The National Institute for Health and Care Excellence (NICE) has issued guidance on the clinical and cost-effectiveness of empagliflozin in combination therapy for treatment of type 2 diabetes.

The guideline, released in March, is for advanced-practice nurses, nurses, physician assistants, and physicians, according to a summary by the National Guideline Clearinghouse (NGC).

The summary lists recommendations by NICE for treatment of type 2 diabetes as follows:

• Empagliflozin in a dual-therapy regimen in combination with metformin, only if a sulfonylurea is contraindicated or not tolerated, or if the person is at significant risk of hypoglycemia or its consequences.

• Empagliflozin in a triple-therapy regimen, in combination with metformin and a sulfonylurea or metformin and a thiazolidinedione.

• Empagliflozin in combination with insulin with or without other antidiabetic drugs.

According to the summary, the most commonly reported adverse reactions for empagliflozin are hypoglycemia in combination with insulin or a sulfonylurea, vulvovaginal candidiasis, urinary tract infection, and polyuria or pollakiuria.

As for the cost-effectiveness, an appraisal committee independent of NICE “concluded that the very small differences in costs and quality-adjusted life years between empagliflozin (10 mg and 25 mg) and its key comparators showed that empagliflozin was a cost-effective use of National Health Service resources as dual therapy in combination with metformin, triple therapy in combination with metformin and either a sulfonylurea or a thiazolidinedione, and as an add-on treatment to insulin.”

[email protected]

The National Institute for Health and Care Excellence (NICE) has issued guidance on the clinical and cost-effectiveness of empagliflozin in combination therapy for treatment of type 2 diabetes.

The guideline, released in March, is for advanced-practice nurses, nurses, physician assistants, and physicians, according to a summary by the National Guideline Clearinghouse (NGC).

The summary lists recommendations by NICE for treatment of type 2 diabetes as follows:

• Empagliflozin in a dual-therapy regimen in combination with metformin, only if a sulfonylurea is contraindicated or not tolerated, or if the person is at significant risk of hypoglycemia or its consequences.

• Empagliflozin in a triple-therapy regimen, in combination with metformin and a sulfonylurea or metformin and a thiazolidinedione.

• Empagliflozin in combination with insulin with or without other antidiabetic drugs.

According to the summary, the most commonly reported adverse reactions for empagliflozin are hypoglycemia in combination with insulin or a sulfonylurea, vulvovaginal candidiasis, urinary tract infection, and polyuria or pollakiuria.

As for the cost-effectiveness, an appraisal committee independent of NICE “concluded that the very small differences in costs and quality-adjusted life years between empagliflozin (10 mg and 25 mg) and its key comparators showed that empagliflozin was a cost-effective use of National Health Service resources as dual therapy in combination with metformin, triple therapy in combination with metformin and either a sulfonylurea or a thiazolidinedione, and as an add-on treatment to insulin.”

[email protected]

The National Institute for Health and Care Excellence (NICE) has issued guidance on the clinical and cost-effectiveness of empagliflozin in combination therapy for treatment of type 2 diabetes.

The guideline, released in March, is for advanced-practice nurses, nurses, physician assistants, and physicians, according to a summary by the National Guideline Clearinghouse (NGC).

The summary lists recommendations by NICE for treatment of type 2 diabetes as follows:

• Empagliflozin in a dual-therapy regimen in combination with metformin, only if a sulfonylurea is contraindicated or not tolerated, or if the person is at significant risk of hypoglycemia or its consequences.

• Empagliflozin in a triple-therapy regimen, in combination with metformin and a sulfonylurea or metformin and a thiazolidinedione.

• Empagliflozin in combination with insulin with or without other antidiabetic drugs.

According to the summary, the most commonly reported adverse reactions for empagliflozin are hypoglycemia in combination with insulin or a sulfonylurea, vulvovaginal candidiasis, urinary tract infection, and polyuria or pollakiuria.

As for the cost-effectiveness, an appraisal committee independent of NICE “concluded that the very small differences in costs and quality-adjusted life years between empagliflozin (10 mg and 25 mg) and its key comparators showed that empagliflozin was a cost-effective use of National Health Service resources as dual therapy in combination with metformin, triple therapy in combination with metformin and either a sulfonylurea or a thiazolidinedione, and as an add-on treatment to insulin.”

