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Company resubmits BLA for andexanet alfa
Portola Pharmaceuticals Inc. has resubmitted its biologics license application (BLA) for andexanet alfa (AndexXa®) to the US Food and Drug Administration (FDA).
With this BLA, Portola is seeking approval of andexanet alfa for reversal of the anticoagulant effects of apixaban and rivaroxaban in patients experiencing uncontrolled or life-threatening bleeding.
The resubmission includes supplemental information requested by the FDA in a complete response letter issued in August 2016.
At that time, Portola was seeking approval for andexanet alfa in patients treated with apixaban, rivaroxaban, edoxaban, or enoxaparin when reversal of anticoagulation is needed.
However, the FDA said it could not approve andexanet alfa for that indication. The FDA requested that Portola provide information related to manufacturing of andexanet alfa as well as additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.
The initial BLA for andexanet alfa included data from a pair of phase 3 studies—ANNEXA-A and ANNEXA-R—which were designed to assess andexanet alfa’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers.
Results from ANNEXA-A and ANNEXA-R were published in NEJM in 2015.
The BLA also included limited adjudicated efficacy and safety data from patients enrolled in the phase 3b/4 ANNEXA-4 study. This ongoing study is enrolling patients receiving apixaban, rivaroxaban, edoxaban, and enoxaparin who present with an acute major bleed.
Preliminary results from ANNEXA-4 were presented at ESC Congress 2016 and published in NEJM. 
Portola Pharmaceuticals Inc. has resubmitted its biologics license application (BLA) for andexanet alfa (AndexXa®) to the US Food and Drug Administration (FDA).
With this BLA, Portola is seeking approval of andexanet alfa for reversal of the anticoagulant effects of apixaban and rivaroxaban in patients experiencing uncontrolled or life-threatening bleeding.
The resubmission includes supplemental information requested by the FDA in a complete response letter issued in August 2016.
At that time, Portola was seeking approval for andexanet alfa in patients treated with apixaban, rivaroxaban, edoxaban, or enoxaparin when reversal of anticoagulation is needed.
However, the FDA said it could not approve andexanet alfa for that indication. The FDA requested that Portola provide information related to manufacturing of andexanet alfa as well as additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.
The initial BLA for andexanet alfa included data from a pair of phase 3 studies—ANNEXA-A and ANNEXA-R—which were designed to assess andexanet alfa’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers.
Results from ANNEXA-A and ANNEXA-R were published in NEJM in 2015.
The BLA also included limited adjudicated efficacy and safety data from patients enrolled in the phase 3b/4 ANNEXA-4 study. This ongoing study is enrolling patients receiving apixaban, rivaroxaban, edoxaban, and enoxaparin who present with an acute major bleed.
Preliminary results from ANNEXA-4 were presented at ESC Congress 2016 and published in NEJM.
Portola Pharmaceuticals Inc. has resubmitted its biologics license application (BLA) for andexanet alfa (AndexXa®) to the US Food and Drug Administration (FDA).
With this BLA, Portola is seeking approval of andexanet alfa for reversal of the anticoagulant effects of apixaban and rivaroxaban in patients experiencing uncontrolled or life-threatening bleeding.
The resubmission includes supplemental information requested by the FDA in a complete response letter issued in August 2016.
At that time, Portola was seeking approval for andexanet alfa in patients treated with apixaban, rivaroxaban, edoxaban, or enoxaparin when reversal of anticoagulation is needed.
However, the FDA said it could not approve andexanet alfa for that indication. The FDA requested that Portola provide information related to manufacturing of andexanet alfa as well as additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.
The initial BLA for andexanet alfa included data from a pair of phase 3 studies—ANNEXA-A and ANNEXA-R—which were designed to assess andexanet alfa’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers.
Results from ANNEXA-A and ANNEXA-R were published in NEJM in 2015.
The BLA also included limited adjudicated efficacy and safety data from patients enrolled in the phase 3b/4 ANNEXA-4 study. This ongoing study is enrolling patients receiving apixaban, rivaroxaban, edoxaban, and enoxaparin who present with an acute major bleed.
Preliminary results from ANNEXA-4 were presented at ESC Congress 2016 and published in NEJM.
FDA approves drug to treat 2 types of AML
The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.
CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.
The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.
The company says the drug will be commercially available within a week.
The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).
The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.
The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).
All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.
Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.
The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.
The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.
For more information on CPX-351, visit http://www.vyxeos.com.
The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.
CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.
The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.
