds observed in some patients likely reflects insufficient therapy, inappropriate dose-interval, presence of target joints, poor adherence, or patient difficulty in correctly assessing bleeds.
The team said the overall results of the study suggest there is room for improvement of hemophilia therapy, even for patients currently on prophylactic treatment.
Results of a real-world, retrospective study suggest there may be a need to improve the standard of care for hemophilia A and B in some European countries.
Hemophilia treatment practices varied widely among the 7 countries studied, as did annual bleeding rates (ABRs).
Some countries had low median ABRs in hemophilia A and B patients receiving prophylaxis—in the range of 1.0 to 2.0.
However, the median ABR was as high as 8.0 for some patients, despite receiving prophylaxis. And these were patients with moderate disease.
The study, which was sponsored by Sobi, was published in Haemophilia.
“The overall results indicate that there is a significant need to advance standard of care within hemophilia,” said Stefan Lethagen, vice president medical & clinical sciences, haemophilia at Sobi.
“Even when prophylaxis is the norm, it appears that prophylactic treatment is driven to the minimal acceptable level or even lower, which increases the risk of joint injury and limits the ability to live a full and active life.”
The study was designed to provide insight into current hemophilia treatment practice and outcomes in 7 European countries—Belgium, France, Germany, Italy, Spain, Sweden, and the UK.
The researchers analyzed data on 1346 patients with hemophilia A and 312 with hemophilia B treated in these countries.
Treatment type, dosing
Prophylaxis was, overall, the most dominating treatment for patients with severe hemophilia A. It was the most common treatment regimen among children and decreased with increasing age.
On-demand treatment was reported to be most common in moderate hemophilia A, and there was no trend across age groups.
For patients with hemophilia B, prophylaxis was the most common treatment in 4 out of the 7 countries (France, Germany, Sweden, and UK).
Overall, a majority of patients received a recombinant antihemophilic factor product as opposed to a plasma-derived product. The one exception was patients with hemophilia B in Germany. A majority of these patients (66%) received a plasma-derived product.
The mean prescribed prophylactic treatment ranged from 67.9 IU kg-1 per week (Belgium) to 108.4 IU kg-1 per week (Germany) for hemophilia A and 32.3 IU kg-1 per week (Belgium) to 97.7 IU kg-1 per week (France) for hemophilia B.
Most patients on prophylaxis were treated 3 or more times a week if they had hemophilia A and 2 times a week if they had hemophilia B.
ABRs across countries
For hemophilia A patients on prophylaxis, the median ABR ranged from 1.0 (Belgium, Italy, Sweden) to 4.0 (France, UK) for patients with severe disease and from 2.0 (Sweden) to 8.0 (Belgium) for patients with moderate disease.
The researchers pointed out that ABRs were higher for patients with moderate hemophilia A, but low patient numbers should be taken into account when interpreting these data.
The median ABRs for hemophilia A patients who received on-demand treatment ranged from 4.5 (Sweden) to 18.0 (UK, Belgium) for patients with severe disease and from 1.0 (Spain, Sweden) to 12.0 (UK) for patients with moderate disease.
For hemophilia B patients on prophylaxis, the median ABRs ranged from 1.0 (Germany, Sweden) to 6.0 (Belgium) for patients with severe disease and from 1.5 (Sweden) to 8.0 (Belgium) for patients with moderate disease. Again, ABRs were higher for patients with moderate disease.
The median ABRs for hemophilia B patients who received on-demand treatment ranged from 1.5 (Germany) to 14.0 (UK) for patients with severe disease and from 1.0 (Belgium, France, Germany, Italy) to 6.5 (UK) for patients with moderate disease.
The researchers said the high number of bleeds observed in some patients likely reflects insufficient therapy, inappropriate dose-interval, presence of target joints, poor adherence, or patient difficulty in correctly assessing bleeds.
The team said the overall results of the study suggest there is room for improvement of hemophilia therapy, even for patients currently on prophylactic treatment.
