Elizabeth Mechcatie

WASHINGTON – Beneficial effects of peginterferon beta-1a administered every 2 weeks were evident as early as 12 weeks after starting treatment, in the pivotal phase III study comparing peginterferon beta-1a to placebo in patients with relapsing remitting multiple sclerosis, Dr. Scott Newsome, said at the annual meeting of the American Academy of Neurology.

At 12 weeks, treatment with peginterferon beta-1a was associated with a 37% reduction in the adjusted annualized relapse rate (ARR) compared with placebo, in the ADVANCE study, said Dr. Newsome of the department of neurology at Johns Hopkins University, Baltimore.

ADVANCE compared 125 mcg of peginterferon beta-1a administered every 2 or 4 weeks to placebo in patients with relapsing remitting MS. The efficacy of peginterferon beta-1a was maintained over 2 years. Greater efficacy was seen with administration every 2 weeks (Lancet Neurol. 2014;13:657-65). In August 2014, the Food and Drug Administration approved peginterferon beta-1a, at a dose of 125 mcg administered subcutaneously every 14 days, for relapsing forms of multiple sclerosis; it is marketed as Plegridy by Biogen Idec.

Interim results of the follow-up study of patients enrolled in ADVANCE – the ATTAIN trial – have shown that over 3 years of treatment, no new safety issues or concerns have emerged, and the clinical effects of treatment are maintained, according to Dr. Marcelo Kremenchutzky of Western University, London, Ont., who presented those results at the meeting.

Dr. Newsome presented the 12-week data among 512 patients randomized to treatment every 2 weeks and 500 randomized to placebo in the ADVANCE study; their mean age was 36-37 years, almost two-thirds were female, and 81%-82% were white. They were enrolled for a mean of 6-7 years from their first MS symptoms and had had a mean of 2.6 relapses within the previous 3 years. Their mean Expanded Disability Status Scale (EDSS) scores were 2.44-2.47.

At 12 weeks, the ARR, the primary endpoint, among those on peginterferon beta-1a was 0.259 vs. 0.414 among those on placebo, a 37.4% reduction over placebo (P = .045), Dr. Newsome said. The ARR was adjusted for baseline EDSS, relapse rate, and age. (At 48 weeks, the ARR among those on peginterferon beta-1a every 2 weeks was 0.26, compared with 0.40 among those on placebo, a significantly reduced risk of 36%, with a P value of .0007.)

The proportion of patients who relapsed at 12 weeks – 6% of those on peginterferon beta-1a vs. 9.5% of those on placebo – was reduced by 36.8% (P = .041), with a “clear separation” between the treatment and control arms at 12 weeks, he noted.

In addition, the estimated proportion of patients with an onset of 24-week confirmed disability progression (CDP) was 0 among those on peginterferon beta-1a versus 1.0% among those on placebo (P = .026). This result was not as robust as the relapse results, but there was a clear separation between the arms with statistical significance, said Dr. Newsome, director of outpatient neurology services at Johns Hopkins.

In the ADVANCE study, PEG administered every 2 or 4 weeks was well tolerated with a favorable safety profile in the first year, and a similar safety profile between the two dosing regimens, he added.

Dr. Kremenchutzky, director of the Multiple Sclerosis Clinic in London, Ont., presented the 1-year data in the ongoing extension study that is evaluating long-term MS outcomes, safety, and tolerability of peginterferon beta-1a among patients enrolled in ADVANCE, including those treated with peginterferon beta-1a every 2 weeks (376) or every 4 weeks (354).

Also included are 344 patients who were on placebo but were rerandomized to peginterferon beta-1a every 2 or 4 weeks (the delayed treatment group) after 1 year in the ADVANCE study; they were included in the analyses after they had been on treatment for 2 years.

After 1 year in the ATTAIN study, injection-site reactions and flu-like symptoms remained the most frequent adverse events associated with peginterferon beta-1a, and most were mild to moderate. Treatment has also been associated with “low levels” of laboratory abnormalities and immunogenicity, and clinical efficacy has been maintained for 3 years, Dr. Kremenchutzky said at the meeting.

Adverse events were “very similar” in the 4-week and 2-week treatment groups. Over 3 years, 96% of patients in both groups had experienced an adverse event, and the rates of treatment-related adverse events (91%), and severe adverse events (24%) were the same in both groups. The rates of treatment discontinuations due to an adverse event (7%-8%) and withdrawal from the study due to an adverse event (8%-9%) were similar.

The rates of flu-like symptoms over 3 years were also similar (62%-64%) in the two groups, and influenza-like illness was reported in 55% of those dosed every 2 weeks and in 45% of those dosed every 4 weeks. In addition to influenza-like illness, pyrexia was the most common flu-like symptom reported over 3 years (43%-45%).

About 65%-69% of those in the two groups reported injection-site reactions, with erythema the most common (62%-64%), followed by pain (17%-18%) and pruritus (12%-16%).

Lab abnormalities were comparable with both dosing schedules: Over 3 years, white blood cell counts were reduced in 6% of those on the 2-week schedule, compared with 8% among those on the 4-week schedule. Lymphocyte counts were reduced in 12% and 9% of those on the 2-week and 4-week schedules, respectively. In addition, 8% of those on the 2-week dose and 6% of those on the 4-week dose had low hemoglobin (100 g/L or less) over the 3 years.

Rates of anti-IFN and anti-PEG antibodies associated with both schedules were low, Dr. Kremenchutzkysaid. Over 3 years, 7%-9% tested positive for IFN binding antibody at least once, and 4%-6% of the total were “persistent positive.” Another 9% of those on the 4-week schedule and 6% of those on the 2-week schedule were anti-PEG antibody positive at least once, and 3%-5% of the patients in total had persistent levels. Titers were high in less than 1% of the total.

In ATTAIN, efficacy endpoints were secondary, and included ARR, which was reduced by 25.1% over 3 years among those receiving the dose every 2 weeks, compared with every 4 weeks (P = .0199). By 144 weeks, 30.5% of those on the 2-week schedule and 41.1% of those on the 4-week schedule had experienced a relapse, a significant difference (P = .0070), Dr. Kremenchutzky said.

The proportion of those with CDP by 144 weeks was 15.5% among those on the 4-week schedule, vs. 9.2% among those on the 2-week schedule (P = .0098), he added.

The studies were funded by Biogen Idec. Dr. Newsome and Dr. Kremenchutzky both disclosed having been compensated for activities with Biogen Idec and other companies that market MS drugs.

[email protected]

WASHINGTON – Beneficial effects of peginterferon beta-1a administered every 2 weeks were evident as early as 12 weeks after starting treatment, in the pivotal phase III study comparing peginterferon beta-1a to placebo in patients with relapsing remitting multiple sclerosis, Dr. Scott Newsome, said at the annual meeting of the American Academy of Neurology.

At 12 weeks, treatment with peginterferon beta-1a was associated with a 37% reduction in the adjusted annualized relapse rate (ARR) compared with placebo, in the ADVANCE study, said Dr. Newsome of the department of neurology at Johns Hopkins University, Baltimore.

ADVANCE compared 125 mcg of peginterferon beta-1a administered every 2 or 4 weeks to placebo in patients with relapsing remitting MS. The efficacy of peginterferon beta-1a was maintained over 2 years. Greater efficacy was seen with administration every 2 weeks (Lancet Neurol. 2014;13:657-65). In August 2014, the Food and Drug Administration approved peginterferon beta-1a, at a dose of 125 mcg administered subcutaneously every 14 days, for relapsing forms of multiple sclerosis; it is marketed as Plegridy by Biogen Idec.

Interim results of the follow-up study of patients enrolled in ADVANCE – the ATTAIN trial – have shown that over 3 years of treatment, no new safety issues or concerns have emerged, and the clinical effects of treatment are maintained, according to Dr. Marcelo Kremenchutzky of Western University, London, Ont., who presented those results at the meeting.

Dr. Newsome presented the 12-week data among 512 patients randomized to treatment every 2 weeks and 500 randomized to placebo in the ADVANCE study; their mean age was 36-37 years, almost two-thirds were female, and 81%-82% were white. They were enrolled for a mean of 6-7 years from their first MS symptoms and had had a mean of 2.6 relapses within the previous 3 years. Their mean Expanded Disability Status Scale (EDSS) scores were 2.44-2.47.

At 12 weeks, the ARR, the primary endpoint, among those on peginterferon beta-1a was 0.259 vs. 0.414 among those on placebo, a 37.4% reduction over placebo (P = .045), Dr. Newsome said. The ARR was adjusted for baseline EDSS, relapse rate, and age. (At 48 weeks, the ARR among those on peginterferon beta-1a every 2 weeks was 0.26, compared with 0.40 among those on placebo, a significantly reduced risk of 36%, with a P value of .0007.)

The proportion of patients who relapsed at 12 weeks – 6% of those on peginterferon beta-1a vs. 9.5% of those on placebo – was reduced by 36.8% (P = .041), with a “clear separation” between the treatment and control arms at 12 weeks, he noted.

In addition, the estimated proportion of patients with an onset of 24-week confirmed disability progression (CDP) was 0 among those on peginterferon beta-1a versus 1.0% among those on placebo (P = .026). This result was not as robust as the relapse results, but there was a clear separation between the arms with statistical significance, said Dr. Newsome, director of outpatient neurology services at Johns Hopkins.

In the ADVANCE study, PEG administered every 2 or 4 weeks was well tolerated with a favorable safety profile in the first year, and a similar safety profile between the two dosing regimens, he added.

Dr. Kremenchutzky, director of the Multiple Sclerosis Clinic in London, Ont., presented the 1-year data in the ongoing extension study that is evaluating long-term MS outcomes, safety, and tolerability of peginterferon beta-1a among patients enrolled in ADVANCE, including those treated with peginterferon beta-1a every 2 weeks (376) or every 4 weeks (354).

Also included are 344 patients who were on placebo but were rerandomized to peginterferon beta-1a every 2 or 4 weeks (the delayed treatment group) after 1 year in the ADVANCE study; they were included in the analyses after they had been on treatment for 2 years.

After 1 year in the ATTAIN study, injection-site reactions and flu-like symptoms remained the most frequent adverse events associated with peginterferon beta-1a, and most were mild to moderate. Treatment has also been associated with “low levels” of laboratory abnormalities and immunogenicity, and clinical efficacy has been maintained for 3 years, Dr. Kremenchutzky said at the meeting.

