Pharmacy

Blood collection

Credit: Charles Haymond

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with  relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.

The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.

The FDA recently granted JCAR015 orphan designation to treat ALL as well.

JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.

Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.

At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.

The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.

Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.

Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.

Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.

The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.

So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.

And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.

In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.

Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.

JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco.

Blood collection

Credit: Charles Haymond

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with  relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.

The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.

The FDA recently granted JCAR015 orphan designation to treat ALL as well.

JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.

Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.

At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.

The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.

Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.

Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.

Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.

The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.

So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.

And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.

In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.

Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.

JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco.

Blood collection

Credit: Charles Haymond

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with  relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.

The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.

The FDA recently granted JCAR015 orphan designation to treat ALL as well.

JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.

Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.

At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.

The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.

Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.

Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.

Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.

The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.

So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.

And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.

In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.

Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.

JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco.

Thrombus

Credit: Kevin MacKenzie

The US Food and Drug Administration (FDA) has granted orphan drug designation for CCX168, an oral inhibitor targeting the receptor for the complement protein C5a, to treat atypical hemolytic uremic syndrome (aHUS).

This rare but life-threatening disease causes inflammation of the blood vessels and thrombus formation throughout the body.

Patients with aHUS are at constant risk of sudden and progressive damage to, and failure of, vital organs. Roughly 10% to 15% of patients die in the initial, acute phase of aHUS.

The majority of patients—up to 70%—develop end-stage kidney failure requiring dialysis. And 1 in 5 patients has aHUS affecting organs other than the kidneys, most commonly the brain or heart.

“Given the life-threatening nature of aHUS, we are very pleased with the granting of orphan drug designation for CCX168 in this disease,” said Thomas J. Schall, PhD, president and chief executive officer of ChemoCentryx, Inc., the company developing CCX168.

ChemoCentryx has generated positive preclinical data that suggest an important role of C5a receptor inhibition in reducing microvasculature thrombosis formation in aHUS.

The company plans to initiate a phase 2 proof-of-concept study in patients with aHUS by the end of 2014.

CCX168 is also in phase 2 development for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

The orphan designation for CCX168 will provide ChemoCentryx with a 7-year period of US marketing exclusivity if the drug is approved to treat aHUS, tax credits for clinical research costs, the ability to apply for annual grant funding, clinical research trial design assistance, and the waiver of prescription drug user fees.

Thrombus

Credit: Kevin MacKenzie

The US Food and Drug Administration (FDA) has granted orphan drug designation for CCX168, an oral inhibitor targeting the receptor for the complement protein C5a, to treat atypical hemolytic uremic syndrome (aHUS).

This rare but life-threatening disease causes inflammation of the blood vessels and thrombus formation throughout the body.

Patients with aHUS are at constant risk of sudden and progressive damage to, and failure of, vital organs. Roughly 10% to 15% of patients die in the initial, acute phase of aHUS.

The majority of patients—up to 70%—develop end-stage kidney failure requiring dialysis. And 1 in 5 patients has aHUS affecting organs other than the kidneys, most commonly the brain or heart.

“Given the life-threatening nature of aHUS, we are very pleased with the granting of orphan drug designation for CCX168 in this disease,” said Thomas J. Schall, PhD, president and chief executive officer of ChemoCentryx, Inc., the company developing CCX168.

ChemoCentryx has generated positive preclinical data that suggest an important role of C5a receptor inhibition in reducing microvasculature thrombosis formation in aHUS.

The company plans to initiate a phase 2 proof-of-concept study in patients with aHUS by the end of 2014.

CCX168 is also in phase 2 development for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

The orphan designation for CCX168 will provide ChemoCentryx with a 7-year period of US marketing exclusivity if the drug is approved to treat aHUS, tax credits for clinical research costs, the ability to apply for annual grant funding, clinical research trial design assistance, and the waiver of prescription drug user fees.

Thrombus

Credit: Kevin MacKenzie

The US Food and Drug Administration (FDA) has granted orphan drug designation for CCX168, an oral inhibitor targeting the receptor for the complement protein C5a, to treat atypical hemolytic uremic syndrome (aHUS).

This rare but life-threatening disease causes inflammation of the blood vessels and thrombus formation throughout the body.

Patients with aHUS are at constant risk of sudden and progressive damage to, and failure of, vital organs. Roughly 10% to 15% of patients die in the initial, acute phase of aHUS.

The majority of patients—up to 70%—develop end-stage kidney failure requiring dialysis. And 1 in 5 patients has aHUS affecting organs other than the kidneys, most commonly the brain or heart.

“Given the life-threatening nature of aHUS, we are very pleased with the granting of orphan drug designation for CCX168 in this disease,” said Thomas J. Schall, PhD, president and chief executive officer of ChemoCentryx, Inc., the company developing CCX168.

ChemoCentryx has generated positive preclinical data that suggest an important role of C5a receptor inhibition in reducing microvasculature thrombosis formation in aHUS.

The company plans to initiate a phase 2 proof-of-concept study in patients with aHUS by the end of 2014.

CCX168 is also in phase 2 development for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

The orphan designation for CCX168 will provide ChemoCentryx with a 7-year period of US marketing exclusivity if the drug is approved to treat aHUS, tax credits for clinical research costs, the ability to apply for annual grant funding, clinical research trial design assistance, and the waiver of prescription drug user fees.

AML cells

Credit: Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan drug designation for the Axl inhibitor BGB324 to treat acute myeloid leukemia (AML).

BGB324 is a highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition, a key driver in drug resistance and metastasis.

BerGenBio, the company developing BGB324, has estimated that more than 50% of AML patients have elevated levels of Axl.

And a study published in Blood last year showed that Axl inhibition by BGB324 prompts antileukemic activity in FLT3-mutated and FLT3-wild-type AML.

Earlier this month, BerGenBio said the first patient had been dosed in its multicenter phase 1b trial of BGB324 in patients with AML.

The primary goal of this 2-part trial is to investigate the safety and tolerability of BGB324 as a single agent and in combination with cytarabine. Secondary endpoints include clinical response and assessment of novel biomarkers.

The study will be conducted at 6 sites in Norway, Germany, and the US. BerGenBio expects data from this trial to be available in 2015.

The FDA’s orphan designation will provide BerGenBio with access to various development incentives for BGB324.

This includes tax credits for qualified clinical testing, exemption from prescription drug user fees for BGB324 in AML, and 7 years of market exclusivity in the US upon FDA approval.

