FDA approves brentuximab vedotin for primary cutaneous anaplastic large cell lymphoma

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The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

Complete response in the brentuximab vedotin arm was 16% versus 2% in the physician’s choice arm (P = .007). Median progression-free survival was 17 months in the brentuximab vedotin arm versus 4 months in the physician’s choice arm.

The most common adverse reactions for patients in the brentuximab vedotin arm were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia. The most common adverse event leading to discontinuation of brentuximab vedotin was peripheral neuropathy.

The recommended dose of brentuximab vedotin is 1.8 mg/kg up to a maximum of 180 mg/kg as an IV infusion over 30 minutes every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity, the FDA wrote.

Brentuximab vedotin is marketed as Adcetris by Seattle Genetics.

ALCANZA results were presented at ASH 2016 and published in the Lancet in Aug. 5, 2017.

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The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

Complete response in the brentuximab vedotin arm was 16% versus 2% in the physician’s choice arm (P = .007). Median progression-free survival was 17 months in the brentuximab vedotin arm versus 4 months in the physician’s choice arm.

The most common adverse reactions for patients in the brentuximab vedotin arm were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia. The most common adverse event leading to discontinuation of brentuximab vedotin was peripheral neuropathy.

The recommended dose of brentuximab vedotin is 1.8 mg/kg up to a maximum of 180 mg/kg as an IV infusion over 30 minutes every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity, the FDA wrote.

Brentuximab vedotin is marketed as Adcetris by Seattle Genetics.

ALCANZA results were presented at ASH 2016 and published in the Lancet in Aug. 5, 2017.

 

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

Complete response in the brentuximab vedotin arm was 16% versus 2% in the physician’s choice arm (P = .007). Median progression-free survival was 17 months in the brentuximab vedotin arm versus 4 months in the physician’s choice arm.

The most common adverse reactions for patients in the brentuximab vedotin arm were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia. The most common adverse event leading to discontinuation of brentuximab vedotin was peripheral neuropathy.

The recommended dose of brentuximab vedotin is 1.8 mg/kg up to a maximum of 180 mg/kg as an IV infusion over 30 minutes every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity, the FDA wrote.

Brentuximab vedotin is marketed as Adcetris by Seattle Genetics.

ALCANZA results were presented at ASH 2016 and published in the Lancet in Aug. 5, 2017.

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FDA approves alectinib as frontline therapy for ALK-positive metastatic NSCLC

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The Food and Drug Administration has approved frontline alectinib for the treatment of anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) that has been detected by an FDA-approved test.

The drug previously received accelerated approval for treatment of patients with ALK-positive metastatic NSCLC whose disease progressed while receiving crizotinib or who were intolerant of that treatment.

Wikimedia Commons/FitzColinGerald/Creative Commons License
Current approval of alectinib (Alecensa) as a frontline treatment was based on improvement in progression-free survival (hazard ratio, 0.53; P less than .0001) in a randomized, open-label trial of 303 patients with ALK-positive metastatic NSCLC who received either alectinib or crizotinib. The median progression-free survival time was 25.7 months in the alectinib group and 10.4 months in the crizotinib group.

There was also a lower incidence of progression to the central nervous system as first site of disease progression with alectinib: Incidence of progression to the CNS was 12% for patients receiving alectinib and 45% for patients receiving crizotinib.

The most common adverse events in patients receiving alectinib were fatigue, constipation, edema, myalgia, and anemia. Serious adverse events occurred in 28% of patients. Adverse events resulting in discontinuation occurred in 11% of patients.

“All patients in the trial were required to have evidence of ALK-rearrangement identified by the VENTANA ALK (D5F3) CDx Assay performed through central laboratory testing,” the FDA said in a press statement.

The recommended dose is 600 mg orally taken twice daily with food.

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The Food and Drug Administration has approved frontline alectinib for the treatment of anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) that has been detected by an FDA-approved test.

The drug previously received accelerated approval for treatment of patients with ALK-positive metastatic NSCLC whose disease progressed while receiving crizotinib or who were intolerant of that treatment.

Wikimedia Commons/FitzColinGerald/Creative Commons License
Current approval of alectinib (Alecensa) as a frontline treatment was based on improvement in progression-free survival (hazard ratio, 0.53; P less than .0001) in a randomized, open-label trial of 303 patients with ALK-positive metastatic NSCLC who received either alectinib or crizotinib. The median progression-free survival time was 25.7 months in the alectinib group and 10.4 months in the crizotinib group.

There was also a lower incidence of progression to the central nervous system as first site of disease progression with alectinib: Incidence of progression to the CNS was 12% for patients receiving alectinib and 45% for patients receiving crizotinib.

The most common adverse events in patients receiving alectinib were fatigue, constipation, edema, myalgia, and anemia. Serious adverse events occurred in 28% of patients. Adverse events resulting in discontinuation occurred in 11% of patients.

“All patients in the trial were required to have evidence of ALK-rearrangement identified by the VENTANA ALK (D5F3) CDx Assay performed through central laboratory testing,” the FDA said in a press statement.

The recommended dose is 600 mg orally taken twice daily with food.

 

The Food and Drug Administration has approved frontline alectinib for the treatment of anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) that has been detected by an FDA-approved test.

The drug previously received accelerated approval for treatment of patients with ALK-positive metastatic NSCLC whose disease progressed while receiving crizotinib or who were intolerant of that treatment.

Wikimedia Commons/FitzColinGerald/Creative Commons License
Current approval of alectinib (Alecensa) as a frontline treatment was based on improvement in progression-free survival (hazard ratio, 0.53; P less than .0001) in a randomized, open-label trial of 303 patients with ALK-positive metastatic NSCLC who received either alectinib or crizotinib. The median progression-free survival time was 25.7 months in the alectinib group and 10.4 months in the crizotinib group.

There was also a lower incidence of progression to the central nervous system as first site of disease progression with alectinib: Incidence of progression to the CNS was 12% for patients receiving alectinib and 45% for patients receiving crizotinib.

The most common adverse events in patients receiving alectinib were fatigue, constipation, edema, myalgia, and anemia. Serious adverse events occurred in 28% of patients. Adverse events resulting in discontinuation occurred in 11% of patients.

“All patients in the trial were required to have evidence of ALK-rearrangement identified by the VENTANA ALK (D5F3) CDx Assay performed through central laboratory testing,” the FDA said in a press statement.