Adverse events were “very similar” in the 4-week and 2-week treatment groups. Over 3 years, 96% of patients in both groups had experienced an adverse event, and the rates of treatment-related adverse events (91%), and severe adverse events (24%) were the same in both groups. The rates of treatment discontinuations due to an adverse event (7%-8%) and withdrawal from the study due to an adverse event (8%-9%) were similar.

The rates of flu-like symptoms over 3 years were also similar (62%-64%) in the two groups, and influenza-like illness was reported in 55% of those dosed every 2 weeks and in 45% of those dosed every 4 weeks. In addition to influenza-like illness, pyrexia was the most common flu-like symptom reported over 3 years (43%-45%).

About 65%-69% of those in the two groups reported injection-site reactions, with erythema the most common (62%-64%), followed by pain (17%-18%) and pruritus (12%-16%).

Lab abnormalities were comparable with both dosing schedules: Over 3 years, white blood cell counts were reduced in 6% of those on the 2-week schedule, compared with 8% among those on the 4-week schedule. Lymphocyte counts were reduced in 12% and 9% of those on the 2-week and 4-week schedules, respectively. In addition, 8% of those on the 2-week dose and 6% of those on the 4-week dose had low hemoglobin (100 g/L or less) over the 3 years.

Rates of anti-IFN and anti-PEG antibodies associated with both schedules were low, Dr. Kremenchutzkysaid. Over 3 years, 7%-9% tested positive for IFN binding antibody at least once, and 4%-6% of the total were “persistent positive.” Another 9% of those on the 4-week schedule and 6% of those on the 2-week schedule were anti-PEG antibody positive at least once, and 3%-5% of the patients in total had persistent levels. Titers were high in less than 1% of the total.

In ATTAIN, efficacy endpoints were secondary, and included ARR, which was reduced by 25.1% over 3 years among those receiving the dose every 2 weeks, compared with every 4 weeks (P = .0199). By 144 weeks, 30.5% of those on the 2-week schedule and 41.1% of those on the 4-week schedule had experienced a relapse, a significant difference (P = .0070), Dr. Kremenchutzky said.

The proportion of those with CDP by 144 weeks was 15.5% among those on the 4-week schedule, vs. 9.2% among those on the 2-week schedule (P = .0098), he added.

The studies were funded by Biogen Idec. Dr. Newsome and Dr. Kremenchutzky both disclosed having been compensated for activities with Biogen Idec and other companies that market MS drugs.

[email protected]

WASHINGTON – Beneficial effects of peginterferon beta-1a administered every 2 weeks were evident as early as 12 weeks after starting treatment, in the pivotal phase III study comparing peginterferon beta-1a to placebo in patients with relapsing remitting multiple sclerosis, Dr. Scott Newsome, said at the annual meeting of the American Academy of Neurology.

At 12 weeks, treatment with peginterferon beta-1a was associated with a 37% reduction in the adjusted annualized relapse rate (ARR) compared with placebo, in the ADVANCE study, said Dr. Newsome of the department of neurology at Johns Hopkins University, Baltimore.

ADVANCE compared 125 mcg of peginterferon beta-1a administered every 2 or 4 weeks to placebo in patients with relapsing remitting MS. The efficacy of peginterferon beta-1a was maintained over 2 years. Greater efficacy was seen with administration every 2 weeks (Lancet Neurol. 2014;13:657-65). In August 2014, the Food and Drug Administration approved peginterferon beta-1a, at a dose of 125 mcg administered subcutaneously every 14 days, for relapsing forms of multiple sclerosis; it is marketed as Plegridy by Biogen Idec.

Interim results of the follow-up study of patients enrolled in ADVANCE – the ATTAIN trial – have shown that over 3 years of treatment, no new safety issues or concerns have emerged, and the clinical effects of treatment are maintained, according to Dr. Marcelo Kremenchutzky of Western University, London, Ont., who presented those results at the meeting.

Dr. Newsome presented the 12-week data among 512 patients randomized to treatment every 2 weeks and 500 randomized to placebo in the ADVANCE study; their mean age was 36-37 years, almost two-thirds were female, and 81%-82% were white. They were enrolled for a mean of 6-7 years from their first MS symptoms and had had a mean of 2.6 relapses within the previous 3 years. Their mean Expanded Disability Status Scale (EDSS) scores were 2.44-2.47.

At 12 weeks, the ARR, the primary endpoint, among those on peginterferon beta-1a was 0.259 vs. 0.414 among those on placebo, a 37.4% reduction over placebo (P = .045), Dr. Newsome said. The ARR was adjusted for baseline EDSS, relapse rate, and age. (At 48 weeks, the ARR among those on peginterferon beta-1a every 2 weeks was 0.26, compared with 0.40 among those on placebo, a significantly reduced risk of 36%, with a P value of .0007.)

The proportion of patients who relapsed at 12 weeks – 6% of those on peginterferon beta-1a vs. 9.5% of those on placebo – was reduced by 36.8% (P = .041), with a “clear separation” between the treatment and control arms at 12 weeks, he noted.

In addition, the estimated proportion of patients with an onset of 24-week confirmed disability progression (CDP) was 0 among those on peginterferon beta-1a versus 1.0% among those on placebo (P = .026). This result was not as robust as the relapse results, but there was a clear separation between the arms with statistical significance, said Dr. Newsome, director of outpatient neurology services at Johns Hopkins.

In the ADVANCE study, PEG administered every 2 or 4 weeks was well tolerated with a favorable safety profile in the first year, and a similar safety profile between the two dosing regimens, he added.

Dr. Kremenchutzky, director of the Multiple Sclerosis Clinic in London, Ont., presented the 1-year data in the ongoing extension study that is evaluating long-term MS outcomes, safety, and tolerability of peginterferon beta-1a among patients enrolled in ADVANCE, including those treated with peginterferon beta-1a every 2 weeks (376) or every 4 weeks (354).

Also included are 344 patients who were on placebo but were rerandomized to peginterferon beta-1a every 2 or 4 weeks (the delayed treatment group) after 1 year in the ADVANCE study; they were included in the analyses after they had been on treatment for 2 years.

After 1 year in the ATTAIN study, injection-site reactions and flu-like symptoms remained the most frequent adverse events associated with peginterferon beta-1a, and most were mild to moderate. Treatment has also been associated with “low levels” of laboratory abnormalities and immunogenicity, and clinical efficacy has been maintained for 3 years, Dr. Kremenchutzky said at the meeting.

Adverse events were “very similar” in the 4-week and 2-week treatment groups. Over 3 years, 96% of patients in both groups had experienced an adverse event, and the rates of treatment-related adverse events (91%), and severe adverse events (24%) were the same in both groups. The rates of treatment discontinuations due to an adverse event (7%-8%) and withdrawal from the study due to an adverse event (8%-9%) were similar.

The rates of flu-like symptoms over 3 years were also similar (62%-64%) in the two groups, and influenza-like illness was reported in 55% of those dosed every 2 weeks and in 45% of those dosed every 4 weeks. In addition to influenza-like illness, pyrexia was the most common flu-like symptom reported over 3 years (43%-45%).

About 65%-69% of those in the two groups reported injection-site reactions, with erythema the most common (62%-64%), followed by pain (17%-18%) and pruritus (12%-16%).

Lab abnormalities were comparable with both dosing schedules: Over 3 years, white blood cell counts were reduced in 6% of those on the 2-week schedule, compared with 8% among those on the 4-week schedule. Lymphocyte counts were reduced in 12% and 9% of those on the 2-week and 4-week schedules, respectively. In addition, 8% of those on the 2-week dose and 6% of those on the 4-week dose had low hemoglobin (100 g/L or less) over the 3 years.

Rates of anti-IFN and anti-PEG antibodies associated with both schedules were low, Dr. Kremenchutzkysaid. Over 3 years, 7%-9% tested positive for IFN binding antibody at least once, and 4%-6% of the total were “persistent positive.” Another 9% of those on the 4-week schedule and 6% of those on the 2-week schedule were anti-PEG antibody positive at least once, and 3%-5% of the patients in total had persistent levels. Titers were high in less than 1% of the total.

In ATTAIN, efficacy endpoints were secondary, and included ARR, which was reduced by 25.1% over 3 years among those receiving the dose every 2 weeks, compared with every 4 weeks (P = .0199). By 144 weeks, 30.5% of those on the 2-week schedule and 41.1% of those on the 4-week schedule had experienced a relapse, a significant difference (P = .0070), Dr. Kremenchutzky said.

The proportion of those with CDP by 144 weeks was 15.5% among those on the 4-week schedule, vs. 9.2% among those on the 2-week schedule (P = .0098), he added.

The studies were funded by Biogen Idec. Dr. Newsome and Dr. Kremenchutzky both disclosed having been compensated for activities with Biogen Idec and other companies that market MS drugs.

[email protected]

A product that contains a spray-dried, blended formulation of fibrinogen and thrombin, derived from human plasma, has been approved for use in helping control surgical bleeding, the Food and Drug Administration announced.

The approved indication for the fibrin sealant is for use with an absorbable gelatin sponge; it is the first spray-dried fibrin sealant approved by the FDA, according to its statement. The product, which will be marketed as Raplixa, can be applied from the product vial or sprayed onto the site of bleeding with a spray device.

“This approval provides surgeons an additional option to help control bleeding during surgery when needed,” Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA’s statement. “The spray-drying process used to manufacture Raplixa produces dried powders that can be combined into a single vial. This eliminates the need to combine the fibrinogen and thrombin before use and allows the product to be stored at room temperature,” she added.

Approval was based on a study of 719 people undergoing different types of surgical procedures, which showed that use of the fibrin sealant with an absorbable gelatin sponge reduced the time required to achieve hemostasis, compared with the use of a sponge alone. The manufacturing process includes viral inactivation and removal to reduce the risk of transmitting of blood-borne viruses, the FDA statement said.

The approved indication is “to provide adjunctive hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature and cautery) is ineffective or impractical,” according to an April 30 statement issued by the Medicines Company. The statement said that the product does not need to be thawed, reconstituted or mixed before use, and it describes the spray device as “a low-pressure spray applicator designed to deliver Raplixa to larger bleeding surfaces in difficult to reach areas.”

The product is manufactured by ProFibrix BV, a subsidiary of the Medicines Company.

[email protected]

A product that contains a spray-dried, blended formulation of fibrinogen and thrombin, derived from human plasma, has been approved for use in helping control surgical bleeding, the Food and Drug Administration announced.

The approved indication for the fibrin sealant is for use with an absorbable gelatin sponge; it is the first spray-dried fibrin sealant approved by the FDA, according to its statement. The product, which will be marketed as Raplixa, can be applied from the product vial or sprayed onto the site of bleeding with a spray device.