AML cells

Credit: Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan drug designation for the Axl inhibitor BGB324 to treat acute myeloid leukemia (AML).

BGB324 is a highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition, a key driver in drug resistance and metastasis.

BerGenBio, the company developing BGB324, has estimated that more than 50% of AML patients have elevated levels of Axl.

And a study published in Blood last year showed that Axl inhibition by BGB324 prompts antileukemic activity in FLT3-mutated and FLT3-wild-type AML.

Earlier this month, BerGenBio said the first patient had been dosed in its multicenter phase 1b trial of BGB324 in patients with AML.

The primary goal of this 2-part trial is to investigate the safety and tolerability of BGB324 as a single agent and in combination with cytarabine. Secondary endpoints include clinical response and assessment of novel biomarkers.

The study will be conducted at 6 sites in Norway, Germany, and the US. BerGenBio expects data from this trial to be available in 2015.

The FDA’s orphan designation will provide BerGenBio with access to various development incentives for BGB324.

This includes tax credits for qualified clinical testing, exemption from prescription drug user fees for BGB324 in AML, and 7 years of market exclusivity in the US upon FDA approval.

AML cells

Credit: Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan drug designation for the Axl inhibitor BGB324 to treat acute myeloid leukemia (AML).

BGB324 is a highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition, a key driver in drug resistance and metastasis.

BerGenBio, the company developing BGB324, has estimated that more than 50% of AML patients have elevated levels of Axl.

And a study published in Blood last year showed that Axl inhibition by BGB324 prompts antileukemic activity in FLT3-mutated and FLT3-wild-type AML.

Earlier this month, BerGenBio said the first patient had been dosed in its multicenter phase 1b trial of BGB324 in patients with AML.

The primary goal of this 2-part trial is to investigate the safety and tolerability of BGB324 as a single agent and in combination with cytarabine. Secondary endpoints include clinical response and assessment of novel biomarkers.

The study will be conducted at 6 sites in Norway, Germany, and the US. BerGenBio expects data from this trial to be available in 2015.

The FDA’s orphan designation will provide BerGenBio with access to various development incentives for BGB324.

This includes tax credits for qualified clinical testing, exemption from prescription drug user fees for BGB324 in AML, and 7 years of market exclusivity in the US upon FDA approval.

B-cell ALL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy JCAR015 to treat acute lymphoblastic leukemia (ALL).

The designation will provide the product’s developer, Juno Therapeutics, with multiple benefits, including the availability of grant money, certain tax credits, and 7 years of market exclusivity, as well as the possibility of an expedited regulatory process.

JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.

Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.

At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.

The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.

Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.

Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.

Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.

The 2 remaining deaths prompted a temporary suspension of enrollment in this trial.

Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following “persistent seizure activity.”

So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases.

The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.

And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures.

The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.

In addition to this trial, JCAR015 is under investigation in another phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.

B-cell ALL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy JCAR015 to treat acute lymphoblastic leukemia (ALL).

The designation will provide the product’s developer, Juno Therapeutics, with multiple benefits, including the availability of grant money, certain tax credits, and 7 years of market exclusivity, as well as the possibility of an expedited regulatory process.

JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.

Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.

At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.

The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.

Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.

Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.

Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.

The 2 remaining deaths prompted a temporary suspension of enrollment in this trial.

Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following “persistent seizure activity.”

So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases.

The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.

And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures.

The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.

In addition to this trial, JCAR015 is under investigation in another phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.

B-cell ALL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy JCAR015 to treat acute lymphoblastic leukemia (ALL).

The designation will provide the product’s developer, Juno Therapeutics, with multiple benefits, including the availability of grant money, certain tax credits, and 7 years of market exclusivity, as well as the possibility of an expedited regulatory process.

JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.

Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.

At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.

The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.

Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.

Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.

Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.

The 2 remaining deaths prompted a temporary suspension of enrollment in this trial.

Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following “persistent seizure activity.”

So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases.

The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.

And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures.

The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.

In addition to this trial, JCAR015 is under investigation in another phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.

Antihemophilic factor

Health Canada and Australia’s Therapeutic Goods Administration (TGA) have both approved a recombinant FVIII product known as simoctocog alfa (Nuwiq).

Health Canada has approved the product to treat and prevent bleeding in hemophilia A patients of all ages.

And the TGA has approved simoctocog alfa for the treatment and prevention of bleeding in previously treated pediatric (≥ 2 years) and adult patients with

hemophilia A.

Simoctocog alfa is a recombinant FVIII product produced in a human cell line cultured without additives of human or animal origin or any exposure to human blood or plasma, making it inherently free from blood-borne pathogens.

Simoctocog alfa is also devoid of antigenic non-human protein epitopes, similar to FVIII produced in healthy humans. It has a high affinity for the von Willebrand coagulation factor.

“The way Nuwiq is produced is exciting, as it allows the molecule to closely resemble the naturally occurring FVIII,” said Anthony Chan, MBBS, Director of the Hemophilia Program at McMaster Children’s Hospital in Hamilton, Ontario.

“Health Canada’s approval of Nuwiq provides patients with hemophilia A a new recombinant product option that will allow further customization of hemophilia treatment on an individual basis.”

Researchers have evaluated the immunogenicity of simoctocog alfa in 135 previously treated patients with hemophilia A (74 adults and 61 children). And none of the patients developed inhibitors.

In the ongoing, phase 3 NuProtect study, researchers are investigating 100 previously untreated patients, a group typically characterized by a higher risk of inhibitor development. The researchers will assess whether the molecular properties of simoctocog alfa will result in lower inhibitor development.

Two additional phase 3 studies in previously treated patients are ongoing. The NuPreviq study and the Canadian Gena-21b study were designed to assess the efficacy and safety of individually tailored prophylaxis.

The goal of these studies is to provide optimal treatment for each patient based on his or her own pharmacokinetic properties, with a potential reduction in the frequency of FVIII infusions.

Simoctocog alfa was approved in the European Union earlier this year and is under review by regulatory authorities in the US. For more details on simoctocog alfa, see the prescribing information.

Antihemophilic factor

Health Canada and Australia’s Therapeutic Goods Administration (TGA) have both approved a recombinant FVIII product known as simoctocog alfa (Nuwiq).

Health Canada has approved the product to treat and prevent bleeding in hemophilia A patients of all ages.

And the TGA has approved simoctocog alfa for the treatment and prevention of bleeding in previously treated pediatric (≥ 2 years) and adult patients with

hemophilia A.