The recommended dose is 600 mg orally taken twice daily with food.

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FDA approves first Erdheim-Chester disease treatment

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The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

ECD is a rare blood cancer estimated to affect 600-700 patients worldwide. More than half of patients with ECD also have the BRAF V600 mutation, according to the FDA.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

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The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

ECD is a rare blood cancer estimated to affect 600-700 patients worldwide. More than half of patients with ECD also have the BRAF V600 mutation, according to the FDA.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

 

The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

ECD is a rare blood cancer estimated to affect 600-700 patients worldwide. More than half of patients with ECD also have the BRAF V600 mutation, according to the FDA.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

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FDA panels support two NDAs for buprenorphine subcutaneous injections

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– Two Food and Drug Administration advisory panels have recommended approval of two new drug applications (NDA) for buprenorphine subcutaneous injections for the treatment of opioid dependence.

On Nov. 1, panelists recommended approval of some of the doses proposed in the NDA submitted by Braeburn Pharmaceuticals at the joint meeting of the Psychopharmacologic Drugs Advisory and the Drug Safety and Risk Management committees. The formulation, currently known as CAM2038, is intended to be used as part of a treatment plan that can include counseling and psychosocial support. The subcutaneous depot is available weekly, in 8-, 16-, 24-, and 32-mg injections, and monthly, in 64-, 96-, 128-, and 160-mg injections.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

On the previous day, Oct. 31, the panelists voted 18-1 with no abstentions to recommend an NDA submitted by Indivior. This formulation is known as RBP-6000.

Both formulations must be administered by a health care provider using a prefilled syringe with a predetermined dosage. The injection forms a biodegradable subcutaneous depot that, as it degrades, releases buprenorphine at a steady and controlled pace over the course of treatment – increasing the success of treatment for opioid use disorder.

Braeburn’s NDA was based on results of a double-blind, randomized, within-subject, inpatient laboratory study of 47 patients over 14 days. Patients were randomized into two groups: 22 patients in the 24-mg group and 25 patients in the 32-mg group. Patients were administered an initial dose on day 0 and a follow-up dose on day 7. The results of the study found a complete blockade of opioids after the first injection that was sustained over the 1-week interdosing interval.

The committees said that of most of the doses should be approved, but a majority of committee members were uncomfortable with the higher doses.

Voting on Indivior’s NDA was based, in part, on the results of a randomized, double-blind, placebo-controlled, multicenter phase 3 study. The study lasted 24 weeks and randomly assigned 504 patients into one of three groups based on monthly dosing regimen of buprenorphine: 300 mg/300 mg, 300 mg/100 mg, and placebo. After randomization, the 300 mg/300 mg group had 201 patients, the 300 mg/100 mg group had 203 patients, and the placebo group had 100 patients. The study found that the primary and secondary endpoints were met, and significantly higher percentage of abstinence with subcutaneous buprenorphine were observed. Patients in both the 300 mg/300 mg and 300 mg/100 mg groups had very similar distributions of percentage of weeks patients abstained from opioid use with more than 20% of patients achieving 80%-100% abstinence from opioids during the course of the study, a significant improvement over the placebo group.

The panels’ recommendations come against the backdrop of the opioid epidemic in the United States, which President Trump has deemed a public health emergency. Many of the panel members and speakers at both meetings expressed support for the NDAs in that context and emphasized that, unlike sublingual administration of buprenorphine, these treatments do not require daily intervention. In addition, sublingual tablets are easier to abuse or more likely to lead to overdose because the patient must self-administer the medication. Expanding the toolkit of physicians who treat opioid use disorder might help stem the tide of the epidemic, some speakers said.

Usually, the FDA follows its advisory panels’ recommendations, which are not binding.

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– Two Food and Drug Administration advisory panels have recommended approval of two new drug applications (NDA) for buprenorphine subcutaneous injections for the treatment of opioid dependence.

On Nov. 1, panelists recommended approval of some of the doses proposed in the NDA submitted by Braeburn Pharmaceuticals at the joint meeting of the Psychopharmacologic Drugs Advisory and the Drug Safety and Risk Management committees. The formulation, currently known as CAM2038, is intended to be used as part of a treatment plan that can include counseling and psychosocial support. The subcutaneous depot is available weekly, in 8-, 16-, 24-, and 32-mg injections, and monthly, in 64-, 96-, 128-, and 160-mg injections.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

On the previous day, Oct. 31, the panelists voted 18-1 with no abstentions to recommend an NDA submitted by Indivior. This formulation is known as RBP-6000.

Both formulations must be administered by a health care provider using a prefilled syringe with a predetermined dosage. The injection forms a biodegradable subcutaneous depot that, as it degrades, releases buprenorphine at a steady and controlled pace over the course of treatment – increasing the success of treatment for opioid use disorder.

Braeburn’s NDA was based on results of a double-blind, randomized, within-subject, inpatient laboratory study of 47 patients over 14 days. Patients were randomized into two groups: 22 patients in the 24-mg group and 25 patients in the 32-mg group. Patients were administered an initial dose on day 0 and a follow-up dose on day 7. The results of the study found a complete blockade of opioids after the first injection that was sustained over the 1-week interdosing interval.

The committees said that of most of the doses should be approved, but a majority of committee members were uncomfortable with the higher doses.

Voting on Indivior’s NDA was based, in part, on the results of a randomized, double-blind, placebo-controlled, multicenter phase 3 study. The study lasted 24 weeks and randomly assigned 504 patients into one of three groups based on monthly dosing regimen of buprenorphine: 300 mg/300 mg, 300 mg/100 mg, and placebo. After randomization, the 300 mg/300 mg group had 201 patients, the 300 mg/100 mg group had 203 patients, and the placebo group had 100 patients. The study found that the primary and secondary endpoints were met, and significantly higher percentage of abstinence with subcutaneous buprenorphine were observed. Patients in both the 300 mg/300 mg and 300 mg/100 mg groups had very similar distributions of percentage of weeks patients abstained from opioid use with more than 20% of patients achieving 80%-100% abstinence from opioids during the course of the study, a significant improvement over the placebo group.