“This approval provides surgeons an additional option to help control bleeding during surgery when needed,” Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA’s statement. “The spray-drying process used to manufacture Raplixa produces dried powders that can be combined into a single vial. This eliminates the need to combine the fibrinogen and thrombin before use and allows the product to be stored at room temperature,” she added.

Approval was based on a study of 719 people undergoing different types of surgical procedures, which showed that use of the fibrin sealant with an absorbable gelatin sponge reduced the time required to achieve hemostasis, compared with the use of a sponge alone. The manufacturing process includes viral inactivation and removal to reduce the risk of transmitting of blood-borne viruses, the FDA statement said.

The approved indication is “to provide adjunctive hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature and cautery) is ineffective or impractical,” according to an April 30 statement issued by the Medicines Company. The statement said that the product does not need to be thawed, reconstituted or mixed before use, and it describes the spray device as “a low-pressure spray applicator designed to deliver Raplixa to larger bleeding surfaces in difficult to reach areas.”

The product is manufactured by ProFibrix BV, a subsidiary of the Medicines Company.

[email protected]

A product that contains a spray-dried, blended formulation of fibrinogen and thrombin, derived from human plasma, has been approved for use in helping control surgical bleeding, the Food and Drug Administration announced.

The approved indication for the fibrin sealant is for use with an absorbable gelatin sponge; it is the first spray-dried fibrin sealant approved by the FDA, according to its statement. The product, which will be marketed as Raplixa, can be applied from the product vial or sprayed onto the site of bleeding with a spray device.

“This approval provides surgeons an additional option to help control bleeding during surgery when needed,” Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA’s statement. “The spray-drying process used to manufacture Raplixa produces dried powders that can be combined into a single vial. This eliminates the need to combine the fibrinogen and thrombin before use and allows the product to be stored at room temperature,” she added.

Approval was based on a study of 719 people undergoing different types of surgical procedures, which showed that use of the fibrin sealant with an absorbable gelatin sponge reduced the time required to achieve hemostasis, compared with the use of a sponge alone. The manufacturing process includes viral inactivation and removal to reduce the risk of transmitting of blood-borne viruses, the FDA statement said.

The approved indication is “to provide adjunctive hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature and cautery) is ineffective or impractical,” according to an April 30 statement issued by the Medicines Company. The statement said that the product does not need to be thawed, reconstituted or mixed before use, and it describes the spray device as “a low-pressure spray applicator designed to deliver Raplixa to larger bleeding surfaces in difficult to reach areas.”

The product is manufactured by ProFibrix BV, a subsidiary of the Medicines Company.

[email protected]

Fixed-dose combinations of the inhaled corticosteroid (ICS) fluticasone and the long-acting beta-agonist (LABA) vilanterol have been approved by the Food and Drug Administration for treating asthma in adults, the manufacturer, GlaxoSmithKline, announced on April 30.

Vilanterol, as part of the combination product, is the first new LABA approved for asthma in 15 years and fluticasone-vilanterol is the first once-daily inhaled ICS-LABA combination treatment approved for asthma.

Two strengths have been approved, 100 mcg or 200 mcg of fluticasone with 25 mcg of vilanterol, administered once a day with a dry powder inhaler, for people aged 18 years and older, according to the company’s statement. The products are marketed as Breo Ellipta. In 2013, the 100/25 mcg dose was approved to treat chronic obstructive pulmonary disease.

The company had filed for approval for treating asthma in adolescents aged 12-17 years who were studied in the same trials as adults, but the FDA did not approve the product in this age group. In the statement, GSK said that the FDA issued a “complete response” letter for the younger age group, “stating that the data submitted do not show adequate risk-benefit to support the approval in these patients,” and that more data “would be required to further demonstrate the safety and efficacy in this population.”

(The FDA issues complete response letters to companies when approval is not supported by the company’s application; the agency does not make this information public, but manufacturers often make that information available.)

The FDA decision reflects the recommendations of the FDA’s Pulmonary-Allergy Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee, which, at a meeting on March 19, voted 16-4 that the efficacy and safety data supported the approval of both proposed doses in adults. But the panels voted 19-1 that the data did not support approval for adolescents, aged 12-17 years, citing uncertainty about safety and inconsistent efficacy results in this age group; panelists said that a separate safety and efficacy study in adolescents was needed.

As with other LABA products, the prescribing information for Breo Ellipta includes a boxed warning about the increased risk of asthma-related deaths associated with LABAs.

Unlike the LABAs salmeterol and formoterol, vilanterol is not approved for use as a single agent. Fluticasone (100 mcg and 200 mcg) is approved for treating asthma.

Serious adverse events associated with Breo Ellipta should be reported to the FDA’s MedWatch program at 800-332-1088. Prescribing information can be found at www.gsksource.com.

[email protected]

Fixed-dose combinations of the inhaled corticosteroid (ICS) fluticasone and the long-acting beta-agonist (LABA) vilanterol have been approved by the Food and Drug Administration for treating asthma in adults, the manufacturer, GlaxoSmithKline, announced on April 30.

Vilanterol, as part of the combination product, is the first new LABA approved for asthma in 15 years and fluticasone-vilanterol is the first once-daily inhaled ICS-LABA combination treatment approved for asthma.

Two strengths have been approved, 100 mcg or 200 mcg of fluticasone with 25 mcg of vilanterol, administered once a day with a dry powder inhaler, for people aged 18 years and older, according to the company’s statement. The products are marketed as Breo Ellipta. In 2013, the 100/25 mcg dose was approved to treat chronic obstructive pulmonary disease.

The company had filed for approval for treating asthma in adolescents aged 12-17 years who were studied in the same trials as adults, but the FDA did not approve the product in this age group. In the statement, GSK said that the FDA issued a “complete response” letter for the younger age group, “stating that the data submitted do not show adequate risk-benefit to support the approval in these patients,” and that more data “would be required to further demonstrate the safety and efficacy in this population.”

(The FDA issues complete response letters to companies when approval is not supported by the company’s application; the agency does not make this information public, but manufacturers often make that information available.)

The FDA decision reflects the recommendations of the FDA’s Pulmonary-Allergy Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee, which, at a meeting on March 19, voted 16-4 that the efficacy and safety data supported the approval of both proposed doses in adults. But the panels voted 19-1 that the data did not support approval for adolescents, aged 12-17 years, citing uncertainty about safety and inconsistent efficacy results in this age group; panelists said that a separate safety and efficacy study in adolescents was needed.

As with other LABA products, the prescribing information for Breo Ellipta includes a boxed warning about the increased risk of asthma-related deaths associated with LABAs.

Unlike the LABAs salmeterol and formoterol, vilanterol is not approved for use as a single agent. Fluticasone (100 mcg and 200 mcg) is approved for treating asthma.

Serious adverse events associated with Breo Ellipta should be reported to the FDA’s MedWatch program at 800-332-1088. Prescribing information can be found at www.gsksource.com.

[email protected]

Fixed-dose combinations of the inhaled corticosteroid (ICS) fluticasone and the long-acting beta-agonist (LABA) vilanterol have been approved by the Food and Drug Administration for treating asthma in adults, the manufacturer, GlaxoSmithKline, announced on April 30.

Vilanterol, as part of the combination product, is the first new LABA approved for asthma in 15 years and fluticasone-vilanterol is the first once-daily inhaled ICS-LABA combination treatment approved for asthma.

Two strengths have been approved, 100 mcg or 200 mcg of fluticasone with 25 mcg of vilanterol, administered once a day with a dry powder inhaler, for people aged 18 years and older, according to the company’s statement. The products are marketed as Breo Ellipta. In 2013, the 100/25 mcg dose was approved to treat chronic obstructive pulmonary disease.

The company had filed for approval for treating asthma in adolescents aged 12-17 years who were studied in the same trials as adults, but the FDA did not approve the product in this age group. In the statement, GSK said that the FDA issued a “complete response” letter for the younger age group, “stating that the data submitted do not show adequate risk-benefit to support the approval in these patients,” and that more data “would be required to further demonstrate the safety and efficacy in this population.”

(The FDA issues complete response letters to companies when approval is not supported by the company’s application; the agency does not make this information public, but manufacturers often make that information available.)

The FDA decision reflects the recommendations of the FDA’s Pulmonary-Allergy Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee, which, at a meeting on March 19, voted 16-4 that the efficacy and safety data supported the approval of both proposed doses in adults. But the panels voted 19-1 that the data did not support approval for adolescents, aged 12-17 years, citing uncertainty about safety and inconsistent efficacy results in this age group; panelists said that a separate safety and efficacy study in adolescents was needed.

As with other LABA products, the prescribing information for Breo Ellipta includes a boxed warning about the increased risk of asthma-related deaths associated with LABAs.

Unlike the LABAs salmeterol and formoterol, vilanterol is not approved for use as a single agent. Fluticasone (100 mcg and 200 mcg) is approved for treating asthma.

Serious adverse events associated with Breo Ellipta should be reported to the FDA’s MedWatch program at 800-332-1088. Prescribing information can be found at www.gsksource.com.

[email protected]

The Food and Drug Administration is requesting more scientific data on the safety and effectiveness of the active ingredients in antiseptic products used in hospitals, physician’s offices, and other health care settings in a proposed rule issued April 30.

“Today’s proposal seeks to ensure the FDA’s evaluations and determinations for all health care antiseptic active ingredients are consistent, up-to-date and appropriately reflect current scientific knowledge and patterns of use by health care professionals,” Dr. Theresa Michele, director of the division of nonprescription drug products in the FDA’s Center for Drug Evaluation and Research, said in a statement. The proposed rule “should not be taken to mean” that the agency believes these products are not effective or safe, according to the statement.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

Alcohol and iodine are among the most common active ingredients in these products, which include hand washes and rubs, surgical hand scrubs and rubs, and preoperative skin preparations used on patients. These products are marketed under an over-the-counter drug monograph and are different than antibacterial soaps, hand sanitizers, and other consumer antiseptic products, which are not included in this proposed rule. To continue to market these products under the monograph, manufacturers must provide the FDA with more data on the safety and effectiveness of the active ingredients, including absorption, hormonal effects, and bacterial resistance, the statement said.

“Emerging science” suggests that, for at least some active ingredients used in these products, “systemic exposure … is higher than previously thought, and existing data raise potential concerns about the effects of repeated daily human exposure to some antiseptic active ingredients,” the statement said. The agency “is particularly interested in gathering additional data on the long-term safety of daily, repeated exposure to these ingredients in the health care setting and on the use of these products by certain populations, including pregnant and breastfeeding health care workers, for which topical absorption of the active ingredients may be important.”