Simoctocog alfa is a recombinant FVIII product produced in a human cell line cultured without additives of human or animal origin or any exposure to human blood or plasma, making it inherently free from blood-borne pathogens.

Simoctocog alfa is also devoid of antigenic non-human protein epitopes, similar to FVIII produced in healthy humans. It has a high affinity for the von Willebrand coagulation factor.

“The way Nuwiq is produced is exciting, as it allows the molecule to closely resemble the naturally occurring FVIII,” said Anthony Chan, MBBS, Director of the Hemophilia Program at McMaster Children’s Hospital in Hamilton, Ontario.

“Health Canada’s approval of Nuwiq provides patients with hemophilia A a new recombinant product option that will allow further customization of hemophilia treatment on an individual basis.”

Researchers have evaluated the immunogenicity of simoctocog alfa in 135 previously treated patients with hemophilia A (74 adults and 61 children). And none of the patients developed inhibitors.

In the ongoing, phase 3 NuProtect study, researchers are investigating 100 previously untreated patients, a group typically characterized by a higher risk of inhibitor development. The researchers will assess whether the molecular properties of simoctocog alfa will result in lower inhibitor development.

Two additional phase 3 studies in previously treated patients are ongoing. The NuPreviq study and the Canadian Gena-21b study were designed to assess the efficacy and safety of individually tailored prophylaxis.

The goal of these studies is to provide optimal treatment for each patient based on his or her own pharmacokinetic properties, with a potential reduction in the frequency of FVIII infusions.

Simoctocog alfa was approved in the European Union earlier this year and is under review by regulatory authorities in the US. For more details on simoctocog alfa, see the prescribing information.

Antihemophilic factor

Health Canada and Australia’s Therapeutic Goods Administration (TGA) have both approved a recombinant FVIII product known as simoctocog alfa (Nuwiq).

Health Canada has approved the product to treat and prevent bleeding in hemophilia A patients of all ages.

And the TGA has approved simoctocog alfa for the treatment and prevention of bleeding in previously treated pediatric (≥ 2 years) and adult patients with

hemophilia A.

Simoctocog alfa is a recombinant FVIII product produced in a human cell line cultured without additives of human or animal origin or any exposure to human blood or plasma, making it inherently free from blood-borne pathogens.

Simoctocog alfa is also devoid of antigenic non-human protein epitopes, similar to FVIII produced in healthy humans. It has a high affinity for the von Willebrand coagulation factor.

“The way Nuwiq is produced is exciting, as it allows the molecule to closely resemble the naturally occurring FVIII,” said Anthony Chan, MBBS, Director of the Hemophilia Program at McMaster Children’s Hospital in Hamilton, Ontario.

“Health Canada’s approval of Nuwiq provides patients with hemophilia A a new recombinant product option that will allow further customization of hemophilia treatment on an individual basis.”

Researchers have evaluated the immunogenicity of simoctocog alfa in 135 previously treated patients with hemophilia A (74 adults and 61 children). And none of the patients developed inhibitors.

In the ongoing, phase 3 NuProtect study, researchers are investigating 100 previously untreated patients, a group typically characterized by a higher risk of inhibitor development. The researchers will assess whether the molecular properties of simoctocog alfa will result in lower inhibitor development.

Two additional phase 3 studies in previously treated patients are ongoing. The NuPreviq study and the Canadian Gena-21b study were designed to assess the efficacy and safety of individually tailored prophylaxis.

The goal of these studies is to provide optimal treatment for each patient based on his or her own pharmacokinetic properties, with a potential reduction in the frequency of FVIII infusions.

Simoctocog alfa was approved in the European Union earlier this year and is under review by regulatory authorities in the US. For more details on simoctocog alfa, see the prescribing information.

Drugs in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted fast track designation to two hematology drugs: the monoclonal antibody MOR208 to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and the antifibrotic agent PRM-151 to treat myelofibrosis (MF).

The FDA’s fast track program aims to expedite the development and review of drugs that have the potential to fill an unmet medical need in serious or life-threatening conditions.

MOR208

MOR208 is a humanized monoclonal antibody targeting CD19. It is under development by MorphoSys AG to treat B-cell malignancies. The program is in phase 2 clinical development in chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and non-Hodgkin lymphoma.

Preclinical research with MOR208 revealed that it can trigger natural killer cell-mediated lysis of ALL cells. The drug had lytic activity against ALL cells from both adult and pediatric patients.

In a phase 1 study, MOR208 exhibited preliminary efficacy in patients with high-risk, heavily pretreated CLL, prompting responses in 67% of patients. Researchers said toxicity was acceptable, but infusion reactions were common.

“First results of our ongoing phase 2 trial, which we will present at this year’s ASH conference in December, have helped to identify diffuse large B-cell lymphoma as a valuable development opportunity for MOR208,” said Arndt Schottelius, chief development officer of MorphoSys AG.

“We are therefore delighted to have received the fast track designation for further development of MOR208 in DLBCL. The more frequent interactions with the FDA that this enables will help us to expedite the development of MOR208 in this particular subset of non-Hodgkin’s lymphoma patients.”

PRM-151

PRM-151 is a recombinant form of an endogenous human protein, pentraxin-2, that is specifically active at the site of tissue damage. PRM-151 is an agonist that acts as a monocyte/macrophage differentiation factor to prevent and potentially reverse fibrosis.

The drug has shown broad anti-fibrotic activity in preclinical models of fibrotic disease, including pulmonary fibrosis, acute and chronic nephropathy, liver fibrosis, and age-related macular degeneration.

PRM-151 has orphan designation in the US for MF and in both the US and European Union for the treatment of idiopathic pulmonary fibrosis.

The FDA’s fast track designation for PRM-151 covers primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF.

“This designation validates our perspective that there is a clear and compelling need for a novel mechanism for the treatment of myelofibrosis that specifically targets the underlying fibrotic processes of the disease,” said Beth Tréhu, MD, FACP, chief medical officer of Promedior Inc., the company developing PRM-151.

“We will continue to work expeditiously to advance this program through the clinic and look forward to presenting the full data set from the first stage of our phase 2 study later this year.”

Preliminary data from the phase 2 study of PRM-151 demonstrated benefits across all clinically relevant measures of MF, including decreases in bone marrow fibrosis, symptom responses, improvements in hemoglobin and platelets, and reductions in spleen size.

The drug also appeared to be well-tolerated and did not prompt myelosuppression.