Results of a real-world, retrospective study suggest there may be a need to improve the standard of care for hemophilia A and B in some European countries.
Hemophilia treatment practices varied widely among the 7 countries studied, as did annual bleeding rates (ABRs).
Some countries had low median ABRs in hemophilia A and B patients receiving prophylaxis—in the range of 1.0 to 2.0.
However, the median ABR was as high as 8.0 for some patients, despite receiving prophylaxis. And these were patients with moderate disease.
The study, which was sponsored by Sobi, was published in Haemophilia.
“The overall results indicate that there is a significant need to advance standard of care within hemophilia,” said Stefan Lethagen, vice president medical & clinical sciences, haemophilia at Sobi.
“Even when prophylaxis is the norm, it appears that prophylactic treatment is driven to the minimal acceptable level or even lower, which increases the risk of joint injury and limits the ability to live a full and active life.”
The study was designed to provide insight into current hemophilia treatment practice and outcomes in 7 European countries—Belgium, France, Germany, Italy, Spain, Sweden, and the UK.
The researchers analyzed data on 1346 patients with hemophilia A and 312 with hemophilia B treated in these countries.
Treatment type, dosing
Prophylaxis was, overall, the most dominating treatment for patients with severe hemophilia A. It was the most common treatment regimen among children and decreased with increasing age.
On-demand treatment was reported to be most common in moderate hemophilia A, and there was no trend across age groups.
For patients with hemophilia B, prophylaxis was the most common treatment in 4 out of the 7 countries (France, Germany, Sweden, and UK).
Overall, a majority of patients received a recombinant antihemophilic factor product as opposed to a plasma-derived product. The one exception was patients with hemophilia B in Germany. A majority of these patients (66%) received a plasma-derived product.
The mean prescribed prophylactic treatment ranged from 67.9 IU kg-1 per week (Belgium) to 108.4 IU kg-1 per week (Germany) for hemophilia A and 32.3 IU kg-1 per week (Belgium) to 97.7 IU kg-1 per week (France) for hemophilia B.
Most patients on prophylaxis were treated 3 or more times a week if they had hemophilia A and 2 times a week if they had hemophilia B.
ABRs across countries
For hemophilia A patients on prophylaxis, the median ABR ranged from 1.0 (Belgium, Italy, Sweden) to 4.0 (France, UK) for patients with severe disease and from 2.0 (Sweden) to 8.0 (Belgium) for patients with moderate disease.
The researchers pointed out that ABRs were higher for patients with moderate hemophilia A, but low patient numbers should be taken into account when interpreting these data.
The median ABRs for hemophilia A patients who received on-demand treatment ranged from 4.5 (Sweden) to 18.0 (UK, Belgium) for patients with severe disease and from 1.0 (Spain, Sweden) to 12.0 (UK) for patients with moderate disease.
For hemophilia B patients on prophylaxis, the median ABRs ranged from 1.0 (Germany, Sweden) to 6.0 (Belgium) for patients with severe disease and from 1.5 (Sweden) to 8.0 (Belgium) for patients with moderate disease. Again, ABRs were higher for patients with moderate disease.
The median ABRs for hemophilia B patients who received on-demand treatment ranged from 1.5 (Germany) to 14.0 (UK) for patients with severe disease and from 1.0 (Belgium, France, Germany, Italy) to 6.5 (UK) for patients with moderate disease.
The researchers said the high number of bleeds observed in some patients likely reflects insufficient therapy, inappropriate dose-interval, presence of target joints, poor adherence, or patient difficulty in correctly assessing bleeds.
The team said the overall results of the study suggest there is room for improvement of hemophilia therapy, even for patients currently on prophylactic treatment.
Company withdraws application for eryaspase in ALL
ERYTECH Pharma has announced its decision to withdraw the European marketing authorization application (MAA) for eryaspase (GRASPA®) as a treatment for acute lymphoblastic leukemia (ALL).
The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) asked for additional data on eryaspase, but ERYTECH said the time allowed by the EMA’s approval process is not sufficient to provide the data requested.
