Thoracic Surgery News (Archived)

The Food and Drug Administration has approved a biosimilar to bevacizumab (Avastin) for the treatment of certain colorectal, lung, brain, kidney, and cervical cancers.

Bevacizumab-awwb is the first biosimilar approved in the United States for the treatment of cancer, the FDA said in a press release.

Approval is based on structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrate bevacizumab-awwb is biosimilar to bevacizumab, the FDA said.

[email protected]

The Food and Drug Administration has approved a biosimilar to bevacizumab (Avastin) for the treatment of certain colorectal, lung, brain, kidney, and cervical cancers.

Bevacizumab-awwb is the first biosimilar approved in the United States for the treatment of cancer, the FDA said in a press release.

Approval is based on structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrate bevacizumab-awwb is biosimilar to bevacizumab, the FDA said.

[email protected]

The Food and Drug Administration has approved a biosimilar to bevacizumab (Avastin) for the treatment of certain colorectal, lung, brain, kidney, and cervical cancers.

Bevacizumab-awwb is the first biosimilar approved in the United States for the treatment of cancer, the FDA said in a press release.

Approval is based on structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrate bevacizumab-awwb is biosimilar to bevacizumab, the FDA said.

[email protected]

The American College of Cardiology Task Force on Expert Consensus Decision Pathways has released a “focused update” for the 2016 ACC Expert Consensus Decision Pathway (ECDP) on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk.

The update was deemed by the ECDP writing committee to be desirable given the additional evidence and perspectives that have emerged since the publication of the 2016 version, particularly with respect to the efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors for the secondary prevention of ASCVD, as well as the best use of ezetimibe in addition to statin therapy after acute coronary syndrome.

• Consideration of new randomized clinical trial data for the PCSK9 inhibitors evolocumab and bococizumab. Namely, they included results from the cardiovascular outcomes trials FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) and SPIRE-1 and SPIRE-2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), which were published in early 2017.
• An adjustment in the ECDP algorithms with respect to thresholds for consideration of net ASCVD risk reduction. The 2016 ECDP thresholds for risk reduction benefit were percent reduction in LDL-C with consideration of absolute LDL-C level in patients with clinical ASCVD, baseline LDL-C of 190 mg/dL or greater, and primary prevention. In patients with diabetes with or without clinical ASCVD, clinicians were allowed to consider absolute LDL-C and/or non-HDL-cholesterol levels. In the 2017 ECDP update, the thresholds are percent reduction in LDL-C with consideration of absolute LDL-C or non-HDL-C levels for patients in each of the four statin benefit groups. This change was based on the inclusion criteria of the FOURIER trial, the ongoing ODYSSEY Outcomes trial (Evaluation of Cardiovascular Outcomes after an Acute Coronary Syndrome During Treatment with Alirocumab), and the SPIRE-2 trial, all of which included non-HDL-C thresholds. “In alignment with these inclusion criteria, the 2017 Focused Update includes both LDL-C and non-HDL-C thresholds for evaluation of net ASCVD risk-reduction benefit when considering the addition of nonstatin therapies for patients in each of the four statin benefit groups” the update explained.
• An expansion of the threshold for consideration of net ASCVD risk-reduction benefit from a reduction of LDL C of at least 50%, as well as consideration of LDL-C less than 70 mg/dL or non-HDL-C less than 100 mg/dL for all patients (that is, both those with and those without comorbidities) who have clinical ASCVD and baseline LDL-C of 70-189 mg/dL. The 2016 ECDP had different thresholds for those with versus those without comorbidities. This change was based on findings from the FOURIER trial and the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).“Based on consideration of all available evidence, the consensus of the writing committee members is that lower LDL-C levels are safe and optimal in patients with clinical ASCVD due to [their] increased risk of recurrent events,” they said.
• An expanded recommendation on the use of ezetimibe and PCSK9 inhibition. The 2016 ECDP stated that “if a decision is made to proceed with the addition of nonstatin therapy to maximally tolerated statin therapy, it is reasonable to consider the addition of ezetimibe as the initial agent and a PCSK9 inhibitor as the second agent.” However, based on the FOURIER findings, the ongoing ODYSSEY Outcomes trial, and the IMPROVE-IT trial, the 2017 Focused Update states that, if such a decision is made in patients with clinical ASCVD with comorbidities and baseline LDL-C of 70-189 mg/dL, it is reasonable to weigh the addition of either ezetimibe or a PCSK9 inhibitor in light of “considerations of the additional percent LDL-C reduction desired, patient preferences, costs, route of administration, and other factors.” The update also spells out considerations that may favor the initial choice of ezetimibe versus a PCSK9 inhibitor (such as requiring less than 25% additional lowering of LDL-C, an age of over 75 years, cost, and other patient factors and preferences) .
• Additional factors, based on the FOURIER trial results and inclusion criteria, that may be considered for the identification of higher-risk patients with clinical ASCVD. The 2016 ECDP included on this list diabetes, a recent ASCVD event, an ASCVD event while already taking a statin, poorly controlled other major ASCVD risk factors, elevated lipoprotein, chronic kidney disease, symptomatic heart failure, maintenance hemodialysis, and baseline LDL-C of at least 190 mg/dL not due to secondary causes. The 2017 update added being 65 years or older, prior MI or nonhemorrhagic stroke, current daily cigarette smoking, symptomatic peripheral artery disease with prior MI or stroke, history of non-MI related coronary revascularization, residual coronary artery disease with at least 40% stenosis in at least two large vessels, HDL-C less than 40 mg/dL for men and less than 50 mg/dL for women, high-sensitivity C-reactive protein greater than 2 mg/L, and metabolic syndrome.

The content of the full ECDP has been changed in accordance with these updates and now includes more extensive and detailed guidance for decision making – both in the text and in treatment algorithms.

Aspects that remain unchanged include the decision pathways and algorithms for the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C less than 190 mg/dL or in those without ASCVD and LDL-C of 190 mg/dL or greater unattributable to secondary causes.

In addition to other changes made for the purpose of clarification and consistency, recommendations regarding bile acid–sequestrant use were downgraded; these are now only recommended as optional secondary agents for consideration in patients who cannot tolerate ezetimibe.

“[These] recommendations attempt to provide practical guidance for clinicians and patients regarding the use of nonstatin therapies to further reduce ASCVD risk in situations not covered by the guideline until such time as the scientific evidence base expands and cardiovascular outcomes trials are completed with new agents for ASCVD risk reduction,” the committee concluded.

Dr. Lloyd-Jones reported having no disclosures.

[email protected]

The American College of Cardiology Task Force on Expert Consensus Decision Pathways has released a “focused update” for the 2016 ACC Expert Consensus Decision Pathway (ECDP) on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk.

The update was deemed by the ECDP writing committee to be desirable given the additional evidence and perspectives that have emerged since the publication of the 2016 version, particularly with respect to the efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors for the secondary prevention of ASCVD, as well as the best use of ezetimibe in addition to statin therapy after acute coronary syndrome.