Drugs in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted fast track designation to two hematology drugs: the monoclonal antibody MOR208 to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and the antifibrotic agent PRM-151 to treat myelofibrosis (MF).

The FDA’s fast track program aims to expedite the development and review of drugs that have the potential to fill an unmet medical need in serious or life-threatening conditions.

MOR208

MOR208 is a humanized monoclonal antibody targeting CD19. It is under development by MorphoSys AG to treat B-cell malignancies. The program is in phase 2 clinical development in chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and non-Hodgkin lymphoma.

Preclinical research with MOR208 revealed that it can trigger natural killer cell-mediated lysis of ALL cells. The drug had lytic activity against ALL cells from both adult and pediatric patients.

In a phase 1 study, MOR208 exhibited preliminary efficacy in patients with high-risk, heavily pretreated CLL, prompting responses in 67% of patients. Researchers said toxicity was acceptable, but infusion reactions were common.

“First results of our ongoing phase 2 trial, which we will present at this year’s ASH conference in December, have helped to identify diffuse large B-cell lymphoma as a valuable development opportunity for MOR208,” said Arndt Schottelius, chief development officer of MorphoSys AG.

“We are therefore delighted to have received the fast track designation for further development of MOR208 in DLBCL. The more frequent interactions with the FDA that this enables will help us to expedite the development of MOR208 in this particular subset of non-Hodgkin’s lymphoma patients.”

PRM-151

PRM-151 is a recombinant form of an endogenous human protein, pentraxin-2, that is specifically active at the site of tissue damage. PRM-151 is an agonist that acts as a monocyte/macrophage differentiation factor to prevent and potentially reverse fibrosis.

The drug has shown broad anti-fibrotic activity in preclinical models of fibrotic disease, including pulmonary fibrosis, acute and chronic nephropathy, liver fibrosis, and age-related macular degeneration.

PRM-151 has orphan designation in the US for MF and in both the US and European Union for the treatment of idiopathic pulmonary fibrosis.

The FDA’s fast track designation for PRM-151 covers primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF.

“This designation validates our perspective that there is a clear and compelling need for a novel mechanism for the treatment of myelofibrosis that specifically targets the underlying fibrotic processes of the disease,” said Beth Tréhu, MD, FACP, chief medical officer of Promedior Inc., the company developing PRM-151.

“We will continue to work expeditiously to advance this program through the clinic and look forward to presenting the full data set from the first stage of our phase 2 study later this year.”

Preliminary data from the phase 2 study of PRM-151 demonstrated benefits across all clinically relevant measures of MF, including decreases in bone marrow fibrosis, symptom responses, improvements in hemoglobin and platelets, and reductions in spleen size.

The drug also appeared to be well-tolerated and did not prompt myelosuppression.

Drugs in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted fast track designation to two hematology drugs: the monoclonal antibody MOR208 to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and the antifibrotic agent PRM-151 to treat myelofibrosis (MF).

The FDA’s fast track program aims to expedite the development and review of drugs that have the potential to fill an unmet medical need in serious or life-threatening conditions.

MOR208

MOR208 is a humanized monoclonal antibody targeting CD19. It is under development by MorphoSys AG to treat B-cell malignancies. The program is in phase 2 clinical development in chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and non-Hodgkin lymphoma.

Preclinical research with MOR208 revealed that it can trigger natural killer cell-mediated lysis of ALL cells. The drug had lytic activity against ALL cells from both adult and pediatric patients.

In a phase 1 study, MOR208 exhibited preliminary efficacy in patients with high-risk, heavily pretreated CLL, prompting responses in 67% of patients. Researchers said toxicity was acceptable, but infusion reactions were common.

“First results of our ongoing phase 2 trial, which we will present at this year’s ASH conference in December, have helped to identify diffuse large B-cell lymphoma as a valuable development opportunity for MOR208,” said Arndt Schottelius, chief development officer of MorphoSys AG.

“We are therefore delighted to have received the fast track designation for further development of MOR208 in DLBCL. The more frequent interactions with the FDA that this enables will help us to expedite the development of MOR208 in this particular subset of non-Hodgkin’s lymphoma patients.”

PRM-151

PRM-151 is a recombinant form of an endogenous human protein, pentraxin-2, that is specifically active at the site of tissue damage. PRM-151 is an agonist that acts as a monocyte/macrophage differentiation factor to prevent and potentially reverse fibrosis.

The drug has shown broad anti-fibrotic activity in preclinical models of fibrotic disease, including pulmonary fibrosis, acute and chronic nephropathy, liver fibrosis, and age-related macular degeneration.

PRM-151 has orphan designation in the US for MF and in both the US and European Union for the treatment of idiopathic pulmonary fibrosis.

The FDA’s fast track designation for PRM-151 covers primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF.

“This designation validates our perspective that there is a clear and compelling need for a novel mechanism for the treatment of myelofibrosis that specifically targets the underlying fibrotic processes of the disease,” said Beth Tréhu, MD, FACP, chief medical officer of Promedior Inc., the company developing PRM-151.

“We will continue to work expeditiously to advance this program through the clinic and look forward to presenting the full data set from the first stage of our phase 2 study later this year.”

Preliminary data from the phase 2 study of PRM-151 demonstrated benefits across all clinically relevant measures of MF, including decreases in bone marrow fibrosis, symptom responses, improvements in hemoglobin and platelets, and reductions in spleen size.

The drug also appeared to be well-tolerated and did not prompt myelosuppression.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance recommending ofatumumab (Arzerra) for use in patients with chronic lymphocytic leukemia (CLL).

The agency is recommending the anti-CD20 monoclonal antibody in combination with chlorambucil for patients with untreated CLL who are ineligible for treatment with fludarabine combination therapy and for whom bendamustine is unsuitable.

NICE believes ofatumumab is a cost-effective use of National Health Service (NHS) resources for this patient population, as GlaxoSmithKline, the company developing ofatumumab, has agreed to provide the drug at a reduced price.

The company has agreed with the Department of Health that the size of the discount be confidential.

Clinical effectiveness

“The information provided by GlaxoSmithKline, who market the drug, showed that ofatumumab with chlorambucil is a clinically effective treatment option for those people unable to take fludarabine combination therapy or bendamustine,” said Sir Andrew Dillon, NICE chief executive.

In the phase 3 COMPLEMENT 1 trial, ofatumumab plus chlorambucil improved progression-free survival compared to chlorambucil alone. The median times were 22.4 months and 13.1 months, respectively, and the hazard ratio was 0.57 (P<0.001).