The company says the drug will be commercially available within a week.
The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).
The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.
The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).
All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.
Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.
The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.
The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.
For more information on CPX-351, visit http://www.vyxeos.com.
The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.
CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.
The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.
The company says the drug will be commercially available within a week.
The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).
The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.
The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).
All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.
Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.
The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.
The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.
For more information on CPX-351, visit http://www.vyxeos.com.
Mast cell inhibitors might be effective against DVT
Preclinical research suggests common anti-allergy medicines might be able to treat deep vein thrombosis (DVT).
Researchers discovered that mice genetically depleted of mast cells were protected from developing DVT but still had normal hemostasis.
The team therefore theorized that mast cell inhibitors, which are already approved to treat some allergic diseases, might be effective against DVT.
Alex Brill, MD, PhD, of the University of Birmingham in the UK, and his colleagues reported these findings in Circulation Research.
“These findings offer new hope for the treatment of deep vein thrombosis without a risk of bleeding,” Dr Brill said. “If further human studies support our findings in mice, drugs to block mast cell production could be used in the future alongside lower doses of anticoagulants such as warfarin, significantly reducing bleeding risk.”
“This is particularly exciting because this is a group of drugs which already exists, and some forms are approved for the treatment of allergies such as hay fever and asthma, meaning that this discovery could help people with DVT sooner rather than later.”
Preclinical research suggests common anti-allergy medicines might be able to treat deep vein thrombosis (DVT).
Researchers discovered that mice genetically depleted of mast cells were protected from developing DVT but still had normal hemostasis.
The team therefore theorized that mast cell inhibitors, which are already approved to treat some allergic diseases, might be effective against DVT.
Alex Brill, MD, PhD, of the University of Birmingham in the UK, and his colleagues reported these findings in Circulation Research.
“These findings offer new hope for the treatment of deep vein thrombosis without a risk of bleeding,” Dr Brill said. “If further human studies support our findings in mice, drugs to block mast cell production could be used in the future alongside lower doses of anticoagulants such as warfarin, significantly reducing bleeding risk.”
“This is particularly exciting because this is a group of drugs which already exists, and some forms are approved for the treatment of allergies such as hay fever and asthma, meaning that this discovery could help people with DVT sooner rather than later.”
Preclinical research suggests common anti-allergy medicines might be able to treat deep vein thrombosis (DVT).
Researchers discovered that mice genetically depleted of mast cells were protected from developing DVT but still had normal hemostasis.
The team therefore theorized that mast cell inhibitors, which are already approved to treat some allergic diseases, might be effective against DVT.
Alex Brill, MD, PhD, of the University of Birmingham in the UK, and his colleagues reported these findings in Circulation Research.
“These findings offer new hope for the treatment of deep vein thrombosis without a risk of bleeding,” Dr Brill said. “If further human studies support our findings in mice, drugs to block mast cell production could be used in the future alongside lower doses of anticoagulants such as warfarin, significantly reducing bleeding risk.”
“This is particularly exciting because this is a group of drugs which already exists, and some forms are approved for the treatment of allergies such as hay fever and asthma, meaning that this discovery could help people with DVT sooner rather than later.”
FDA approves first treatment for cGVHD
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
FDA grants drug orphan designation for PNH
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
FDA approves enasidenib to treat relapsed/refractory AML
The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).
The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.
Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.
The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.
Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.
Companion diagnostic
Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.
The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.
Enasidenib is licensed from Agios Pharmaceuticals.
Trial results
The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).
Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.
The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.
The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.
The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.
The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).
For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).
Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.
Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.
Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).
The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.
Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.
The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.
The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).
The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.
Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.
The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.
Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.
Companion diagnostic
Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.
The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.
Enasidenib is licensed from Agios Pharmaceuticals.
Trial results
The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).
Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.
The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.
The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.
The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.
The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).
For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).
Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.
Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.
Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).
The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.
Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.
The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.
The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).
The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.
Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.
The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.
Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.
Companion diagnostic
Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.
The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.
Enasidenib is licensed from Agios Pharmaceuticals.
Trial results
The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).
Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.
The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.
The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.
The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.
The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).
For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).
Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.
Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.
Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).
The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.
Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.
The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.
Delirium linked to early death in advanced cancer patients
A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.
The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.
This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.
“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.
He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).
Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.
In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.
Results
The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).
The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).
Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.
He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.
“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.
He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.
A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.
The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.
This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.
“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.
He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).
Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.
In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.
Results
The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).
The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).
Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.
He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.
“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.
He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.
A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.
The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.
This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.
“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.