The panels’ recommendations come against the backdrop of the opioid epidemic in the United States, which President Trump has deemed a public health emergency. Many of the panel members and speakers at both meetings expressed support for the NDAs in that context and emphasized that, unlike sublingual administration of buprenorphine, these treatments do not require daily intervention. In addition, sublingual tablets are easier to abuse or more likely to lead to overdose because the patient must self-administer the medication. Expanding the toolkit of physicians who treat opioid use disorder might help stem the tide of the epidemic, some speakers said.

Usually, the FDA follows its advisory panels’ recommendations, which are not binding.

 

– Two Food and Drug Administration advisory panels have recommended approval of two new drug applications (NDA) for buprenorphine subcutaneous injections for the treatment of opioid dependence.

On Nov. 1, panelists recommended approval of some of the doses proposed in the NDA submitted by Braeburn Pharmaceuticals at the joint meeting of the Psychopharmacologic Drugs Advisory and the Drug Safety and Risk Management committees. The formulation, currently known as CAM2038, is intended to be used as part of a treatment plan that can include counseling and psychosocial support. The subcutaneous depot is available weekly, in 8-, 16-, 24-, and 32-mg injections, and monthly, in 64-, 96-, 128-, and 160-mg injections.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

On the previous day, Oct. 31, the panelists voted 18-1 with no abstentions to recommend an NDA submitted by Indivior. This formulation is known as RBP-6000.

Both formulations must be administered by a health care provider using a prefilled syringe with a predetermined dosage. The injection forms a biodegradable subcutaneous depot that, as it degrades, releases buprenorphine at a steady and controlled pace over the course of treatment – increasing the success of treatment for opioid use disorder.

Braeburn’s NDA was based on results of a double-blind, randomized, within-subject, inpatient laboratory study of 47 patients over 14 days. Patients were randomized into two groups: 22 patients in the 24-mg group and 25 patients in the 32-mg group. Patients were administered an initial dose on day 0 and a follow-up dose on day 7. The results of the study found a complete blockade of opioids after the first injection that was sustained over the 1-week interdosing interval.

The committees said that of most of the doses should be approved, but a majority of committee members were uncomfortable with the higher doses.

Voting on Indivior’s NDA was based, in part, on the results of a randomized, double-blind, placebo-controlled, multicenter phase 3 study. The study lasted 24 weeks and randomly assigned 504 patients into one of three groups based on monthly dosing regimen of buprenorphine: 300 mg/300 mg, 300 mg/100 mg, and placebo. After randomization, the 300 mg/300 mg group had 201 patients, the 300 mg/100 mg group had 203 patients, and the placebo group had 100 patients. The study found that the primary and secondary endpoints were met, and significantly higher percentage of abstinence with subcutaneous buprenorphine were observed. Patients in both the 300 mg/300 mg and 300 mg/100 mg groups had very similar distributions of percentage of weeks patients abstained from opioid use with more than 20% of patients achieving 80%-100% abstinence from opioids during the course of the study, a significant improvement over the placebo group.

The panels’ recommendations come against the backdrop of the opioid epidemic in the United States, which President Trump has deemed a public health emergency. Many of the panel members and speakers at both meetings expressed support for the NDAs in that context and emphasized that, unlike sublingual administration of buprenorphine, these treatments do not require daily intervention. In addition, sublingual tablets are easier to abuse or more likely to lead to overdose because the patient must self-administer the medication. Expanding the toolkit of physicians who treat opioid use disorder might help stem the tide of the epidemic, some speakers said.

Usually, the FDA follows its advisory panels’ recommendations, which are not binding.

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FDA: Ultrasound surgical devices are contraindicated for uterine fibroid removal

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Ultrasonic surgical aspirator devices should not be used for fragmentation, emulsification, and aspiration of uterine fibroids, according to the Food and Drug Administration.

These devices have the potential to disseminate undetected tumor tissue, and there are no proven preoperative screening methods for detecting uterine sarcoma in uterine fibroids that otherwise appear to be benign, FDA officials wrote in a guidance document issued Oct. 30. The FDA is calling for new product labeling for these devices within 120 days.

The recommended label reads: “CONTRAINDICATION: This ultrasonic surgical aspirator device is not indicated for and should not be used for the fragmentation, emulsification, and aspiration of uterine fibroids.”

The devices deliver ultrasonic energy through an oscillating tip, which leads to tissue fragmentation. This can lead to tissue dissemination that cannot be eliminated by suction/aspiration. In advanced cancers, the risk of dissemination may be outweighed by the benefits of the devices, including the debulking effect with no thermal collateral damage, as well as avoidance of the need for organ removal or resection.

The devices are currently labeled in a way that suggests they could be used in removing uterine fibroids, though the agency said that it is not aware that they are used for this purpose.

The agency recommended against their use in uterine fibroids, in part because there are alternative treatment options available. But the American College of Obstetricians and Gynecologists has challenged that assertion. When the FDA first issued a draft notice of the labeling guidance in November 2016, ACOG commented that abdominal hysterectomy is the alternative treatment option and is associated with significant morbidity and mortality beyond that seen with minimally invasive techniques. ACOG urged the FDA to prioritize informed consent and the weighing of risks and benefits.

Ultrasonic surgical aspirator devices are used for a wide range of surgical applications, but the recommendations apply specifically to laparoscopic surgery, open surgery, and gynecologic surgery.

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Ultrasonic surgical aspirator devices should not be used for fragmentation, emulsification, and aspiration of uterine fibroids, according to the Food and Drug Administration.

These devices have the potential to disseminate undetected tumor tissue, and there are no proven preoperative screening methods for detecting uterine sarcoma in uterine fibroids that otherwise appear to be benign, FDA officials wrote in a guidance document issued Oct. 30. The FDA is calling for new product labeling for these devices within 120 days.

The recommended label reads: “CONTRAINDICATION: This ultrasonic surgical aspirator device is not indicated for and should not be used for the fragmentation, emulsification, and aspiration of uterine fibroids.”

The devices deliver ultrasonic energy through an oscillating tip, which leads to tissue fragmentation. This can lead to tissue dissemination that cannot be eliminated by suction/aspiration. In advanced cancers, the risk of dissemination may be outweighed by the benefits of the devices, including the debulking effect with no thermal collateral damage, as well as avoidance of the need for organ removal or resection.

The devices are currently labeled in a way that suggests they could be used in removing uterine fibroids, though the agency said that it is not aware that they are used for this purpose.