Therefore, the company decided to withdraw the MAA and resubmit it next year.
About eryaspase
Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.
Research has suggested this delivery system provides improved pharmacodynamics, protecting L-asparaginase from circulating proteolytic enzymes and preventing early liver or renal clearance.
The system also appears to reduce the risk of adverse events compared to native L-asparaginase.
The EMA and the US Food and Drug Administration have granted orphan drug designations for eryaspase for the treatment of ALL, acute myeloid
leukemia, and pancreatic cancer.
About the MAA
ERYTECH submitted an MAA for eryaspase in September 2015, based on positive results from a phase 2/3 study in which researchers compared eryaspase and native L-asparaginase in patients with relapsed and refractory ALL.
One year later (September 2016), the company received the CHMP’s Day 180 List of Outstanding Issues, which highlighted the need for additional data.
Specifically, the CHMP asked for data regarding the comparability between the old and new form of asparaginase encapsulated in eryaspase and the development of a new immunogenicity assay, as well as the pharmacodynamic effects of eryaspase.
Given the fact that the generation of these data will require more time than allowed in the EMA’s approval procedures, ERYTECH has notified the CHMP of the withdrawal of the MAA.
The company intends to resubmit the MAA in mid-2017, as soon as the newly generated data are available.
ERYTECH stressed that there have been no safety issues with eryaspase, and the withdrawal of this MAA will not affect any ongoing trials.
“We are committed to pursuing regulatory approval for GRASPA and intend to work closely with our investigators and advisors to generate the additional information requested and to resubmit an MAA next year,” said Iman El-Hariry, chief medical officer of ERYTECH.
“We believe we have generated strong clinical data in our different programs of eryaspase, and we continue to execute our plans towards making the product available to patients with aggressive forms of cancer, such as acute lymphoblastic leukemia, acute myeloid leukemia, and pancreatic cancer,” added Gil Beyen, ERYTECH’s chairman and chief executive officer.
ERYTECH Pharma has announced its decision to withdraw the European marketing authorization application (MAA) for eryaspase (GRASPA®) as a treatment for acute lymphoblastic leukemia (ALL).
The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) asked for additional data on eryaspase, but ERYTECH said the time allowed by the EMA’s approval process is not sufficient to provide the data requested.
Therefore, the company decided to withdraw the MAA and resubmit it next year.
About eryaspase
Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.
Research has suggested this delivery system provides improved pharmacodynamics, protecting L-asparaginase from circulating proteolytic enzymes and preventing early liver or renal clearance.
The system also appears to reduce the risk of adverse events compared to native L-asparaginase.
The EMA and the US Food and Drug Administration have granted orphan drug designations for eryaspase for the treatment of ALL, acute myeloid
leukemia, and pancreatic cancer.
About the MAA
ERYTECH submitted an MAA for eryaspase in September 2015, based on positive results from a phase 2/3 study in which researchers compared eryaspase and native L-asparaginase in patients with relapsed and refractory ALL.
One year later (September 2016), the company received the CHMP’s Day 180 List of Outstanding Issues, which highlighted the need for additional data.
Specifically, the CHMP asked for data regarding the comparability between the old and new form of asparaginase encapsulated in eryaspase and the development of a new immunogenicity assay, as well as the pharmacodynamic effects of eryaspase.
Given the fact that the generation of these data will require more time than allowed in the EMA’s approval procedures, ERYTECH has notified the CHMP of the withdrawal of the MAA.
The company intends to resubmit the MAA in mid-2017, as soon as the newly generated data are available.
ERYTECH stressed that there have been no safety issues with eryaspase, and the withdrawal of this MAA will not affect any ongoing trials.
“We are committed to pursuing regulatory approval for GRASPA and intend to work closely with our investigators and advisors to generate the additional information requested and to resubmit an MAA next year,” said Iman El-Hariry, chief medical officer of ERYTECH.
