Elizabeth Mechcatie

Peginterferon beta-1a has been approved by the Food and Drug Administration for treating relapsing forms of multiple sclerosis, based on the results of the ADVANCE trial, the manufacturer, Biogen Idec, announced on August 15.

This is the only pegylated interferon approved for treating relapsing MS, according to a statement from the company.

Biogen Idec will be marketing the drug as Plegridy. The recommended dose is 125 mcg administered subcutaneously every 14 days. It can be administered with a prefilled syringe or a new autoinjector the company is marketing as the Plegridy Pen, according to the statement.

The approval is based on the results of the ADVANCE study, a randomized, double-blind, phase III, 2-year study of about 1,516 patients with relapsing MS, which was placebo-controlled during the first year. The annualized relapse rate, the primary outcome, was reduced by 36% among those treated with peginterferon beta-1a, compared with those on placebo, a statistically significant difference.

Secondary outcomes including the proportion of patients who relapsed, which was reduced by 19%, compared with placebo; the mean number of new or newly enlarging T2 hyperintense lesions, which was reduced by 67%, compared with placebo; and the mean number of new gadolinium-enhancing lesions, which was reduced by 86%, compared with placebo.

Injection-site erythema, influenzalike illness, fever, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia were the most common adverse events associated with treatment, affecting at least 10% of treated patients and occurring at a rate that was at least 2% greater than among those on placebo, according to the prescribing information.

Postmarketing studies that the company will be required to conduct include a pediatric study and a registry study in the United States that will compare the maternal, fetal, and infant outcomes, including birth defects, of women with MS who are treated with peginterferon beta-1a during pregnancy against women with MS who are not treated with the drug during pregnancy and women who do not have MS.

The product has already been approved in Europe.

Serious adverse events associated with this product should be reported to the FDA at 800-332-1088 or www. fda.gov/medwatch.

[email protected]

Peginterferon beta-1a has been approved by the Food and Drug Administration for treating relapsing forms of multiple sclerosis, based on the results of the ADVANCE trial, the manufacturer, Biogen Idec, announced on August 15.

This is the only pegylated interferon approved for treating relapsing MS, according to a statement from the company.

Biogen Idec will be marketing the drug as Plegridy. The recommended dose is 125 mcg administered subcutaneously every 14 days. It can be administered with a prefilled syringe or a new autoinjector the company is marketing as the Plegridy Pen, according to the statement.

The approval is based on the results of the ADVANCE study, a randomized, double-blind, phase III, 2-year study of about 1,516 patients with relapsing MS, which was placebo-controlled during the first year. The annualized relapse rate, the primary outcome, was reduced by 36% among those treated with peginterferon beta-1a, compared with those on placebo, a statistically significant difference.

Secondary outcomes including the proportion of patients who relapsed, which was reduced by 19%, compared with placebo; the mean number of new or newly enlarging T2 hyperintense lesions, which was reduced by 67%, compared with placebo; and the mean number of new gadolinium-enhancing lesions, which was reduced by 86%, compared with placebo.

Injection-site erythema, influenzalike illness, fever, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia were the most common adverse events associated with treatment, affecting at least 10% of treated patients and occurring at a rate that was at least 2% greater than among those on placebo, according to the prescribing information.

Postmarketing studies that the company will be required to conduct include a pediatric study and a registry study in the United States that will compare the maternal, fetal, and infant outcomes, including birth defects, of women with MS who are treated with peginterferon beta-1a during pregnancy against women with MS who are not treated with the drug during pregnancy and women who do not have MS.

The product has already been approved in Europe.

Serious adverse events associated with this product should be reported to the FDA at 800-332-1088 or www. fda.gov/medwatch.

[email protected]

Peginterferon beta-1a has been approved by the Food and Drug Administration for treating relapsing forms of multiple sclerosis, based on the results of the ADVANCE trial, the manufacturer, Biogen Idec, announced on August 15.

This is the only pegylated interferon approved for treating relapsing MS, according to a statement from the company.

Biogen Idec will be marketing the drug as Plegridy. The recommended dose is 125 mcg administered subcutaneously every 14 days. It can be administered with a prefilled syringe or a new autoinjector the company is marketing as the Plegridy Pen, according to the statement.

The approval is based on the results of the ADVANCE study, a randomized, double-blind, phase III, 2-year study of about 1,516 patients with relapsing MS, which was placebo-controlled during the first year. The annualized relapse rate, the primary outcome, was reduced by 36% among those treated with peginterferon beta-1a, compared with those on placebo, a statistically significant difference.

Secondary outcomes including the proportion of patients who relapsed, which was reduced by 19%, compared with placebo; the mean number of new or newly enlarging T2 hyperintense lesions, which was reduced by 67%, compared with placebo; and the mean number of new gadolinium-enhancing lesions, which was reduced by 86%, compared with placebo.

Injection-site erythema, influenzalike illness, fever, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia were the most common adverse events associated with treatment, affecting at least 10% of treated patients and occurring at a rate that was at least 2% greater than among those on placebo, according to the prescribing information.

Postmarketing studies that the company will be required to conduct include a pediatric study and a registry study in the United States that will compare the maternal, fetal, and infant outcomes, including birth defects, of women with MS who are treated with peginterferon beta-1a during pregnancy against women with MS who are not treated with the drug during pregnancy and women who do not have MS.

The product has already been approved in Europe.

Serious adverse events associated with this product should be reported to the FDA at 800-332-1088 or www. fda.gov/medwatch.

[email protected]

SILVER SPRING, MD. – Reassured by the cardiovascular safety data in a large randomized study, the majority of a Food and Drug Administration advisory panel supported the approval of an inhaled liquid spray formulation of tiotropium bromide in a new delivery device for the long-term maintenance treatment of chronic obstructive pulmonary disease.

At the Aug. 14 meeting of the FDA Pulmonary-Allergy Drugs Advisory Committee, the panel voted 10-3 that the safety and efficacy data supported the approval of tiotropium bromide inhalation spray, at a dose of 5 mcg/day, administered via a device that contains 30 doses, for the long-term, once-daily maintenance treatment of bronchospasm associated with COPD and for reducing COPD exacerbations.

If the FDA approves the product, Boehringer Ingelheim plans to market it as Spiriva Respimat. It has been available outside of the United States since 2007 and is now available in more than 85 countries, according to the company.

The panel unanimously voted that the available data supported the efficacy of the Respimat device for the indication. This is the same indication approved for the dry powder formulation of tiotropium in the single dose, breath-actuated HandiHaler device, marketed as Spiriva HandiHaler by Boehringer Ingelheim, approved in 2004 by the FDA. A capsule is inserted into the HandiHaler device for each dose.

Like others voting for approval, Dr. Francis McCormack agreed the data had met the criteria for safety and efficacy required for approval and that the new tiotropium product, Spiriva Respimat, was comparable to the existing Spiriva HandiHaler product. “I’m enthusiastic about being able to offer this delivery device to my patients,” commented Dr. McCormack, professor of medicine and director of the division of pulmonary, critical care, and sleep medicine at the University of Cincinnati.

The Respimat device delivers a 5-mcg dose, and the HandiHaler device delivers an 18-mcg dose, with similar pharmacokinetic effects and systemic exposure, according to the company. Panelists agreed that treatment with the Respimat device was not shown to be more effective than with the HandiHaler, and the company did not have any data showing that compliance was better with the Respimat device.

Those voting in favor of approval were reassured by the results of a large study that addressed concerns about a cardiovascular mortality signal in earlier studies associated with tiotropium Respimat.

Boehringer Ingelheim filed for approval of tiotropium Respimat almost 7 years ago. At that time, the FDA requested more data from the company to support the exacerbation claim and to address the mortality imbalance among those treated with tiotropium Respimat in 48-week, placebo-controlled studies, and concerns over cardiovascular safety raised during the review.

The randomized, double-blind, parallel group study, the Tiotropium Safety and Performance in Respimat (TIOSPIR) trial of more than 17,000 patients with COPD followed for at least 2 years adjudicated the cause of deaths, comparing 2.5 mg and 5 mg of tiotropium in the Respimat device to the tiotropium HandiHaler device. All-cause mortality in the three groups was similar.

Fatal MACE (major adverse cardiovascular events) rates were similar between the treatment groups, noted Dr. Robert Lim, a clinical reviewer in the FDA’s division of pulmonary, allergy, and rheumatology products. While there were numerical differences in two fatal MACE components – cardiac disorders and fatal myocardial infarction – the differences were small.

Panelists said that the imbalance in fatal MIs could be a random finding and was not strong enough to vote against approval. However, some panelists cited lingering concerns about a cardiovascular safety signal in different studies.

Although she voted in favor of approval, Erica H. Brittain, Ph.D., a biostatistician at the National Institute of Allergy and Infectious Diseases, Bethesda, Md., said that she had “lingering unease” about a cardiovascular safety signal cropping up in several studies. But she was confident with the all-cause mortality finding and the “clear-cut” efficacy. However, if the ease-of-use feature of the Respimat inhaler was not important to a patient, Dr. Brittain noted that she would probably recommend the HandiHaler product.

A cardiologist on the panel, Dr. Philip Sager, said that he was reassured by the data, and that overall safety, cardiovascular safety, and “clear efficacy in treating patients with COPD has been demonstrated.” Breaking the MACE endpoint down by subgroups gets complicated, and the MI finding could be “statistical noise,” added Dr. Sager, chair of the scientific programs committee of the Cardiac Safety Research Consortium, San Francisco.

Voting against approval, Sean Hennessy, Pharm.D., director of the Center for Pharmacoepidemiology Research and Training, University of Pennsylvania, Philadelphia, said he remained concerned about cardiac safety and the absence of data showing Respimat provided benefits over the HandiHaler. He referred to the consistent finding of an increased rate of fatal MIs in multiple randomized clinical trials.

The FDA is expected to make a decision on approval by Sept. 21. The agency usually follows the recommendations of its advisory panels. Panel members had no relevant conflicts of interest to disclose.