The proposed rule is available at www.federalregister.gov. Public comments can be submitted until Oct. 27.

[email protected]

The Food and Drug Administration is requesting more scientific data on the safety and effectiveness of the active ingredients in antiseptic products used in hospitals, physician’s offices, and other health care settings in a proposed rule issued April 30.

“Today’s proposal seeks to ensure the FDA’s evaluations and determinations for all health care antiseptic active ingredients are consistent, up-to-date and appropriately reflect current scientific knowledge and patterns of use by health care professionals,” Dr. Theresa Michele, director of the division of nonprescription drug products in the FDA’s Center for Drug Evaluation and Research, said in a statement. The proposed rule “should not be taken to mean” that the agency believes these products are not effective or safe, according to the statement.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

Alcohol and iodine are among the most common active ingredients in these products, which include hand washes and rubs, surgical hand scrubs and rubs, and preoperative skin preparations used on patients. These products are marketed under an over-the-counter drug monograph and are different than antibacterial soaps, hand sanitizers, and other consumer antiseptic products, which are not included in this proposed rule. To continue to market these products under the monograph, manufacturers must provide the FDA with more data on the safety and effectiveness of the active ingredients, including absorption, hormonal effects, and bacterial resistance, the statement said.

“Emerging science” suggests that, for at least some active ingredients used in these products, “systemic exposure … is higher than previously thought, and existing data raise potential concerns about the effects of repeated daily human exposure to some antiseptic active ingredients,” the statement said. The agency “is particularly interested in gathering additional data on the long-term safety of daily, repeated exposure to these ingredients in the health care setting and on the use of these products by certain populations, including pregnant and breastfeeding health care workers, for which topical absorption of the active ingredients may be important.”

The proposed rule is available at www.federalregister.gov. Public comments can be submitted until Oct. 27.

[email protected]

The Food and Drug Administration is requesting more scientific data on the safety and effectiveness of the active ingredients in antiseptic products used in hospitals, physician’s offices, and other health care settings in a proposed rule issued April 30.

“Today’s proposal seeks to ensure the FDA’s evaluations and determinations for all health care antiseptic active ingredients are consistent, up-to-date and appropriately reflect current scientific knowledge and patterns of use by health care professionals,” Dr. Theresa Michele, director of the division of nonprescription drug products in the FDA’s Center for Drug Evaluation and Research, said in a statement. The proposed rule “should not be taken to mean” that the agency believes these products are not effective or safe, according to the statement.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

Alcohol and iodine are among the most common active ingredients in these products, which include hand washes and rubs, surgical hand scrubs and rubs, and preoperative skin preparations used on patients. These products are marketed under an over-the-counter drug monograph and are different than antibacterial soaps, hand sanitizers, and other consumer antiseptic products, which are not included in this proposed rule. To continue to market these products under the monograph, manufacturers must provide the FDA with more data on the safety and effectiveness of the active ingredients, including absorption, hormonal effects, and bacterial resistance, the statement said.

“Emerging science” suggests that, for at least some active ingredients used in these products, “systemic exposure … is higher than previously thought, and existing data raise potential concerns about the effects of repeated daily human exposure to some antiseptic active ingredients,” the statement said. The agency “is particularly interested in gathering additional data on the long-term safety of daily, repeated exposure to these ingredients in the health care setting and on the use of these products by certain populations, including pregnant and breastfeeding health care workers, for which topical absorption of the active ingredients may be important.”

The proposed rule is available at www.federalregister.gov. Public comments can be submitted until Oct. 27.

[email protected]

SILVER SPRING, MD. – A Food and Drug Administration advisory panel supports approval of talimogene laherparepvec (T-VEC), an oncolytic immunotherapy, voting 22-1 that the overall risk-benefit profile is favorable for treatment of patients with injectable regionally or distantly metastatic melanoma.

At a joint meeting of the FDA’s Oncologic Drugs Advisory Committee and the Cellular, Tissue and Gene Therapies Advisory Committee on April 29, panelists agreed that it was clear that at least some subpopulations of patients can benefit from this treatment, but cautioned that while nonvisceral metastases may respond to treatment, it was not clear whether visceral metastases responded, and that it should not be used to treat visceral disease. They also recommended that labeling should discourage clinicians from using this treatment in patients with substantial metastatic disease.

T-VEC is a first-in-class oncolytic immunotherapy derived from herpes simplex virus type 1 (HSV-1) the virus that causes most cold sores. It has been genetically modified to attenuate its virulence and engineered to express granulocyte-macrophage colony-stimulating factor (GM-CSF), while remaining susceptible to antiviral treatments such as acyclovir. T-VEC is injected directly into cutaneous, subcutaneous, or nodal lesions, “resulting in selective lysis of the injected tumor cells (and not normal tissue),” which “results in the release and presentation of tumor-derived antigens and local expression of GM-CSF to initiate a systemic anti-tumor immune response that also induces regression of non-injected and distant lesions,” according to the Amgen briefing documents. If approved, this would be the first virus-based cancer treatment, the company noted.

The FDA panel looked at a phase III, open-label, multicenter randomized study that compared treatment with T-VEC to GM-CSF (administered subcutaneously) in 436 people with melanoma (stage IIIB/C or stage IV with limited visceral disease burden that was considered unresectable); the trial began before several targeted and biologic treatments that are now available for advanced melanoma were approved. About half the patients had been treated previously for melanoma and more than 20% were older than 75 years; 292 patients were treated with T-VEC (up to 4 mL injected into one or more subcutaneous or nodal melanoma lesions every 1 or 2 weeks until clinically relevant disease progression occurred or there was no more residual tumor to inject) and 141 received GM-CSF daily in the control arm (for 14 days and off for 14 days).

The primary efficacy endpoint was the durable response rate (DRR), defined as the proportion of patients with responses (complete or partial) “maintained continuously for 6 or more months and beginning at any point within 12 months of initiating therapy,” as assessed by a blinded independent committee. That endpoint was met by 16.3% of those treated with T-VEC vs. 2.1% of those on GM-CSF, a significant difference (P < .0001).

Other results included the overall response rate – complete or partial – which was 26.4% in the T-VEC group vs. 5.7% in the control group; Complete response was 10.8% among those on T-VEC, vs. 0.7% among those on GM-CSF.

Among the approximately 400 patients treated with T-VEC in this and five other studies, the most common adverse events were expected, namely, cellulitis and flu-like symptoms, and most adverse events were mild or moderate.

Disease progression and cellulitis were the most common serious adverse events and occurred more often among those on T-VEC (3.1% vs. 1.6%, and 2.4% vs. 0.8%, respectively). Fatal adverse events were higher among those on T-VEC (3.4% vs. 1.6%); disease progression was the most commonly reported.

Almost 6% of those on T-VEC reported herpetic events, mostly oral herpes, but there were no serious herpes complications or cases of secondary transmission. Amgen has proposed a risk management plan to address the risks of the treatment, including herpetic lesions, accidental exposures to health care professionals, and secondary transmission, and postmarketing studies.

Several panelists pointed out that the company‘s claims that T-VEC has a systemic effect was not necessarily substantiated by the data, and that the unresectable disease qualifier should be added to the indication. Other points made by panel members were that the dosing instructions were not sufficient, and that while the safety profile was acceptable, the risks of cellulitis and of shedding on family members, pregnant women, children, health care professionals, and other cancer patients were concerns. Panelists also noted that it is unclear how T-VEC compares to the other treatments that have been approved for advanced melanoma over the past several years.

“What’s very, very clear is there is a response of the injected lesions.” and local control of lesions is important to patients, said panelist Dr. Patrick Hwu, professor in the department of melanoma medical oncology, University of Texas M.D. Anderson Cancer Center, Houston. Based on the data, “this clearly ... will be among the least toxic agents for cancer given in the [melanoma] clinic,” compared to other treatments, he added.

The FDA usually follows advisory panels’ recommendations. An FDA decision on approval is expected by Oct. 27, 2015, according to Amgen. Panelists had no potential conflicts of interest related to this meeting.

[email protected]

SILVER SPRING, MD. – A Food and Drug Administration advisory panel supports approval of talimogene laherparepvec (T-VEC), an oncolytic immunotherapy, voting 22-1 that the overall risk-benefit profile is favorable for treatment of patients with injectable regionally or distantly metastatic melanoma.

At a joint meeting of the FDA’s Oncologic Drugs Advisory Committee and the Cellular, Tissue and Gene Therapies Advisory Committee on April 29, panelists agreed that it was clear that at least some subpopulations of patients can benefit from this treatment, but cautioned that while nonvisceral metastases may respond to treatment, it was not clear whether visceral metastases responded, and that it should not be used to treat visceral disease. They also recommended that labeling should discourage clinicians from using this treatment in patients with substantial metastatic disease.

T-VEC is a first-in-class oncolytic immunotherapy derived from herpes simplex virus type 1 (HSV-1) the virus that causes most cold sores. It has been genetically modified to attenuate its virulence and engineered to express granulocyte-macrophage colony-stimulating factor (GM-CSF), while remaining susceptible to antiviral treatments such as acyclovir. T-VEC is injected directly into cutaneous, subcutaneous, or nodal lesions, “resulting in selective lysis of the injected tumor cells (and not normal tissue),” which “results in the release and presentation of tumor-derived antigens and local expression of GM-CSF to initiate a systemic anti-tumor immune response that also induces regression of non-injected and distant lesions,” according to the Amgen briefing documents. If approved, this would be the first virus-based cancer treatment, the company noted.

The FDA panel looked at a phase III, open-label, multicenter randomized study that compared treatment with T-VEC to GM-CSF (administered subcutaneously) in 436 people with melanoma (stage IIIB/C or stage IV with limited visceral disease burden that was considered unresectable); the trial began before several targeted and biologic treatments that are now available for advanced melanoma were approved. About half the patients had been treated previously for melanoma and more than 20% were older than 75 years; 292 patients were treated with T-VEC (up to 4 mL injected into one or more subcutaneous or nodal melanoma lesions every 1 or 2 weeks until clinically relevant disease progression occurred or there was no more residual tumor to inject) and 141 received GM-CSF daily in the control arm (for 14 days and off for 14 days).

The primary efficacy endpoint was the durable response rate (DRR), defined as the proportion of patients with responses (complete or partial) “maintained continuously for 6 or more months and beginning at any point within 12 months of initiating therapy,” as assessed by a blinded independent committee. That endpoint was met by 16.3% of those treated with T-VEC vs. 2.1% of those on GM-CSF, a significant difference (P < .0001).