• Consideration of new randomized clinical trial data for the PCSK9 inhibitors evolocumab and bococizumab. Namely, they included results from the cardiovascular outcomes trials FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) and SPIRE-1 and SPIRE-2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), which were published in early 2017.
• An adjustment in the ECDP algorithms with respect to thresholds for consideration of net ASCVD risk reduction. The 2016 ECDP thresholds for risk reduction benefit were percent reduction in LDL-C with consideration of absolute LDL-C level in patients with clinical ASCVD, baseline LDL-C of 190 mg/dL or greater, and primary prevention. In patients with diabetes with or without clinical ASCVD, clinicians were allowed to consider absolute LDL-C and/or non-HDL-cholesterol levels. In the 2017 ECDP update, the thresholds are percent reduction in LDL-C with consideration of absolute LDL-C or non-HDL-C levels for patients in each of the four statin benefit groups. This change was based on the inclusion criteria of the FOURIER trial, the ongoing ODYSSEY Outcomes trial (Evaluation of Cardiovascular Outcomes after an Acute Coronary Syndrome During Treatment with Alirocumab), and the SPIRE-2 trial, all of which included non-HDL-C thresholds. “In alignment with these inclusion criteria, the 2017 Focused Update includes both LDL-C and non-HDL-C thresholds for evaluation of net ASCVD risk-reduction benefit when considering the addition of nonstatin therapies for patients in each of the four statin benefit groups” the update explained.
• An expansion of the threshold for consideration of net ASCVD risk-reduction benefit from a reduction of LDL C of at least 50%, as well as consideration of LDL-C less than 70 mg/dL or non-HDL-C less than 100 mg/dL for all patients (that is, both those with and those without comorbidities) who have clinical ASCVD and baseline LDL-C of 70-189 mg/dL. The 2016 ECDP had different thresholds for those with versus those without comorbidities. This change was based on findings from the FOURIER trial and the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).“Based on consideration of all available evidence, the consensus of the writing committee members is that lower LDL-C levels are safe and optimal in patients with clinical ASCVD due to [their] increased risk of recurrent events,” they said.
• An expanded recommendation on the use of ezetimibe and PCSK9 inhibition. The 2016 ECDP stated that “if a decision is made to proceed with the addition of nonstatin therapy to maximally tolerated statin therapy, it is reasonable to consider the addition of ezetimibe as the initial agent and a PCSK9 inhibitor as the second agent.” However, based on the FOURIER findings, the ongoing ODYSSEY Outcomes trial, and the IMPROVE-IT trial, the 2017 Focused Update states that, if such a decision is made in patients with clinical ASCVD with comorbidities and baseline LDL-C of 70-189 mg/dL, it is reasonable to weigh the addition of either ezetimibe or a PCSK9 inhibitor in light of “considerations of the additional percent LDL-C reduction desired, patient preferences, costs, route of administration, and other factors.” The update also spells out considerations that may favor the initial choice of ezetimibe versus a PCSK9 inhibitor (such as requiring less than 25% additional lowering of LDL-C, an age of over 75 years, cost, and other patient factors and preferences) .
• Additional factors, based on the FOURIER trial results and inclusion criteria, that may be considered for the identification of higher-risk patients with clinical ASCVD. The 2016 ECDP included on this list diabetes, a recent ASCVD event, an ASCVD event while already taking a statin, poorly controlled other major ASCVD risk factors, elevated lipoprotein, chronic kidney disease, symptomatic heart failure, maintenance hemodialysis, and baseline LDL-C of at least 190 mg/dL not due to secondary causes. The 2017 update added being 65 years or older, prior MI or nonhemorrhagic stroke, current daily cigarette smoking, symptomatic peripheral artery disease with prior MI or stroke, history of non-MI related coronary revascularization, residual coronary artery disease with at least 40% stenosis in at least two large vessels, HDL-C less than 40 mg/dL for men and less than 50 mg/dL for women, high-sensitivity C-reactive protein greater than 2 mg/L, and metabolic syndrome.

The content of the full ECDP has been changed in accordance with these updates and now includes more extensive and detailed guidance for decision making – both in the text and in treatment algorithms.

Aspects that remain unchanged include the decision pathways and algorithms for the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C less than 190 mg/dL or in those without ASCVD and LDL-C of 190 mg/dL or greater unattributable to secondary causes.

In addition to other changes made for the purpose of clarification and consistency, recommendations regarding bile acid–sequestrant use were downgraded; these are now only recommended as optional secondary agents for consideration in patients who cannot tolerate ezetimibe.

“[These] recommendations attempt to provide practical guidance for clinicians and patients regarding the use of nonstatin therapies to further reduce ASCVD risk in situations not covered by the guideline until such time as the scientific evidence base expands and cardiovascular outcomes trials are completed with new agents for ASCVD risk reduction,” the committee concluded.

Dr. Lloyd-Jones reported having no disclosures.

[email protected]

The American College of Cardiology Task Force on Expert Consensus Decision Pathways has released a “focused update” for the 2016 ACC Expert Consensus Decision Pathway (ECDP) on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk.

The update was deemed by the ECDP writing committee to be desirable given the additional evidence and perspectives that have emerged since the publication of the 2016 version, particularly with respect to the efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors for the secondary prevention of ASCVD, as well as the best use of ezetimibe in addition to statin therapy after acute coronary syndrome.

• Consideration of new randomized clinical trial data for the PCSK9 inhibitors evolocumab and bococizumab. Namely, they included results from the cardiovascular outcomes trials FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) and SPIRE-1 and SPIRE-2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), which were published in early 2017.
• An adjustment in the ECDP algorithms with respect to thresholds for consideration of net ASCVD risk reduction. The 2016 ECDP thresholds for risk reduction benefit were percent reduction in LDL-C with consideration of absolute LDL-C level in patients with clinical ASCVD, baseline LDL-C of 190 mg/dL or greater, and primary prevention. In patients with diabetes with or without clinical ASCVD, clinicians were allowed to consider absolute LDL-C and/or non-HDL-cholesterol levels. In the 2017 ECDP update, the thresholds are percent reduction in LDL-C with consideration of absolute LDL-C or non-HDL-C levels for patients in each of the four statin benefit groups. This change was based on the inclusion criteria of the FOURIER trial, the ongoing ODYSSEY Outcomes trial (Evaluation of Cardiovascular Outcomes after an Acute Coronary Syndrome During Treatment with Alirocumab), and the SPIRE-2 trial, all of which included non-HDL-C thresholds. “In alignment with these inclusion criteria, the 2017 Focused Update includes both LDL-C and non-HDL-C thresholds for evaluation of net ASCVD risk-reduction benefit when considering the addition of nonstatin therapies for patients in each of the four statin benefit groups” the update explained.
• An expansion of the threshold for consideration of net ASCVD risk-reduction benefit from a reduction of LDL C of at least 50%, as well as consideration of LDL-C less than 70 mg/dL or non-HDL-C less than 100 mg/dL for all patients (that is, both those with and those without comorbidities) who have clinical ASCVD and baseline LDL-C of 70-189 mg/dL. The 2016 ECDP had different thresholds for those with versus those without comorbidities. This change was based on findings from the FOURIER trial and the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).“Based on consideration of all available evidence, the consensus of the writing committee members is that lower LDL-C levels are safe and optimal in patients with clinical ASCVD due to [their] increased risk of recurrent events,” they said.
• An expanded recommendation on the use of ezetimibe and PCSK9 inhibition. The 2016 ECDP stated that “if a decision is made to proceed with the addition of nonstatin therapy to maximally tolerated statin therapy, it is reasonable to consider the addition of ezetimibe as the initial agent and a PCSK9 inhibitor as the second agent.” However, based on the FOURIER findings, the ongoing ODYSSEY Outcomes trial, and the IMPROVE-IT trial, the 2017 Focused Update states that, if such a decision is made in patients with clinical ASCVD with comorbidities and baseline LDL-C of 70-189 mg/dL, it is reasonable to weigh the addition of either ezetimibe or a PCSK9 inhibitor in light of “considerations of the additional percent LDL-C reduction desired, patient preferences, costs, route of administration, and other factors.” The update also spells out considerations that may favor the initial choice of ezetimibe versus a PCSK9 inhibitor (such as requiring less than 25% additional lowering of LDL-C, an age of over 75 years, cost, and other patient factors and preferences) .
• Additional factors, based on the FOURIER trial results and inclusion criteria, that may be considered for the identification of higher-risk patients with clinical ASCVD. The 2016 ECDP included on this list diabetes, a recent ASCVD event, an ASCVD event while already taking a statin, poorly controlled other major ASCVD risk factors, elevated lipoprotein, chronic kidney disease, symptomatic heart failure, maintenance hemodialysis, and baseline LDL-C of at least 190 mg/dL not due to secondary causes. The 2017 update added being 65 years or older, prior MI or nonhemorrhagic stroke, current daily cigarette smoking, symptomatic peripheral artery disease with prior MI or stroke, history of non-MI related coronary revascularization, residual coronary artery disease with at least 40% stenosis in at least two large vessels, HDL-C less than 40 mg/dL for men and less than 50 mg/dL for women, high-sensitivity C-reactive protein greater than 2 mg/L, and metabolic syndrome.

The content of the full ECDP has been changed in accordance with these updates and now includes more extensive and detailed guidance for decision making – both in the text and in treatment algorithms.

Aspects that remain unchanged include the decision pathways and algorithms for the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C less than 190 mg/dL or in those without ASCVD and LDL-C of 190 mg/dL or greater unattributable to secondary causes.