The agency recommended against their use in uterine fibroids, in part because there are alternative treatment options available. But the American College of Obstetricians and Gynecologists has challenged that assertion. When the FDA first issued a draft notice of the labeling guidance in November 2016, ACOG commented that abdominal hysterectomy is the alternative treatment option and is associated with significant morbidity and mortality beyond that seen with minimally invasive techniques. ACOG urged the FDA to prioritize informed consent and the weighing of risks and benefits.

Ultrasonic surgical aspirator devices are used for a wide range of surgical applications, but the recommendations apply specifically to laparoscopic surgery, open surgery, and gynecologic surgery.

 

Ultrasonic surgical aspirator devices should not be used for fragmentation, emulsification, and aspiration of uterine fibroids, according to the Food and Drug Administration.

These devices have the potential to disseminate undetected tumor tissue, and there are no proven preoperative screening methods for detecting uterine sarcoma in uterine fibroids that otherwise appear to be benign, FDA officials wrote in a guidance document issued Oct. 30. The FDA is calling for new product labeling for these devices within 120 days.

The recommended label reads: “CONTRAINDICATION: This ultrasonic surgical aspirator device is not indicated for and should not be used for the fragmentation, emulsification, and aspiration of uterine fibroids.”

The devices deliver ultrasonic energy through an oscillating tip, which leads to tissue fragmentation. This can lead to tissue dissemination that cannot be eliminated by suction/aspiration. In advanced cancers, the risk of dissemination may be outweighed by the benefits of the devices, including the debulking effect with no thermal collateral damage, as well as avoidance of the need for organ removal or resection.

The devices are currently labeled in a way that suggests they could be used in removing uterine fibroids, though the agency said that it is not aware that they are used for this purpose.

The agency recommended against their use in uterine fibroids, in part because there are alternative treatment options available. But the American College of Obstetricians and Gynecologists has challenged that assertion. When the FDA first issued a draft notice of the labeling guidance in November 2016, ACOG commented that abdominal hysterectomy is the alternative treatment option and is associated with significant morbidity and mortality beyond that seen with minimally invasive techniques. ACOG urged the FDA to prioritize informed consent and the weighing of risks and benefits.

Ultrasonic surgical aspirator devices are used for a wide range of surgical applications, but the recommendations apply specifically to laparoscopic surgery, open surgery, and gynecologic surgery.

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FDA approves acalabrutinib for second-line treatment of MCL

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The Food and Drug Administration has granted accelerated approval to acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of adults with mantle cell lymphoma (MCL) who have received at least one prior therapy.

Approval was based on an 81% overall response rate in a phase 2, single-arm trial (ACE-LY-004) of 124 patients with MCL who had received at least one prior treatment (40% complete response, 41% partial response), the FDA said in a statement.

Common adverse effects of acalabrutinib include headache, diarrhea, bruising, myalgia, anemia, thrombocytopenia, and neutropenia.

Serious adverse effects include hemorrhage and atrial fibrillation. Second primary malignancies have occurred in some patients, according to the FDA.

Acalabrutinib will be marketed as Calquence by AstraZeneca. The company is currently enrolling patients in a phase 3 trial evaluating acalabrutinib as a first-line treatment for patients with MCL in combination with bendamustine and rituximab.

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The Food and Drug Administration has granted accelerated approval to acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of adults with mantle cell lymphoma (MCL) who have received at least one prior therapy.

Approval was based on an 81% overall response rate in a phase 2, single-arm trial (ACE-LY-004) of 124 patients with MCL who had received at least one prior treatment (40% complete response, 41% partial response), the FDA said in a statement.

Common adverse effects of acalabrutinib include headache, diarrhea, bruising, myalgia, anemia, thrombocytopenia, and neutropenia.

Serious adverse effects include hemorrhage and atrial fibrillation. Second primary malignancies have occurred in some patients, according to the FDA.

Acalabrutinib will be marketed as Calquence by AstraZeneca. The company is currently enrolling patients in a phase 3 trial evaluating acalabrutinib as a first-line treatment for patients with MCL in combination with bendamustine and rituximab.

 

The Food and Drug Administration has granted accelerated approval to acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of adults with mantle cell lymphoma (MCL) who have received at least one prior therapy.

Approval was based on an 81% overall response rate in a phase 2, single-arm trial (ACE-LY-004) of 124 patients with MCL who had received at least one prior treatment (40% complete response, 41% partial response), the FDA said in a statement.

Common adverse effects of acalabrutinib include headache, diarrhea, bruising, myalgia, anemia, thrombocytopenia, and neutropenia.

Serious adverse effects include hemorrhage and atrial fibrillation. Second primary malignancies have occurred in some patients, according to the FDA.

Acalabrutinib will be marketed as Calquence by AstraZeneca. The company is currently enrolling patients in a phase 3 trial evaluating acalabrutinib as a first-line treatment for patients with MCL in combination with bendamustine and rituximab.

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In close vote, advisory panel prefers Shingrix over Zostavax

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Herpes zoster subunit vaccine (Shingrix) was preferentially recommended over zoster vaccine live (Zostavax) for preventing herpes zoster and related complications Oct. 25 at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Eight committee members voted for the recommendation, and seven voted against it.

After the decision, ACIP Chair Nancy Bennett, MD, professor of medicine at the University of Rochester (N.Y.), noted that it was the “closest vote” in her term as chair of the committee, which provides advice and recommendations on vaccine-preventable diseases to the CDC.

In discussions leading up to the vote, some committee members cited potential supply issues, as well as the need for longer-term safety data, among other issues.

“I think it would be nice to see data on a larger population that is not just research-based, especially because we have very little data on ethnic minorities,” said Laura E. Riley, MD, of Harvard Medical School, Boston, who voted against the recommendation.

The vote comes several days after GlaxoSmithKline announced the Food and Drug Administration approval of Shingrix for the prevention of herpes zoster (shingles) in adults aged 50 years or older. In pooled clinical trial results, the vaccine demonstrated greater than 90% efficacy in all age groups, according to a company statement.

Shingrix is a non-live, recombinant subunit vaccine that is given in two doses, intramuscularly. Zostavax, also indicated in individuals aged 50 years or older, is a live attenuated virus vaccine.