He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).
Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.
In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.
Results
The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).
The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).
Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.
He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.
“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.
He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.
FDA grants acalabrutinib breakthrough designation
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.
The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.
Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.
The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.
Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.
The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.
Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.
Understanding childhood cancer in sub-Saharan Africa
Researchers say they have published the most extensive data ever collected on childhood cancer in sub-Saharan Africa.
On the African continent, only South Africa operates a childhood cancer registry on the national level.
Researchers brought together data from 16 of the smaller, local registries, collecting this information for the first time and presenting it in an accessible format.
The data were published in ecancermedicalscience.
Examining the data in context allowed the researchers to notice trends in cancer incidence. For example, they found that, in Blantyre, Malawi’s second-largest city, the cumulative risk of a child developing Burkitt lymphoma is 2 in every thousand.
The researchers called this incidence “remarkable” and noted that the global research community is largely unaware of this.
“Everything starts with awareness,” said study author Cristina Stefan, global clinical leader of oncology for Roche Diagnostics International Ltd of Switzerland and director of the African Medical Research and Innovation Institute.
“It is highly necessary to publicize these data, which, at the moment, represent the best image of the malignant disease in children in the respective regions.”
The researchers also noted that factors such as the prevalence of malaria and the Epstein-Barr virus contribute to the unique epidemiology of childhood cancer in Africa.
“Our colleagues can learn that the patterns and distribution of cancers in Africa are totally different from Europe, and there is a need for further research into the roles of factors such as genetic predispositions and the influence of infections and other comorbidities in the evolution of cancer,” Dr Stefan said.
“We have learned many universal lessons about data collection as we prepared this work. Our hope is that the publication of this monograph will open the forums for future discussions and that the work will be referenced for the better understanding of cancer in children in Africa and used to improve outcomes for children affected there.”
Researchers say they have published the most extensive data ever collected on childhood cancer in sub-Saharan Africa.
On the African continent, only South Africa operates a childhood cancer registry on the national level.
Researchers brought together data from 16 of the smaller, local registries, collecting this information for the first time and presenting it in an accessible format.
The data were published in ecancermedicalscience.
Examining the data in context allowed the researchers to notice trends in cancer incidence. For example, they found that, in Blantyre, Malawi’s second-largest city, the cumulative risk of a child developing Burkitt lymphoma is 2 in every thousand.
The researchers called this incidence “remarkable” and noted that the global research community is largely unaware of this.
“Everything starts with awareness,” said study author Cristina Stefan, global clinical leader of oncology for Roche Diagnostics International Ltd of Switzerland and director of the African Medical Research and Innovation Institute.
“It is highly necessary to publicize these data, which, at the moment, represent the best image of the malignant disease in children in the respective regions.”
The researchers also noted that factors such as the prevalence of malaria and the Epstein-Barr virus contribute to the unique epidemiology of childhood cancer in Africa.
“Our colleagues can learn that the patterns and distribution of cancers in Africa are totally different from Europe, and there is a need for further research into the roles of factors such as genetic predispositions and the influence of infections and other comorbidities in the evolution of cancer,” Dr Stefan said.
“We have learned many universal lessons about data collection as we prepared this work. Our hope is that the publication of this monograph will open the forums for future discussions and that the work will be referenced for the better understanding of cancer in children in Africa and used to improve outcomes for children affected there.”
Researchers say they have published the most extensive data ever collected on childhood cancer in sub-Saharan Africa.
On the African continent, only South Africa operates a childhood cancer registry on the national level.
Researchers brought together data from 16 of the smaller, local registries, collecting this information for the first time and presenting it in an accessible format.
The data were published in ecancermedicalscience.
Examining the data in context allowed the researchers to notice trends in cancer incidence. For example, they found that, in Blantyre, Malawi’s second-largest city, the cumulative risk of a child developing Burkitt lymphoma is 2 in every thousand.
The researchers called this incidence “remarkable” and noted that the global research community is largely unaware of this.
“Everything starts with awareness,” said study author Cristina Stefan, global clinical leader of oncology for Roche Diagnostics International Ltd of Switzerland and director of the African Medical Research and Innovation Institute.
“It is highly necessary to publicize these data, which, at the moment, represent the best image of the malignant disease in children in the respective regions.”
The researchers also noted that factors such as the prevalence of malaria and the Epstein-Barr virus contribute to the unique epidemiology of childhood cancer in Africa.