The TIOSPIR study was published in October 2013 (N. Engl. J. Med. 2013;369:1491-501).

[email protected]

SILVER SPRING, MD. – Reassured by the cardiovascular safety data in a large randomized study, the majority of a Food and Drug Administration advisory panel supported the approval of an inhaled liquid spray formulation of tiotropium bromide in a new delivery device for the long-term maintenance treatment of chronic obstructive pulmonary disease.

At the Aug. 14 meeting of the FDA Pulmonary-Allergy Drugs Advisory Committee, the panel voted 10-3 that the safety and efficacy data supported the approval of tiotropium bromide inhalation spray, at a dose of 5 mcg/day, administered via a device that contains 30 doses, for the long-term, once-daily maintenance treatment of bronchospasm associated with COPD and for reducing COPD exacerbations.

If the FDA approves the product, Boehringer Ingelheim plans to market it as Spiriva Respimat. It has been available outside of the United States since 2007 and is now available in more than 85 countries, according to the company.

The panel unanimously voted that the available data supported the efficacy of the Respimat device for the indication. This is the same indication approved for the dry powder formulation of tiotropium in the single dose, breath-actuated HandiHaler device, marketed as Spiriva HandiHaler by Boehringer Ingelheim, approved in 2004 by the FDA. A capsule is inserted into the HandiHaler device for each dose.

Like others voting for approval, Dr. Francis McCormack agreed the data had met the criteria for safety and efficacy required for approval and that the new tiotropium product, Spiriva Respimat, was comparable to the existing Spiriva HandiHaler product. “I’m enthusiastic about being able to offer this delivery device to my patients,” commented Dr. McCormack, professor of medicine and director of the division of pulmonary, critical care, and sleep medicine at the University of Cincinnati.

The Respimat device delivers a 5-mcg dose, and the HandiHaler device delivers an 18-mcg dose, with similar pharmacokinetic effects and systemic exposure, according to the company. Panelists agreed that treatment with the Respimat device was not shown to be more effective than with the HandiHaler, and the company did not have any data showing that compliance was better with the Respimat device.

Those voting in favor of approval were reassured by the results of a large study that addressed concerns about a cardiovascular mortality signal in earlier studies associated with tiotropium Respimat.

Boehringer Ingelheim filed for approval of tiotropium Respimat almost 7 years ago. At that time, the FDA requested more data from the company to support the exacerbation claim and to address the mortality imbalance among those treated with tiotropium Respimat in 48-week, placebo-controlled studies, and concerns over cardiovascular safety raised during the review.

The randomized, double-blind, parallel group study, the Tiotropium Safety and Performance in Respimat (TIOSPIR) trial of more than 17,000 patients with COPD followed for at least 2 years adjudicated the cause of deaths, comparing 2.5 mg and 5 mg of tiotropium in the Respimat device to the tiotropium HandiHaler device. All-cause mortality in the three groups was similar.

Fatal MACE (major adverse cardiovascular events) rates were similar between the treatment groups, noted Dr. Robert Lim, a clinical reviewer in the FDA’s division of pulmonary, allergy, and rheumatology products. While there were numerical differences in two fatal MACE components – cardiac disorders and fatal myocardial infarction – the differences were small.

Panelists said that the imbalance in fatal MIs could be a random finding and was not strong enough to vote against approval. However, some panelists cited lingering concerns about a cardiovascular safety signal in different studies.

Although she voted in favor of approval, Erica H. Brittain, Ph.D., a biostatistician at the National Institute of Allergy and Infectious Diseases, Bethesda, Md., said that she had “lingering unease” about a cardiovascular safety signal cropping up in several studies. But she was confident with the all-cause mortality finding and the “clear-cut” efficacy. However, if the ease-of-use feature of the Respimat inhaler was not important to a patient, Dr. Brittain noted that she would probably recommend the HandiHaler product.

A cardiologist on the panel, Dr. Philip Sager, said that he was reassured by the data, and that overall safety, cardiovascular safety, and “clear efficacy in treating patients with COPD has been demonstrated.” Breaking the MACE endpoint down by subgroups gets complicated, and the MI finding could be “statistical noise,” added Dr. Sager, chair of the scientific programs committee of the Cardiac Safety Research Consortium, San Francisco.

Voting against approval, Sean Hennessy, Pharm.D., director of the Center for Pharmacoepidemiology Research and Training, University of Pennsylvania, Philadelphia, said he remained concerned about cardiac safety and the absence of data showing Respimat provided benefits over the HandiHaler. He referred to the consistent finding of an increased rate of fatal MIs in multiple randomized clinical trials.

The FDA is expected to make a decision on approval by Sept. 21. The agency usually follows the recommendations of its advisory panels. Panel members had no relevant conflicts of interest to disclose.

The TIOSPIR study was published in October 2013 (N. Engl. J. Med. 2013;369:1491-501).

[email protected]

SILVER SPRING, MD. – Reassured by the cardiovascular safety data in a large randomized study, the majority of a Food and Drug Administration advisory panel supported the approval of an inhaled liquid spray formulation of tiotropium bromide in a new delivery device for the long-term maintenance treatment of chronic obstructive pulmonary disease.

At the Aug. 14 meeting of the FDA Pulmonary-Allergy Drugs Advisory Committee, the panel voted 10-3 that the safety and efficacy data supported the approval of tiotropium bromide inhalation spray, at a dose of 5 mcg/day, administered via a device that contains 30 doses, for the long-term, once-daily maintenance treatment of bronchospasm associated with COPD and for reducing COPD exacerbations.

If the FDA approves the product, Boehringer Ingelheim plans to market it as Spiriva Respimat. It has been available outside of the United States since 2007 and is now available in more than 85 countries, according to the company.

The panel unanimously voted that the available data supported the efficacy of the Respimat device for the indication. This is the same indication approved for the dry powder formulation of tiotropium in the single dose, breath-actuated HandiHaler device, marketed as Spiriva HandiHaler by Boehringer Ingelheim, approved in 2004 by the FDA. A capsule is inserted into the HandiHaler device for each dose.

Like others voting for approval, Dr. Francis McCormack agreed the data had met the criteria for safety and efficacy required for approval and that the new tiotropium product, Spiriva Respimat, was comparable to the existing Spiriva HandiHaler product. “I’m enthusiastic about being able to offer this delivery device to my patients,” commented Dr. McCormack, professor of medicine and director of the division of pulmonary, critical care, and sleep medicine at the University of Cincinnati.

The Respimat device delivers a 5-mcg dose, and the HandiHaler device delivers an 18-mcg dose, with similar pharmacokinetic effects and systemic exposure, according to the company. Panelists agreed that treatment with the Respimat device was not shown to be more effective than with the HandiHaler, and the company did not have any data showing that compliance was better with the Respimat device.

Those voting in favor of approval were reassured by the results of a large study that addressed concerns about a cardiovascular mortality signal in earlier studies associated with tiotropium Respimat.

Boehringer Ingelheim filed for approval of tiotropium Respimat almost 7 years ago. At that time, the FDA requested more data from the company to support the exacerbation claim and to address the mortality imbalance among those treated with tiotropium Respimat in 48-week, placebo-controlled studies, and concerns over cardiovascular safety raised during the review.

The randomized, double-blind, parallel group study, the Tiotropium Safety and Performance in Respimat (TIOSPIR) trial of more than 17,000 patients with COPD followed for at least 2 years adjudicated the cause of deaths, comparing 2.5 mg and 5 mg of tiotropium in the Respimat device to the tiotropium HandiHaler device. All-cause mortality in the three groups was similar.

Fatal MACE (major adverse cardiovascular events) rates were similar between the treatment groups, noted Dr. Robert Lim, a clinical reviewer in the FDA’s division of pulmonary, allergy, and rheumatology products. While there were numerical differences in two fatal MACE components – cardiac disorders and fatal myocardial infarction – the differences were small.

Panelists said that the imbalance in fatal MIs could be a random finding and was not strong enough to vote against approval. However, some panelists cited lingering concerns about a cardiovascular safety signal in different studies.

Although she voted in favor of approval, Erica H. Brittain, Ph.D., a biostatistician at the National Institute of Allergy and Infectious Diseases, Bethesda, Md., said that she had “lingering unease” about a cardiovascular safety signal cropping up in several studies. But she was confident with the all-cause mortality finding and the “clear-cut” efficacy. However, if the ease-of-use feature of the Respimat inhaler was not important to a patient, Dr. Brittain noted that she would probably recommend the HandiHaler product.

A cardiologist on the panel, Dr. Philip Sager, said that he was reassured by the data, and that overall safety, cardiovascular safety, and “clear efficacy in treating patients with COPD has been demonstrated.” Breaking the MACE endpoint down by subgroups gets complicated, and the MI finding could be “statistical noise,” added Dr. Sager, chair of the scientific programs committee of the Cardiac Safety Research Consortium, San Francisco.

Voting against approval, Sean Hennessy, Pharm.D., director of the Center for Pharmacoepidemiology Research and Training, University of Pennsylvania, Philadelphia, said he remained concerned about cardiac safety and the absence of data showing Respimat provided benefits over the HandiHaler. He referred to the consistent finding of an increased rate of fatal MIs in multiple randomized clinical trials.

The FDA is expected to make a decision on approval by Sept. 21. The agency usually follows the recommendations of its advisory panels. Panel members had no relevant conflicts of interest to disclose.

The TIOSPIR study was published in October 2013 (N. Engl. J. Med. 2013;369:1491-501).

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported the approval of an inhaled liquid spray formulation of tiotropium bromide in a new delivery device for the long-term maintenance of chronic obstructive pulmonary disease.

At a Aug. 14 meeting of the FDA Pulmonary-Allergy Drugs Advisory Committee, the panel voted 10-3 that the safety and efficacy data supported the approval of tiotropium bromide inhalation spray, at a dose of 5 mcg/day, administered via a device that contains 30 doses, for the long-term, once-daily maintenance treatment of bronchospasm associated with COPD and for reducing COPD exacerbations.