In a related decision, ACIP voted 14-1 to recommend Shingrix for prevention of herpes zoster and related complications for immunocompetent adults aged 50 years and older.

They also voted 12-3 to recommend Shingrix to prevent herpes zoster and its complications for immunocompetent adults who previously received Zostavax.

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Herpes zoster subunit vaccine (Shingrix) was preferentially recommended over zoster vaccine live (Zostavax) for preventing herpes zoster and related complications Oct. 25 at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Eight committee members voted for the recommendation, and seven voted against it.

After the decision, ACIP Chair Nancy Bennett, MD, professor of medicine at the University of Rochester (N.Y.), noted that it was the “closest vote” in her term as chair of the committee, which provides advice and recommendations on vaccine-preventable diseases to the CDC.

In discussions leading up to the vote, some committee members cited potential supply issues, as well as the need for longer-term safety data, among other issues.

“I think it would be nice to see data on a larger population that is not just research-based, especially because we have very little data on ethnic minorities,” said Laura E. Riley, MD, of Harvard Medical School, Boston, who voted against the recommendation.

The vote comes several days after GlaxoSmithKline announced the Food and Drug Administration approval of Shingrix for the prevention of herpes zoster (shingles) in adults aged 50 years or older. In pooled clinical trial results, the vaccine demonstrated greater than 90% efficacy in all age groups, according to a company statement.

Shingrix is a non-live, recombinant subunit vaccine that is given in two doses, intramuscularly. Zostavax, also indicated in individuals aged 50 years or older, is a live attenuated virus vaccine.

In a related decision, ACIP voted 14-1 to recommend Shingrix for prevention of herpes zoster and related complications for immunocompetent adults aged 50 years and older.

They also voted 12-3 to recommend Shingrix to prevent herpes zoster and its complications for immunocompetent adults who previously received Zostavax.

 

Herpes zoster subunit vaccine (Shingrix) was preferentially recommended over zoster vaccine live (Zostavax) for preventing herpes zoster and related complications Oct. 25 at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Eight committee members voted for the recommendation, and seven voted against it.

After the decision, ACIP Chair Nancy Bennett, MD, professor of medicine at the University of Rochester (N.Y.), noted that it was the “closest vote” in her term as chair of the committee, which provides advice and recommendations on vaccine-preventable diseases to the CDC.

In discussions leading up to the vote, some committee members cited potential supply issues, as well as the need for longer-term safety data, among other issues.

“I think it would be nice to see data on a larger population that is not just research-based, especially because we have very little data on ethnic minorities,” said Laura E. Riley, MD, of Harvard Medical School, Boston, who voted against the recommendation.

The vote comes several days after GlaxoSmithKline announced the Food and Drug Administration approval of Shingrix for the prevention of herpes zoster (shingles) in adults aged 50 years or older. In pooled clinical trial results, the vaccine demonstrated greater than 90% efficacy in all age groups, according to a company statement.

Shingrix is a non-live, recombinant subunit vaccine that is given in two doses, intramuscularly. Zostavax, also indicated in individuals aged 50 years or older, is a live attenuated virus vaccine.

In a related decision, ACIP voted 14-1 to recommend Shingrix for prevention of herpes zoster and related complications for immunocompetent adults aged 50 years and older.

They also voted 12-3 to recommend Shingrix to prevent herpes zoster and its complications for immunocompetent adults who previously received Zostavax.

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Golimumab earns new FDA approvals

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The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).

Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.

The approval of Simponi Aria was supported by phase 3 clinical trials showing consistent safety profiles and significant improvement in symptoms in patients, compared with placebo.

“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.

Read the revised prescribing information for Simponi Aria here.

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The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).

Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.

The approval of Simponi Aria was supported by phase 3 clinical trials showing consistent safety profiles and significant improvement in symptoms in patients, compared with placebo.

“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.

Read the revised prescribing information for Simponi Aria here.

 

The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).

Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.

The approval of Simponi Aria was supported by phase 3 clinical trials showing consistent safety profiles and significant improvement in symptoms in patients, compared with placebo.

“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.

Read the revised prescribing information for Simponi Aria here.

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CDC: Zika-exposed newborns need intensified eye, hearing, and neurological testing

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Infants with possible prenatal Zika exposure who test positive for the virus should receive an in-depth ophthalmologic exam, intensified hearing testing, and a thorough neurological evaluation with brain imaging within 1 month of birth, according to new interim guidance set forth by the Centers for Disease Control and Prevention.

The new clinical management guidelines, published in the Oct. 20 issue of the Morbidity and Mortality Weekly Report, supersede the most recent CDC guidance, issued in August 2016. The agency deemed the update necessary after a recent convocation sponsored by the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. The meeting drew dozens of practicing clinicians and federal agency representatives, who reviewed the ever-evolving body of knowledge on how to best manage the care of these infants. Since Zika emerged as a public health threat, clinicians have reported postnatal onset of some symptoms, including eye abnormalities, a developing microcephaly in infants with a normal head circumference at birth, EEG abnormalities, and diaphragmatic paralysis.

CDC/Cynthia Goldsmith
“The updated interim guidance is based on current, limited data about Zika virus infection, the interpretation of individual expert opinion during the forum, and knowledge about other congenital infections, and reflects the information available as of September 2017,” according to Tolulope Adebanjo, MD, of the National Center for Immunization and Respiratory Diseases, at the CDC in Atlanta. “As more information becomes available, this guidance will be updated.”

The guidance focuses on three groups: infants with clinical findings of Zika syndrome born to mothers with possible Zika exposure during pregnancy; infants without clinical findings of Zika syndrome whose mothers had lab-confirmed Zika exposure; and infants without symptoms whose mothers might have been exposed, but who did not have laboratory-confirmed infection (MMWR. 2017 Oct 20;66[41]:1089-120).

Infants with clinical findings consistent with Zika syndrome and mothers with possible prenatal Zika exposure

These infants should be tested for Zika virus with serum and urine tests. If those are negative and there is no other apparent cause of the symptoms, they should have a cerebrospinal fluid sample tested for Zika RNA and IgM Zika antibodies.

By 1 month, these infants need a head ultrasound and a detailed ophthalmologic exam. The eye exam should pick up any anomalies of the anterior and posterior eye, including microphthalmia, coloboma, intraocular calcifications, optic nerve hypoplasia and atrophy, and macular scarring with focal pigmentary retinal mottling.