A NICE advisory committee also considered the use of ofatumumab in combination with bendamustine. But the committee said that, due to limited clinical evidence and the absence of cost-effectiveness estimates, it could not make a recommendation on this combination.

In a phase 2 trial known as OMB115991, ofatumumab plus bendamustine elicited an overall response rate of 95% and a complete response rate of 43%.

Cost-effectiveness

Ofatumumab’s list price is £182 for a 100 mg vial and £1820 for a 1000 mg vial. Assuming 6 cycles and no drug wastage, the mean cost of a treatment course for ofatumumab at its list price is £11,466 for 6300 mg.

GlaxoSmithKline has agreed to a patient access scheme with the Department of Health that makes ofatumumab available with a discount on the list price, though the exact amount is confidential.

The NICE advisory committee said the most plausible cost-effectiveness estimate for ofatumumab plus chlorambucil compared with chlorambucil alone using the

ofatumumab patient access scheme price was £26,000 per quality-adjusted life year gained.

Consultees, including GlaxoSmithKline, healthcare professionals, and members of the public, can now comment on NICE’s preliminary draft guidance. It will be available for public consultation until November 25, 2014.

Until the final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance recommending ofatumumab (Arzerra) for use in patients with chronic lymphocytic leukemia (CLL).

The agency is recommending the anti-CD20 monoclonal antibody in combination with chlorambucil for patients with untreated CLL who are ineligible for treatment with fludarabine combination therapy and for whom bendamustine is unsuitable.

NICE believes ofatumumab is a cost-effective use of National Health Service (NHS) resources for this patient population, as GlaxoSmithKline, the company developing ofatumumab, has agreed to provide the drug at a reduced price.

The company has agreed with the Department of Health that the size of the discount be confidential.

Clinical effectiveness

“The information provided by GlaxoSmithKline, who market the drug, showed that ofatumumab with chlorambucil is a clinically effective treatment option for those people unable to take fludarabine combination therapy or bendamustine,” said Sir Andrew Dillon, NICE chief executive.

In the phase 3 COMPLEMENT 1 trial, ofatumumab plus chlorambucil improved progression-free survival compared to chlorambucil alone. The median times were 22.4 months and 13.1 months, respectively, and the hazard ratio was 0.57 (P<0.001).

A NICE advisory committee also considered the use of ofatumumab in combination with bendamustine. But the committee said that, due to limited clinical evidence and the absence of cost-effectiveness estimates, it could not make a recommendation on this combination.

In a phase 2 trial known as OMB115991, ofatumumab plus bendamustine elicited an overall response rate of 95% and a complete response rate of 43%.

Cost-effectiveness

Ofatumumab’s list price is £182 for a 100 mg vial and £1820 for a 1000 mg vial. Assuming 6 cycles and no drug wastage, the mean cost of a treatment course for ofatumumab at its list price is £11,466 for 6300 mg.

GlaxoSmithKline has agreed to a patient access scheme with the Department of Health that makes ofatumumab available with a discount on the list price, though the exact amount is confidential.

The NICE advisory committee said the most plausible cost-effectiveness estimate for ofatumumab plus chlorambucil compared with chlorambucil alone using the

ofatumumab patient access scheme price was £26,000 per quality-adjusted life year gained.

Consultees, including GlaxoSmithKline, healthcare professionals, and members of the public, can now comment on NICE’s preliminary draft guidance. It will be available for public consultation until November 25, 2014.

Until the final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance recommending ofatumumab (Arzerra) for use in patients with chronic lymphocytic leukemia (CLL).

The agency is recommending the anti-CD20 monoclonal antibody in combination with chlorambucil for patients with untreated CLL who are ineligible for treatment with fludarabine combination therapy and for whom bendamustine is unsuitable.

NICE believes ofatumumab is a cost-effective use of National Health Service (NHS) resources for this patient population, as GlaxoSmithKline, the company developing ofatumumab, has agreed to provide the drug at a reduced price.

The company has agreed with the Department of Health that the size of the discount be confidential.

Clinical effectiveness

“The information provided by GlaxoSmithKline, who market the drug, showed that ofatumumab with chlorambucil is a clinically effective treatment option for those people unable to take fludarabine combination therapy or bendamustine,” said Sir Andrew Dillon, NICE chief executive.

In the phase 3 COMPLEMENT 1 trial, ofatumumab plus chlorambucil improved progression-free survival compared to chlorambucil alone. The median times were 22.4 months and 13.1 months, respectively, and the hazard ratio was 0.57 (P<0.001).

A NICE advisory committee also considered the use of ofatumumab in combination with bendamustine. But the committee said that, due to limited clinical evidence and the absence of cost-effectiveness estimates, it could not make a recommendation on this combination.

In a phase 2 trial known as OMB115991, ofatumumab plus bendamustine elicited an overall response rate of 95% and a complete response rate of 43%.

Cost-effectiveness

Ofatumumab’s list price is £182 for a 100 mg vial and £1820 for a 1000 mg vial. Assuming 6 cycles and no drug wastage, the mean cost of a treatment course for ofatumumab at its list price is £11,466 for 6300 mg.

GlaxoSmithKline has agreed to a patient access scheme with the Department of Health that makes ofatumumab available with a discount on the list price, though the exact amount is confidential.

The NICE advisory committee said the most plausible cost-effectiveness estimate for ofatumumab plus chlorambucil compared with chlorambucil alone using the

ofatumumab patient access scheme price was £26,000 per quality-adjusted life year gained.

Consultees, including GlaxoSmithKline, healthcare professionals, and members of the public, can now comment on NICE’s preliminary draft guidance. It will be available for public consultation until November 25, 2014.

Until the final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

The US Food and Drug Administration (FDA) has removed the full clinical hold placed on the investigational new drug application for the telomerase inhibitor imetelstat.

The hold, which was placed in March, suspended a phase 2 study of imetelstat in patients with essential thrombocythemia (ET) or polycythemia vera (PV), as well as a phase 2 study of the drug in patients with multiple myeloma (MM).

The hold also delayed a planned phase 2 trial in patients with myelofibrosis (MF).

And it temporarily suspended an investigator-sponsored trial of imetelstat in MF. The FDA lifted the hold on the investigator-sponsored trial in June.

The FDA halted these trials due to reports of persistent, low-grade liver function test (LFT) abnormalities observed in the phase 2 study of ET/PV patients and the potential risk of chronic liver injury following long-term exposure to imetelstat. The FDA expressed concern about whether these LFT abnormalities are reversible.