The panel unanimously voted that the available data supported the efficacy of the device for the indication. This is the same indication approved for the dry powder formulation of tiotropium in the single dose, breath-actuated device, marketed as Spiriva HandiHaler by Boehringer Ingelheim, approved in 2004 by the FDA.

The Respimat device delivers 5-mcg dose and the HandiHaler device delivers 18-mcg dose, with similar pharmacokinetic effects and systemic exposure, according to the company.

Those voting in favor of approval were reassured by the results of a large safety study that addressed concerns about a cardiovascular mortality signal in earlier studies associated with tiotropium Respimat. Boehringer Ingelheim filed for approval of tiotropium Respimat almost 7 years ago; at that time, the FDA requested more data from the company to support the exacerbation claim and to address the mortality imbalance among those treated with tiotropium Respimat in 48-week placebo-controlled studies, and concerns over cardiovascular safety raised during the review.

The safety study of more than 17,000 patients with COPD followed for at least 2 years adjudicated the cause of deaths, comparing 2.5 mg and 5 mg of tiotropium in the Respimat device to the tiotropium HandiHaler device. All-cause mortality in the three groups was similar. There were more fatal MIs in the Respimat-treated patients, but panelists said that this could be a statistical finding and was not strong enough to vote against approval. Some panelists cited lingering concerns about a cardiovascular safety signal in different studies.

If approved, Boehringer Ingelheim plans to market the product as Spiriva Respimat.

The FDA is expected to make a decision on approval by Sept. 21. The agency usually follows the recommendations of its advisory panels. Panel members had no relevant conflicts of interest to disclose.

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported the approval of an inhaled liquid spray formulation of tiotropium bromide in a new delivery device for the long-term maintenance of chronic obstructive pulmonary disease.

At a Aug. 14 meeting of the FDA Pulmonary-Allergy Drugs Advisory Committee, the panel voted 10-3 that the safety and efficacy data supported the approval of tiotropium bromide inhalation spray, at a dose of 5 mcg/day, administered via a device that contains 30 doses, for the long-term, once-daily maintenance treatment of bronchospasm associated with COPD and for reducing COPD exacerbations.

The panel unanimously voted that the available data supported the efficacy of the device for the indication. This is the same indication approved for the dry powder formulation of tiotropium in the single dose, breath-actuated device, marketed as Spiriva HandiHaler by Boehringer Ingelheim, approved in 2004 by the FDA.

The Respimat device delivers 5-mcg dose and the HandiHaler device delivers 18-mcg dose, with similar pharmacokinetic effects and systemic exposure, according to the company.

Those voting in favor of approval were reassured by the results of a large safety study that addressed concerns about a cardiovascular mortality signal in earlier studies associated with tiotropium Respimat. Boehringer Ingelheim filed for approval of tiotropium Respimat almost 7 years ago; at that time, the FDA requested more data from the company to support the exacerbation claim and to address the mortality imbalance among those treated with tiotropium Respimat in 48-week placebo-controlled studies, and concerns over cardiovascular safety raised during the review.

The safety study of more than 17,000 patients with COPD followed for at least 2 years adjudicated the cause of deaths, comparing 2.5 mg and 5 mg of tiotropium in the Respimat device to the tiotropium HandiHaler device. All-cause mortality in the three groups was similar. There were more fatal MIs in the Respimat-treated patients, but panelists said that this could be a statistical finding and was not strong enough to vote against approval. Some panelists cited lingering concerns about a cardiovascular safety signal in different studies.

If approved, Boehringer Ingelheim plans to market the product as Spiriva Respimat.

The FDA is expected to make a decision on approval by Sept. 21. The agency usually follows the recommendations of its advisory panels. Panel members had no relevant conflicts of interest to disclose.

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported the approval of an inhaled liquid spray formulation of tiotropium bromide in a new delivery device for the long-term maintenance of chronic obstructive pulmonary disease.

At a Aug. 14 meeting of the FDA Pulmonary-Allergy Drugs Advisory Committee, the panel voted 10-3 that the safety and efficacy data supported the approval of tiotropium bromide inhalation spray, at a dose of 5 mcg/day, administered via a device that contains 30 doses, for the long-term, once-daily maintenance treatment of bronchospasm associated with COPD and for reducing COPD exacerbations.

The panel unanimously voted that the available data supported the efficacy of the device for the indication. This is the same indication approved for the dry powder formulation of tiotropium in the single dose, breath-actuated device, marketed as Spiriva HandiHaler by Boehringer Ingelheim, approved in 2004 by the FDA.

The Respimat device delivers 5-mcg dose and the HandiHaler device delivers 18-mcg dose, with similar pharmacokinetic effects and systemic exposure, according to the company.

Those voting in favor of approval were reassured by the results of a large safety study that addressed concerns about a cardiovascular mortality signal in earlier studies associated with tiotropium Respimat. Boehringer Ingelheim filed for approval of tiotropium Respimat almost 7 years ago; at that time, the FDA requested more data from the company to support the exacerbation claim and to address the mortality imbalance among those treated with tiotropium Respimat in 48-week placebo-controlled studies, and concerns over cardiovascular safety raised during the review.

The safety study of more than 17,000 patients with COPD followed for at least 2 years adjudicated the cause of deaths, comparing 2.5 mg and 5 mg of tiotropium in the Respimat device to the tiotropium HandiHaler device. All-cause mortality in the three groups was similar. There were more fatal MIs in the Respimat-treated patients, but panelists said that this could be a statistical finding and was not strong enough to vote against approval. Some panelists cited lingering concerns about a cardiovascular safety signal in different studies.

If approved, Boehringer Ingelheim plans to market the product as Spiriva Respimat.

The FDA is expected to make a decision on approval by Sept. 21. The agency usually follows the recommendations of its advisory panels. Panel members had no relevant conflicts of interest to disclose.

[email protected]

The Food and Drug Administration has issued a warning about adverse events associated with use of the Expression intranasal splint as a dermal filler – an unapproved indication for this product.

The FDA released its statement on Aug. 5.

Expression, also known as "Expression Injectable," manufactured by Enhancement Medical LLC, is a hyaluronic acid product packaged in a syringe, and it is cleared by the FDA for use only as an intranasal splint.

But off-label use of the product as a dermal filler has been associated with reports of swelling, tenderness, firmness, bruising, pain, redness, discoloration, itching, and the development of hard nodules, according to the FDA statement. The reports include one case of a patient who developed firm masses in the face after the Expression product was injected as a dermal filler. "An attempt was made to dissolve the masses, but the report notes that the patient was left with an ‘obvious deformity,’ " the FDA statement said.

The agency noted that the components of Expression are similar to those of dermal fillers approved by the FDA, and the adverse event reports "appear similar" to those reported with those approved products. However, dermal fillers are classified by the agency as class III, high-risk medical devices and "without reviewing clinical data supporting the safety and effectiveness the FDA cannot not fully understand the nature, severity, or rate of occurrence of adverse events associated with Expression and has no assurance of this product’s safety or effectiveness when used as a dermal filler," the statement said.

A list of FDA-approved dermal fillers is available here.

Health care professionals and consumers should report adverse events associated with this product by visiting the FDA’s MedWatch site, or by calling 800-332-1088.

[email protected]

The Food and Drug Administration has issued a warning about adverse events associated with use of the Expression intranasal splint as a dermal filler – an unapproved indication for this product.

The FDA released its statement on Aug. 5.

Expression, also known as "Expression Injectable," manufactured by Enhancement Medical LLC, is a hyaluronic acid product packaged in a syringe, and it is cleared by the FDA for use only as an intranasal splint.

But off-label use of the product as a dermal filler has been associated with reports of swelling, tenderness, firmness, bruising, pain, redness, discoloration, itching, and the development of hard nodules, according to the FDA statement. The reports include one case of a patient who developed firm masses in the face after the Expression product was injected as a dermal filler. "An attempt was made to dissolve the masses, but the report notes that the patient was left with an ‘obvious deformity,’ " the FDA statement said.

The agency noted that the components of Expression are similar to those of dermal fillers approved by the FDA, and the adverse event reports "appear similar" to those reported with those approved products. However, dermal fillers are classified by the agency as class III, high-risk medical devices and "without reviewing clinical data supporting the safety and effectiveness the FDA cannot not fully understand the nature, severity, or rate of occurrence of adverse events associated with Expression and has no assurance of this product’s safety or effectiveness when used as a dermal filler," the statement said.

A list of FDA-approved dermal fillers is available here.

Health care professionals and consumers should report adverse events associated with this product by visiting the FDA’s MedWatch site, or by calling 800-332-1088.

[email protected]

The Food and Drug Administration has issued a warning about adverse events associated with use of the Expression intranasal splint as a dermal filler – an unapproved indication for this product.

The FDA released its statement on Aug. 5.

Expression, also known as "Expression Injectable," manufactured by Enhancement Medical LLC, is a hyaluronic acid product packaged in a syringe, and it is cleared by the FDA for use only as an intranasal splint.

But off-label use of the product as a dermal filler has been associated with reports of swelling, tenderness, firmness, bruising, pain, redness, discoloration, itching, and the development of hard nodules, according to the FDA statement. The reports include one case of a patient who developed firm masses in the face after the Expression product was injected as a dermal filler. "An attempt was made to dissolve the masses, but the report notes that the patient was left with an ‘obvious deformity,’ " the FDA statement said.

The agency noted that the components of Expression are similar to those of dermal fillers approved by the FDA, and the adverse event reports "appear similar" to those reported with those approved products. However, dermal fillers are classified by the agency as class III, high-risk medical devices and "without reviewing clinical data supporting the safety and effectiveness the FDA cannot not fully understand the nature, severity, or rate of occurrence of adverse events associated with Expression and has no assurance of this product’s safety or effectiveness when used as a dermal filler," the statement said.

A list of FDA-approved dermal fillers is available here.

Health care professionals and consumers should report adverse events associated with this product by visiting the FDA’s MedWatch site, or by calling 800-332-1088.

[email protected]

The use of an insufflated collection bag during minimally invasive hysterectomy or myomectomy that involved a power morcellator was successful in containing morcellation in a small series, according to the authors of the study.