[email protected]

Effective systems and processes are a key part of minimizing the risk of preventable medicine-related problems and ensuring best possible outcomes for care, according to newly released clinical guidelines from the Medicines Prescribing Centre of the U.K.-based National Institute for Health and Care Excellence (NICE).

The guidelines, developed by a multidisciplinary Guideline Development Group (GDG) of NICE staff, health professionals, and lay members, were designed to ensure that National Health Service patients get the best possible outcomes from their medicines.

“Relevant information about medicines should be shared with patients, and their family members or carers, where appropriate, and between health and social care practitioners when a person moves from one care setting to another, to support high-quality care,” wrote the authors of the guidelines, led by Dr. Weeliat Chong, chair of the GDG.

The report identified four key recommendations as priorities for implementation:

• Consider using multiple methods (such as health record review, patient surveys and direct observation of medicines administration) to identify medicine-related patient safety incidents

• Organizations should ensure that medicines reconciliation (i.e., making sure medicines prescribed on admission correspond to those that the patient was taking before admission) is carried out by a trained and competent health professional with effective communication skills, technical knowledge of processes for managing medicines, and therapeutic knowledge of medicines use.

• Health and social care practitioners should share relevant information about the [patients] and their medicines via medicines-related communication systems when a person transfers from one care setting to another.

• Consider sending the patient’s medicines discharge information to [his or her] nominated community pharmacy, when possible and in agreement with the patient.

Click here for the full report.

[email protected]

Effective systems and processes are a key part of minimizing the risk of preventable medicine-related problems and ensuring best possible outcomes for care, according to newly released clinical guidelines from the Medicines Prescribing Centre of the U.K.-based National Institute for Health and Care Excellence (NICE).

The guidelines, developed by a multidisciplinary Guideline Development Group (GDG) of NICE staff, health professionals, and lay members, were designed to ensure that National Health Service patients get the best possible outcomes from their medicines.

“Relevant information about medicines should be shared with patients, and their family members or carers, where appropriate, and between health and social care practitioners when a person moves from one care setting to another, to support high-quality care,” wrote the authors of the guidelines, led by Dr. Weeliat Chong, chair of the GDG.

The report identified four key recommendations as priorities for implementation:

• Consider using multiple methods (such as health record review, patient surveys and direct observation of medicines administration) to identify medicine-related patient safety incidents

• Organizations should ensure that medicines reconciliation (i.e., making sure medicines prescribed on admission correspond to those that the patient was taking before admission) is carried out by a trained and competent health professional with effective communication skills, technical knowledge of processes for managing medicines, and therapeutic knowledge of medicines use.

• Health and social care practitioners should share relevant information about the [patients] and their medicines via medicines-related communication systems when a person transfers from one care setting to another.

• Consider sending the patient’s medicines discharge information to [his or her] nominated community pharmacy, when possible and in agreement with the patient.

Click here for the full report.

[email protected]

Effective systems and processes are a key part of minimizing the risk of preventable medicine-related problems and ensuring best possible outcomes for care, according to newly released clinical guidelines from the Medicines Prescribing Centre of the U.K.-based National Institute for Health and Care Excellence (NICE).

The guidelines, developed by a multidisciplinary Guideline Development Group (GDG) of NICE staff, health professionals, and lay members, were designed to ensure that National Health Service patients get the best possible outcomes from their medicines.

“Relevant information about medicines should be shared with patients, and their family members or carers, where appropriate, and between health and social care practitioners when a person moves from one care setting to another, to support high-quality care,” wrote the authors of the guidelines, led by Dr. Weeliat Chong, chair of the GDG.

The report identified four key recommendations as priorities for implementation:

• Consider using multiple methods (such as health record review, patient surveys and direct observation of medicines administration) to identify medicine-related patient safety incidents

• Organizations should ensure that medicines reconciliation (i.e., making sure medicines prescribed on admission correspond to those that the patient was taking before admission) is carried out by a trained and competent health professional with effective communication skills, technical knowledge of processes for managing medicines, and therapeutic knowledge of medicines use.