Other results included the overall response rate – complete or partial – which was 26.4% in the T-VEC group vs. 5.7% in the control group; Complete response was 10.8% among those on T-VEC, vs. 0.7% among those on GM-CSF.

Among the approximately 400 patients treated with T-VEC in this and five other studies, the most common adverse events were expected, namely, cellulitis and flu-like symptoms, and most adverse events were mild or moderate.

Disease progression and cellulitis were the most common serious adverse events and occurred more often among those on T-VEC (3.1% vs. 1.6%, and 2.4% vs. 0.8%, respectively). Fatal adverse events were higher among those on T-VEC (3.4% vs. 1.6%); disease progression was the most commonly reported.

Almost 6% of those on T-VEC reported herpetic events, mostly oral herpes, but there were no serious herpes complications or cases of secondary transmission. Amgen has proposed a risk management plan to address the risks of the treatment, including herpetic lesions, accidental exposures to health care professionals, and secondary transmission, and postmarketing studies.

Several panelists pointed out that the company‘s claims that T-VEC has a systemic effect was not necessarily substantiated by the data, and that the unresectable disease qualifier should be added to the indication. Other points made by panel members were that the dosing instructions were not sufficient, and that while the safety profile was acceptable, the risks of cellulitis and of shedding on family members, pregnant women, children, health care professionals, and other cancer patients were concerns. Panelists also noted that it is unclear how T-VEC compares to the other treatments that have been approved for advanced melanoma over the past several years.

“What’s very, very clear is there is a response of the injected lesions.” and local control of lesions is important to patients, said panelist Dr. Patrick Hwu, professor in the department of melanoma medical oncology, University of Texas M.D. Anderson Cancer Center, Houston. Based on the data, “this clearly ... will be among the least toxic agents for cancer given in the [melanoma] clinic,” compared to other treatments, he added.

The FDA usually follows advisory panels’ recommendations. An FDA decision on approval is expected by Oct. 27, 2015, according to Amgen. Panelists had no potential conflicts of interest related to this meeting.

[email protected]

SILVER SPRING, MD. – A Food and Drug Administration advisory panel supports approval of talimogene laherparepvec (T-VEC), an oncolytic immunotherapy, voting 22-1 that the overall risk-benefit profile is favorable for treatment of patients with injectable regionally or distantly metastatic melanoma.

At a joint meeting of the FDA’s Oncologic Drugs Advisory Committee and the Cellular, Tissue and Gene Therapies Advisory Committee on April 29, panelists agreed that it was clear that at least some subpopulations of patients can benefit from this treatment, but cautioned that while nonvisceral metastases may respond to treatment, it was not clear whether visceral metastases responded, and that it should not be used to treat visceral disease. They also recommended that labeling should discourage clinicians from using this treatment in patients with substantial metastatic disease.

T-VEC is a first-in-class oncolytic immunotherapy derived from herpes simplex virus type 1 (HSV-1) the virus that causes most cold sores. It has been genetically modified to attenuate its virulence and engineered to express granulocyte-macrophage colony-stimulating factor (GM-CSF), while remaining susceptible to antiviral treatments such as acyclovir. T-VEC is injected directly into cutaneous, subcutaneous, or nodal lesions, “resulting in selective lysis of the injected tumor cells (and not normal tissue),” which “results in the release and presentation of tumor-derived antigens and local expression of GM-CSF to initiate a systemic anti-tumor immune response that also induces regression of non-injected and distant lesions,” according to the Amgen briefing documents. If approved, this would be the first virus-based cancer treatment, the company noted.

The FDA panel looked at a phase III, open-label, multicenter randomized study that compared treatment with T-VEC to GM-CSF (administered subcutaneously) in 436 people with melanoma (stage IIIB/C or stage IV with limited visceral disease burden that was considered unresectable); the trial began before several targeted and biologic treatments that are now available for advanced melanoma were approved. About half the patients had been treated previously for melanoma and more than 20% were older than 75 years; 292 patients were treated with T-VEC (up to 4 mL injected into one or more subcutaneous or nodal melanoma lesions every 1 or 2 weeks until clinically relevant disease progression occurred or there was no more residual tumor to inject) and 141 received GM-CSF daily in the control arm (for 14 days and off for 14 days).

The primary efficacy endpoint was the durable response rate (DRR), defined as the proportion of patients with responses (complete or partial) “maintained continuously for 6 or more months and beginning at any point within 12 months of initiating therapy,” as assessed by a blinded independent committee. That endpoint was met by 16.3% of those treated with T-VEC vs. 2.1% of those on GM-CSF, a significant difference (P < .0001).

Other results included the overall response rate – complete or partial – which was 26.4% in the T-VEC group vs. 5.7% in the control group; Complete response was 10.8% among those on T-VEC, vs. 0.7% among those on GM-CSF.

Among the approximately 400 patients treated with T-VEC in this and five other studies, the most common adverse events were expected, namely, cellulitis and flu-like symptoms, and most adverse events were mild or moderate.

Disease progression and cellulitis were the most common serious adverse events and occurred more often among those on T-VEC (3.1% vs. 1.6%, and 2.4% vs. 0.8%, respectively). Fatal adverse events were higher among those on T-VEC (3.4% vs. 1.6%); disease progression was the most commonly reported.

Almost 6% of those on T-VEC reported herpetic events, mostly oral herpes, but there were no serious herpes complications or cases of secondary transmission. Amgen has proposed a risk management plan to address the risks of the treatment, including herpetic lesions, accidental exposures to health care professionals, and secondary transmission, and postmarketing studies.

Several panelists pointed out that the company‘s claims that T-VEC has a systemic effect was not necessarily substantiated by the data, and that the unresectable disease qualifier should be added to the indication. Other points made by panel members were that the dosing instructions were not sufficient, and that while the safety profile was acceptable, the risks of cellulitis and of shedding on family members, pregnant women, children, health care professionals, and other cancer patients were concerns. Panelists also noted that it is unclear how T-VEC compares to the other treatments that have been approved for advanced melanoma over the past several years.

“What’s very, very clear is there is a response of the injected lesions.” and local control of lesions is important to patients, said panelist Dr. Patrick Hwu, professor in the department of melanoma medical oncology, University of Texas M.D. Anderson Cancer Center, Houston. Based on the data, “this clearly ... will be among the least toxic agents for cancer given in the [melanoma] clinic,” compared to other treatments, he added.

The FDA usually follows advisory panels’ recommendations. An FDA decision on approval is expected by Oct. 27, 2015, according to Amgen. Panelists had no potential conflicts of interest related to this meeting.

[email protected]

The Food and Drug Administration has approved several generic formulations of the atypical antipsychotic aripiprazole, the agency announced April 28.

Aripiprazole was approved in 2002 for the treatment of schizophrenia and is marketed as Abilify by the Otsuka Pharmaceutical. It is now also approved for indications that include bipolar disorder. Multiple dosage forms and strengths of generic aripiprazole have been approved, according to the FDA statement.

The generic manufacturers are Alembic Pharmaceuticals, Hetero Drugs, Teva Pharmaceuticals, and Torrent Pharmaceuticals.

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The Food and Drug Administration has approved several generic formulations of the atypical antipsychotic aripiprazole, the agency announced April 28.

Aripiprazole was approved in 2002 for the treatment of schizophrenia and is marketed as Abilify by the Otsuka Pharmaceutical. It is now also approved for indications that include bipolar disorder. Multiple dosage forms and strengths of generic aripiprazole have been approved, according to the FDA statement.

The generic manufacturers are Alembic Pharmaceuticals, Hetero Drugs, Teva Pharmaceuticals, and Torrent Pharmaceuticals.

[email protected]

The Food and Drug Administration has approved several generic formulations of the atypical antipsychotic aripiprazole, the agency announced April 28.

Aripiprazole was approved in 2002 for the treatment of schizophrenia and is marketed as Abilify by the Otsuka Pharmaceutical. It is now also approved for indications that include bipolar disorder. Multiple dosage forms and strengths of generic aripiprazole have been approved, according to the FDA statement.

The generic manufacturers are Alembic Pharmaceuticals, Hetero Drugs, Teva Pharmaceuticals, and Torrent Pharmaceuticals.

[email protected]

Tasimelteon, a melatonin-receptor agonist available in the United States, is getting closer to becoming available in the European Union to help regulate sleep patterns in blind people.

On April 24, the European Medicines Agency (EMA) announced that the Committee for Medicinal Products for Human Use (CHMP) had recommended granting authorization for marketing of the drug in the European Union for non-24-hour sleep-wake disorder in “totally blind” adults. Once marketed, this would be the first treatment in Europe for this indication, which the statement describes as a rare and “long-term debilitating condition.”

The drug was shown to be effective in two clinical trials, the results of which showed that treatment resulted in significant improvement, compared with placebo, “both in increasing night-time sleep and decreasing daytime sleep duration,” according to the statement. Headache, drowsiness, and nightmares or “unusual dreams” were among the most common adverse effects associated with treatment.

Tasimelteon was approved in the United States in January 2014 for treating non-24-hour sleep-wake disorder, referred to as “non-24,” at a dose of 20 mg taken before bedtime at the same time every night.

“The precise mechanism by which tasimelteon exerts its therapeutic effect” in patients with non-24 is not known, according to the U.S. prescribing information, which adds that the drug is an agonist at melatonin MT₁ and MT₂ receptors, which are thought to be involved in the control of circadian rhythms.

The trade name used in the EMA release is Hetlioz, the trade name used in the United States.

The EMA is similar to the FDA and the EMA’s CHMP committee prepares opinions on questions related to medications used to treat humans.

The CHMP opinion, adopted at a meeting in April, will be sent to the European Commission for a decision on marketing authorization in the EU. After authorization for marketing has been granted, the decision about cost and reimbursement “will then take place at the level of each Member State considering the potential role/use of this medicine in the context of the national health system of that country,” the EMA release stated.

The drug is manufactured by Vanda Pharmaceuticals.

[email protected]

Tasimelteon, a melatonin-receptor agonist available in the United States, is getting closer to becoming available in the European Union to help regulate sleep patterns in blind people.

On April 24, the European Medicines Agency (EMA) announced that the Committee for Medicinal Products for Human Use (CHMP) had recommended granting authorization for marketing of the drug in the European Union for non-24-hour sleep-wake disorder in “totally blind” adults. Once marketed, this would be the first treatment in Europe for this indication, which the statement describes as a rare and “long-term debilitating condition.”