"The benefits of morcellation under direct vision within an insufflated isolation bag include the potential reduction of tissue dissemination while preserving the well-known benefits of minimally invasive gynecologic surgery," said Dr. Sarah Cohen of the division of minimally invasive gynecologic surgery, Brigham and Women’s Hospital, Boston, and her associates (Obstet. Gynecol. 2014;124:491-7).

The technique entails placing the specimen into the 50-by-50-cm bag, insufflated in the peritoneal cavity, and using the power morcellator within the bag, which captures small fragments and fluids. It was used in 73 women who underwent uterine tissue morcellation at four institutions from January 2013 through April 2014; almost 70% had leiomyomas. No perforations were seen in the bags, and visual inspection revealed no dissemination of morcellated material. The technique is "evolving" and needs to be tested further, the investigators said.

The median operative time was 114 minutes (range, 32-380 minutes), and the median estimated blood loss was 50 mL (range, 10-500 mL). The median weight of the specimens was 257 g (range, 53-1,481 g). No cases required conversion to laparotomy, readmission, or reoperation; 78% of patients were discharged home the same day, Dr. Cohen and her associates reported.

In an accompanying editorial, Dr. Charles R. Rardin said that although morcellating within a bag to mitigate the risk of spreading tissue during procedures that involve power morcellation "may appear to be a tempting solution, there are several issues and questions regarding the plausibility, safety, and efficacy of in-bag morcellation" (Obstet. Gynecol. 2014;124:489-90).

This study, which did not formally investigate the integrity of the bag or spread of tissue, primarily addressed "the technical plausibility of in-bag morcellation during laparoscopic myomectomy or hysterectomy (supracervical or total)," he wrote, noting that whether tissue had spread beyond the bag "was essentially assessed by a visual judgment by the surgeon."

Dr. Rardin of the division of urogynecology in the department of obstetrics and gynecology at Women and Infants’ Hospital, Providence, R.I., described the study "as a first scientific step toward understanding whether this is a viable answer."

He did suggest that although comparative data were lacking, gynecologic surgeons should remember their skills at performing vaginal hysterectomy with extraction techniques, the "original minimally invasive surgery."

Before publication of this article, the Food and Drug Administration held a 2-day meeting of its Obstetrics and Gynecology Devices Advisory Panel in July 2014 to discuss the benefits, risks, and clinical role of laparoscopic power morcellators (LPMs) in the treatment of women with uterine fibroids.

Panelists also discussed strategies that might reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma. Two panelists said that LPMs should not be used for gynecologic indications until better data are available, and during the open public hearing, Dr. Hooman Nourchashm, a cardiothoracic surgeon, reiterated his call for a worldwide moratorium on all gynecologic tissue morcellation devices and on the practice of intracorporeal uterine morcellation during minimally invasive hysterectomy. He and his wife, anesthesiologist Amy Reed, who was diagnosed in 2013 with stage IV leiomyosarcoma after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, are leading a campaign calling for the ban.

At the end of July 2014, Ethicon initiated a worldwide withdrawal of the company’s morcellation devices because of the uncertainty over the risk-benefit profile of these devices when used in hysterectomies and myomectomies for women with fibroids, the company announced in a letter. It is the only company manufacturing or distributing LPMs to have done so at press time. There are five other manufacturers or distributors of LPMs with gynecologic indications that have been marketed in the past year, according to the FDA.

Dr. Rardin said he had no relevant financial disclosures. One of the study’s authors, Dr. Tony Shibley, who developed the technique, is developing a device to "facilitate contained morcellation" with Advanced Surgical Concepts, a company based in Dublin. The remaining authors did not report any potential conflicts of interest.

[email protected]

The use of an insufflated collection bag during minimally invasive hysterectomy or myomectomy that involved a power morcellator was successful in containing morcellation in a small series, according to the authors of the study.

"The benefits of morcellation under direct vision within an insufflated isolation bag include the potential reduction of tissue dissemination while preserving the well-known benefits of minimally invasive gynecologic surgery," said Dr. Sarah Cohen of the division of minimally invasive gynecologic surgery, Brigham and Women’s Hospital, Boston, and her associates (Obstet. Gynecol. 2014;124:491-7).

The technique entails placing the specimen into the 50-by-50-cm bag, insufflated in the peritoneal cavity, and using the power morcellator within the bag, which captures small fragments and fluids. It was used in 73 women who underwent uterine tissue morcellation at four institutions from January 2013 through April 2014; almost 70% had leiomyomas. No perforations were seen in the bags, and visual inspection revealed no dissemination of morcellated material. The technique is "evolving" and needs to be tested further, the investigators said.

The median operative time was 114 minutes (range, 32-380 minutes), and the median estimated blood loss was 50 mL (range, 10-500 mL). The median weight of the specimens was 257 g (range, 53-1,481 g). No cases required conversion to laparotomy, readmission, or reoperation; 78% of patients were discharged home the same day, Dr. Cohen and her associates reported.

In an accompanying editorial, Dr. Charles R. Rardin said that although morcellating within a bag to mitigate the risk of spreading tissue during procedures that involve power morcellation "may appear to be a tempting solution, there are several issues and questions regarding the plausibility, safety, and efficacy of in-bag morcellation" (Obstet. Gynecol. 2014;124:489-90).

This study, which did not formally investigate the integrity of the bag or spread of tissue, primarily addressed "the technical plausibility of in-bag morcellation during laparoscopic myomectomy or hysterectomy (supracervical or total)," he wrote, noting that whether tissue had spread beyond the bag "was essentially assessed by a visual judgment by the surgeon."

Dr. Rardin of the division of urogynecology in the department of obstetrics and gynecology at Women and Infants’ Hospital, Providence, R.I., described the study "as a first scientific step toward understanding whether this is a viable answer."

He did suggest that although comparative data were lacking, gynecologic surgeons should remember their skills at performing vaginal hysterectomy with extraction techniques, the "original minimally invasive surgery."

Before publication of this article, the Food and Drug Administration held a 2-day meeting of its Obstetrics and Gynecology Devices Advisory Panel in July 2014 to discuss the benefits, risks, and clinical role of laparoscopic power morcellators (LPMs) in the treatment of women with uterine fibroids.

Panelists also discussed strategies that might reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma. Two panelists said that LPMs should not be used for gynecologic indications until better data are available, and during the open public hearing, Dr. Hooman Nourchashm, a cardiothoracic surgeon, reiterated his call for a worldwide moratorium on all gynecologic tissue morcellation devices and on the practice of intracorporeal uterine morcellation during minimally invasive hysterectomy. He and his wife, anesthesiologist Amy Reed, who was diagnosed in 2013 with stage IV leiomyosarcoma after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, are leading a campaign calling for the ban.

At the end of July 2014, Ethicon initiated a worldwide withdrawal of the company’s morcellation devices because of the uncertainty over the risk-benefit profile of these devices when used in hysterectomies and myomectomies for women with fibroids, the company announced in a letter. It is the only company manufacturing or distributing LPMs to have done so at press time. There are five other manufacturers or distributors of LPMs with gynecologic indications that have been marketed in the past year, according to the FDA.

Dr. Rardin said he had no relevant financial disclosures. One of the study’s authors, Dr. Tony Shibley, who developed the technique, is developing a device to "facilitate contained morcellation" with Advanced Surgical Concepts, a company based in Dublin. The remaining authors did not report any potential conflicts of interest.

[email protected]

The use of an insufflated collection bag during minimally invasive hysterectomy or myomectomy that involved a power morcellator was successful in containing morcellation in a small series, according to the authors of the study.

"The benefits of morcellation under direct vision within an insufflated isolation bag include the potential reduction of tissue dissemination while preserving the well-known benefits of minimally invasive gynecologic surgery," said Dr. Sarah Cohen of the division of minimally invasive gynecologic surgery, Brigham and Women’s Hospital, Boston, and her associates (Obstet. Gynecol. 2014;124:491-7).

The technique entails placing the specimen into the 50-by-50-cm bag, insufflated in the peritoneal cavity, and using the power morcellator within the bag, which captures small fragments and fluids. It was used in 73 women who underwent uterine tissue morcellation at four institutions from January 2013 through April 2014; almost 70% had leiomyomas. No perforations were seen in the bags, and visual inspection revealed no dissemination of morcellated material. The technique is "evolving" and needs to be tested further, the investigators said.

The median operative time was 114 minutes (range, 32-380 minutes), and the median estimated blood loss was 50 mL (range, 10-500 mL). The median weight of the specimens was 257 g (range, 53-1,481 g). No cases required conversion to laparotomy, readmission, or reoperation; 78% of patients were discharged home the same day, Dr. Cohen and her associates reported.

In an accompanying editorial, Dr. Charles R. Rardin said that although morcellating within a bag to mitigate the risk of spreading tissue during procedures that involve power morcellation "may appear to be a tempting solution, there are several issues and questions regarding the plausibility, safety, and efficacy of in-bag morcellation" (Obstet. Gynecol. 2014;124:489-90).

This study, which did not formally investigate the integrity of the bag or spread of tissue, primarily addressed "the technical plausibility of in-bag morcellation during laparoscopic myomectomy or hysterectomy (supracervical or total)," he wrote, noting that whether tissue had spread beyond the bag "was essentially assessed by a visual judgment by the surgeon."

Dr. Rardin of the division of urogynecology in the department of obstetrics and gynecology at Women and Infants’ Hospital, Providence, R.I., described the study "as a first scientific step toward understanding whether this is a viable answer."

He did suggest that although comparative data were lacking, gynecologic surgeons should remember their skills at performing vaginal hysterectomy with extraction techniques, the "original minimally invasive surgery."

Before publication of this article, the Food and Drug Administration held a 2-day meeting of its Obstetrics and Gynecology Devices Advisory Panel in July 2014 to discuss the benefits, risks, and clinical role of laparoscopic power morcellators (LPMs) in the treatment of women with uterine fibroids.