Also by that time, they should undergo auditory brainstem response (ABR) audiometry – especially if the initial newborn hearing screen was done by otoacoustic emissions. Sensorineural hearing loss can be part of Zika syndrome, although late-onset hearing loss has not been seen. Therefore, the 4- to 6-month-old follow-up ABR previously recommended is no longer deemed necessary.

A comprehensive neurological exam also is part of the recommendation. Seizures are sometimes part of Zika syndrome, but infants can also have subclinical EEG abnormalities. Advanced neuroimaging can identify both obvious and subtle brain abnormalities: cortical thinning, corpus callosum abnormalities, calcifications at the white/gray matter junction, and ventricular enlargement are possible findings.

As infants grow, clinicians should be alert for signs of increased intracranial pressure that could signal postnatal hydrocephalus. Diaphragmatic paralysis also has been seen; this manifests by respiratory distress. Dysphagia that interferes with feeding can develop as well.

The complicated clinical picture calls for a team approach, Dr. Adebanjo said. “The follow-up care of [these infants] requires a multidisciplinary team and an established medical home to facilitate the coordination of care and ensure that abnormal findings are addressed.”

Infants without clinical findings, whose mothers have lab-confirmed Zika exposure

Initially, these infants should have the same early head ultrasound, hearing, and eye exams as those who display clinical findings. All of these infants also should be tested for Zika virus in the same way as those with clinical findings.

If tests return a positive result, they should have all the investigations and follow-ups recommended for babies with clinical findings. If lab testing is negative, and clinical findings are normal, Zika infection is highly unlikely and they can receive routine care, although clinicians and parents should be on the lookout for any new symptoms that might suggest postnatal Zika syndrome.

Infants without clinical findings, whose mothers had possible, but unconfirmed, Zika exposure

This is a varied and large group, which includes women who were never tested during pregnancy, as well as those who could have had a false negative test. “Because the latter issue is not easily discerned, all mothers with possible exposure to Zika virus infection, including those who tested negative with currently available technology, should be considered in this group,” Dr. Adebanjo said.

 

 

CDC does not recommend further Zika evaluation for these infants unless additional testing confirms maternal infection. For older infants, parents and clinicians should decide together whether any further evaluations would be helpful. But, Dr. Adebanjo said, “If findings consistent with congenital Zika syndrome are identified at any time, referrals to appropriate specialties should be made, and subsequent evaluation should follow recommendations for infants with clinical findings consistent with congenital Zika.”

CDC also reiterated its special recommendations for infants who had a prenatal diagnosis of Zika infection. For now, these remain unchanged from 2016, although “as more data become available, understanding of the diagnostic role of prenatal ultrasound and amniocentesis will improve and guidance will be updated.”

No one has yet identified the optimal timing for a Zika diagnostic ultrasound. CDC recommends serial ultrasounds be done every 3-4 weeks for women with lab-confirmed prenatal Zika exposure. Women with possible exposure need only routine ultrasound screenings.

While Zika RNA has been identified in amniotic fluid, there is no consensus on the value of amniocentesis as a prenatal diagnostic tool. Investigations of serial amniocentesis suggests that viral shedding into the amniotic fluid might be transient. If the procedure is done for other reasons, Zika nucleic acid testing can be incorporated.

A shared decision-making process is key when making screening decisions that should be individually weighed, Dr. Adebanjo said. “For example, serial ultrasounds might be inconvenient, unpleasant, and expensive, and might prompt unnecessary interventions; amniocentesis carries additional known risks such as fetal loss. These potential harms of prenatal screening for congenital Zika syndrome might outweigh the clinical benefits for some patients. Therefore, these decisions should be individualized.”

Neither Dr. Adebanjo nor any of the coauthors had any financial disclosures.

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Infants with possible prenatal Zika exposure who test positive for the virus should receive an in-depth ophthalmologic exam, intensified hearing testing, and a thorough neurological evaluation with brain imaging within 1 month of birth, according to new interim guidance set forth by the Centers for Disease Control and Prevention.

The new clinical management guidelines, published in the Oct. 20 issue of the Morbidity and Mortality Weekly Report, supersede the most recent CDC guidance, issued in August 2016. The agency deemed the update necessary after a recent convocation sponsored by the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. The meeting drew dozens of practicing clinicians and federal agency representatives, who reviewed the ever-evolving body of knowledge on how to best manage the care of these infants. Since Zika emerged as a public health threat, clinicians have reported postnatal onset of some symptoms, including eye abnormalities, a developing microcephaly in infants with a normal head circumference at birth, EEG abnormalities, and diaphragmatic paralysis.

CDC/Cynthia Goldsmith
“The updated interim guidance is based on current, limited data about Zika virus infection, the interpretation of individual expert opinion during the forum, and knowledge about other congenital infections, and reflects the information available as of September 2017,” according to Tolulope Adebanjo, MD, of the National Center for Immunization and Respiratory Diseases, at the CDC in Atlanta. “As more information becomes available, this guidance will be updated.”

The guidance focuses on three groups: infants with clinical findings of Zika syndrome born to mothers with possible Zika exposure during pregnancy; infants without clinical findings of Zika syndrome whose mothers had lab-confirmed Zika exposure; and infants without symptoms whose mothers might have been exposed, but who did not have laboratory-confirmed infection (MMWR. 2017 Oct 20;66[41]:1089-120).

Infants with clinical findings consistent with Zika syndrome and mothers with possible prenatal Zika exposure

These infants should be tested for Zika virus with serum and urine tests. If those are negative and there is no other apparent cause of the symptoms, they should have a cerebrospinal fluid sample tested for Zika RNA and IgM Zika antibodies.

By 1 month, these infants need a head ultrasound and a detailed ophthalmologic exam. The eye exam should pick up any anomalies of the anterior and posterior eye, including microphthalmia, coloboma, intraocular calcifications, optic nerve hypoplasia and atrophy, and macular scarring with focal pigmentary retinal mottling.

Also by that time, they should undergo auditory brainstem response (ABR) audiometry – especially if the initial newborn hearing screen was done by otoacoustic emissions. Sensorineural hearing loss can be part of Zika syndrome, although late-onset hearing loss has not been seen. Therefore, the 4- to 6-month-old follow-up ABR previously recommended is no longer deemed necessary.