The drug was shown to be effective in two clinical trials, the results of which showed that treatment resulted in significant improvement, compared with placebo, “both in increasing night-time sleep and decreasing daytime sleep duration,” according to the statement. Headache, drowsiness, and nightmares or “unusual dreams” were among the most common adverse effects associated with treatment.

Tasimelteon was approved in the United States in January 2014 for treating non-24-hour sleep-wake disorder, referred to as “non-24,” at a dose of 20 mg taken before bedtime at the same time every night.

“The precise mechanism by which tasimelteon exerts its therapeutic effect” in patients with non-24 is not known, according to the U.S. prescribing information, which adds that the drug is an agonist at melatonin MT₁ and MT₂ receptors, which are thought to be involved in the control of circadian rhythms.

The trade name used in the EMA release is Hetlioz, the trade name used in the United States.

The EMA is similar to the FDA and the EMA’s CHMP committee prepares opinions on questions related to medications used to treat humans.

The CHMP opinion, adopted at a meeting in April, will be sent to the European Commission for a decision on marketing authorization in the EU. After authorization for marketing has been granted, the decision about cost and reimbursement “will then take place at the level of each Member State considering the potential role/use of this medicine in the context of the national health system of that country,” the EMA release stated.

The drug is manufactured by Vanda Pharmaceuticals.

[email protected]

Tasimelteon, a melatonin-receptor agonist available in the United States, is getting closer to becoming available in the European Union to help regulate sleep patterns in blind people.

On April 24, the European Medicines Agency (EMA) announced that the Committee for Medicinal Products for Human Use (CHMP) had recommended granting authorization for marketing of the drug in the European Union for non-24-hour sleep-wake disorder in “totally blind” adults. Once marketed, this would be the first treatment in Europe for this indication, which the statement describes as a rare and “long-term debilitating condition.”

The drug was shown to be effective in two clinical trials, the results of which showed that treatment resulted in significant improvement, compared with placebo, “both in increasing night-time sleep and decreasing daytime sleep duration,” according to the statement. Headache, drowsiness, and nightmares or “unusual dreams” were among the most common adverse effects associated with treatment.

Tasimelteon was approved in the United States in January 2014 for treating non-24-hour sleep-wake disorder, referred to as “non-24,” at a dose of 20 mg taken before bedtime at the same time every night.

“The precise mechanism by which tasimelteon exerts its therapeutic effect” in patients with non-24 is not known, according to the U.S. prescribing information, which adds that the drug is an agonist at melatonin MT₁ and MT₂ receptors, which are thought to be involved in the control of circadian rhythms.

The trade name used in the EMA release is Hetlioz, the trade name used in the United States.

The EMA is similar to the FDA and the EMA’s CHMP committee prepares opinions on questions related to medications used to treat humans.

The CHMP opinion, adopted at a meeting in April, will be sent to the European Commission for a decision on marketing authorization in the EU. After authorization for marketing has been granted, the decision about cost and reimbursement “will then take place at the level of each Member State considering the potential role/use of this medicine in the context of the national health system of that country,” the EMA release stated.

The drug is manufactured by Vanda Pharmaceuticals.

[email protected]

The Food and Drug Administration has expanded approval of the antiangiogenic agent ramucirumab for use in combination with FOLFIRI for “the treatment of metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine,” according to the updated prescribing information.

The FDA announced the expanded approval on April 24 in a statement, which said that it was based on the results of an international study of 1,072 patients with mCRC that progressed during or within 6 months of discontinuing bevacizumab-, oxaliplatin- and fluoropyrimidine-based combination chemotherapy, randomized to treatment with FOLFIRI alone, or to FOLFIRI plus ramucirumab. Their median age was 62 years, almost 60% were men, and 99% had an ECOG performance status of 0 or 1. In both arms, treatment was administered every 2 weeks; the dose of ramucirumab was 8mg/kg, administered by an intravenous infusion every 2 weeks, and was continued until disease progressed or toxicity became unacceptable.

Median overall survival (OS), the primary endpoint, was 13.3 months among those on ramucirumab, vs. 11.7 months among those on placebo. The improvement in OS was statistically significant (P = .023), with a reduced risk of 15%. Compared with those on FOLFIRI alone, there was also a significant improvement in progression-free survival (PFS) among those treated with the combination, a median of 5.7 months vs. 4.5 months (P < 0.001) and a reduced risk of 21%.

“In general, the safety data was consistent with the known safety profile established in previously approved indications,” although thyroid monitoring identified hypothyroidism in 2.6% of patients, according to the statement. The label includes a boxed warning about the risks of hemorrhage, gastrointestinal perforation, and impaired wound healing associated with treatment.

Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist, marketed as Cyramza by Eli Lilly. It was initially approved for advanced gastric cancer and gastroesophageal junction adenocarcinoma, and metastatic non–small cell lung cancer indications in late 2014.

Serious adverse events associated with treatment should be reported to the FDA’s MedWatch program at 800-332-1088 or online https://www.accessdata.fda.gov/scripts/medwatch/.

The Food and Drug Administration has expanded approval of the antiangiogenic agent ramucirumab for use in combination with FOLFIRI for “the treatment of metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine,” according to the updated prescribing information.

The FDA announced the expanded approval on April 24 in a statement, which said that it was based on the results of an international study of 1,072 patients with mCRC that progressed during or within 6 months of discontinuing bevacizumab-, oxaliplatin- and fluoropyrimidine-based combination chemotherapy, randomized to treatment with FOLFIRI alone, or to FOLFIRI plus ramucirumab. Their median age was 62 years, almost 60% were men, and 99% had an ECOG performance status of 0 or 1. In both arms, treatment was administered every 2 weeks; the dose of ramucirumab was 8mg/kg, administered by an intravenous infusion every 2 weeks, and was continued until disease progressed or toxicity became unacceptable.

Median overall survival (OS), the primary endpoint, was 13.3 months among those on ramucirumab, vs. 11.7 months among those on placebo. The improvement in OS was statistically significant (P = .023), with a reduced risk of 15%. Compared with those on FOLFIRI alone, there was also a significant improvement in progression-free survival (PFS) among those treated with the combination, a median of 5.7 months vs. 4.5 months (P < 0.001) and a reduced risk of 21%.

“In general, the safety data was consistent with the known safety profile established in previously approved indications,” although thyroid monitoring identified hypothyroidism in 2.6% of patients, according to the statement. The label includes a boxed warning about the risks of hemorrhage, gastrointestinal perforation, and impaired wound healing associated with treatment.

Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist, marketed as Cyramza by Eli Lilly. It was initially approved for advanced gastric cancer and gastroesophageal junction adenocarcinoma, and metastatic non–small cell lung cancer indications in late 2014.

Serious adverse events associated with treatment should be reported to the FDA’s MedWatch program at 800-332-1088 or online https://www.accessdata.fda.gov/scripts/medwatch/.

The Food and Drug Administration has expanded approval of the antiangiogenic agent ramucirumab for use in combination with FOLFIRI for “the treatment of metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine,” according to the updated prescribing information.

The FDA announced the expanded approval on April 24 in a statement, which said that it was based on the results of an international study of 1,072 patients with mCRC that progressed during or within 6 months of discontinuing bevacizumab-, oxaliplatin- and fluoropyrimidine-based combination chemotherapy, randomized to treatment with FOLFIRI alone, or to FOLFIRI plus ramucirumab. Their median age was 62 years, almost 60% were men, and 99% had an ECOG performance status of 0 or 1. In both arms, treatment was administered every 2 weeks; the dose of ramucirumab was 8mg/kg, administered by an intravenous infusion every 2 weeks, and was continued until disease progressed or toxicity became unacceptable.

Median overall survival (OS), the primary endpoint, was 13.3 months among those on ramucirumab, vs. 11.7 months among those on placebo. The improvement in OS was statistically significant (P = .023), with a reduced risk of 15%. Compared with those on FOLFIRI alone, there was also a significant improvement in progression-free survival (PFS) among those treated with the combination, a median of 5.7 months vs. 4.5 months (P < 0.001) and a reduced risk of 21%.

“In general, the safety data was consistent with the known safety profile established in previously approved indications,” although thyroid monitoring identified hypothyroidism in 2.6% of patients, according to the statement. The label includes a boxed warning about the risks of hemorrhage, gastrointestinal perforation, and impaired wound healing associated with treatment.

Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist, marketed as Cyramza by Eli Lilly. It was initially approved for advanced gastric cancer and gastroesophageal junction adenocarcinoma, and metastatic non–small cell lung cancer indications in late 2014.

Serious adverse events associated with treatment should be reported to the FDA’s MedWatch program at 800-332-1088 or online https://www.accessdata.fda.gov/scripts/medwatch/.

WASHINGTON – A mobile stroke unit significantly reduced the time to evaluation, diagnosis, and treatment when compared with standard emergency medical units for patients experiencing symptoms of an acute stroke, Dr. Ken Uchino reported at the annual meeting of the American Academy of Neurology.

In a 1-year prospective study conducted in Cleveland, patients who were evaluated at the mobile stroke unit and diagnosed with an acute ischemic stroke received treatment with intravenous tissue plasminogen activator (TPA) a median of about 26 minutes earlier than did patients transported via EMS to the hospital’s stroke center, a statistically significant difference, said Dr. Uchino of the Cleveland Clinic’s cerebrovascular center and the Cleveland Pre-Hospital Acute Stroke Treatment (PHAST) study group.

In addition, 25% of the patients who were having an acute ischemic stroke received TPA within the first hour of the onset of symptoms, “the golden hour of thrombolysis.” No one in the control group met that goal, he noted.

American Heart Association/American Stroke Association guidelines recommend a door-to-needle time of 60 minutes or less and set a goal for participating hospitals to administer TPA to at least 50% of their patients with acute ischemic stroke within 60 minutes of arriving at the hospital.

Of the 100 patients evaluated for stroke, 33 had a probable acute ischemic stroke and 16 of 19 patients who qualified received intravenous TPA.* One patient did not receive TPA because of crew error, and there were problems with intravenous access in two patients. Another 30 were diagnosed with a possible acute ischemic stroke. Of the remainder, 4 were diagnosed with a transient ischemic attack, 5 were diagnosed with intracerebral hemorrhage, and 28 were classified as “other.”

One patient with an intracerebral hemorrhage, a 93-year-old woman on warfarin, was successfully treated with prothrombin complex concentrate for warfarin reversal before arriving at the hospital.

Further study is needed to obtain data on the outcomes and cost-effectiveness of the mobile stroke units, he said.