Panelists also discussed strategies that might reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma. Two panelists said that LPMs should not be used for gynecologic indications until better data are available, and during the open public hearing, Dr. Hooman Nourchashm, a cardiothoracic surgeon, reiterated his call for a worldwide moratorium on all gynecologic tissue morcellation devices and on the practice of intracorporeal uterine morcellation during minimally invasive hysterectomy. He and his wife, anesthesiologist Amy Reed, who was diagnosed in 2013 with stage IV leiomyosarcoma after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, are leading a campaign calling for the ban.

At the end of July 2014, Ethicon initiated a worldwide withdrawal of the company’s morcellation devices because of the uncertainty over the risk-benefit profile of these devices when used in hysterectomies and myomectomies for women with fibroids, the company announced in a letter. It is the only company manufacturing or distributing LPMs to have done so at press time. There are five other manufacturers or distributors of LPMs with gynecologic indications that have been marketed in the past year, according to the FDA.

Dr. Rardin said he had no relevant financial disclosures. One of the study’s authors, Dr. Tony Shibley, who developed the technique, is developing a device to "facilitate contained morcellation" with Advanced Surgical Concepts, a company based in Dublin. The remaining authors did not report any potential conflicts of interest.

[email protected]

The Food and Drug Administration has approved once-daily oral empagliflozin for adults with type 2 diabetes, based on seven studies with nearly 4,500 patients.

Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels. It has been studied "as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylureas, pioglitazone, and insulin," according to an Aug. 1 FDA statement announcing the approval.

Boehringer Ingelheim Pharmaceuticals will market empagliflozin as Jardiance.

This is the third SGLT2 inhibitor approved by the FDA, following the approval of dapagliflozin (Farxiga) in January 2014 and canagliflozin (Invokana) in March 2013.

The most common side effects of treatment are genital infections in women and urinary tract infections, according to the FDA. Treatment can also cause dehydration resulting in hypotension, with dizziness and/or fainting, as well as reduced renal function. "The elderly, patients with impaired renal function, and patients on diuretics to treat other conditions appeared to be more susceptible to this risk," the FDA noted.

Empagliflozin should not be used to treat patients with severe renal impairment or end-stage renal disease, or who are on dialysis. The drug also should not be used in patients with diabetic ketoacidosis and those with type 1 diabetes.

Boehringer Ingelheim must conduct four postmarketing studies of empagliflozin: a cardiovascular outcomes trial, which is already underway; a pediatric pharmacokinetic/pharmacodynamic study; a pediatric safety and efficacy study (which will include evaluations of bone health and development); and a juvenile animal toxicity study. The animal study will have "a particular focus on renal development, bone development, and growth," the FDA statement said.

In May, the European Commission approved empagliflozin for treating adults with type 2 diabetes.

[email protected]

The Food and Drug Administration has approved once-daily oral empagliflozin for adults with type 2 diabetes, based on seven studies with nearly 4,500 patients.

Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels. It has been studied "as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylureas, pioglitazone, and insulin," according to an Aug. 1 FDA statement announcing the approval.

Boehringer Ingelheim Pharmaceuticals will market empagliflozin as Jardiance.

This is the third SGLT2 inhibitor approved by the FDA, following the approval of dapagliflozin (Farxiga) in January 2014 and canagliflozin (Invokana) in March 2013.

The most common side effects of treatment are genital infections in women and urinary tract infections, according to the FDA. Treatment can also cause dehydration resulting in hypotension, with dizziness and/or fainting, as well as reduced renal function. "The elderly, patients with impaired renal function, and patients on diuretics to treat other conditions appeared to be more susceptible to this risk," the FDA noted.

Empagliflozin should not be used to treat patients with severe renal impairment or end-stage renal disease, or who are on dialysis. The drug also should not be used in patients with diabetic ketoacidosis and those with type 1 diabetes.

Boehringer Ingelheim must conduct four postmarketing studies of empagliflozin: a cardiovascular outcomes trial, which is already underway; a pediatric pharmacokinetic/pharmacodynamic study; a pediatric safety and efficacy study (which will include evaluations of bone health and development); and a juvenile animal toxicity study. The animal study will have "a particular focus on renal development, bone development, and growth," the FDA statement said.

In May, the European Commission approved empagliflozin for treating adults with type 2 diabetes.

[email protected]

The Food and Drug Administration has approved once-daily oral empagliflozin for adults with type 2 diabetes, based on seven studies with nearly 4,500 patients.

Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels. It has been studied "as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylureas, pioglitazone, and insulin," according to an Aug. 1 FDA statement announcing the approval.

Boehringer Ingelheim Pharmaceuticals will market empagliflozin as Jardiance.

This is the third SGLT2 inhibitor approved by the FDA, following the approval of dapagliflozin (Farxiga) in January 2014 and canagliflozin (Invokana) in March 2013.

The most common side effects of treatment are genital infections in women and urinary tract infections, according to the FDA. Treatment can also cause dehydration resulting in hypotension, with dizziness and/or fainting, as well as reduced renal function. "The elderly, patients with impaired renal function, and patients on diuretics to treat other conditions appeared to be more susceptible to this risk," the FDA noted.

Empagliflozin should not be used to treat patients with severe renal impairment or end-stage renal disease, or who are on dialysis. The drug also should not be used in patients with diabetic ketoacidosis and those with type 1 diabetes.

Boehringer Ingelheim must conduct four postmarketing studies of empagliflozin: a cardiovascular outcomes trial, which is already underway; a pediatric pharmacokinetic/pharmacodynamic study; a pediatric safety and efficacy study (which will include evaluations of bone health and development); and a juvenile animal toxicity study. The animal study will have "a particular focus on renal development, bone development, and growth," the FDA statement said.

In May, the European Commission approved empagliflozin for treating adults with type 2 diabetes.

[email protected]

Ethicon has initiated a worldwide withdrawal of the company’s morcellation devices because of the uncertainty over the risk-benefit profile of these devices when used in hysterectomies and myomectomies for women with fibroids, the company announced in a letter on July 30.

The withdrawal – which is voluntary – is an expansion of the company’s suspension of worldwide sales of these devices in April, following the Food and Drug Administration (FDA) announcement recommending that the use of power morcellation during laparoscopic hysterectomy or myomectomy to remove uterine fibroids should be "discouraged," because the procedure could spread cancerous tissue in women with an unsuspected sarcoma.

In its letter, Ethicon stated that the company believes that its morcellation devices "perform as intended and there are patients who can benefit from procedures using laparoscopic power morcellators."

However, the letter adds that "the risk-benefit assessment associated with the use of these devices in hysterectomy and myomectomy procedures remains uncertain," and the company believes that market withdrawal "is the appropriate course of action at this time until further medical guidelines are established and/or new technologies are developed to mitigate the risk."

The Ethicon withdrawal was announced less than 3 weeks after the FDA held a 2-day meeting of its Obstetrics and Gynecology Devices Advisory Panel to discuss the benefits, risks, and clinical role of laparoscopic power morcellators (LPMs) in the treatment of women with uterine fibroids.

Panelists also discussed strategies that might reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma (LMS). Two panelists said that LPMs should not be used for gynecologic indications until better data are available, and during the open public hearing, Dr. Hooman Nourchashm, a cardiothoracic surgeon, reiterated his call for a worldwide moratorium on all gynecological tissue morcellation devices and on the practice of intracorporeal uterine morcellation during minimally invasive hysterectomy. He and his wife, anesthesiologist Dr. Amy Reed, who was diagnosed in 2013 with stage IV LMS after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, are leading a campaign calling for the ban.

The Ethicon letter states that the discussion during the meeting "demonstrated the complexity of this issue, particularly with respect to the difficulty for medical professionals to preoperatively diagnose some malignancies, such as leiomyosarcoma ... [and] the risk of disseminating unsuspected malignant tissue while using power morcellation devices," as well as methods to mitigate this risk.

But to date, Ethicon, a Johnson & Johnson company, is the only manufacturer of morcellation devices used in gynecology to suspend and withdraw its products. There are five other manufacturers or distributors of LPMs with gynecologic indications that have been marketed in the past year, according to the FDA.

Dr. David Jaspan, chairman of the department of obstetrics and gynecology at Einstein Medical Center, Philadelphia, said in an interview that he views the Ethicon move to withdraw all morcellation devices as a business decision. This "may be the first domino to fall," and whether competing manufacturers of morcellation devices also decide to withdraw their products or choose an alternative path "remains to be seen."

At the Einstein health care network in Philadelphia, there is currently a moratorium prohibiting the use of power morcellation in gynecologic surgery, while a standard acceptable counseling form is being developed. Dr. Jaspan is working with robotic and minimally invasive surgeons "to create a document that we feel will provide patients with transparency, alternatives, and choice," he noted.

As a result of the FDA’s safety announcement, there has been an increase in open procedures for fibroids in patients who would have been "excellent candidates" for a robotic procedure; did not have a sarcoma; and would have avoided a prolonged length of stay, time away from work, delay in activities of daily living, more blood loss, and pain, he said.

But the FDA estimates that among women who undergo a hysterectomy or myomectomy for a presumed fibroid, about 1 in 350 has a uterine sarcoma, and about 1 in 500 has an LMS. Dr. Jaspan is among those who believe this is an overestimate.

Dr. Jaspan had no disclosures.

Ethicon can be contacted at 877-384-4266 for more information. Adverse events related to LPMs or other medical devices should be reported to the FDA at 800-332-1088 or here.

[email protected]

Ethicon has initiated a worldwide withdrawal of the company’s morcellation devices because of the uncertainty over the risk-benefit profile of these devices when used in hysterectomies and myomectomies for women with fibroids, the company announced in a letter on July 30.

The withdrawal – which is voluntary – is an expansion of the company’s suspension of worldwide sales of these devices in April, following the Food and Drug Administration (FDA) announcement recommending that the use of power morcellation during laparoscopic hysterectomy or myomectomy to remove uterine fibroids should be "discouraged," because the procedure could spread cancerous tissue in women with an unsuspected sarcoma.