In addition to other changes made for the purpose of clarification and consistency, recommendations regarding bile acid–sequestrant use were downgraded; these are now only recommended as optional secondary agents for consideration in patients who cannot tolerate ezetimibe.

“[These] recommendations attempt to provide practical guidance for clinicians and patients regarding the use of nonstatin therapies to further reduce ASCVD risk in situations not covered by the guideline until such time as the scientific evidence base expands and cardiovascular outcomes trials are completed with new agents for ASCVD risk reduction,” the committee concluded.

Dr. Lloyd-Jones reported having no disclosures.

[email protected]

The Food and Drug Administration is changing the way it approves orphan drugs after revelations that drugmakers may be abusing a law intended to help patients with rare diseases.

In a blog post Sept. 12, FDA Commissioner Scott Gottlieb, MD, said he wants to ensure financial incentives are granted “in a way that’s consistent with the manner Congress intended” when the Orphan Drug Act was passed in 1983. That legislation gave drugmakers a package of incentives, including tax credits, user-fee waivers and 7 years of market exclusivity if they developed medicines for rare diseases.

A Kaiser Health News investigation published in January 2017 found many drugs that now have orphan status aren’t entirely new. Of about 450 drugs that have won orphan approval since 1983, more than 70 were drugs first approved by the FDA for mass-market use. Those include rosuvastatin (Crestor), aripiprazole (Abilify), and adalimumab (Humira), the world’s best-selling drug.

Dr. Gottlieb announced plans to close a loophole that allows manufacturers to skip pediatric testing requirements when developing a common-disease drug for orphan use in children. He also signaled that bigger changes are being considered, announcing a public meeting to explore issues raised by scientific advances, such as the increase in precision medicine and biologics.

“We need to make sure our policies take notice of all of these new challenges and opportunities,” he wrote. Dr. Gottlieb, through his agency, declined multiple requests for interviews.

Over the years, drugmakers have fueled a boom in orphan drugs, which often carry six-figure price tags. Nearly half of the new drugs approved by the FDA are now for rare diseases – even though many of them also treat and are marketed for common diseases.

Dr. Gottlieb became commissioner in May, a few months after three key Republican senators called for a federal investigation into potential abuses of the Orphan Drug Act, and the Government Accountability Office agreed to investigate.

The GAO has yet to begin its investigation, saying it doesn’t expect to start work until late this year, when staff is available. Regardless, in late June, Dr. Gottlieb announced what would be the first in a series of updates that shift the way the FDA handles orphan drugs.

Those include:

• Eliminating a backlog in drug applications for orphan designation or status. Getting a designation is a critical first step if a company wants to win orphan incentives once the drug is approved for treatment use. And, much like the rise in approvals, the requests by companies to get drugs designated with orphan status has also skyrocketed. Dr. Gottlieb said in June that he wanted to get rid of the backlog; his blog post noted the effort was complete. About half of the 200 applications from drugmakers won orphan status.
• Mandating that drugmakers prove their medicine is clinically superior before getting the market exclusivity that comes with orphan drug status. The agency had lost a lawsuit in which a company said it was owed the exclusivity period regardless of whether its medicine was better. And two more lawsuits had been filed by Eagle Pharmaceuticals and United Therapeutics. The FDA Reauthorization Act, which passed in August, made it law that a drug has to be clinically superior to get the incentives.
• Closing the loophole for pediatric orphan drugs by requiring all drugs approved for common adult diseases, like inflammatory bowel disease, undergo pediatric testing when getting approval as a pediatric orphan drug. Pediatric testing is not required for orphan drugs, and last month Congress mandated that orphan drugs for cancer be tested for children. Still, the American Academy of Pediatrics celebrated the proposed change but warned it was only a first step. Bridgette Jones, MD, chair of American Academy of Pediatrics Committee on Drugs, said Sept. 12 that orphan drugs are “still mostly exempt from pediatric study requirements … children deserve access to safe, effective medications.”

Martin Makary, MD, who wrote a critical 2015 paper on orphan approvals, said the changes at the agency indicate that Dr. Gottlieb seems “concerned about all the right things. The government does a lot of lip service in general. This is not lip service.”

The restructuring has been swift in some ways.

Sandra Heibel, PhD, a senior consultant at Haffner Associates, a firm that helps companies submit orphan drug applications, noted that the approval process for designations definitely sped up over the summer, and “we are absolutely getting responses from the FDA back in 90 days. That has come through.”

Other changes to the agency, though, will evolve slowly. For example, the orphan drug office has begun reaching across the FDA’s divisions for help in reviewing drugs. In May, the FDA’s orphan reviews began to work with the office of pediatric therapeutics to review pediatric applications – ideally increasing the expertise applied when considering a company’s request for orphan drug use in children.

In an interview, FDA confirmed that Dr. Gottlieb’s orphan modernization plan is part of a larger effort to increase competition and decrease drug prices. One focus is on targeted drugs – especially those that affect rare diseases or diseases for which there is no effective therapy, the agency said.

“Such drugs present some of the biggest opportunities in medicine to treat and cure debilitating and very costly diseases,” the agency stated.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

The Food and Drug Administration is changing the way it approves orphan drugs after revelations that drugmakers may be abusing a law intended to help patients with rare diseases.

In a blog post Sept. 12, FDA Commissioner Scott Gottlieb, MD, said he wants to ensure financial incentives are granted “in a way that’s consistent with the manner Congress intended” when the Orphan Drug Act was passed in 1983. That legislation gave drugmakers a package of incentives, including tax credits, user-fee waivers and 7 years of market exclusivity if they developed medicines for rare diseases.

A Kaiser Health News investigation published in January 2017 found many drugs that now have orphan status aren’t entirely new. Of about 450 drugs that have won orphan approval since 1983, more than 70 were drugs first approved by the FDA for mass-market use. Those include rosuvastatin (Crestor), aripiprazole (Abilify), and adalimumab (Humira), the world’s best-selling drug.

Dr. Gottlieb announced plans to close a loophole that allows manufacturers to skip pediatric testing requirements when developing a common-disease drug for orphan use in children. He also signaled that bigger changes are being considered, announcing a public meeting to explore issues raised by scientific advances, such as the increase in precision medicine and biologics.

“We need to make sure our policies take notice of all of these new challenges and opportunities,” he wrote. Dr. Gottlieb, through his agency, declined multiple requests for interviews.

Over the years, drugmakers have fueled a boom in orphan drugs, which often carry six-figure price tags. Nearly half of the new drugs approved by the FDA are now for rare diseases – even though many of them also treat and are marketed for common diseases.

Dr. Gottlieb became commissioner in May, a few months after three key Republican senators called for a federal investigation into potential abuses of the Orphan Drug Act, and the Government Accountability Office agreed to investigate.

The GAO has yet to begin its investigation, saying it doesn’t expect to start work until late this year, when staff is available. Regardless, in late June, Dr. Gottlieb announced what would be the first in a series of updates that shift the way the FDA handles orphan drugs.

Those include:

• Eliminating a backlog in drug applications for orphan designation or status. Getting a designation is a critical first step if a company wants to win orphan incentives once the drug is approved for treatment use. And, much like the rise in approvals, the requests by companies to get drugs designated with orphan status has also skyrocketed. Dr. Gottlieb said in June that he wanted to get rid of the backlog; his blog post noted the effort was complete. About half of the 200 applications from drugmakers won orphan status.
• Mandating that drugmakers prove their medicine is clinically superior before getting the market exclusivity that comes with orphan drug status. The agency had lost a lawsuit in which a company said it was owed the exclusivity period regardless of whether its medicine was better. And two more lawsuits had been filed by Eagle Pharmaceuticals and United Therapeutics. The FDA Reauthorization Act, which passed in August, made it law that a drug has to be clinically superior to get the incentives.
• Closing the loophole for pediatric orphan drugs by requiring all drugs approved for common adult diseases, like inflammatory bowel disease, undergo pediatric testing when getting approval as a pediatric orphan drug. Pediatric testing is not required for orphan drugs, and last month Congress mandated that orphan drugs for cancer be tested for children. Still, the American Academy of Pediatrics celebrated the proposed change but warned it was only a first step. Bridgette Jones, MD, chair of American Academy of Pediatrics Committee on Drugs, said Sept. 12 that orphan drugs are “still mostly exempt from pediatric study requirements … children deserve access to safe, effective medications.”