“We believe we have generated strong clinical data in our different programs of eryaspase, and we continue to execute our plans towards making the product available to patients with aggressive forms of cancer, such as acute lymphoblastic leukemia, acute myeloid leukemia, and pancreatic cancer,” added Gil Beyen, ERYTECH’s chairman and chief executive officer.
ERYTECH Pharma has announced its decision to withdraw the European marketing authorization application (MAA) for eryaspase (GRASPA®) as a treatment for acute lymphoblastic leukemia (ALL).
The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) asked for additional data on eryaspase, but ERYTECH said the time allowed by the EMA’s approval process is not sufficient to provide the data requested.
Therefore, the company decided to withdraw the MAA and resubmit it next year.
About eryaspase
Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.
Research has suggested this delivery system provides improved pharmacodynamics, protecting L-asparaginase from circulating proteolytic enzymes and preventing early liver or renal clearance.
The system also appears to reduce the risk of adverse events compared to native L-asparaginase.
The EMA and the US Food and Drug Administration have granted orphan drug designations for eryaspase for the treatment of ALL, acute myeloid
leukemia, and pancreatic cancer.
About the MAA
ERYTECH submitted an MAA for eryaspase in September 2015, based on positive results from a phase 2/3 study in which researchers compared eryaspase and native L-asparaginase in patients with relapsed and refractory ALL.
One year later (September 2016), the company received the CHMP’s Day 180 List of Outstanding Issues, which highlighted the need for additional data.
Specifically, the CHMP asked for data regarding the comparability between the old and new form of asparaginase encapsulated in eryaspase and the development of a new immunogenicity assay, as well as the pharmacodynamic effects of eryaspase.
Given the fact that the generation of these data will require more time than allowed in the EMA’s approval procedures, ERYTECH has notified the CHMP of the withdrawal of the MAA.
The company intends to resubmit the MAA in mid-2017, as soon as the newly generated data are available.
ERYTECH stressed that there have been no safety issues with eryaspase, and the withdrawal of this MAA will not affect any ongoing trials.
“We are committed to pursuing regulatory approval for GRASPA and intend to work closely with our investigators and advisors to generate the additional information requested and to resubmit an MAA next year,” said Iman El-Hariry, chief medical officer of ERYTECH.
“We believe we have generated strong clinical data in our different programs of eryaspase, and we continue to execute our plans towards making the product available to patients with aggressive forms of cancer, such as acute lymphoblastic leukemia, acute myeloid leukemia, and pancreatic cancer,” added Gil Beyen, ERYTECH’s chairman and chief executive officer.
MRI detects early stages of MF in mice
Magnetic resonance imaging (MRI) can effectively detect myelofibrosis (MF) in a mouse model, according to research published in the journal Blood Cancer.
In fact, researchers found that MRI could detect early and late stages of primary MF.
The researchers believe this discovery could potentially change the way MF is diagnosed, as MRI might be used to help physicians decide if or where to biopsy.
Katya Ravid, PhD, of Boston University School of Medicine in Massachusetts, and her colleagues conducted this research, aiming to determine whether T2-weighted MRI could detect bone marrow fibrosis in a mouse model of primary MF.
The team looked specifically at how effectively MRI could detect MF during the pre-fibrotic stage (when mice were less than 16 weeks old), when the mice had early MF (16 to 36 weeks old), and once the mice had overt MF (older than 36 weeks).
The researchers found that MRI could detect MF at the pre-fibrotic stage as well as detecting progressive MF.
The team said they observed a clear, bright signal that allowed them to differentiate mice with MF from healthy control mice.
The researchers proposed that the abundance of large megakaryocytes contributed to the bright signal they observed, since, in T2-weighted MR images, increased water/proton content, as in increased cellularity, yields high MR-signal intensity.
The team said this study provides proof of concept that T2-weighted MRI can detect primary MF in the early and late stages.
Magnetic resonance imaging (MRI) can effectively detect myelofibrosis (MF) in a mouse model, according to research published in the journal Blood Cancer.
In fact, researchers found that MRI could detect early and late stages of primary MF.