In its letter, Ethicon stated that the company believes that its morcellation devices "perform as intended and there are patients who can benefit from procedures using laparoscopic power morcellators."

However, the letter adds that "the risk-benefit assessment associated with the use of these devices in hysterectomy and myomectomy procedures remains uncertain," and the company believes that market withdrawal "is the appropriate course of action at this time until further medical guidelines are established and/or new technologies are developed to mitigate the risk."

The Ethicon withdrawal was announced less than 3 weeks after the FDA held a 2-day meeting of its Obstetrics and Gynecology Devices Advisory Panel to discuss the benefits, risks, and clinical role of laparoscopic power morcellators (LPMs) in the treatment of women with uterine fibroids.

Panelists also discussed strategies that might reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma (LMS). Two panelists said that LPMs should not be used for gynecologic indications until better data are available, and during the open public hearing, Dr. Hooman Nourchashm, a cardiothoracic surgeon, reiterated his call for a worldwide moratorium on all gynecological tissue morcellation devices and on the practice of intracorporeal uterine morcellation during minimally invasive hysterectomy. He and his wife, anesthesiologist Dr. Amy Reed, who was diagnosed in 2013 with stage IV LMS after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, are leading a campaign calling for the ban.

The Ethicon letter states that the discussion during the meeting "demonstrated the complexity of this issue, particularly with respect to the difficulty for medical professionals to preoperatively diagnose some malignancies, such as leiomyosarcoma ... [and] the risk of disseminating unsuspected malignant tissue while using power morcellation devices," as well as methods to mitigate this risk.

But to date, Ethicon, a Johnson & Johnson company, is the only manufacturer of morcellation devices used in gynecology to suspend and withdraw its products. There are five other manufacturers or distributors of LPMs with gynecologic indications that have been marketed in the past year, according to the FDA.

Dr. David Jaspan, chairman of the department of obstetrics and gynecology at Einstein Medical Center, Philadelphia, said in an interview that he views the Ethicon move to withdraw all morcellation devices as a business decision. This "may be the first domino to fall," and whether competing manufacturers of morcellation devices also decide to withdraw their products or choose an alternative path "remains to be seen."

At the Einstein health care network in Philadelphia, there is currently a moratorium prohibiting the use of power morcellation in gynecologic surgery, while a standard acceptable counseling form is being developed. Dr. Jaspan is working with robotic and minimally invasive surgeons "to create a document that we feel will provide patients with transparency, alternatives, and choice," he noted.

As a result of the FDA’s safety announcement, there has been an increase in open procedures for fibroids in patients who would have been "excellent candidates" for a robotic procedure; did not have a sarcoma; and would have avoided a prolonged length of stay, time away from work, delay in activities of daily living, more blood loss, and pain, he said.

But the FDA estimates that among women who undergo a hysterectomy or myomectomy for a presumed fibroid, about 1 in 350 has a uterine sarcoma, and about 1 in 500 has an LMS. Dr. Jaspan is among those who believe this is an overestimate.

Dr. Jaspan had no disclosures.

Ethicon can be contacted at 877-384-4266 for more information. Adverse events related to LPMs or other medical devices should be reported to the FDA at 800-332-1088 or here.

[email protected]

Ethicon has initiated a worldwide withdrawal of the company’s morcellation devices because of the uncertainty over the risk-benefit profile of these devices when used in hysterectomies and myomectomies for women with fibroids, the company announced in a letter on July 30.

The withdrawal – which is voluntary – is an expansion of the company’s suspension of worldwide sales of these devices in April, following the Food and Drug Administration (FDA) announcement recommending that the use of power morcellation during laparoscopic hysterectomy or myomectomy to remove uterine fibroids should be "discouraged," because the procedure could spread cancerous tissue in women with an unsuspected sarcoma.

In its letter, Ethicon stated that the company believes that its morcellation devices "perform as intended and there are patients who can benefit from procedures using laparoscopic power morcellators."

However, the letter adds that "the risk-benefit assessment associated with the use of these devices in hysterectomy and myomectomy procedures remains uncertain," and the company believes that market withdrawal "is the appropriate course of action at this time until further medical guidelines are established and/or new technologies are developed to mitigate the risk."

The Ethicon withdrawal was announced less than 3 weeks after the FDA held a 2-day meeting of its Obstetrics and Gynecology Devices Advisory Panel to discuss the benefits, risks, and clinical role of laparoscopic power morcellators (LPMs) in the treatment of women with uterine fibroids.

Panelists also discussed strategies that might reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma (LMS). Two panelists said that LPMs should not be used for gynecologic indications until better data are available, and during the open public hearing, Dr. Hooman Nourchashm, a cardiothoracic surgeon, reiterated his call for a worldwide moratorium on all gynecological tissue morcellation devices and on the practice of intracorporeal uterine morcellation during minimally invasive hysterectomy. He and his wife, anesthesiologist Dr. Amy Reed, who was diagnosed in 2013 with stage IV LMS after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, are leading a campaign calling for the ban.

The Ethicon letter states that the discussion during the meeting "demonstrated the complexity of this issue, particularly with respect to the difficulty for medical professionals to preoperatively diagnose some malignancies, such as leiomyosarcoma ... [and] the risk of disseminating unsuspected malignant tissue while using power morcellation devices," as well as methods to mitigate this risk.

But to date, Ethicon, a Johnson & Johnson company, is the only manufacturer of morcellation devices used in gynecology to suspend and withdraw its products. There are five other manufacturers or distributors of LPMs with gynecologic indications that have been marketed in the past year, according to the FDA.

Dr. David Jaspan, chairman of the department of obstetrics and gynecology at Einstein Medical Center, Philadelphia, said in an interview that he views the Ethicon move to withdraw all morcellation devices as a business decision. This "may be the first domino to fall," and whether competing manufacturers of morcellation devices also decide to withdraw their products or choose an alternative path "remains to be seen."

At the Einstein health care network in Philadelphia, there is currently a moratorium prohibiting the use of power morcellation in gynecologic surgery, while a standard acceptable counseling form is being developed. Dr. Jaspan is working with robotic and minimally invasive surgeons "to create a document that we feel will provide patients with transparency, alternatives, and choice," he noted.

As a result of the FDA’s safety announcement, there has been an increase in open procedures for fibroids in patients who would have been "excellent candidates" for a robotic procedure; did not have a sarcoma; and would have avoided a prolonged length of stay, time away from work, delay in activities of daily living, more blood loss, and pain, he said.

But the FDA estimates that among women who undergo a hysterectomy or myomectomy for a presumed fibroid, about 1 in 350 has a uterine sarcoma, and about 1 in 500 has an LMS. Dr. Jaspan is among those who believe this is an overestimate.

Dr. Jaspan had no disclosures.

Ethicon can be contacted at 877-384-4266 for more information. Adverse events related to LPMs or other medical devices should be reported to the FDA at 800-332-1088 or here.

[email protected]

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel agreed that a device that thermally ablates the prostate gland using high-intensity focused ultrasound should not be approved for treating men with localized prostate cancer now, because of issues that included no proof of efficacy and a high rate of adverse events for a noninvasive treatment.

At a meeting on July 30, the FDA’s Gastroenterology and Urology Devices Panel voted 8-0, with one abstention, that the benefits of the high-intensity focused ultrasound (HIFU) therapy did not outweigh the risks for the proposed indication, the primary treatment of prostate cancer in subjects with low-risk, localized prostate cancer. Available in Europe for 15 years, the Ablatherm integrated imaging device is manufactured by EDAP TMS, a French company. The components of the computer-controlled device include a treatment module, a control console, and an endorectal probe that is inserted rectally, heating the target tissue to therapeutic levels, while the patient is under general or spinal anesthesia. The company describes HIFU therapy as a "minimally invasive treatment during which the Ablatherm device precisely focuses ablative energy on the prostate gland while avoiding damage to sensitive adjacent anatomy."

But in separate questions, the panel unanimously voted that there was not reasonable assurance that the device was effective for the proposed indication. The vote on the safety issue alone was mixed, with panelists voting 5-3, with one abstention, that there was not reasonable assurance that the device was safe for the indication.

The company had problems completing enrollment in the U.S. pivotal trial, which compared HIFU treatment to cryotherapy, and provided several other analyses, including comparisons of the results with data from a registry and other clinical trials. The FDA reviewers raised multiple issues with the data, and panelists agreed, citing issues with safety and efficacy, including the efficacy endpoint used in the pivotal trial.

"I don’t think the potential benefits outweigh the risk," said Dr. Eric Klein, chairman of the Glickman Urological and Kidney Institute, at the Cleveland Clinic. His negative vote on the efficacy question, he noted, "relates mostly to the fact that patients with low-risk prostate cancer are at low risk for progression andbeing harmed by their disease and there are other management strategies that have lower risk than this proposed therapy."

Dr. Patrick Walsh, professor of urology, Johns Hopkins University, Baltimore, said that "at the present time, I do not believe there’s any evidence that efficacy, which has not been proven, outweighs what I look at as significant side effects." Describing a noninvasive treatment that has a 41% rate of serious adverse events as safe was "excessive," he added. (In the pivotal study, the rate of severe adverse events was 41%.)

Another panelist, Dr. Marc Garnick, professor of medicine, Harvard Medical School, Boston, said that he appreciated the technologic advance that HIFU represents and acknowledged the difficulties involved in studying the treatment in the low-risk population. However, as a practicing physician who counsels many patients with early-stage, low-risk cancer trying to make a decision about primary therapy versus active surveillance, he said it "would be very, very difficult for me to make a recommendation for HIFU therapy if one takes a look at the metastasis-free survival and the cancer-specific survival in patients with low-risk features that basically don’t get any therapy and compared that to some of the vagaries of the safety considerations that they would be subjected to with HIFU."

The U.S. pivotal study was a nonrandomized, multicenter prospective study comparing HIFU to cryotherapy in patients with low-risk, localized prostate cancer (a prostate-specific antigen level of 10 ng/mL or less, clinical stage T1 to T2a cancer, and a Gleason score of 6 or less). But the study was not completed because of problems enrolling patents, and only 135 patients were enrolled in the HIFU arm and 5 in the cryotherapy arm, instead of 205 patients in each arm, as planned.