Martin Makary, MD, who wrote a critical 2015 paper on orphan approvals, said the changes at the agency indicate that Dr. Gottlieb seems “concerned about all the right things. The government does a lot of lip service in general. This is not lip service.”

The restructuring has been swift in some ways.

Sandra Heibel, PhD, a senior consultant at Haffner Associates, a firm that helps companies submit orphan drug applications, noted that the approval process for designations definitely sped up over the summer, and “we are absolutely getting responses from the FDA back in 90 days. That has come through.”

Other changes to the agency, though, will evolve slowly. For example, the orphan drug office has begun reaching across the FDA’s divisions for help in reviewing drugs. In May, the FDA’s orphan reviews began to work with the office of pediatric therapeutics to review pediatric applications – ideally increasing the expertise applied when considering a company’s request for orphan drug use in children.

In an interview, FDA confirmed that Dr. Gottlieb’s orphan modernization plan is part of a larger effort to increase competition and decrease drug prices. One focus is on targeted drugs – especially those that affect rare diseases or diseases for which there is no effective therapy, the agency said.

“Such drugs present some of the biggest opportunities in medicine to treat and cure debilitating and very costly diseases,” the agency stated.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

The Food and Drug Administration is changing the way it approves orphan drugs after revelations that drugmakers may be abusing a law intended to help patients with rare diseases.

In a blog post Sept. 12, FDA Commissioner Scott Gottlieb, MD, said he wants to ensure financial incentives are granted “in a way that’s consistent with the manner Congress intended” when the Orphan Drug Act was passed in 1983. That legislation gave drugmakers a package of incentives, including tax credits, user-fee waivers and 7 years of market exclusivity if they developed medicines for rare diseases.

A Kaiser Health News investigation published in January 2017 found many drugs that now have orphan status aren’t entirely new. Of about 450 drugs that have won orphan approval since 1983, more than 70 were drugs first approved by the FDA for mass-market use. Those include rosuvastatin (Crestor), aripiprazole (Abilify), and adalimumab (Humira), the world’s best-selling drug.

Dr. Gottlieb announced plans to close a loophole that allows manufacturers to skip pediatric testing requirements when developing a common-disease drug for orphan use in children. He also signaled that bigger changes are being considered, announcing a public meeting to explore issues raised by scientific advances, such as the increase in precision medicine and biologics.

“We need to make sure our policies take notice of all of these new challenges and opportunities,” he wrote. Dr. Gottlieb, through his agency, declined multiple requests for interviews.

Over the years, drugmakers have fueled a boom in orphan drugs, which often carry six-figure price tags. Nearly half of the new drugs approved by the FDA are now for rare diseases – even though many of them also treat and are marketed for common diseases.

Dr. Gottlieb became commissioner in May, a few months after three key Republican senators called for a federal investigation into potential abuses of the Orphan Drug Act, and the Government Accountability Office agreed to investigate.

The GAO has yet to begin its investigation, saying it doesn’t expect to start work until late this year, when staff is available. Regardless, in late June, Dr. Gottlieb announced what would be the first in a series of updates that shift the way the FDA handles orphan drugs.

Those include:

• Eliminating a backlog in drug applications for orphan designation or status. Getting a designation is a critical first step if a company wants to win orphan incentives once the drug is approved for treatment use. And, much like the rise in approvals, the requests by companies to get drugs designated with orphan status has also skyrocketed. Dr. Gottlieb said in June that he wanted to get rid of the backlog; his blog post noted the effort was complete. About half of the 200 applications from drugmakers won orphan status.
• Mandating that drugmakers prove their medicine is clinically superior before getting the market exclusivity that comes with orphan drug status. The agency had lost a lawsuit in which a company said it was owed the exclusivity period regardless of whether its medicine was better. And two more lawsuits had been filed by Eagle Pharmaceuticals and United Therapeutics. The FDA Reauthorization Act, which passed in August, made it law that a drug has to be clinically superior to get the incentives.
• Closing the loophole for pediatric orphan drugs by requiring all drugs approved for common adult diseases, like inflammatory bowel disease, undergo pediatric testing when getting approval as a pediatric orphan drug. Pediatric testing is not required for orphan drugs, and last month Congress mandated that orphan drugs for cancer be tested for children. Still, the American Academy of Pediatrics celebrated the proposed change but warned it was only a first step. Bridgette Jones, MD, chair of American Academy of Pediatrics Committee on Drugs, said Sept. 12 that orphan drugs are “still mostly exempt from pediatric study requirements … children deserve access to safe, effective medications.”

Martin Makary, MD, who wrote a critical 2015 paper on orphan approvals, said the changes at the agency indicate that Dr. Gottlieb seems “concerned about all the right things. The government does a lot of lip service in general. This is not lip service.”

The restructuring has been swift in some ways.

Sandra Heibel, PhD, a senior consultant at Haffner Associates, a firm that helps companies submit orphan drug applications, noted that the approval process for designations definitely sped up over the summer, and “we are absolutely getting responses from the FDA back in 90 days. That has come through.”

Other changes to the agency, though, will evolve slowly. For example, the orphan drug office has begun reaching across the FDA’s divisions for help in reviewing drugs. In May, the FDA’s orphan reviews began to work with the office of pediatric therapeutics to review pediatric applications – ideally increasing the expertise applied when considering a company’s request for orphan drug use in children.

In an interview, FDA confirmed that Dr. Gottlieb’s orphan modernization plan is part of a larger effort to increase competition and decrease drug prices. One focus is on targeted drugs – especially those that affect rare diseases or diseases for which there is no effective therapy, the agency said.

“Such drugs present some of the biggest opportunities in medicine to treat and cure debilitating and very costly diseases,” the agency stated.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Three years after the Affordable Care Act’s coverage expansion took effect, the number of Americans without health insurance fell to 28.1 million in 2016, down from 29 million in 2015, according to a federal report released Sept. 12.

The latest numbers from the U.S. Census Bureau showed the nation’s uninsured rate dropped to 8.8%. It had been 9.1% in 2015.

Both the overall number of uninsured and the percentage are record lows.

The latest figures from the Census Bureau effectively close the book on President Barack Obama’s record on lowering the number of uninsured. He made that a linchpin of his 2008 campaign, and his administration’s effort to overhaul the nation’s health system through the ACA focused on expanding coverage.

When Mr. Obama took office in 2009, during the worst economic recession since the Great Depression, more than 50 million Americans were uninsured, or nearly 17% of the population.

The number of uninsured has fallen from 42 million in 2013 – before the ACA in 2014 allowed states to expand Medicaid, the federal-state program that provides coverage to low-income people, and provided federal subsidies to help lower- and middle-income Americans buy coverage on the insurance marketplaces. The decline also reflected the improving economy, which has put more Americans in jobs that offer health coverage.

The dramatic drop in the uninsured over the past few years played a major role in the congressional debate over the summer about whether to replace the 2010 health law. Advocates pleaded with the Republican-controlled Congress not to take steps to reverse the gains in coverage.

The Census Bureau numbers are considered the gold standard for tracking who has insurance because the survey samples are so large.

The uninsured rate has fallen in all 50 states and the District of Columbia since 2013, although the rate has been lower among the 31 states that expanded Medicaid as part of the health law. The lowest uninsured rate last year was 2.5% in Massachusetts, and the highest was 16.6% in Texas, the Census Bureau reported. States that expanded Medicaid had an average uninsured rate of 6.5%, compared with an 11.7% average among states that did not expand.

More than half of Americans – 55.7% – get health insurance through their jobs. But government coverage is becoming more common. Medicaid now covers more than 19% of the population and Medicare, nearly 17%.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Three years after the Affordable Care Act’s coverage expansion took effect, the number of Americans without health insurance fell to 28.1 million in 2016, down from 29 million in 2015, according to a federal report released Sept. 12.

The latest numbers from the U.S. Census Bureau showed the nation’s uninsured rate dropped to 8.8%. It had been 9.1% in 2015.

Both the overall number of uninsured and the percentage are record lows.