The researchers believe this discovery could potentially change the way MF is diagnosed, as MRI might be used to help physicians decide if or where to biopsy.
Katya Ravid, PhD, of Boston University School of Medicine in Massachusetts, and her colleagues conducted this research, aiming to determine whether T2-weighted MRI could detect bone marrow fibrosis in a mouse model of primary MF.
The team looked specifically at how effectively MRI could detect MF during the pre-fibrotic stage (when mice were less than 16 weeks old), when the mice had early MF (16 to 36 weeks old), and once the mice had overt MF (older than 36 weeks).
The researchers found that MRI could detect MF at the pre-fibrotic stage as well as detecting progressive MF.
The team said they observed a clear, bright signal that allowed them to differentiate mice with MF from healthy control mice.
The researchers proposed that the abundance of large megakaryocytes contributed to the bright signal they observed, since, in T2-weighted MR images, increased water/proton content, as in increased cellularity, yields high MR-signal intensity.
The team said this study provides proof of concept that T2-weighted MRI can detect primary MF in the early and late stages.
Magnetic resonance imaging (MRI) can effectively detect myelofibrosis (MF) in a mouse model, according to research published in the journal Blood Cancer.
In fact, researchers found that MRI could detect early and late stages of primary MF.
The researchers believe this discovery could potentially change the way MF is diagnosed, as MRI might be used to help physicians decide if or where to biopsy.
Katya Ravid, PhD, of Boston University School of Medicine in Massachusetts, and her colleagues conducted this research, aiming to determine whether T2-weighted MRI could detect bone marrow fibrosis in a mouse model of primary MF.
The team looked specifically at how effectively MRI could detect MF during the pre-fibrotic stage (when mice were less than 16 weeks old), when the mice had early MF (16 to 36 weeks old), and once the mice had overt MF (older than 36 weeks).
The researchers found that MRI could detect MF at the pre-fibrotic stage as well as detecting progressive MF.
The team said they observed a clear, bright signal that allowed them to differentiate mice with MF from healthy control mice.
The researchers proposed that the abundance of large megakaryocytes contributed to the bright signal they observed, since, in T2-weighted MR images, increased water/proton content, as in increased cellularity, yields high MR-signal intensity.
The team said this study provides proof of concept that T2-weighted MRI can detect primary MF in the early and late stages.
Antiplatelet drugs produce similar results in PAD
Photo from AstraZeneca
NEW ORLEANS—Results of the EUCLID trial suggest ticagrelor does not a provide a benefit over clopidogrel in patients with symptomatic peripheral artery disease (PAD).
The incidence of atherothrombotic events was similar in patients who received ticagrelor and those who received clopidogrel.
Likewise, there was no significant difference between the treatment arms with regard to major bleeding.
Manesh R. Patel, MD, of Duke University Medical Center in Durham, North Carolina, presented results from the EUCLID trial at the American Heart Association Scientific Sessions.
Results were also published in NEJM. The trial was supported by AstraZeneca.
EUCLID included 13,885 patients with symptomatic PAD. They had median age of 66, and 72% were male.
The patients were randomized to receive ticagrelor at 90 mg twice daily or clopidogrel at 75 mg once daily.
The study’s primary efficacy endpoint was a composite of adjudicated cardiovascular death, myocardial infarction, and ischemic stroke.
At a median follow-up of 30 months, the primary efficacy endpoint had occurred in 10.8% (751/6930) of patients in the ticagrelor arm and 10.6% (740/6955) in the clopidogrel arm (P=0.65).
When the researchers assessed each of the components of the primary endpoint alone, they found a significant difference between the treatment groups in the incidence of ischemic stroke but not cardiovascular death or myocardial infarction.
Cardiovascular death occurred in 5.2% of patients in the ticagrelor arm and 4.9% of those in the clopidogrel arm (P=0.40). Myocardial infarction occurred in 5% and 4.8%, respectively (P=0.48). And ischemic stroke occurred in 1.9% and 2.4%, respectively (P=0.03).
The study’s primary safety endpoint was major bleeding, which occurred in 1.6% of patients in both treatment arms (P=0.49).