Among the 135 HIFU-treated patients, the primary endpoint, biochemical relapse-free survival (based on the Phoenix criteria for biochemical recurrence, the nadir PSA level plus 2.0 ng/mL) at 2 years was 90.5%, and the cumulative positive biopsy rate was 28%.

Other analyses provided by the manufacturer included a comparison of long-term follow-up data on a subgroup of 227 patients from a European registry of patients treated with Ablatherm HIFU, who met the criteria of those on the pivotal study, with outcomes among 148 patients with low-risk prostate cancer in the radical prostatectomy arm of the U.S. Veterans Affairs PIVOT (Prostate Cancer Intervention Versus Observation Trial). PIVOT investigators compared radical prostatectomy with observation among men with clinically localized prostate cancer; the trial was conducted between 1996 and 2002. Metastases were reported in 3 of the 227 HIFU-treated patients (1.3%) and in 6 of 148 (4.1%) of those in PIVOT. The cumulative risk at 8 years was similar in both groups, 1.1 % among those treated with HIFU and 1.4% among the low-risk PIVOT patients.

In the pivotal study, almost all of the patients (97%) treated with HIFU had an adverse event; 82% had a moderate or severe adverse event. Adverse events included erectile dysfunction in 67%, urinary retention in 49%, urinary incontinence in 39%, urinary stricture in 35%, urethral injury in 15%, and bowel dysfunction in 21%. Most of these adverse events resolved in most patients over time, but at 24 months, 44% of the treated patients still had erectile dysfunction.

The FDA reviewers said that it was unclear whether HIFU therapy provides a benefit for patients with low-risk prostate cancer, and said that they were concerned about the 28% positive biopsy rate in the pivotal trial. Based on the evidence provided, "we can conclude that a single whole-gland HIFU treatment session does not get rid of all the cancer within the prostate gland in a significant percentage of patients," said one of the FDA reviewers, Dr. Jonathan Jarow of the FDA’s office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research. The FDA has never approved a treatment for prostate cancer based on PSA results, he pointed out.

Panelists generally agreed that the biochemical survival rate at 2 years using the Phoenix criteria could not be used to show the treatment was effective for a nonradiation treatment in patients with low-risk prostate cancer, pointing out that the criteria had not been validated with this technology. Several panelists said that the device might be effective but that it was not possible to determine that with the available data.

In a statement issued by EDAP after the meeting concluded, Marc Oczachowski, the company’s chief executive officer, said that the company "will continue to work diligently with the FDA as it carefully completes its final review" of the Ablatherm HIFU application.

The device has been used to treat about 40,000 patients with low-risk disease worldwide, according to EDAP.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts.

[email protected]

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel agreed that a device that thermally ablates the prostate gland using high-intensity focused ultrasound should not be approved for treating men with localized prostate cancer now, because of issues that included no proof of efficacy and a high rate of adverse events for a noninvasive treatment.

At a meeting on July 30, the FDA’s Gastroenterology and Urology Devices Panel voted 8-0, with one abstention, that the benefits of the high-intensity focused ultrasound (HIFU) therapy did not outweigh the risks for the proposed indication, the primary treatment of prostate cancer in subjects with low-risk, localized prostate cancer. Available in Europe for 15 years, the Ablatherm integrated imaging device is manufactured by EDAP TMS, a French company. The components of the computer-controlled device include a treatment module, a control console, and an endorectal probe that is inserted rectally, heating the target tissue to therapeutic levels, while the patient is under general or spinal anesthesia. The company describes HIFU therapy as a "minimally invasive treatment during which the Ablatherm device precisely focuses ablative energy on the prostate gland while avoiding damage to sensitive adjacent anatomy."

But in separate questions, the panel unanimously voted that there was not reasonable assurance that the device was effective for the proposed indication. The vote on the safety issue alone was mixed, with panelists voting 5-3, with one abstention, that there was not reasonable assurance that the device was safe for the indication.

The company had problems completing enrollment in the U.S. pivotal trial, which compared HIFU treatment to cryotherapy, and provided several other analyses, including comparisons of the results with data from a registry and other clinical trials. The FDA reviewers raised multiple issues with the data, and panelists agreed, citing issues with safety and efficacy, including the efficacy endpoint used in the pivotal trial.

"I don’t think the potential benefits outweigh the risk," said Dr. Eric Klein, chairman of the Glickman Urological and Kidney Institute, at the Cleveland Clinic. His negative vote on the efficacy question, he noted, "relates mostly to the fact that patients with low-risk prostate cancer are at low risk for progression andbeing harmed by their disease and there are other management strategies that have lower risk than this proposed therapy."

Dr. Patrick Walsh, professor of urology, Johns Hopkins University, Baltimore, said that "at the present time, I do not believe there’s any evidence that efficacy, which has not been proven, outweighs what I look at as significant side effects." Describing a noninvasive treatment that has a 41% rate of serious adverse events as safe was "excessive," he added. (In the pivotal study, the rate of severe adverse events was 41%.)

Another panelist, Dr. Marc Garnick, professor of medicine, Harvard Medical School, Boston, said that he appreciated the technologic advance that HIFU represents and acknowledged the difficulties involved in studying the treatment in the low-risk population. However, as a practicing physician who counsels many patients with early-stage, low-risk cancer trying to make a decision about primary therapy versus active surveillance, he said it "would be very, very difficult for me to make a recommendation for HIFU therapy if one takes a look at the metastasis-free survival and the cancer-specific survival in patients with low-risk features that basically don’t get any therapy and compared that to some of the vagaries of the safety considerations that they would be subjected to with HIFU."

The U.S. pivotal study was a nonrandomized, multicenter prospective study comparing HIFU to cryotherapy in patients with low-risk, localized prostate cancer (a prostate-specific antigen level of 10 ng/mL or less, clinical stage T1 to T2a cancer, and a Gleason score of 6 or less). But the study was not completed because of problems enrolling patents, and only 135 patients were enrolled in the HIFU arm and 5 in the cryotherapy arm, instead of 205 patients in each arm, as planned.

Among the 135 HIFU-treated patients, the primary endpoint, biochemical relapse-free survival (based on the Phoenix criteria for biochemical recurrence, the nadir PSA level plus 2.0 ng/mL) at 2 years was 90.5%, and the cumulative positive biopsy rate was 28%.

Other analyses provided by the manufacturer included a comparison of long-term follow-up data on a subgroup of 227 patients from a European registry of patients treated with Ablatherm HIFU, who met the criteria of those on the pivotal study, with outcomes among 148 patients with low-risk prostate cancer in the radical prostatectomy arm of the U.S. Veterans Affairs PIVOT (Prostate Cancer Intervention Versus Observation Trial). PIVOT investigators compared radical prostatectomy with observation among men with clinically localized prostate cancer; the trial was conducted between 1996 and 2002. Metastases were reported in 3 of the 227 HIFU-treated patients (1.3%) and in 6 of 148 (4.1%) of those in PIVOT. The cumulative risk at 8 years was similar in both groups, 1.1 % among those treated with HIFU and 1.4% among the low-risk PIVOT patients.

In the pivotal study, almost all of the patients (97%) treated with HIFU had an adverse event; 82% had a moderate or severe adverse event. Adverse events included erectile dysfunction in 67%, urinary retention in 49%, urinary incontinence in 39%, urinary stricture in 35%, urethral injury in 15%, and bowel dysfunction in 21%. Most of these adverse events resolved in most patients over time, but at 24 months, 44% of the treated patients still had erectile dysfunction.

The FDA reviewers said that it was unclear whether HIFU therapy provides a benefit for patients with low-risk prostate cancer, and said that they were concerned about the 28% positive biopsy rate in the pivotal trial. Based on the evidence provided, "we can conclude that a single whole-gland HIFU treatment session does not get rid of all the cancer within the prostate gland in a significant percentage of patients," said one of the FDA reviewers, Dr. Jonathan Jarow of the FDA’s office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research. The FDA has never approved a treatment for prostate cancer based on PSA results, he pointed out.

Panelists generally agreed that the biochemical survival rate at 2 years using the Phoenix criteria could not be used to show the treatment was effective for a nonradiation treatment in patients with low-risk prostate cancer, pointing out that the criteria had not been validated with this technology. Several panelists said that the device might be effective but that it was not possible to determine that with the available data.

In a statement issued by EDAP after the meeting concluded, Marc Oczachowski, the company’s chief executive officer, said that the company "will continue to work diligently with the FDA as it carefully completes its final review" of the Ablatherm HIFU application.

The device has been used to treat about 40,000 patients with low-risk disease worldwide, according to EDAP.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts.

[email protected]

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel agreed that a device that thermally ablates the prostate gland using high-intensity focused ultrasound should not be approved for treating men with localized prostate cancer now, because of issues that included no proof of efficacy and a high rate of adverse events for a noninvasive treatment.

At a meeting on July 30, the FDA’s Gastroenterology and Urology Devices Panel voted 8-0, with one abstention, that the benefits of the high-intensity focused ultrasound (HIFU) therapy did not outweigh the risks for the proposed indication, the primary treatment of prostate cancer in subjects with low-risk, localized prostate cancer. Available in Europe for 15 years, the Ablatherm integrated imaging device is manufactured by EDAP TMS, a French company. The components of the computer-controlled device include a treatment module, a control console, and an endorectal probe that is inserted rectally, heating the target tissue to therapeutic levels, while the patient is under general or spinal anesthesia. The company describes HIFU therapy as a "minimally invasive treatment during which the Ablatherm device precisely focuses ablative energy on the prostate gland while avoiding damage to sensitive adjacent anatomy."

But in separate questions, the panel unanimously voted that there was not reasonable assurance that the device was effective for the proposed indication. The vote on the safety issue alone was mixed, with panelists voting 5-3, with one abstention, that there was not reasonable assurance that the device was safe for the indication.