The latest figures from the Census Bureau effectively close the book on President Barack Obama’s record on lowering the number of uninsured. He made that a linchpin of his 2008 campaign, and his administration’s effort to overhaul the nation’s health system through the ACA focused on expanding coverage.

When Mr. Obama took office in 2009, during the worst economic recession since the Great Depression, more than 50 million Americans were uninsured, or nearly 17% of the population.

The number of uninsured has fallen from 42 million in 2013 – before the ACA in 2014 allowed states to expand Medicaid, the federal-state program that provides coverage to low-income people, and provided federal subsidies to help lower- and middle-income Americans buy coverage on the insurance marketplaces. The decline also reflected the improving economy, which has put more Americans in jobs that offer health coverage.

The dramatic drop in the uninsured over the past few years played a major role in the congressional debate over the summer about whether to replace the 2010 health law. Advocates pleaded with the Republican-controlled Congress not to take steps to reverse the gains in coverage.

The Census Bureau numbers are considered the gold standard for tracking who has insurance because the survey samples are so large.

The uninsured rate has fallen in all 50 states and the District of Columbia since 2013, although the rate has been lower among the 31 states that expanded Medicaid as part of the health law. The lowest uninsured rate last year was 2.5% in Massachusetts, and the highest was 16.6% in Texas, the Census Bureau reported. States that expanded Medicaid had an average uninsured rate of 6.5%, compared with an 11.7% average among states that did not expand.

More than half of Americans – 55.7% – get health insurance through their jobs. But government coverage is becoming more common. Medicaid now covers more than 19% of the population and Medicare, nearly 17%.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Three years after the Affordable Care Act’s coverage expansion took effect, the number of Americans without health insurance fell to 28.1 million in 2016, down from 29 million in 2015, according to a federal report released Sept. 12.

The latest numbers from the U.S. Census Bureau showed the nation’s uninsured rate dropped to 8.8%. It had been 9.1% in 2015.

Both the overall number of uninsured and the percentage are record lows.

The latest figures from the Census Bureau effectively close the book on President Barack Obama’s record on lowering the number of uninsured. He made that a linchpin of his 2008 campaign, and his administration’s effort to overhaul the nation’s health system through the ACA focused on expanding coverage.

When Mr. Obama took office in 2009, during the worst economic recession since the Great Depression, more than 50 million Americans were uninsured, or nearly 17% of the population.

The number of uninsured has fallen from 42 million in 2013 – before the ACA in 2014 allowed states to expand Medicaid, the federal-state program that provides coverage to low-income people, and provided federal subsidies to help lower- and middle-income Americans buy coverage on the insurance marketplaces. The decline also reflected the improving economy, which has put more Americans in jobs that offer health coverage.

The dramatic drop in the uninsured over the past few years played a major role in the congressional debate over the summer about whether to replace the 2010 health law. Advocates pleaded with the Republican-controlled Congress not to take steps to reverse the gains in coverage.

The Census Bureau numbers are considered the gold standard for tracking who has insurance because the survey samples are so large.

The uninsured rate has fallen in all 50 states and the District of Columbia since 2013, although the rate has been lower among the 31 states that expanded Medicaid as part of the health law. The lowest uninsured rate last year was 2.5% in Massachusetts, and the highest was 16.6% in Texas, the Census Bureau reported. States that expanded Medicaid had an average uninsured rate of 6.5%, compared with an 11.7% average among states that did not expand.

More than half of Americans – 55.7% – get health insurance through their jobs. But government coverage is becoming more common. Medicaid now covers more than 19% of the population and Medicare, nearly 17%.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

COLORADO SPRINGS – The survival advantage of bilateral internal over left internal mammary artery grafts persists even among multivessel CABG patients perceived to be at high surgical risk, Nishant Saran, MD, reported at the annual meeting of the Western Thoracic Surgical Association.

Many surgeons hesitate to perform bilateral internal mammary artery (BIMA) grafting in high-risk patients on the presumption that BIMA might not benefit them. It’s a concern that appears to be without merit, however, based on a retrospective analysis of the 6,468 multivessel CABG procedures performed at the Mayo Clinic during 2000-2015, said Dr. Saran of the Mayo Clinic in Rochester, Minn.
 

[email protected]

COLORADO SPRINGS – The survival advantage of bilateral internal over left internal mammary artery grafts persists even among multivessel CABG patients perceived to be at high surgical risk, Nishant Saran, MD, reported at the annual meeting of the Western Thoracic Surgical Association.

Many surgeons hesitate to perform bilateral internal mammary artery (BIMA) grafting in high-risk patients on the presumption that BIMA might not benefit them. It’s a concern that appears to be without merit, however, based on a retrospective analysis of the 6,468 multivessel CABG procedures performed at the Mayo Clinic during 2000-2015, said Dr. Saran of the Mayo Clinic in Rochester, Minn.
 

[email protected]

COLORADO SPRINGS – The survival advantage of bilateral internal over left internal mammary artery grafts persists even among multivessel CABG patients perceived to be at high surgical risk, Nishant Saran, MD, reported at the annual meeting of the Western Thoracic Surgical Association.

Many surgeons hesitate to perform bilateral internal mammary artery (BIMA) grafting in high-risk patients on the presumption that BIMA might not benefit them. It’s a concern that appears to be without merit, however, based on a retrospective analysis of the 6,468 multivessel CABG procedures performed at the Mayo Clinic during 2000-2015, said Dr. Saran of the Mayo Clinic in Rochester, Minn.
 

[email protected]

Obese individuals with no metabolic abnormalities, such as dyslipidemia, high blood pressure, or high blood sugar levels, still have a higher risk of cardiovascular disease than do metabolically healthy people of normal weight, new data suggests.

“Our study robustly challenges the assertion that MHO [metabolically healthy obese] is a benign condition and adds to the evidence base that MHO is a high-risk state for future CVD events,” wrote Rishi Caleyachetty, MD, of the University of Birmingham, England, and his coauthors online (J Am Coll Cardiol. 2017, Sep 11. doi. 10.1016/j.jacc.2017.07.763).

Dr. Caleyachetty and his associates reported findings from a population-based study using the electronic health records of nearly 3.5 million individuals aged 18 years or older who were free of cardiovascular disease at baseline.

Overall, 15% of the population were classified as being metabolically healthy obese, meaning that they had a body mass index (BMI) of at least 30 kg/m² with no sign of diabetes, hypertension, or hyperlipidemia, and 26% were overweight with no metabolic abnormalities. Despite their lack of metabolic disease, these obese individuals still had a significant 49% higher risk of coronary heart disease, 7% higher risk of cerebrovascular disease, and 96% higher risk of heart failure, compared with normal-weight individuals with no metabolic disease, after researchers adjusted for age, sex, smoking status, and social deprivation.

Individuals who were overweight but metabolically healthy had a 30% increased risk of ischemic heart disease, 11% increased risk of heart failure, and the same risk of cerebrovascular disease as normal-weight, healthy individuals.

They also saw an increasing risk of ischemic heart disease, cerebrovascular disease, heart failure, and peripheral vascular disease with each additional metabolic abnormality, even among underweight and normal-weight individuals, and suggested that a focus on screening overweight and obese individuals only could miss metabolic abnormalities in many patients.

Overweight and obese individuals without metabolic disease had a significantly lower risk of peripheral vascular disease, compared with healthy normal-weight individuals. The authors said this was a surprising finding but suggested cigarette smoking could be a confounding factor, as this is associated with both peripheral vascular disease and lower BMI.

“In sensitivity analyses restricted to individuals who were obese with no metabolic abnormalities and reported never smoking cigarettes, risk for PVD [peripheral vascular disease] was increased, compared [with] normal-weight individuals with no metabolic abnormalities,” Dr. Caleyachetty and his coinvestigators wrote.

Over the mean follow-up of 5.4 years, 5.6% of initially metabolically healthy obese individuals developed diabetes, 11.5% developed hyperlipidemia and 10.5% developed hypertension. In contrast, among the metabolically healthy overweight individuals at baseline, 1.9% developed diabetes, 9.4% developed hyperlipidemia, and 7.2% developed hypertension.

While the analysis adjusted for sex, the authors did note that women who were overweight or obese but metabolically healthy had stronger positive associations than did males with cerebrovascular disease and heart failure.