Now, data provided by the Geron Corporation, the company developing imetelstat, has convinced the FDA to lift the hold on all trials.

The FDA said the proposed clinical development plan for imetelstat, which is focused on high-risk myeloid disorders such as MF, is acceptable. Geron Corporation has said it does not intend to conduct further studies with, or develop imetelstat for, patients with ET or PV.

To address the clinical hold, the FDA required Geron to provide follow-up information from imetelstat-treated patients who experienced LFT abnormalities until such abnormalities resolved to normal or baseline.

Geron obtained follow-up information from patients in the previously ongoing company-sponsored phase 2 trials in ET/PV and MM. These data were submitted to the FDA as part of the company’s complete response.

The company’s analysis of these data showed that, in the ET/PV trial, LFT abnormalities resolved to normal or baseline in 14 of 18 follow-up patients. For the remaining 4 patients, at the time of the data cut-off, 3 patients showed improvement in LFT abnormalities, and 1 patient had unresolved LFT abnormalities. Two of the remaining 4 patients continue in follow-up.

In the MM trial, LFT abnormalities resolved to normal or baseline in all 9 follow-up patients. In addition, no emergent hepatic adverse events were reported during follow-up for either study.

The FDA also requested information regarding the reversibility of liver toxicity after chronic imetelstat administration in animals. Geron submitted data from its non-clinical toxicology studies, which included a 6-month study in mice and a 9-month study in cynomolgus monkeys.

In these studies, no clinical pathology changes indicative of hepatocellular injury were observed, and no clear signal of LFT abnormalities were identified.

With the clinical hold lifted, a multicenter phase 2 trial in MF is projected to begin in the first half of 2015.

The US Food and Drug Administration (FDA) has removed the full clinical hold placed on the investigational new drug application for the telomerase inhibitor imetelstat.

The hold, which was placed in March, suspended a phase 2 study of imetelstat in patients with essential thrombocythemia (ET) or polycythemia vera (PV), as well as a phase 2 study of the drug in patients with multiple myeloma (MM).

The hold also delayed a planned phase 2 trial in patients with myelofibrosis (MF).

And it temporarily suspended an investigator-sponsored trial of imetelstat in MF. The FDA lifted the hold on the investigator-sponsored trial in June.

The FDA halted these trials due to reports of persistent, low-grade liver function test (LFT) abnormalities observed in the phase 2 study of ET/PV patients and the potential risk of chronic liver injury following long-term exposure to imetelstat. The FDA expressed concern about whether these LFT abnormalities are reversible.

Now, data provided by the Geron Corporation, the company developing imetelstat, has convinced the FDA to lift the hold on all trials.

The FDA said the proposed clinical development plan for imetelstat, which is focused on high-risk myeloid disorders such as MF, is acceptable. Geron Corporation has said it does not intend to conduct further studies with, or develop imetelstat for, patients with ET or PV.

To address the clinical hold, the FDA required Geron to provide follow-up information from imetelstat-treated patients who experienced LFT abnormalities until such abnormalities resolved to normal or baseline.

Geron obtained follow-up information from patients in the previously ongoing company-sponsored phase 2 trials in ET/PV and MM. These data were submitted to the FDA as part of the company’s complete response.

The company’s analysis of these data showed that, in the ET/PV trial, LFT abnormalities resolved to normal or baseline in 14 of 18 follow-up patients. For the remaining 4 patients, at the time of the data cut-off, 3 patients showed improvement in LFT abnormalities, and 1 patient had unresolved LFT abnormalities. Two of the remaining 4 patients continue in follow-up.

In the MM trial, LFT abnormalities resolved to normal or baseline in all 9 follow-up patients. In addition, no emergent hepatic adverse events were reported during follow-up for either study.

The FDA also requested information regarding the reversibility of liver toxicity after chronic imetelstat administration in animals. Geron submitted data from its non-clinical toxicology studies, which included a 6-month study in mice and a 9-month study in cynomolgus monkeys.

In these studies, no clinical pathology changes indicative of hepatocellular injury were observed, and no clear signal of LFT abnormalities were identified.

With the clinical hold lifted, a multicenter phase 2 trial in MF is projected to begin in the first half of 2015.

The US Food and Drug Administration (FDA) has removed the full clinical hold placed on the investigational new drug application for the telomerase inhibitor imetelstat.

The hold, which was placed in March, suspended a phase 2 study of imetelstat in patients with essential thrombocythemia (ET) or polycythemia vera (PV), as well as a phase 2 study of the drug in patients with multiple myeloma (MM).

The hold also delayed a planned phase 2 trial in patients with myelofibrosis (MF).

And it temporarily suspended an investigator-sponsored trial of imetelstat in MF. The FDA lifted the hold on the investigator-sponsored trial in June.

The FDA halted these trials due to reports of persistent, low-grade liver function test (LFT) abnormalities observed in the phase 2 study of ET/PV patients and the potential risk of chronic liver injury following long-term exposure to imetelstat. The FDA expressed concern about whether these LFT abnormalities are reversible.

Now, data provided by the Geron Corporation, the company developing imetelstat, has convinced the FDA to lift the hold on all trials.

The FDA said the proposed clinical development plan for imetelstat, which is focused on high-risk myeloid disorders such as MF, is acceptable. Geron Corporation has said it does not intend to conduct further studies with, or develop imetelstat for, patients with ET or PV.

To address the clinical hold, the FDA required Geron to provide follow-up information from imetelstat-treated patients who experienced LFT abnormalities until such abnormalities resolved to normal or baseline.

Geron obtained follow-up information from patients in the previously ongoing company-sponsored phase 2 trials in ET/PV and MM. These data were submitted to the FDA as part of the company’s complete response.

The company’s analysis of these data showed that, in the ET/PV trial, LFT abnormalities resolved to normal or baseline in 14 of 18 follow-up patients. For the remaining 4 patients, at the time of the data cut-off, 3 patients showed improvement in LFT abnormalities, and 1 patient had unresolved LFT abnormalities. Two of the remaining 4 patients continue in follow-up.

In the MM trial, LFT abnormalities resolved to normal or baseline in all 9 follow-up patients. In addition, no emergent hepatic adverse events were reported during follow-up for either study.

The FDA also requested information regarding the reversibility of liver toxicity after chronic imetelstat administration in animals. Geron submitted data from its non-clinical toxicology studies, which included a 6-month study in mice and a 9-month study in cynomolgus monkeys.