The company had problems completing enrollment in the U.S. pivotal trial, which compared HIFU treatment to cryotherapy, and provided several other analyses, including comparisons of the results with data from a registry and other clinical trials. The FDA reviewers raised multiple issues with the data, and panelists agreed, citing issues with safety and efficacy, including the efficacy endpoint used in the pivotal trial.

"I don’t think the potential benefits outweigh the risk," said Dr. Eric Klein, chairman of the Glickman Urological and Kidney Institute, at the Cleveland Clinic. His negative vote on the efficacy question, he noted, "relates mostly to the fact that patients with low-risk prostate cancer are at low risk for progression andbeing harmed by their disease and there are other management strategies that have lower risk than this proposed therapy."

Dr. Patrick Walsh, professor of urology, Johns Hopkins University, Baltimore, said that "at the present time, I do not believe there’s any evidence that efficacy, which has not been proven, outweighs what I look at as significant side effects." Describing a noninvasive treatment that has a 41% rate of serious adverse events as safe was "excessive," he added. (In the pivotal study, the rate of severe adverse events was 41%.)

Another panelist, Dr. Marc Garnick, professor of medicine, Harvard Medical School, Boston, said that he appreciated the technologic advance that HIFU represents and acknowledged the difficulties involved in studying the treatment in the low-risk population. However, as a practicing physician who counsels many patients with early-stage, low-risk cancer trying to make a decision about primary therapy versus active surveillance, he said it "would be very, very difficult for me to make a recommendation for HIFU therapy if one takes a look at the metastasis-free survival and the cancer-specific survival in patients with low-risk features that basically don’t get any therapy and compared that to some of the vagaries of the safety considerations that they would be subjected to with HIFU."

The U.S. pivotal study was a nonrandomized, multicenter prospective study comparing HIFU to cryotherapy in patients with low-risk, localized prostate cancer (a prostate-specific antigen level of 10 ng/mL or less, clinical stage T1 to T2a cancer, and a Gleason score of 6 or less). But the study was not completed because of problems enrolling patents, and only 135 patients were enrolled in the HIFU arm and 5 in the cryotherapy arm, instead of 205 patients in each arm, as planned.

Among the 135 HIFU-treated patients, the primary endpoint, biochemical relapse-free survival (based on the Phoenix criteria for biochemical recurrence, the nadir PSA level plus 2.0 ng/mL) at 2 years was 90.5%, and the cumulative positive biopsy rate was 28%.

Other analyses provided by the manufacturer included a comparison of long-term follow-up data on a subgroup of 227 patients from a European registry of patients treated with Ablatherm HIFU, who met the criteria of those on the pivotal study, with outcomes among 148 patients with low-risk prostate cancer in the radical prostatectomy arm of the U.S. Veterans Affairs PIVOT (Prostate Cancer Intervention Versus Observation Trial). PIVOT investigators compared radical prostatectomy with observation among men with clinically localized prostate cancer; the trial was conducted between 1996 and 2002. Metastases were reported in 3 of the 227 HIFU-treated patients (1.3%) and in 6 of 148 (4.1%) of those in PIVOT. The cumulative risk at 8 years was similar in both groups, 1.1 % among those treated with HIFU and 1.4% among the low-risk PIVOT patients.

In the pivotal study, almost all of the patients (97%) treated with HIFU had an adverse event; 82% had a moderate or severe adverse event. Adverse events included erectile dysfunction in 67%, urinary retention in 49%, urinary incontinence in 39%, urinary stricture in 35%, urethral injury in 15%, and bowel dysfunction in 21%. Most of these adverse events resolved in most patients over time, but at 24 months, 44% of the treated patients still had erectile dysfunction.

The FDA reviewers said that it was unclear whether HIFU therapy provides a benefit for patients with low-risk prostate cancer, and said that they were concerned about the 28% positive biopsy rate in the pivotal trial. Based on the evidence provided, "we can conclude that a single whole-gland HIFU treatment session does not get rid of all the cancer within the prostate gland in a significant percentage of patients," said one of the FDA reviewers, Dr. Jonathan Jarow of the FDA’s office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research. The FDA has never approved a treatment for prostate cancer based on PSA results, he pointed out.

Panelists generally agreed that the biochemical survival rate at 2 years using the Phoenix criteria could not be used to show the treatment was effective for a nonradiation treatment in patients with low-risk prostate cancer, pointing out that the criteria had not been validated with this technology. Several panelists said that the device might be effective but that it was not possible to determine that with the available data.

In a statement issued by EDAP after the meeting concluded, Marc Oczachowski, the company’s chief executive officer, said that the company "will continue to work diligently with the FDA as it carefully completes its final review" of the Ablatherm HIFU application.

The device has been used to treat about 40,000 patients with low-risk disease worldwide, according to EDAP.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts.

[email protected]

WASHINGTON – Obese women experienced significant improvements in sexual function over 6-24 months after bariatric surgery in a multistudy review, indicating that this outcome should be listed among the possible benefits of surgery in this patient population, Dr. Kalaivani Ramalingam said at a joint annual meeting of the American Urogynecologic Society.

In a review of studies published between 1996 and 2013, Dr. Ramalingam of the department of gynecology at Kingston Hospital, Kingston upon Thames, England, and her associates identified five original studies of 254 obese women undergoing bariatric surgery that reported Female Sexual Function Index (FSFI) scores before and after surgery. Studies of nonsurgical weight loss treatments and those that included both men and women were not included. The FSFI evaluates sexual function in six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain.

Patients in the studies had statistically significant reductions in body mass index over 6-24 months of follow-up (P = .001). In one of the five studies, which enrolled 36 patients, FSFI scores did not improve after surgery.

But in the remaining four studies, there were statistically significant improvements in the overall FSFI scores after surgery (P = .003), Dr. Ramalingam said. In addition, statistically significant improvements in all domains of the score were observed after surgery: increased desire (P = .005), arousal (P = .001), lubrication (P = .003), satisfaction (P = .012) and orgasm (P =.003) – and a decrease in the levels of pain during intercourse (P = .014).

She noted that in one of the five studies, sexual function improved in women with pelvic floor dysfunction and that further studies in this specific group of patients are needed to evaluate the effect of surgery among obese women who are undergoing bariatric surgery and have pelvic floor dysfunction.

An estimated 51% of female bariatric surgery patients report sexual dysfunction, she said.

Dr. Ramalingam and one of her coauthors had no relevant disclosures. The third author disclosed being a speaker for and receiving honoraria from Pfizer, Astellas, and Shire; and serving on an advisory committee for Allergan.

[email protected]

WASHINGTON – Obese women experienced significant improvements in sexual function over 6-24 months after bariatric surgery in a multistudy review, indicating that this outcome should be listed among the possible benefits of surgery in this patient population, Dr. Kalaivani Ramalingam said at a joint annual meeting of the American Urogynecologic Society.

In a review of studies published between 1996 and 2013, Dr. Ramalingam of the department of gynecology at Kingston Hospital, Kingston upon Thames, England, and her associates identified five original studies of 254 obese women undergoing bariatric surgery that reported Female Sexual Function Index (FSFI) scores before and after surgery. Studies of nonsurgical weight loss treatments and those that included both men and women were not included. The FSFI evaluates sexual function in six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain.

Patients in the studies had statistically significant reductions in body mass index over 6-24 months of follow-up (P = .001). In one of the five studies, which enrolled 36 patients, FSFI scores did not improve after surgery.

But in the remaining four studies, there were statistically significant improvements in the overall FSFI scores after surgery (P = .003), Dr. Ramalingam said. In addition, statistically significant improvements in all domains of the score were observed after surgery: increased desire (P = .005), arousal (P = .001), lubrication (P = .003), satisfaction (P = .012) and orgasm (P =.003) – and a decrease in the levels of pain during intercourse (P = .014).

She noted that in one of the five studies, sexual function improved in women with pelvic floor dysfunction and that further studies in this specific group of patients are needed to evaluate the effect of surgery among obese women who are undergoing bariatric surgery and have pelvic floor dysfunction.

An estimated 51% of female bariatric surgery patients report sexual dysfunction, she said.

Dr. Ramalingam and one of her coauthors had no relevant disclosures. The third author disclosed being a speaker for and receiving honoraria from Pfizer, Astellas, and Shire; and serving on an advisory committee for Allergan.

[email protected]

WASHINGTON – Obese women experienced significant improvements in sexual function over 6-24 months after bariatric surgery in a multistudy review, indicating that this outcome should be listed among the possible benefits of surgery in this patient population, Dr. Kalaivani Ramalingam said at a joint annual meeting of the American Urogynecologic Society.

In a review of studies published between 1996 and 2013, Dr. Ramalingam of the department of gynecology at Kingston Hospital, Kingston upon Thames, England, and her associates identified five original studies of 254 obese women undergoing bariatric surgery that reported Female Sexual Function Index (FSFI) scores before and after surgery. Studies of nonsurgical weight loss treatments and those that included both men and women were not included. The FSFI evaluates sexual function in six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain.

Patients in the studies had statistically significant reductions in body mass index over 6-24 months of follow-up (P = .001). In one of the five studies, which enrolled 36 patients, FSFI scores did not improve after surgery.

But in the remaining four studies, there were statistically significant improvements in the overall FSFI scores after surgery (P = .003), Dr. Ramalingam said. In addition, statistically significant improvements in all domains of the score were observed after surgery: increased desire (P = .005), arousal (P = .001), lubrication (P = .003), satisfaction (P = .012) and orgasm (P =.003) – and a decrease in the levels of pain during intercourse (P = .014).

She noted that in one of the five studies, sexual function improved in women with pelvic floor dysfunction and that further studies in this specific group of patients are needed to evaluate the effect of surgery among obese women who are undergoing bariatric surgery and have pelvic floor dysfunction.

An estimated 51% of female bariatric surgery patients report sexual dysfunction, she said.

Dr. Ramalingam and one of her coauthors had no relevant disclosures. The third author disclosed being a speaker for and receiving honoraria from Pfizer, Astellas, and Shire; and serving on an advisory committee for Allergan.

[email protected]