“Our colleagues can learn that the patterns and distribution of cancers in Africa are totally different from Europe, and there is a need for further research into the roles of factors such as genetic predispositions and the influence of infections and other comorbidities in the evolution of cancer,” Dr Stefan said.
“We have learned many universal lessons about data collection as we prepared this work. Our hope is that the publication of this monograph will open the forums for future discussions and that the work will be referenced for the better understanding of cancer in children in Africa and used to improve outcomes for children affected there.”
Thalassemia case provides insight into history of malaria
The earliest documented case of β-thalassemia in Sardinia suggests malaria was widespread on the island long before the Middle Ages, according to researchers.
The team noted that Sardinia has one of the highest incidence rates of β-thalassemia in Europe due to its long history of endemic malaria.
However, it has been assumed that malaria was only endemic on the island since the Middle Ages (500-1500 CE).
New research, published in the American Journal of Physical Anthropology, suggests malaria was probably already endemic on Sardinia during the Roman period.
Since ancient DNA of malaria is difficult to extract, the researchers studied thalassemia and other genetic adaptations in its place.
The team studied a thalassemia allele called cod39 β-thalassemia, which is dominant on Sardinia. They were able to confirm the presence of the cod39 allele in the 2000-year-old (approximately 300 BCE to 100 CE) remains of a Roman man.
“This is the very first documented case of the genetic adaptation to malaria on Sardinia,” said study author Claudia Vigano, of the Institute for Evolutionary Medicine of the University of Zurich in Switzerland.
“We also discovered that the person was genetically a Sardinian in all probability and not an immigrant from another area.”
“Our study shows the importance of a multidisciplinary approach to history,” said Abigail Bouwman, also of the Institute for Evolutionary Medicine of the University of Zurich.
“We are researching the evolution of today’s diseases, such as malaria, to explain why the human body becomes sick at all and how adaptations occur.”
The earliest documented case of β-thalassemia in Sardinia suggests malaria was widespread on the island long before the Middle Ages, according to researchers.
The team noted that Sardinia has one of the highest incidence rates of β-thalassemia in Europe due to its long history of endemic malaria.
However, it has been assumed that malaria was only endemic on the island since the Middle Ages (500-1500 CE).
New research, published in the American Journal of Physical Anthropology, suggests malaria was probably already endemic on Sardinia during the Roman period.
Since ancient DNA of malaria is difficult to extract, the researchers studied thalassemia and other genetic adaptations in its place.
The team studied a thalassemia allele called cod39 β-thalassemia, which is dominant on Sardinia. They were able to confirm the presence of the cod39 allele in the 2000-year-old (approximately 300 BCE to 100 CE) remains of a Roman man.
“This is the very first documented case of the genetic adaptation to malaria on Sardinia,” said study author Claudia Vigano, of the Institute for Evolutionary Medicine of the University of Zurich in Switzerland.
“We also discovered that the person was genetically a Sardinian in all probability and not an immigrant from another area.”
“Our study shows the importance of a multidisciplinary approach to history,” said Abigail Bouwman, also of the Institute for Evolutionary Medicine of the University of Zurich.
“We are researching the evolution of today’s diseases, such as malaria, to explain why the human body becomes sick at all and how adaptations occur.”
The earliest documented case of β-thalassemia in Sardinia suggests malaria was widespread on the island long before the Middle Ages, according to researchers.
The team noted that Sardinia has one of the highest incidence rates of β-thalassemia in Europe due to its long history of endemic malaria.
However, it has been assumed that malaria was only endemic on the island since the Middle Ages (500-1500 CE).
New research, published in the American Journal of Physical Anthropology, suggests malaria was probably already endemic on Sardinia during the Roman period.
Since ancient DNA of malaria is difficult to extract, the researchers studied thalassemia and other genetic adaptations in its place.
The team studied a thalassemia allele called cod39 β-thalassemia, which is dominant on Sardinia. They were able to confirm the presence of the cod39 allele in the 2000-year-old (approximately 300 BCE to 100 CE) remains of a Roman man.
“This is the very first documented case of the genetic adaptation to malaria on Sardinia,” said study author Claudia Vigano, of the Institute for Evolutionary Medicine of the University of Zurich in Switzerland.
“We also discovered that the person was genetically a Sardinian in all probability and not an immigrant from another area.”
“Our study shows the importance of a multidisciplinary approach to history,” said Abigail Bouwman, also of the Institute for Evolutionary Medicine of the University of Zurich.
“We are researching the evolution of today’s diseases, such as malaria, to explain why the human body becomes sick at all and how adaptations occur.”