“Clinicians need to be aware that individuals who would otherwise be considered nonobese, based on a normal BMI, can have metabolic abnormalities, and therefore also be at high risk for CVD events,” the investigators concluded.

No conflicts of interest were declared.

Obese individuals with no metabolic abnormalities, such as dyslipidemia, high blood pressure, or high blood sugar levels, still have a higher risk of cardiovascular disease than do metabolically healthy people of normal weight, new data suggests.

“Our study robustly challenges the assertion that MHO [metabolically healthy obese] is a benign condition and adds to the evidence base that MHO is a high-risk state for future CVD events,” wrote Rishi Caleyachetty, MD, of the University of Birmingham, England, and his coauthors online (J Am Coll Cardiol. 2017, Sep 11. doi. 10.1016/j.jacc.2017.07.763).

Dr. Caleyachetty and his associates reported findings from a population-based study using the electronic health records of nearly 3.5 million individuals aged 18 years or older who were free of cardiovascular disease at baseline.

Overall, 15% of the population were classified as being metabolically healthy obese, meaning that they had a body mass index (BMI) of at least 30 kg/m² with no sign of diabetes, hypertension, or hyperlipidemia, and 26% were overweight with no metabolic abnormalities. Despite their lack of metabolic disease, these obese individuals still had a significant 49% higher risk of coronary heart disease, 7% higher risk of cerebrovascular disease, and 96% higher risk of heart failure, compared with normal-weight individuals with no metabolic disease, after researchers adjusted for age, sex, smoking status, and social deprivation.

Individuals who were overweight but metabolically healthy had a 30% increased risk of ischemic heart disease, 11% increased risk of heart failure, and the same risk of cerebrovascular disease as normal-weight, healthy individuals.

They also saw an increasing risk of ischemic heart disease, cerebrovascular disease, heart failure, and peripheral vascular disease with each additional metabolic abnormality, even among underweight and normal-weight individuals, and suggested that a focus on screening overweight and obese individuals only could miss metabolic abnormalities in many patients.

Overweight and obese individuals without metabolic disease had a significantly lower risk of peripheral vascular disease, compared with healthy normal-weight individuals. The authors said this was a surprising finding but suggested cigarette smoking could be a confounding factor, as this is associated with both peripheral vascular disease and lower BMI.

“In sensitivity analyses restricted to individuals who were obese with no metabolic abnormalities and reported never smoking cigarettes, risk for PVD [peripheral vascular disease] was increased, compared [with] normal-weight individuals with no metabolic abnormalities,” Dr. Caleyachetty and his coinvestigators wrote.

Over the mean follow-up of 5.4 years, 5.6% of initially metabolically healthy obese individuals developed diabetes, 11.5% developed hyperlipidemia and 10.5% developed hypertension. In contrast, among the metabolically healthy overweight individuals at baseline, 1.9% developed diabetes, 9.4% developed hyperlipidemia, and 7.2% developed hypertension.

While the analysis adjusted for sex, the authors did note that women who were overweight or obese but metabolically healthy had stronger positive associations than did males with cerebrovascular disease and heart failure.

“Clinicians need to be aware that individuals who would otherwise be considered nonobese, based on a normal BMI, can have metabolic abnormalities, and therefore also be at high risk for CVD events,” the investigators concluded.

No conflicts of interest were declared.

Obese individuals with no metabolic abnormalities, such as dyslipidemia, high blood pressure, or high blood sugar levels, still have a higher risk of cardiovascular disease than do metabolically healthy people of normal weight, new data suggests.

“Our study robustly challenges the assertion that MHO [metabolically healthy obese] is a benign condition and adds to the evidence base that MHO is a high-risk state for future CVD events,” wrote Rishi Caleyachetty, MD, of the University of Birmingham, England, and his coauthors online (J Am Coll Cardiol. 2017, Sep 11. doi. 10.1016/j.jacc.2017.07.763).

Dr. Caleyachetty and his associates reported findings from a population-based study using the electronic health records of nearly 3.5 million individuals aged 18 years or older who were free of cardiovascular disease at baseline.

Overall, 15% of the population were classified as being metabolically healthy obese, meaning that they had a body mass index (BMI) of at least 30 kg/m² with no sign of diabetes, hypertension, or hyperlipidemia, and 26% were overweight with no metabolic abnormalities. Despite their lack of metabolic disease, these obese individuals still had a significant 49% higher risk of coronary heart disease, 7% higher risk of cerebrovascular disease, and 96% higher risk of heart failure, compared with normal-weight individuals with no metabolic disease, after researchers adjusted for age, sex, smoking status, and social deprivation.

Individuals who were overweight but metabolically healthy had a 30% increased risk of ischemic heart disease, 11% increased risk of heart failure, and the same risk of cerebrovascular disease as normal-weight, healthy individuals.

They also saw an increasing risk of ischemic heart disease, cerebrovascular disease, heart failure, and peripheral vascular disease with each additional metabolic abnormality, even among underweight and normal-weight individuals, and suggested that a focus on screening overweight and obese individuals only could miss metabolic abnormalities in many patients.

Overweight and obese individuals without metabolic disease had a significantly lower risk of peripheral vascular disease, compared with healthy normal-weight individuals. The authors said this was a surprising finding but suggested cigarette smoking could be a confounding factor, as this is associated with both peripheral vascular disease and lower BMI.

“In sensitivity analyses restricted to individuals who were obese with no metabolic abnormalities and reported never smoking cigarettes, risk for PVD [peripheral vascular disease] was increased, compared [with] normal-weight individuals with no metabolic abnormalities,” Dr. Caleyachetty and his coinvestigators wrote.

Over the mean follow-up of 5.4 years, 5.6% of initially metabolically healthy obese individuals developed diabetes, 11.5% developed hyperlipidemia and 10.5% developed hypertension. In contrast, among the metabolically healthy overweight individuals at baseline, 1.9% developed diabetes, 9.4% developed hyperlipidemia, and 7.2% developed hypertension.

While the analysis adjusted for sex, the authors did note that women who were overweight or obese but metabolically healthy had stronger positive associations than did males with cerebrovascular disease and heart failure.

“Clinicians need to be aware that individuals who would otherwise be considered nonobese, based on a normal BMI, can have metabolic abnormalities, and therefore also be at high risk for CVD events,” the investigators concluded.

No conflicts of interest were declared.

MADRID – For patients with locally advanced, unresectable non-small cell lung cancer, consolidation therapy with the anti-programmed death ligand 1 (PD-L1) inhibitor durvalumab after chemoradiation was associated with significantly better progression-free survival (PFS) than placebo, results of an interim analysis of the phase 3 PACIFIC trial showed.

Among 713 patients with stage III NSCLC treated with definitive chemoradiotherapy, the median PFS from randomization was 16.8 months for patients assigned to durvalumab compared with 5.6 months for patients assigned to placebo, reported Luis Paz-Ares, MD, from the University of Madrid, Spain.
“Overall, we think durvalumab is a promising option for patients with stage III non-small cell lung cancer treated with chemoradiation,” he said at a briefing at the European Society of Medical Oncology (ESMO) Congress.

Approximately 25% to 30% of patients with NSCLC have locally advanced disease at the time of presentation. Patients with unresectable disease and good performance status are treated with chemoradiotheraoy consisting of a platinum doublet with concurrent radiation, but median PFS in these patients is generally short, on the order of 8 months. The 5-year overall survival (OS) rate is 15%, he said.
Given the lack of major advances in the care of patients with stage 3 disease, investigators have been looking to newer therapies such as immune checkpoint inhibitors to see whether they could improve outcomes.

PACIFIC is a phase 3 trial in which patients with stage III NSCLC who did not have disease progression after a minimum of two cycles of platinum-based chemotherapy were assigned on a 2:1 basis to receive intravenous durvalumab 10 mg/kg or placebo every 2 weeks for up to 12 months. Patients were stratified by age, sex, and smoking history.
Dr. Paz-Ares presented PFS results from the interim analysis, planned when about 367 events had occurred. Data on the co-primary endpoint of OS were not mature at the time of the data cutoff.