Fatal bleeding occurred in 0.1% of patients in the ticagrelor arm and 0.3% of patients in the clopidogrel arm (P=0.10). And intracranial bleeding occurred in 0.5% of patients in both arms (P=0.82).
However, significantly more patients discontinued ticagrelor due to bleeding—2.4%, compared to 1.6% of patients who discontinued clopidogrel due to bleeding (P<0.001).
Significantly more patients discontinued ticagrelor due to dyspnea as well—4.8% vs 0.8% (P<0.001).
In all, 30.1% of patients in the ticagrelor arm and 25.9% of those in the clopidogrel arm prematurely discontinued treatment. This includes patients who discontinued due to adverse events, meeting the primary efficacy endpoint, and death.
Photo from AstraZeneca
NEW ORLEANS—Results of the EUCLID trial suggest ticagrelor does not a provide a benefit over clopidogrel in patients with symptomatic peripheral artery disease (PAD).
The incidence of atherothrombotic events was similar in patients who received ticagrelor and those who received clopidogrel.
Likewise, there was no significant difference between the treatment arms with regard to major bleeding.
Manesh R. Patel, MD, of Duke University Medical Center in Durham, North Carolina, presented results from the EUCLID trial at the American Heart Association Scientific Sessions.
Results were also published in NEJM. The trial was supported by AstraZeneca.
EUCLID included 13,885 patients with symptomatic PAD. They had median age of 66, and 72% were male.
The patients were randomized to receive ticagrelor at 90 mg twice daily or clopidogrel at 75 mg once daily.
The study’s primary efficacy endpoint was a composite of adjudicated cardiovascular death, myocardial infarction, and ischemic stroke.
At a median follow-up of 30 months, the primary efficacy endpoint had occurred in 10.8% (751/6930) of patients in the ticagrelor arm and 10.6% (740/6955) in the clopidogrel arm (P=0.65).
When the researchers assessed each of the components of the primary endpoint alone, they found a significant difference between the treatment groups in the incidence of ischemic stroke but not cardiovascular death or myocardial infarction.
Cardiovascular death occurred in 5.2% of patients in the ticagrelor arm and 4.9% of those in the clopidogrel arm (P=0.40). Myocardial infarction occurred in 5% and 4.8%, respectively (P=0.48). And ischemic stroke occurred in 1.9% and 2.4%, respectively (P=0.03).
The study’s primary safety endpoint was major bleeding, which occurred in 1.6% of patients in both treatment arms (P=0.49).
Fatal bleeding occurred in 0.1% of patients in the ticagrelor arm and 0.3% of patients in the clopidogrel arm (P=0.10). And intracranial bleeding occurred in 0.5% of patients in both arms (P=0.82).
However, significantly more patients discontinued ticagrelor due to bleeding—2.4%, compared to 1.6% of patients who discontinued clopidogrel due to bleeding (P<0.001).
Significantly more patients discontinued ticagrelor due to dyspnea as well—4.8% vs 0.8% (P<0.001).
In all, 30.1% of patients in the ticagrelor arm and 25.9% of those in the clopidogrel arm prematurely discontinued treatment. This includes patients who discontinued due to adverse events, meeting the primary efficacy endpoint, and death.
Photo from AstraZeneca
NEW ORLEANS—Results of the EUCLID trial suggest ticagrelor does not a provide a benefit over clopidogrel in patients with symptomatic peripheral artery disease (PAD).
The incidence of atherothrombotic events was similar in patients who received ticagrelor and those who received clopidogrel.
Likewise, there was no significant difference between the treatment arms with regard to major bleeding.
Manesh R. Patel, MD, of Duke University Medical Center in Durham, North Carolina, presented results from the EUCLID trial at the American Heart Association Scientific Sessions.
Results were also published in NEJM. The trial was supported by AstraZeneca.
EUCLID included 13,885 patients with symptomatic PAD. They had median age of 66, and 72% were male.