The mobile unit is a modified emergency response vehicle staffed by a nurse, paramedic, emergency medical technician, and a CT technologist. The unit has a mobile CT scanner and telemedicine equipment with point-of-care lab testing; a vascular neurologist and a neuroradiologist work remotely to evaluate patients and images. The protocol starts with the 911 call and activation of the emergency medical system. An algorithm is used to identify patients who might be having a stroke.

Courtesy Cleveland Clinic

Once the mobile stroke unit reaches the patient, the team performs a CT scan and lab testing and the vascular neurologist interacts remotely with the patient and the unit’s personnel. If a diagnosis is confirmed, intravenous TPA is initiated and the patient is triaged to the appropriate hospital, Dr. Uchino explained.The study compared the times to treatment for patients experiencing acute stroke symptoms who were treated at the mobile stroke unit in the city (100 patients) with those presenting to Cleveland Clinic hospital emergency departments with a stroke alert called within 30 minutes of arrival to the hospital (53 patients), from Jan. 1, 2014, through December 2014. The mean age of patients was 63 years, about 56% were females. Intravenous thrombolysis was administered to 16 patients (16%) of those in the mobile stroke unit group and 12 (almost 23%) of those in the control group, which was not a significant difference.

The door-to-CT completion time was a median of 13 minutes (range, 9-21 minutes) in the mobile stroke unit group and 18 minutes (range, 12-26 minutes) among controls (P = .0026).

The door-to-CT read time was a median of 25 minutes in both groups. The door-to-international normalized ratio result time was a median of 13 minutes (range, 7-18) in the mobile stroke unit group and 44 minutes (range, 36-61) among controls, a significant difference (P < .001). The median time for door-to-video login was 11 minutes (range, 7-17) for the mobile stroke unit group and 20 minutes (range, 14-27) for controls.

The door-to-intravenous thrombolysis time was a median of 32 minutes (range, 24-47) in the mobile unit group and 58 minutes (range, 52-66) among controls, a 26-minute difference that was statistically significant, (P = .0012), Dr. Uchino said. The median time from the onset of symptoms to thrombolysis was 97 minutes (range, 61-144) in the mobile stroke unit group and 123 minutes (range, 110-176) in the controls (P = .0485).

Dr. Uchino and his associates at the Cleveland Clinic are part of the Cleveland PHAST study group; other participants include Case Western Reserve University. He had no disclosures. The mobile unit received funding from the Milton and Tamar Maltz Family Foundation and the Cleveland Clinic.

*CORRECTION, 4/27/15: The numbers of patients who actually received TPA out of those who qualified were accidentally transposed.

[email protected]

WASHINGTON – A mobile stroke unit significantly reduced the time to evaluation, diagnosis, and treatment when compared with standard emergency medical units for patients experiencing symptoms of an acute stroke, Dr. Ken Uchino reported at the annual meeting of the American Academy of Neurology.

In a 1-year prospective study conducted in Cleveland, patients who were evaluated at the mobile stroke unit and diagnosed with an acute ischemic stroke received treatment with intravenous tissue plasminogen activator (TPA) a median of about 26 minutes earlier than did patients transported via EMS to the hospital’s stroke center, a statistically significant difference, said Dr. Uchino of the Cleveland Clinic’s cerebrovascular center and the Cleveland Pre-Hospital Acute Stroke Treatment (PHAST) study group.

In addition, 25% of the patients who were having an acute ischemic stroke received TPA within the first hour of the onset of symptoms, “the golden hour of thrombolysis.” No one in the control group met that goal, he noted.

American Heart Association/American Stroke Association guidelines recommend a door-to-needle time of 60 minutes or less and set a goal for participating hospitals to administer TPA to at least 50% of their patients with acute ischemic stroke within 60 minutes of arriving at the hospital.

Of the 100 patients evaluated for stroke, 33 had a probable acute ischemic stroke and 16 of 19 patients who qualified received intravenous TPA.* One patient did not receive TPA because of crew error, and there were problems with intravenous access in two patients. Another 30 were diagnosed with a possible acute ischemic stroke. Of the remainder, 4 were diagnosed with a transient ischemic attack, 5 were diagnosed with intracerebral hemorrhage, and 28 were classified as “other.”

One patient with an intracerebral hemorrhage, a 93-year-old woman on warfarin, was successfully treated with prothrombin complex concentrate for warfarin reversal before arriving at the hospital.

Further study is needed to obtain data on the outcomes and cost-effectiveness of the mobile stroke units, he said.

The mobile unit is a modified emergency response vehicle staffed by a nurse, paramedic, emergency medical technician, and a CT technologist. The unit has a mobile CT scanner and telemedicine equipment with point-of-care lab testing; a vascular neurologist and a neuroradiologist work remotely to evaluate patients and images. The protocol starts with the 911 call and activation of the emergency medical system. An algorithm is used to identify patients who might be having a stroke.

Courtesy Cleveland Clinic

Once the mobile stroke unit reaches the patient, the team performs a CT scan and lab testing and the vascular neurologist interacts remotely with the patient and the unit’s personnel. If a diagnosis is confirmed, intravenous TPA is initiated and the patient is triaged to the appropriate hospital, Dr. Uchino explained.The study compared the times to treatment for patients experiencing acute stroke symptoms who were treated at the mobile stroke unit in the city (100 patients) with those presenting to Cleveland Clinic hospital emergency departments with a stroke alert called within 30 minutes of arrival to the hospital (53 patients), from Jan. 1, 2014, through December 2014. The mean age of patients was 63 years, about 56% were females. Intravenous thrombolysis was administered to 16 patients (16%) of those in the mobile stroke unit group and 12 (almost 23%) of those in the control group, which was not a significant difference.

The door-to-CT completion time was a median of 13 minutes (range, 9-21 minutes) in the mobile stroke unit group and 18 minutes (range, 12-26 minutes) among controls (P = .0026).

The door-to-CT read time was a median of 25 minutes in both groups. The door-to-international normalized ratio result time was a median of 13 minutes (range, 7-18) in the mobile stroke unit group and 44 minutes (range, 36-61) among controls, a significant difference (P < .001). The median time for door-to-video login was 11 minutes (range, 7-17) for the mobile stroke unit group and 20 minutes (range, 14-27) for controls.

The door-to-intravenous thrombolysis time was a median of 32 minutes (range, 24-47) in the mobile unit group and 58 minutes (range, 52-66) among controls, a 26-minute difference that was statistically significant, (P = .0012), Dr. Uchino said. The median time from the onset of symptoms to thrombolysis was 97 minutes (range, 61-144) in the mobile stroke unit group and 123 minutes (range, 110-176) in the controls (P = .0485).

Dr. Uchino and his associates at the Cleveland Clinic are part of the Cleveland PHAST study group; other participants include Case Western Reserve University. He had no disclosures. The mobile unit received funding from the Milton and Tamar Maltz Family Foundation and the Cleveland Clinic.

*CORRECTION, 4/27/15: The numbers of patients who actually received TPA out of those who qualified were accidentally transposed.

[email protected]

WASHINGTON – A mobile stroke unit significantly reduced the time to evaluation, diagnosis, and treatment when compared with standard emergency medical units for patients experiencing symptoms of an acute stroke, Dr. Ken Uchino reported at the annual meeting of the American Academy of Neurology.

In a 1-year prospective study conducted in Cleveland, patients who were evaluated at the mobile stroke unit and diagnosed with an acute ischemic stroke received treatment with intravenous tissue plasminogen activator (TPA) a median of about 26 minutes earlier than did patients transported via EMS to the hospital’s stroke center, a statistically significant difference, said Dr. Uchino of the Cleveland Clinic’s cerebrovascular center and the Cleveland Pre-Hospital Acute Stroke Treatment (PHAST) study group.

In addition, 25% of the patients who were having an acute ischemic stroke received TPA within the first hour of the onset of symptoms, “the golden hour of thrombolysis.” No one in the control group met that goal, he noted.

American Heart Association/American Stroke Association guidelines recommend a door-to-needle time of 60 minutes or less and set a goal for participating hospitals to administer TPA to at least 50% of their patients with acute ischemic stroke within 60 minutes of arriving at the hospital.

Of the 100 patients evaluated for stroke, 33 had a probable acute ischemic stroke and 16 of 19 patients who qualified received intravenous TPA.* One patient did not receive TPA because of crew error, and there were problems with intravenous access in two patients. Another 30 were diagnosed with a possible acute ischemic stroke. Of the remainder, 4 were diagnosed with a transient ischemic attack, 5 were diagnosed with intracerebral hemorrhage, and 28 were classified as “other.”

One patient with an intracerebral hemorrhage, a 93-year-old woman on warfarin, was successfully treated with prothrombin complex concentrate for warfarin reversal before arriving at the hospital.

Further study is needed to obtain data on the outcomes and cost-effectiveness of the mobile stroke units, he said.

The mobile unit is a modified emergency response vehicle staffed by a nurse, paramedic, emergency medical technician, and a CT technologist. The unit has a mobile CT scanner and telemedicine equipment with point-of-care lab testing; a vascular neurologist and a neuroradiologist work remotely to evaluate patients and images. The protocol starts with the 911 call and activation of the emergency medical system. An algorithm is used to identify patients who might be having a stroke.

Courtesy Cleveland Clinic

Once the mobile stroke unit reaches the patient, the team performs a CT scan and lab testing and the vascular neurologist interacts remotely with the patient and the unit’s personnel. If a diagnosis is confirmed, intravenous TPA is initiated and the patient is triaged to the appropriate hospital, Dr. Uchino explained.The study compared the times to treatment for patients experiencing acute stroke symptoms who were treated at the mobile stroke unit in the city (100 patients) with those presenting to Cleveland Clinic hospital emergency departments with a stroke alert called within 30 minutes of arrival to the hospital (53 patients), from Jan. 1, 2014, through December 2014. The mean age of patients was 63 years, about 56% were females. Intravenous thrombolysis was administered to 16 patients (16%) of those in the mobile stroke unit group and 12 (almost 23%) of those in the control group, which was not a significant difference.

The door-to-CT completion time was a median of 13 minutes (range, 9-21 minutes) in the mobile stroke unit group and 18 minutes (range, 12-26 minutes) among controls (P = .0026).

The door-to-CT read time was a median of 25 minutes in both groups. The door-to-international normalized ratio result time was a median of 13 minutes (range, 7-18) in the mobile stroke unit group and 44 minutes (range, 36-61) among controls, a significant difference (P < .001). The median time for door-to-video login was 11 minutes (range, 7-17) for the mobile stroke unit group and 20 minutes (range, 14-27) for controls.