In these studies, no clinical pathology changes indicative of hepatocellular injury were observed, and no clear signal of LFT abnormalities were identified.

With the clinical hold lifted, a multicenter phase 2 trial in MF is projected to begin in the first half of 2015.

Thrombus

Credit: NHS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending dabigatran etexilate (Pradaxa) as an option for treating and preventing recurrent deep-vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

A committee advising NICE concluded that dabigatran is a cost-effective use of resources and a convenient alternative to warfarin, especially for patients who require longer-term anticoagulant therapy.

“For many people, using warfarin can be difficult because of the need for frequent tests to see if the blood is clotting properly and having to adjust the dose of the drug if it is not,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The appraisal committee felt that dabigatran represents a potential benefit for many people who have had a DVT or PE, particularly those who have risk factors for recurrence of a blood clot and who therefore need longer-term treatment. We are pleased, therefore, to be able to recommend dabigatran as a cost-effective option for treating DVT and PE and preventing further episodes in adults.”

Dabigatran, made by Boehringer Ingelheim, costs £65.90 for a 60-capsule pack of the 150 mg or 110 mg doses (excluding value-added tax) and costs £2.20 per day of treatment. However, costs may vary in different settings because of negotiated procurement discounts.

The most plausible incremental cost-effectiveness ratio (ICER) for dabigatran compared with warfarin for acute treatment of venous thromboembolism (VTE) was uncertain.

However, both Boehringer Ingelheim’s ICER and an evidence review group’s ICER remained in the range that could be considered a cost-effective use of National Health Service resources. Both were under £20,000 per quality-adjusted life-year (QALY) gained.

Neither Boehringer Ingelheim nor the evidence review group found any significant difference in efficacy between dabigatran and rivaroxaban for acute treatment of VTE in their indirect comparisons, and the costs were very similar between these two treatments.

For combined treatment and secondary prevention of VTE, the committee noted that Boehringer Ingelheim’s base-case ICER for dabigatran compared with warfarin was likely too low (£9973 per QALY gained).

But the evidence review group’s base-case for dabigatran compared with warfarin may have overestimated the ICER (£35,786 per QALY gained). So the committee said the ICER probably falls somewhere between the two estimates.

The committee also noted that dabigatran and rivaroxaban appear to have similar efficacy for combined treatment and secondary prevention of VTE, and their costs are very similar.

For more details, see the draft guidance.

Thrombus

Credit: NHS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending dabigatran etexilate (Pradaxa) as an option for treating and preventing recurrent deep-vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

A committee advising NICE concluded that dabigatran is a cost-effective use of resources and a convenient alternative to warfarin, especially for patients who require longer-term anticoagulant therapy.

“For many people, using warfarin can be difficult because of the need for frequent tests to see if the blood is clotting properly and having to adjust the dose of the drug if it is not,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The appraisal committee felt that dabigatran represents a potential benefit for many people who have had a DVT or PE, particularly those who have risk factors for recurrence of a blood clot and who therefore need longer-term treatment. We are pleased, therefore, to be able to recommend dabigatran as a cost-effective option for treating DVT and PE and preventing further episodes in adults.”

Dabigatran, made by Boehringer Ingelheim, costs £65.90 for a 60-capsule pack of the 150 mg or 110 mg doses (excluding value-added tax) and costs £2.20 per day of treatment. However, costs may vary in different settings because of negotiated procurement discounts.

The most plausible incremental cost-effectiveness ratio (ICER) for dabigatran compared with warfarin for acute treatment of venous thromboembolism (VTE) was uncertain.

However, both Boehringer Ingelheim’s ICER and an evidence review group’s ICER remained in the range that could be considered a cost-effective use of National Health Service resources. Both were under £20,000 per quality-adjusted life-year (QALY) gained.

Neither Boehringer Ingelheim nor the evidence review group found any significant difference in efficacy between dabigatran and rivaroxaban for acute treatment of VTE in their indirect comparisons, and the costs were very similar between these two treatments.

For combined treatment and secondary prevention of VTE, the committee noted that Boehringer Ingelheim’s base-case ICER for dabigatran compared with warfarin was likely too low (£9973 per QALY gained).

But the evidence review group’s base-case for dabigatran compared with warfarin may have overestimated the ICER (£35,786 per QALY gained). So the committee said the ICER probably falls somewhere between the two estimates.

The committee also noted that dabigatran and rivaroxaban appear to have similar efficacy for combined treatment and secondary prevention of VTE, and their costs are very similar.

For more details, see the draft guidance.

Thrombus

Credit: NHS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending dabigatran etexilate (Pradaxa) as an option for treating and preventing recurrent deep-vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

A committee advising NICE concluded that dabigatran is a cost-effective use of resources and a convenient alternative to warfarin, especially for patients who require longer-term anticoagulant therapy.

“For many people, using warfarin can be difficult because of the need for frequent tests to see if the blood is clotting properly and having to adjust the dose of the drug if it is not,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The appraisal committee felt that dabigatran represents a potential benefit for many people who have had a DVT or PE, particularly those who have risk factors for recurrence of a blood clot and who therefore need longer-term treatment. We are pleased, therefore, to be able to recommend dabigatran as a cost-effective option for treating DVT and PE and preventing further episodes in adults.”

Dabigatran, made by Boehringer Ingelheim, costs £65.90 for a 60-capsule pack of the 150 mg or 110 mg doses (excluding value-added tax) and costs £2.20 per day of treatment. However, costs may vary in different settings because of negotiated procurement discounts.

The most plausible incremental cost-effectiveness ratio (ICER) for dabigatran compared with warfarin for acute treatment of venous thromboembolism (VTE) was uncertain.

However, both Boehringer Ingelheim’s ICER and an evidence review group’s ICER remained in the range that could be considered a cost-effective use of National Health Service resources. Both were under £20,000 per quality-adjusted life-year (QALY) gained.

Neither Boehringer Ingelheim nor the evidence review group found any significant difference in efficacy between dabigatran and rivaroxaban for acute treatment of VTE in their indirect comparisons, and the costs were very similar between these two treatments.

For combined treatment and secondary prevention of VTE, the committee noted that Boehringer Ingelheim’s base-case ICER for dabigatran compared with warfarin was likely too low (£9973 per QALY gained).

But the evidence review group’s base-case for dabigatran compared with warfarin may have overestimated the ICER (£35,786 per QALY gained). So the committee said the ICER probably falls somewhere between the two estimates.