The patients were randomized to receive ticagrelor at 90 mg twice daily or clopidogrel at 75 mg once daily.
The study’s primary efficacy endpoint was a composite of adjudicated cardiovascular death, myocardial infarction, and ischemic stroke.
At a median follow-up of 30 months, the primary efficacy endpoint had occurred in 10.8% (751/6930) of patients in the ticagrelor arm and 10.6% (740/6955) in the clopidogrel arm (P=0.65).
When the researchers assessed each of the components of the primary endpoint alone, they found a significant difference between the treatment groups in the incidence of ischemic stroke but not cardiovascular death or myocardial infarction.
Cardiovascular death occurred in 5.2% of patients in the ticagrelor arm and 4.9% of those in the clopidogrel arm (P=0.40). Myocardial infarction occurred in 5% and 4.8%, respectively (P=0.48). And ischemic stroke occurred in 1.9% and 2.4%, respectively (P=0.03).
The study’s primary safety endpoint was major bleeding, which occurred in 1.6% of patients in both treatment arms (P=0.49).
Fatal bleeding occurred in 0.1% of patients in the ticagrelor arm and 0.3% of patients in the clopidogrel arm (P=0.10). And intracranial bleeding occurred in 0.5% of patients in both arms (P=0.82).
However, significantly more patients discontinued ticagrelor due to bleeding—2.4%, compared to 1.6% of patients who discontinued clopidogrel due to bleeding (P<0.001).
Significantly more patients discontinued ticagrelor due to dyspnea as well—4.8% vs 0.8% (P<0.001).
In all, 30.1% of patients in the ticagrelor arm and 25.9% of those in the clopidogrel arm prematurely discontinued treatment. This includes patients who discontinued due to adverse events, meeting the primary efficacy endpoint, and death.
FDA grants priority review for midostaurin
The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).
The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.
Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.
About priority review
The FDA grants priority review to applications for therapies that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it. The goal in the standard review process is to take action within 10 months.
About midostaurin
Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.
According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.
Midostaurin in AML
In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.
Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).
There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.
Midostaurin in SM
Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.
The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.
Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.
Access to midostaurin
Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.
Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.
The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).
The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.
Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.
About priority review
The FDA grants priority review to applications for therapies that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it. The goal in the standard review process is to take action within 10 months.
About midostaurin
Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.
According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.
Midostaurin in AML
In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.
Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).
There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.
Midostaurin in SM
Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.
The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.
Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.
Access to midostaurin
Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.
Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.
The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).
The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.
Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.
About priority review
The FDA grants priority review to applications for therapies that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it. The goal in the standard review process is to take action within 10 months.
About midostaurin
Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.
According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.
Midostaurin in AML
In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.
Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).
There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.
Midostaurin in SM
Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.
The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.
Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.
Access to midostaurin
Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.
Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.
EMA recommends orphan status for drug in AML
The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).
BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).
BP1001 is being developed by Bio-Path Holdings, Inc.
According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.
Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.
About orphan designation
The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
Trials of BP1001
Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.
The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.
Bio-Path recently released data from these studies.
The phase 1 study included patients who had received an average of 6 prior therapies.
The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m2. There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.
Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.
The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m2 and 90 mg/m2. Patients received BP1001 twice a week for 4 weeks.
Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.
The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).
BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).
BP1001 is being developed by Bio-Path Holdings, Inc.
According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.
Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.
About orphan designation
The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
Trials of BP1001
Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.
The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.
Bio-Path recently released data from these studies.
The phase 1 study included patients who had received an average of 6 prior therapies.
The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m2. There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.
Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.
The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m2 and 90 mg/m2. Patients received BP1001 twice a week for 4 weeks.
Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.
The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).
BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).
BP1001 is being developed by Bio-Path Holdings, Inc.
According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.
Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.
About orphan designation
The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
Trials of BP1001
Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.
The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.
Bio-Path recently released data from these studies.
The phase 1 study included patients who had received an average of 6 prior therapies.
The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m2. There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.
Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.
The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m2 and 90 mg/m2. Patients received BP1001 twice a week for 4 weeks.
Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.