The door-to-intravenous thrombolysis time was a median of 32 minutes (range, 24-47) in the mobile unit group and 58 minutes (range, 52-66) among controls, a 26-minute difference that was statistically significant, (P = .0012), Dr. Uchino said. The median time from the onset of symptoms to thrombolysis was 97 minutes (range, 61-144) in the mobile stroke unit group and 123 minutes (range, 110-176) in the controls (P = .0485).

Dr. Uchino and his associates at the Cleveland Clinic are part of the Cleveland PHAST study group; other participants include Case Western Reserve University. He had no disclosures. The mobile unit received funding from the Milton and Tamar Maltz Family Foundation and the Cleveland Clinic.

*CORRECTION, 4/27/15: The numbers of patients who actually received TPA out of those who qualified were accidentally transposed.

[email protected]

WASHINGTON – Treatment with daclizumab high-yield process, a first-in-class interleukin-2 immunomodulator administered subcutaneously once a month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis than was interferon beta-1a therapy during 96-144 weeks of treatment in the international DECIDE study.

The efficacy of daclizumab high-yield process (DAC HYP) was consistently superior to once-weekly intramuscular interferon (IFN) beta-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over that period, Dr. Ludwig Kappos said at the annual meeting of the American Academy of Neurology.

DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” said Dr. Kappos, chair of neurology at University Hospital Basel and one of the DECIDE study investigators. Dr. Kappos serves as chair of the study’s advisory committee.

Treatment was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which he said were “manageable with standard monitoring and medical interventions.”

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 (IL-2) receptor subunit (CD25), which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

The DECIDE study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every 4 weeks and 922 patients to treatment with 30 mcg of IFN beta-1a (Avonex) administered intramuscularly once a week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of 5 years. Patients in both groups had had a similar mean number of relapses within the previous year (0.7-0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously; their mean Expanded Disability Status Scale (EDSS) score was 1.2-1.3.

The study ended when the last patient had been treated for 2 years. In both arms, 29%-30% discontinued treatment, and adverse events were higher in the DAC HYP-treated group (14% vs. 9%).

During 96-144 weeks, the annualized relapse rate – the primary endpoint – was 0.393 among those on IFN beta-1a, vs. 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant (P < .0001), Dr. Kappos said.

Secondary endpoints included the proportion who remained relapse free, which was higher among those on DAC HYP at different points during the study (including 73% vs. 59% at week 96, and 67% vs. 51% at week 144). The risk of relapse was reduced by 41% (P < .0001).

Other secondary endpoints were MRI-defined lesions at week 96: The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN beta-1a (P < .0001). There were similar reductions in new T1 hypointense lesions (black holes), which were reduced by 52% (P < .0001), and in gadolinium-enhancing lesions, which were reduced by 65% (P < .0001). There was a significant effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At 3 months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN beta-1a (P = .16), a favorable effect, although not statistically significant. At 6 months, the risk was reduced by 27% (P = .033), Dr. Kappos reported. The proportion of patients with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5 point drop on the MSIS-29 PHYS) was reduced by 24% over those on IFN beta-1a, which was not statistically significant.

The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs. 21%); when MS relapses were excluded, the rate was 15% vs. 10%. Treatment discontinuations due to an adverse event, other than an MS relapse, was 14% among those on DAC HYP vs. 9% of those on IFN beta-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs. 57%), as was the rate of serious infectious adverse events (4% vs. 2%). Cutaneous events were more common among those on DAC HYP (37% vs. 19%), as were serious cutaneous adverse events (2% vs. less than 1%).

Dr. Kappos said that hepatic abnormalities were more common among those on DAC HYP, but were reversible. The rate of ALT/AST greater than five times the upper limit of normal (ULN) was 6% among those on the DAC HYP vs. 3% among those on IFN beta-1a; but the rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case that met the “Hy’s law” criteria in each group.

Biogen Idec and AbbVie Biotherapeutics funded the study. Dr. Kappos disclosed that University Hospital Basel has received research support from steering committee/consulting fees, and speakers fees from pharmaceutical companies that include Biogen.

[email protected]

WASHINGTON – Treatment with daclizumab high-yield process, a first-in-class interleukin-2 immunomodulator administered subcutaneously once a month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis than was interferon beta-1a therapy during 96-144 weeks of treatment in the international DECIDE study.

The efficacy of daclizumab high-yield process (DAC HYP) was consistently superior to once-weekly intramuscular interferon (IFN) beta-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over that period, Dr. Ludwig Kappos said at the annual meeting of the American Academy of Neurology.

DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” said Dr. Kappos, chair of neurology at University Hospital Basel and one of the DECIDE study investigators. Dr. Kappos serves as chair of the study’s advisory committee.

Treatment was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which he said were “manageable with standard monitoring and medical interventions.”

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 (IL-2) receptor subunit (CD25), which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

The DECIDE study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every 4 weeks and 922 patients to treatment with 30 mcg of IFN beta-1a (Avonex) administered intramuscularly once a week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of 5 years. Patients in both groups had had a similar mean number of relapses within the previous year (0.7-0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously; their mean Expanded Disability Status Scale (EDSS) score was 1.2-1.3.

The study ended when the last patient had been treated for 2 years. In both arms, 29%-30% discontinued treatment, and adverse events were higher in the DAC HYP-treated group (14% vs. 9%).

During 96-144 weeks, the annualized relapse rate – the primary endpoint – was 0.393 among those on IFN beta-1a, vs. 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant (P < .0001), Dr. Kappos said.

Secondary endpoints included the proportion who remained relapse free, which was higher among those on DAC HYP at different points during the study (including 73% vs. 59% at week 96, and 67% vs. 51% at week 144). The risk of relapse was reduced by 41% (P < .0001).

Other secondary endpoints were MRI-defined lesions at week 96: The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN beta-1a (P < .0001). There were similar reductions in new T1 hypointense lesions (black holes), which were reduced by 52% (P < .0001), and in gadolinium-enhancing lesions, which were reduced by 65% (P < .0001). There was a significant effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At 3 months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN beta-1a (P = .16), a favorable effect, although not statistically significant. At 6 months, the risk was reduced by 27% (P = .033), Dr. Kappos reported. The proportion of patients with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5 point drop on the MSIS-29 PHYS) was reduced by 24% over those on IFN beta-1a, which was not statistically significant.

The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs. 21%); when MS relapses were excluded, the rate was 15% vs. 10%. Treatment discontinuations due to an adverse event, other than an MS relapse, was 14% among those on DAC HYP vs. 9% of those on IFN beta-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs. 57%), as was the rate of serious infectious adverse events (4% vs. 2%). Cutaneous events were more common among those on DAC HYP (37% vs. 19%), as were serious cutaneous adverse events (2% vs. less than 1%).

Dr. Kappos said that hepatic abnormalities were more common among those on DAC HYP, but were reversible. The rate of ALT/AST greater than five times the upper limit of normal (ULN) was 6% among those on the DAC HYP vs. 3% among those on IFN beta-1a; but the rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case that met the “Hy’s law” criteria in each group.

Biogen Idec and AbbVie Biotherapeutics funded the study. Dr. Kappos disclosed that University Hospital Basel has received research support from steering committee/consulting fees, and speakers fees from pharmaceutical companies that include Biogen.

[email protected]

WASHINGTON – Treatment with daclizumab high-yield process, a first-in-class interleukin-2 immunomodulator administered subcutaneously once a month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis than was interferon beta-1a therapy during 96-144 weeks of treatment in the international DECIDE study.

The efficacy of daclizumab high-yield process (DAC HYP) was consistently superior to once-weekly intramuscular interferon (IFN) beta-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over that period, Dr. Ludwig Kappos said at the annual meeting of the American Academy of Neurology.

DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” said Dr. Kappos, chair of neurology at University Hospital Basel and one of the DECIDE study investigators. Dr. Kappos serves as chair of the study’s advisory committee.

Treatment was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which he said were “manageable with standard monitoring and medical interventions.”

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 (IL-2) receptor subunit (CD25), which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

The DECIDE study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every 4 weeks and 922 patients to treatment with 30 mcg of IFN beta-1a (Avonex) administered intramuscularly once a week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of 5 years. Patients in both groups had had a similar mean number of relapses within the previous year (0.7-0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously; their mean Expanded Disability Status Scale (EDSS) score was 1.2-1.3.

The study ended when the last patient had been treated for 2 years. In both arms, 29%-30% discontinued treatment, and adverse events were higher in the DAC HYP-treated group (14% vs. 9%).

During 96-144 weeks, the annualized relapse rate – the primary endpoint – was 0.393 among those on IFN beta-1a, vs. 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant (P < .0001), Dr. Kappos said.

Secondary endpoints included the proportion who remained relapse free, which was higher among those on DAC HYP at different points during the study (including 73% vs. 59% at week 96, and 67% vs. 51% at week 144). The risk of relapse was reduced by 41% (P < .0001).

Other secondary endpoints were MRI-defined lesions at week 96: The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN beta-1a (P < .0001). There were similar reductions in new T1 hypointense lesions (black holes), which were reduced by 52% (P < .0001), and in gadolinium-enhancing lesions, which were reduced by 65% (P < .0001). There was a significant effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At 3 months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN beta-1a (P = .16), a favorable effect, although not statistically significant. At 6 months, the risk was reduced by 27% (P = .033), Dr. Kappos reported. The proportion of patients with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5 point drop on the MSIS-29 PHYS) was reduced by 24% over those on IFN beta-1a, which was not statistically significant.

The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs. 21%); when MS relapses were excluded, the rate was 15% vs. 10%. Treatment discontinuations due to an adverse event, other than an MS relapse, was 14% among those on DAC HYP vs. 9% of those on IFN beta-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs. 57%), as was the rate of serious infectious adverse events (4% vs. 2%). Cutaneous events were more common among those on DAC HYP (37% vs. 19%), as were serious cutaneous adverse events (2% vs. less than 1%).

Dr. Kappos said that hepatic abnormalities were more common among those on DAC HYP, but were reversible. The rate of ALT/AST greater than five times the upper limit of normal (ULN) was 6% among those on the DAC HYP vs. 3% among those on IFN beta-1a; but the rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case that met the “Hy’s law” criteria in each group.

Biogen Idec and AbbVie Biotherapeutics funded the study. Dr. Kappos disclosed that University Hospital Basel has received research support from steering committee/consulting fees, and speakers fees from pharmaceutical companies that include Biogen.

[email protected]