The committee also noted that dabigatran and rivaroxaban appear to have similar efficacy for combined treatment and secondary prevention of VTE, and their costs are very similar.

For more details, see the draft guidance.

The European Medicines Agency (EMA) has granted orphan status to Atir, a product consisting of T-cell-depleted donor immune cells, for the treatment of acute myeloid leukemia (AML).

The EMA and the US Food and Drug Administration previously granted Atir orphan status for the prevention of acute graft-vs-host-disease (GVHD) following hematopoietic stem cell transplant (HSCT).

The EMA’s orphan designation provides incentives to support drug development. This includes fee reductions and a 10-year period of market exclusivity in the European Union after product approval.

About Atir

Atir consists of donor immune cells from which the alloreactive T-cells that would otherwise attack the patient’s body have been selectively eliminated.

The product is produced using a molecule known as TH9402 to selectively remove those T cells from the donor graft, while preserving other immune cells. To activate patient-reactive T cells, the graft is mixed (ex vivo) with patient cells.

Then, TH9402 is added. As this phototoxic compound selectively accumulates in activated T cells, the cells can be eliminated by exposing the cell mixture to light of a specific wavelength. The resulting Atir product can be frozen and stored and is infused into the patient in a scheduled procedure.

Trial data

Researchers said Atir proved safe and effective in a phase 1/2 study in which high-risk leukemia patients with very poor prognosis were treated with escalating doses of Atir after a haploidentical HSCT.

The overall survival of 19 patients who received an optimal dose of Atir was 78% at 1 year and 67% at 5 years, rates that compare favorably to outcomes of HSCTs from fully matched donors. The data also suggest that immune cells responsible for the graft-vs-leukemia effect are retained in Atir.

Five-year follow-up data show that none of the 19 patients developed acute grade 3/4 GVHD, compared to an incidence of 30% in matched unrelated HSCTs. In the 9 patients who received an optimal dose of Atir, there was no transplant-related mortality.

Researchers are currently testing Atir in a phase 2 study of patients with AML, acute lymphoblastic leukemia, and myelodysplastic syndrome, to corroborate and extend the safety and efficacy results from the phase 1/2 study. Data from this trial are expected in the second half of 2014.

Atir is under development by Kiadis Pharma. For more information, visit the company’s website.

The European Medicines Agency (EMA) has granted orphan status to Atir, a product consisting of T-cell-depleted donor immune cells, for the treatment of acute myeloid leukemia (AML).

The EMA and the US Food and Drug Administration previously granted Atir orphan status for the prevention of acute graft-vs-host-disease (GVHD) following hematopoietic stem cell transplant (HSCT).

The EMA’s orphan designation provides incentives to support drug development. This includes fee reductions and a 10-year period of market exclusivity in the European Union after product approval.

About Atir

Atir consists of donor immune cells from which the alloreactive T-cells that would otherwise attack the patient’s body have been selectively eliminated.

The product is produced using a molecule known as TH9402 to selectively remove those T cells from the donor graft, while preserving other immune cells. To activate patient-reactive T cells, the graft is mixed (ex vivo) with patient cells.

Then, TH9402 is added. As this phototoxic compound selectively accumulates in activated T cells, the cells can be eliminated by exposing the cell mixture to light of a specific wavelength. The resulting Atir product can be frozen and stored and is infused into the patient in a scheduled procedure.

Trial data

Researchers said Atir proved safe and effective in a phase 1/2 study in which high-risk leukemia patients with very poor prognosis were treated with escalating doses of Atir after a haploidentical HSCT.

The overall survival of 19 patients who received an optimal dose of Atir was 78% at 1 year and 67% at 5 years, rates that compare favorably to outcomes of HSCTs from fully matched donors. The data also suggest that immune cells responsible for the graft-vs-leukemia effect are retained in Atir.

Five-year follow-up data show that none of the 19 patients developed acute grade 3/4 GVHD, compared to an incidence of 30% in matched unrelated HSCTs. In the 9 patients who received an optimal dose of Atir, there was no transplant-related mortality.

Researchers are currently testing Atir in a phase 2 study of patients with AML, acute lymphoblastic leukemia, and myelodysplastic syndrome, to corroborate and extend the safety and efficacy results from the phase 1/2 study. Data from this trial are expected in the second half of 2014.

Atir is under development by Kiadis Pharma. For more information, visit the company’s website.

The European Medicines Agency (EMA) has granted orphan status to Atir, a product consisting of T-cell-depleted donor immune cells, for the treatment of acute myeloid leukemia (AML).

The EMA and the US Food and Drug Administration previously granted Atir orphan status for the prevention of acute graft-vs-host-disease (GVHD) following hematopoietic stem cell transplant (HSCT).

The EMA’s orphan designation provides incentives to support drug development. This includes fee reductions and a 10-year period of market exclusivity in the European Union after product approval.

About Atir

Atir consists of donor immune cells from which the alloreactive T-cells that would otherwise attack the patient’s body have been selectively eliminated.

The product is produced using a molecule known as TH9402 to selectively remove those T cells from the donor graft, while preserving other immune cells. To activate patient-reactive T cells, the graft is mixed (ex vivo) with patient cells.

Then, TH9402 is added. As this phototoxic compound selectively accumulates in activated T cells, the cells can be eliminated by exposing the cell mixture to light of a specific wavelength. The resulting Atir product can be frozen and stored and is infused into the patient in a scheduled procedure.

Trial data

Researchers said Atir proved safe and effective in a phase 1/2 study in which high-risk leukemia patients with very poor prognosis were treated with escalating doses of Atir after a haploidentical HSCT.

The overall survival of 19 patients who received an optimal dose of Atir was 78% at 1 year and 67% at 5 years, rates that compare favorably to outcomes of HSCTs from fully matched donors. The data also suggest that immune cells responsible for the graft-vs-leukemia effect are retained in Atir.

Five-year follow-up data show that none of the 19 patients developed acute grade 3/4 GVHD, compared to an incidence of 30% in matched unrelated HSCTs. In the 9 patients who received an optimal dose of Atir, there was no transplant-related mortality.

Researchers are currently testing Atir in a phase 2 study of patients with AML, acute lymphoblastic leukemia, and myelodysplastic syndrome, to corroborate and extend the safety and efficacy results from the phase 1/2 study. Data from this trial are expected in the second half of 2014.

Atir is under development by Kiadis Pharma. For more information, visit the company’s website.