Median PFS from randomization according to blinded independent central review for 476 patients treated with durvalumab was 16.8 months, compared with 5.6 months for 237 patients who received the placebo. This translated into a stratified hazard ratio (HR) of 0.52 (P  less than .0001).
The respective PFS rates for durvalumab and placebo, were 59.9% vs. 35.3% at 12 months, and 44.2% vs. 27% at 18 months.
Among 443 patients on durvalumab and 213 on placebo who were evaluable for objective responses (OR), the respective OR rates were 28.4% vs. 16.
There were 6 complete responses (CR), 120 partial responses (PR), and 233 cases of stable disease in the durvalumab arm, compared with one CR, 33 PR, and 119 cases of stable disease in the placebo arm. In the durvalumab arm, 73 patients (16.5%) had progressive disease, compared with 59 patients (27.7%) in the placebo arm.

The median duration of response was not reached in the durvalumab arm, compared with 13.8 months in the placebo arm.
The PD-L1 inhibitor was also associated with a lower incidence of any new lesion among the intention-to-treat population (20.4% vs. 32.1%).
Grade 3 or 4 toxicities from any cause were slightly higher with durvalumab, at 29.9% vs. 26.1%. Events leading to discontinuation were also higher with the active drug, at 15.4% vs. 9.8% for placebo.
There were 21 deaths (4.4%) of patients treated with durvalumab, and 13 deaths (5.6%) of patients treated with placebo.
“In my opinion, this is a very well-designed study, and the results are very promising,” commented Enriqueta Felip, MD, who was not involved in the PACIFIC trial.

“We need to wait for the overall survival results, but in my opinion this is a very valuable trial in a group of patients [for whom] we need new strategies,” she said.
Dr. Felip was invited to the briefing as an independent commentator.
Results of the interim analysis of the PACIFIC trial were also published online in the New England Journal of Medicine.
The PACIFIC trial was funded by AstraZeneca. Dr. Paz-Ares has received consultancy fees from the company. Dr. Felip disclosed financial relationships with multiple companies not including AstraZeneca.
 

MADRID – For patients with locally advanced, unresectable non-small cell lung cancer, consolidation therapy with the anti-programmed death ligand 1 (PD-L1) inhibitor durvalumab after chemoradiation was associated with significantly better progression-free survival (PFS) than placebo, results of an interim analysis of the phase 3 PACIFIC trial showed.

Among 713 patients with stage III NSCLC treated with definitive chemoradiotherapy, the median PFS from randomization was 16.8 months for patients assigned to durvalumab compared with 5.6 months for patients assigned to placebo, reported Luis Paz-Ares, MD, from the University of Madrid, Spain.
“Overall, we think durvalumab is a promising option for patients with stage III non-small cell lung cancer treated with chemoradiation,” he said at a briefing at the European Society of Medical Oncology (ESMO) Congress.

Approximately 25% to 30% of patients with NSCLC have locally advanced disease at the time of presentation. Patients with unresectable disease and good performance status are treated with chemoradiotheraoy consisting of a platinum doublet with concurrent radiation, but median PFS in these patients is generally short, on the order of 8 months. The 5-year overall survival (OS) rate is 15%, he said.
Given the lack of major advances in the care of patients with stage 3 disease, investigators have been looking to newer therapies such as immune checkpoint inhibitors to see whether they could improve outcomes.

PACIFIC is a phase 3 trial in which patients with stage III NSCLC who did not have disease progression after a minimum of two cycles of platinum-based chemotherapy were assigned on a 2:1 basis to receive intravenous durvalumab 10 mg/kg or placebo every 2 weeks for up to 12 months. Patients were stratified by age, sex, and smoking history.
Dr. Paz-Ares presented PFS results from the interim analysis, planned when about 367 events had occurred. Data on the co-primary endpoint of OS were not mature at the time of the data cutoff.

Median PFS from randomization according to blinded independent central review for 476 patients treated with durvalumab was 16.8 months, compared with 5.6 months for 237 patients who received the placebo. This translated into a stratified hazard ratio (HR) of 0.52 (P  less than .0001).
The respective PFS rates for durvalumab and placebo, were 59.9% vs. 35.3% at 12 months, and 44.2% vs. 27% at 18 months.
Among 443 patients on durvalumab and 213 on placebo who were evaluable for objective responses (OR), the respective OR rates were 28.4% vs. 16.
There were 6 complete responses (CR), 120 partial responses (PR), and 233 cases of stable disease in the durvalumab arm, compared with one CR, 33 PR, and 119 cases of stable disease in the placebo arm. In the durvalumab arm, 73 patients (16.5%) had progressive disease, compared with 59 patients (27.7%) in the placebo arm.

The median duration of response was not reached in the durvalumab arm, compared with 13.8 months in the placebo arm.
The PD-L1 inhibitor was also associated with a lower incidence of any new lesion among the intention-to-treat population (20.4% vs. 32.1%).
Grade 3 or 4 toxicities from any cause were slightly higher with durvalumab, at 29.9% vs. 26.1%. Events leading to discontinuation were also higher with the active drug, at 15.4% vs. 9.8% for placebo.
There were 21 deaths (4.4%) of patients treated with durvalumab, and 13 deaths (5.6%) of patients treated with placebo.
“In my opinion, this is a very well-designed study, and the results are very promising,” commented Enriqueta Felip, MD, who was not involved in the PACIFIC trial.

“We need to wait for the overall survival results, but in my opinion this is a very valuable trial in a group of patients [for whom] we need new strategies,” she said.
Dr. Felip was invited to the briefing as an independent commentator.
Results of the interim analysis of the PACIFIC trial were also published online in the New England Journal of Medicine.
The PACIFIC trial was funded by AstraZeneca. Dr. Paz-Ares has received consultancy fees from the company. Dr. Felip disclosed financial relationships with multiple companies not including AstraZeneca.
 

MADRID – For patients with locally advanced, unresectable non-small cell lung cancer, consolidation therapy with the anti-programmed death ligand 1 (PD-L1) inhibitor durvalumab after chemoradiation was associated with significantly better progression-free survival (PFS) than placebo, results of an interim analysis of the phase 3 PACIFIC trial showed.

Among 713 patients with stage III NSCLC treated with definitive chemoradiotherapy, the median PFS from randomization was 16.8 months for patients assigned to durvalumab compared with 5.6 months for patients assigned to placebo, reported Luis Paz-Ares, MD, from the University of Madrid, Spain.
“Overall, we think durvalumab is a promising option for patients with stage III non-small cell lung cancer treated with chemoradiation,” he said at a briefing at the European Society of Medical Oncology (ESMO) Congress.

Approximately 25% to 30% of patients with NSCLC have locally advanced disease at the time of presentation. Patients with unresectable disease and good performance status are treated with chemoradiotheraoy consisting of a platinum doublet with concurrent radiation, but median PFS in these patients is generally short, on the order of 8 months. The 5-year overall survival (OS) rate is 15%, he said.
Given the lack of major advances in the care of patients with stage 3 disease, investigators have been looking to newer therapies such as immune checkpoint inhibitors to see whether they could improve outcomes.

PACIFIC is a phase 3 trial in which patients with stage III NSCLC who did not have disease progression after a minimum of two cycles of platinum-based chemotherapy were assigned on a 2:1 basis to receive intravenous durvalumab 10 mg/kg or placebo every 2 weeks for up to 12 months. Patients were stratified by age, sex, and smoking history.
Dr. Paz-Ares presented PFS results from the interim analysis, planned when about 367 events had occurred. Data on the co-primary endpoint of OS were not mature at the time of the data cutoff.

Median PFS from randomization according to blinded independent central review for 476 patients treated with durvalumab was 16.8 months, compared with 5.6 months for 237 patients who received the placebo. This translated into a stratified hazard ratio (HR) of 0.52 (P  less than .0001).
The respective PFS rates for durvalumab and placebo, were 59.9% vs. 35.3% at 12 months, and 44.2% vs. 27% at 18 months.
Among 443 patients on durvalumab and 213 on placebo who were evaluable for objective responses (OR), the respective OR rates were 28.4% vs. 16.
There were 6 complete responses (CR), 120 partial responses (PR), and 233 cases of stable disease in the durvalumab arm, compared with one CR, 33 PR, and 119 cases of stable disease in the placebo arm. In the durvalumab arm, 73 patients (16.5%) had progressive disease, compared with 59 patients (27.7%) in the placebo arm.