A comprehensive neurological exam also is part of the recommendation. Seizures are sometimes part of Zika syndrome, but infants can also have subclinical EEG abnormalities. Advanced neuroimaging can identify both obvious and subtle brain abnormalities: cortical thinning, corpus callosum abnormalities, calcifications at the white/gray matter junction, and ventricular enlargement are possible findings.

As infants grow, clinicians should be alert for signs of increased intracranial pressure that could signal postnatal hydrocephalus. Diaphragmatic paralysis also has been seen; this manifests by respiratory distress. Dysphagia that interferes with feeding can develop as well.

The complicated clinical picture calls for a team approach, Dr. Adebanjo said. “The follow-up care of [these infants] requires a multidisciplinary team and an established medical home to facilitate the coordination of care and ensure that abnormal findings are addressed.”

Infants without clinical findings, whose mothers have lab-confirmed Zika exposure

Initially, these infants should have the same early head ultrasound, hearing, and eye exams as those who display clinical findings. All of these infants also should be tested for Zika virus in the same way as those with clinical findings.

If tests return a positive result, they should have all the investigations and follow-ups recommended for babies with clinical findings. If lab testing is negative, and clinical findings are normal, Zika infection is highly unlikely and they can receive routine care, although clinicians and parents should be on the lookout for any new symptoms that might suggest postnatal Zika syndrome.

Infants without clinical findings, whose mothers had possible, but unconfirmed, Zika exposure

This is a varied and large group, which includes women who were never tested during pregnancy, as well as those who could have had a false negative test. “Because the latter issue is not easily discerned, all mothers with possible exposure to Zika virus infection, including those who tested negative with currently available technology, should be considered in this group,” Dr. Adebanjo said.

 

 

CDC does not recommend further Zika evaluation for these infants unless additional testing confirms maternal infection. For older infants, parents and clinicians should decide together whether any further evaluations would be helpful. But, Dr. Adebanjo said, “If findings consistent with congenital Zika syndrome are identified at any time, referrals to appropriate specialties should be made, and subsequent evaluation should follow recommendations for infants with clinical findings consistent with congenital Zika.”

CDC also reiterated its special recommendations for infants who had a prenatal diagnosis of Zika infection. For now, these remain unchanged from 2016, although “as more data become available, understanding of the diagnostic role of prenatal ultrasound and amniocentesis will improve and guidance will be updated.”

No one has yet identified the optimal timing for a Zika diagnostic ultrasound. CDC recommends serial ultrasounds be done every 3-4 weeks for women with lab-confirmed prenatal Zika exposure. Women with possible exposure need only routine ultrasound screenings.

While Zika RNA has been identified in amniotic fluid, there is no consensus on the value of amniocentesis as a prenatal diagnostic tool. Investigations of serial amniocentesis suggests that viral shedding into the amniotic fluid might be transient. If the procedure is done for other reasons, Zika nucleic acid testing can be incorporated.

A shared decision-making process is key when making screening decisions that should be individually weighed, Dr. Adebanjo said. “For example, serial ultrasounds might be inconvenient, unpleasant, and expensive, and might prompt unnecessary interventions; amniocentesis carries additional known risks such as fetal loss. These potential harms of prenatal screening for congenital Zika syndrome might outweigh the clinical benefits for some patients. Therefore, these decisions should be individualized.”

Neither Dr. Adebanjo nor any of the coauthors had any financial disclosures.

Infants with possible prenatal Zika exposure who test positive for the virus should receive an in-depth ophthalmologic exam, intensified hearing testing, and a thorough neurological evaluation with brain imaging within 1 month of birth, according to new interim guidance set forth by the Centers for Disease Control and Prevention.

The new clinical management guidelines, published in the Oct. 20 issue of the Morbidity and Mortality Weekly Report, supersede the most recent CDC guidance, issued in August 2016. The agency deemed the update necessary after a recent convocation sponsored by the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. The meeting drew dozens of practicing clinicians and federal agency representatives, who reviewed the ever-evolving body of knowledge on how to best manage the care of these infants. Since Zika emerged as a public health threat, clinicians have reported postnatal onset of some symptoms, including eye abnormalities, a developing microcephaly in infants with a normal head circumference at birth, EEG abnormalities, and diaphragmatic paralysis.

CDC/Cynthia Goldsmith
“The updated interim guidance is based on current, limited data about Zika virus infection, the interpretation of individual expert opinion during the forum, and knowledge about other congenital infections, and reflects the information available as of September 2017,” according to Tolulope Adebanjo, MD, of the National Center for Immunization and Respiratory Diseases, at the CDC in Atlanta. “As more information becomes available, this guidance will be updated.”

The guidance focuses on three groups: infants with clinical findings of Zika syndrome born to mothers with possible Zika exposure during pregnancy; infants without clinical findings of Zika syndrome whose mothers had lab-confirmed Zika exposure; and infants without symptoms whose mothers might have been exposed, but who did not have laboratory-confirmed infection (MMWR. 2017 Oct 20;66[41]:1089-120).

Infants with clinical findings consistent with Zika syndrome and mothers with possible prenatal Zika exposure

These infants should be tested for Zika virus with serum and urine tests. If those are negative and there is no other apparent cause of the symptoms, they should have a cerebrospinal fluid sample tested for Zika RNA and IgM Zika antibodies.

By 1 month, these infants need a head ultrasound and a detailed ophthalmologic exam. The eye exam should pick up any anomalies of the anterior and posterior eye, including microphthalmia, coloboma, intraocular calcifications, optic nerve hypoplasia and atrophy, and macular scarring with focal pigmentary retinal mottling.

Also by that time, they should undergo auditory brainstem response (ABR) audiometry – especially if the initial newborn hearing screen was done by otoacoustic emissions. Sensorineural hearing loss can be part of Zika syndrome, although late-onset hearing loss has not been seen. Therefore, the 4- to 6-month-old follow-up ABR previously recommended is no longer deemed necessary.

A comprehensive neurological exam also is part of the recommendation. Seizures are sometimes part of Zika syndrome, but infants can also have subclinical EEG abnormalities. Advanced neuroimaging can identify both obvious and subtle brain abnormalities: cortical thinning, corpus callosum abnormalities, calcifications at the white/gray matter junction, and ventricular enlargement are possible findings.