The median duration of response was not reached in the durvalumab arm, compared with 13.8 months in the placebo arm.
The PD-L1 inhibitor was also associated with a lower incidence of any new lesion among the intention-to-treat population (20.4% vs. 32.1%).
Grade 3 or 4 toxicities from any cause were slightly higher with durvalumab, at 29.9% vs. 26.1%. Events leading to discontinuation were also higher with the active drug, at 15.4% vs. 9.8% for placebo.
There were 21 deaths (4.4%) of patients treated with durvalumab, and 13 deaths (5.6%) of patients treated with placebo.
“In my opinion, this is a very well-designed study, and the results are very promising,” commented Enriqueta Felip, MD, who was not involved in the PACIFIC trial.

“We need to wait for the overall survival results, but in my opinion this is a very valuable trial in a group of patients [for whom] we need new strategies,” she said.
Dr. Felip was invited to the briefing as an independent commentator.
Results of the interim analysis of the PACIFIC trial were also published online in the New England Journal of Medicine.
The PACIFIC trial was funded by AstraZeneca. Dr. Paz-Ares has received consultancy fees from the company. Dr. Felip disclosed financial relationships with multiple companies not including AstraZeneca.
 

COLORADO SPRINGS – Minimally invasive esophagectomy was associated with a significantly lower rate of postoperative major morbidity as well as a mean 1-day briefer length of stay than open esophagectomy in a propensity-matched analysis of the real-world American College of Surgeons-National Quality Improvement Program database, Mark F. Berry, MD, reported at the annual meeting of the Western Thoracic Surgical Association.

However, both of the study’s discussants questioned whether the reported modest absolute reduction in major morbidity was really attributable to the minimally invasive approach or could instead have resulted from one of several potential confounders that couldn’t be fully adjusted for, given inherent limitations of the ACS-NSQIP database.

“There was a statistically significant difference in morbidity,” replied Dr. Berry of Stanford (Calif.) University. “It was a 4% absolute difference, which I think is probably clinically meaningful, but certainly it’s not really, really dramatic.”

[email protected]


 

COLORADO SPRINGS – Minimally invasive esophagectomy was associated with a significantly lower rate of postoperative major morbidity as well as a mean 1-day briefer length of stay than open esophagectomy in a propensity-matched analysis of the real-world American College of Surgeons-National Quality Improvement Program database, Mark F. Berry, MD, reported at the annual meeting of the Western Thoracic Surgical Association.

However, both of the study’s discussants questioned whether the reported modest absolute reduction in major morbidity was really attributable to the minimally invasive approach or could instead have resulted from one of several potential confounders that couldn’t be fully adjusted for, given inherent limitations of the ACS-NSQIP database.

“There was a statistically significant difference in morbidity,” replied Dr. Berry of Stanford (Calif.) University. “It was a 4% absolute difference, which I think is probably clinically meaningful, but certainly it’s not really, really dramatic.”

[email protected]


 

COLORADO SPRINGS – Minimally invasive esophagectomy was associated with a significantly lower rate of postoperative major morbidity as well as a mean 1-day briefer length of stay than open esophagectomy in a propensity-matched analysis of the real-world American College of Surgeons-National Quality Improvement Program database, Mark F. Berry, MD, reported at the annual meeting of the Western Thoracic Surgical Association.

However, both of the study’s discussants questioned whether the reported modest absolute reduction in major morbidity was really attributable to the minimally invasive approach or could instead have resulted from one of several potential confounders that couldn’t be fully adjusted for, given inherent limitations of the ACS-NSQIP database.

“There was a statistically significant difference in morbidity,” replied Dr. Berry of Stanford (Calif.) University. “It was a 4% absolute difference, which I think is probably clinically meaningful, but certainly it’s not really, really dramatic.”

[email protected]


 

The first bioresorbable vascular scaffold to reach clinical practice is no longer available because of poor sales, following nearly a year of bad news for the innovative device.

"We took this decision for commercial reasons, not for safety," Kristina Becker, director of communications at Abbott's Vascular business. Abbott announced that sales of the Absorb scaffold would cease worldwide as of Sept. 14, 2017, adding that the company would continue to follow patients in existing clinical trials according to their protocols.

The device was approved by the Food and Drug Administration in July 2016, but soon after, long-term trial results took an ominous turn. In March 2017, the agency issued a safety alert regarding the Absorb scaffold after release of the 2-year data from the 2,008-patient ABSORB III trial showing a significantly higher rate of target-lesion failure than with the everolimus-eluting metallic Xience stent, also marketed by Abbott.

Meanwhile, 3-year results of the ABSORB II trial, reported last October, revealed a 1% per year rate of late stent thrombosis during both the second and third years following Absorb placement in coronary arteries, the period when the Absorb scaffold was in the process of disappearing. More bad news came in July, when device thrombosis occurred nearly four times more frequently in recipients of the Absorb scaffold than with the Xience stent during 2 years of prospective follow-up in the randomized, investigator-initiated AIDA trial.

Abbott is not giving up on the idea of nonpermanent stents. “We recognize that [bioresorbable scaffold] technologies offer patients the possibility of life without permanent metallic implants, and we will continue to work on a next generation device while monitoring long-term outcomes after stent resorption in current Absorb trials,” the announcement said.

[email protected]

This article was updated 9/8/17.

The first bioresorbable vascular scaffold to reach clinical practice is no longer available because of poor sales, following nearly a year of bad news for the innovative device.

"We took this decision for commercial reasons, not for safety," Kristina Becker, director of communications at Abbott's Vascular business. Abbott announced that sales of the Absorb scaffold would cease worldwide as of Sept. 14, 2017, adding that the company would continue to follow patients in existing clinical trials according to their protocols.

The device was approved by the Food and Drug Administration in July 2016, but soon after, long-term trial results took an ominous turn. In March 2017, the agency issued a safety alert regarding the Absorb scaffold after release of the 2-year data from the 2,008-patient ABSORB III trial showing a significantly higher rate of target-lesion failure than with the everolimus-eluting metallic Xience stent, also marketed by Abbott.

Meanwhile, 3-year results of the ABSORB II trial, reported last October, revealed a 1% per year rate of late stent thrombosis during both the second and third years following Absorb placement in coronary arteries, the period when the Absorb scaffold was in the process of disappearing. More bad news came in July, when device thrombosis occurred nearly four times more frequently in recipients of the Absorb scaffold than with the Xience stent during 2 years of prospective follow-up in the randomized, investigator-initiated AIDA trial.

Abbott is not giving up on the idea of nonpermanent stents. “We recognize that [bioresorbable scaffold] technologies offer patients the possibility of life without permanent metallic implants, and we will continue to work on a next generation device while monitoring long-term outcomes after stent resorption in current Absorb trials,” the announcement said.

[email protected]

This article was updated 9/8/17.

The first bioresorbable vascular scaffold to reach clinical practice is no longer available because of poor sales, following nearly a year of bad news for the innovative device.

"We took this decision for commercial reasons, not for safety," Kristina Becker, director of communications at Abbott's Vascular business. Abbott announced that sales of the Absorb scaffold would cease worldwide as of Sept. 14, 2017, adding that the company would continue to follow patients in existing clinical trials according to their protocols.

The device was approved by the Food and Drug Administration in July 2016, but soon after, long-term trial results took an ominous turn. In March 2017, the agency issued a safety alert regarding the Absorb scaffold after release of the 2-year data from the 2,008-patient ABSORB III trial showing a significantly higher rate of target-lesion failure than with the everolimus-eluting metallic Xience stent, also marketed by Abbott.

Meanwhile, 3-year results of the ABSORB II trial, reported last October, revealed a 1% per year rate of late stent thrombosis during both the second and third years following Absorb placement in coronary arteries, the period when the Absorb scaffold was in the process of disappearing. More bad news came in July, when device thrombosis occurred nearly four times more frequently in recipients of the Absorb scaffold than with the Xience stent during 2 years of prospective follow-up in the randomized, investigator-initiated AIDA trial.

Abbott is not giving up on the idea of nonpermanent stents. “We recognize that [bioresorbable scaffold] technologies offer patients the possibility of life without permanent metallic implants, and we will continue to work on a next generation device while monitoring long-term outcomes after stent resorption in current Absorb trials,” the announcement said.

[email protected]

This article was updated 9/8/17.