As infants grow, clinicians should be alert for signs of increased intracranial pressure that could signal postnatal hydrocephalus. Diaphragmatic paralysis also has been seen; this manifests by respiratory distress. Dysphagia that interferes with feeding can develop as well.

The complicated clinical picture calls for a team approach, Dr. Adebanjo said. “The follow-up care of [these infants] requires a multidisciplinary team and an established medical home to facilitate the coordination of care and ensure that abnormal findings are addressed.”

Infants without clinical findings, whose mothers have lab-confirmed Zika exposure

Initially, these infants should have the same early head ultrasound, hearing, and eye exams as those who display clinical findings. All of these infants also should be tested for Zika virus in the same way as those with clinical findings.

If tests return a positive result, they should have all the investigations and follow-ups recommended for babies with clinical findings. If lab testing is negative, and clinical findings are normal, Zika infection is highly unlikely and they can receive routine care, although clinicians and parents should be on the lookout for any new symptoms that might suggest postnatal Zika syndrome.

Infants without clinical findings, whose mothers had possible, but unconfirmed, Zika exposure

This is a varied and large group, which includes women who were never tested during pregnancy, as well as those who could have had a false negative test. “Because the latter issue is not easily discerned, all mothers with possible exposure to Zika virus infection, including those who tested negative with currently available technology, should be considered in this group,” Dr. Adebanjo said.

 

 

CDC does not recommend further Zika evaluation for these infants unless additional testing confirms maternal infection. For older infants, parents and clinicians should decide together whether any further evaluations would be helpful. But, Dr. Adebanjo said, “If findings consistent with congenital Zika syndrome are identified at any time, referrals to appropriate specialties should be made, and subsequent evaluation should follow recommendations for infants with clinical findings consistent with congenital Zika.”

CDC also reiterated its special recommendations for infants who had a prenatal diagnosis of Zika infection. For now, these remain unchanged from 2016, although “as more data become available, understanding of the diagnostic role of prenatal ultrasound and amniocentesis will improve and guidance will be updated.”

No one has yet identified the optimal timing for a Zika diagnostic ultrasound. CDC recommends serial ultrasounds be done every 3-4 weeks for women with lab-confirmed prenatal Zika exposure. Women with possible exposure need only routine ultrasound screenings.

While Zika RNA has been identified in amniotic fluid, there is no consensus on the value of amniocentesis as a prenatal diagnostic tool. Investigations of serial amniocentesis suggests that viral shedding into the amniotic fluid might be transient. If the procedure is done for other reasons, Zika nucleic acid testing can be incorporated.

A shared decision-making process is key when making screening decisions that should be individually weighed, Dr. Adebanjo said. “For example, serial ultrasounds might be inconvenient, unpleasant, and expensive, and might prompt unnecessary interventions; amniocentesis carries additional known risks such as fetal loss. These potential harms of prenatal screening for congenital Zika syndrome might outweigh the clinical benefits for some patients. Therefore, these decisions should be individualized.”

Neither Dr. Adebanjo nor any of the coauthors had any financial disclosures.

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FDA panel advises approval of semaglutide to lower HbA1c in patients with type 2 diabetes

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The Food and drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) recommended the approval of a once-weekly semaglutide injection for adults with type 2 diabetes mellitus. The vote was 16-0 in favor of approval, with one committee member abstaining.

The committee based its approval recommendation mainly on data from a global phase 3 clinical trial program known as SUSTAIN (clinical trial number NCT01720446) that included evaluations of cardiovascular outcomes, safety, and efficacy in adults with type 2 diabetes, including some with renal disease and increased cardiovascular risk.

The researchers found some increase in diabetic retinopathy in the SUSTAIN trials, but a post-hoc analysis found that “To the extent that the data suggest a signal that there was progression of diabetic retinopathy in patients with significant decreases in HbA1c, these events should be expected because they are consistent with treatments that decrease HbA1c. While this decrease may result in an initial increase in retinopathy, ocular health is ultimately benefited by decreasing HbA1c.”

Novo Nordisk submitted the application for semaglutide in December 2016; the drug also is being reviewed in Europe and Japan.

The FDA is not obligated to follow the committee’s recommendation but considers it as part of the review process of new drug applications.  

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The Food and drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) recommended the approval of a once-weekly semaglutide injection for adults with type 2 diabetes mellitus. The vote was 16-0 in favor of approval, with one committee member abstaining.

The committee based its approval recommendation mainly on data from a global phase 3 clinical trial program known as SUSTAIN (clinical trial number NCT01720446) that included evaluations of cardiovascular outcomes, safety, and efficacy in adults with type 2 diabetes, including some with renal disease and increased cardiovascular risk.

The researchers found some increase in diabetic retinopathy in the SUSTAIN trials, but a post-hoc analysis found that “To the extent that the data suggest a signal that there was progression of diabetic retinopathy in patients with significant decreases in HbA1c, these events should be expected because they are consistent with treatments that decrease HbA1c. While this decrease may result in an initial increase in retinopathy, ocular health is ultimately benefited by decreasing HbA1c.”

Novo Nordisk submitted the application for semaglutide in December 2016; the drug also is being reviewed in Europe and Japan.

The FDA is not obligated to follow the committee’s recommendation but considers it as part of the review process of new drug applications.  

 

The Food and drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) recommended the approval of a once-weekly semaglutide injection for adults with type 2 diabetes mellitus. The vote was 16-0 in favor of approval, with one committee member abstaining.

The committee based its approval recommendation mainly on data from a global phase 3 clinical trial program known as SUSTAIN (clinical trial number NCT01720446) that included evaluations of cardiovascular outcomes, safety, and efficacy in adults with type 2 diabetes, including some with renal disease and increased cardiovascular risk.

The researchers found some increase in diabetic retinopathy in the SUSTAIN trials, but a post-hoc analysis found that “To the extent that the data suggest a signal that there was progression of diabetic retinopathy in patients with significant decreases in HbA1c, these events should be expected because they are consistent with treatments that decrease HbA1c. While this decrease may result in an initial increase in retinopathy, ocular health is ultimately benefited by decreasing HbA1c.”

Novo Nordisk submitted the application for semaglutide in December 2016; the drug also is being reviewed in Europe and Japan.

The FDA is not obligated to follow the committee’s recommendation but considers it as part of the review process of new drug applications.  

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