• Health and social care practitioners should share relevant information about the [patients] and their medicines via medicines-related communication systems when a person transfers from one care setting to another.

• Consider sending the patient’s medicines discharge information to [his or her] nominated community pharmacy, when possible and in agreement with the patient.

Click here for the full report.

[email protected]

Ultrasonography is the preferred imaging method to evaluate most adnexal cysts. Most types of pelvic cyst pathology have characteristic findings that, when identified, can guide counseling and management decisions. For instance, simple cysts have thin walls, are uniformly hypoechoic, and show no blood flow on color Doppler. Endometriomas, on the other hand, demonstrate diffuse, low-level internal echoes on ultrasonography.

In parts 1 and 2 of this 4-part series on adnexal pathology, we presented images detailing common benign adnexal cysts, including:

• simple and hemorrhagic cysts (Part 1:Telltale sonographic features of simple and hemorrhagic cysts)
• and mature cystic teratomas (dermoid cysts) and endometriomas (Part 2: Imaging the endometrioma and mature cystic teratoma).

In this part 3, we detail imaging for hydrosalpinx and pelvic inclusion cysts. In part 4 we will consider cystadenomas and ovarian neoplasias.

hydrosalpinx

These cysts are caused by fimbrial obstruction and result in tubal distention with serous fluid. A hydrosalpinx may occur following an episode of salpingitis or pelvic surgery.

Sonographic features diagnostic for hydrosalpinx include a tubular or S-shaped cystic mass separate from the ovary, with:

• “beads on a string” or “cogwheel” appearance (small round nodules less than 3 mm in size that represent endosalpingeal folds when viewed in cross section)
• “waist sign” (indentations on opposite sides)
• incomplete septations, which result from segments of distended tube folding over/adhering to other tubal segments

Levine and colleagues noted that 3-dimensional imaging may be helpful when the diagnosis is uncertain.¹

When a mass is noted that has features classic for hydrosalpinx, the Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommends¹:

• no further imaging is necessary to establish the diagnosis
• frequency of follow-up imaging should be based on the patient’s age and clinical symptoms

In FIGURES 1 through 6 below (slides of image collections), we present 5 cases, including one of a 45-year-old patient presenting with chronic pelvic pain who was found to have bilateral hydrosalginges and right-sided tubo-ovarian complex.

pelvic inclusion cysts

Pelvic/peritoneal inclusion cysts, or peritoneal pseudocysts, are typically associated with factors that increase the risk for pelvic adhesive disease (including endometriosis, pelvic inflammatory disease, or prior pelvic surgery).

Classic sonographic features of pelvic inclusion cysts are:

• cystic mass, usually with septations/loculations
• the mass follows the contour of adjacent organs
• ovary at edge of the mass or sometimes suspended within it
• with or without flow in septation on color Doppler

When a mass is noted that has features classic for a peritoneal inclusion cyst, the US Society of Radiologists in Ultrasound recommends that¹:

• no further imaging is necessary to establish the diagnosis (although further imaging may be needed if the diagnosis is uncertain)
• the frequency of follow-up imaging should be based on the patient’s age and clinical symptoms

In FIGURES 7 through 22 below (slides of image collections), we present several cases that demonstrate pelvic inclusion cysts on imaging. One case involves a 25-year-old patient presenting for 2- and 3-dimensional pelvic imaging due to infertility. She had a history of laparoscopic left ovarian cystectomy, right paratubal cystectomy, and lysis of adhesions. She was found to have a pelvic inclusion cyst and an endometrioma in the left ovary.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Figure 16

Figure 17

Figure 18

Figure 19

Figure 20

Figure 21

Figure 22

Ultrasonography is the preferred imaging method to evaluate most adnexal cysts. Most types of pelvic cyst pathology have characteristic findings that, when identified, can guide counseling and management decisions. For instance, simple cysts have thin walls, are uniformly hypoechoic, and show no blood flow on color Doppler. Endometriomas, on the other hand, demonstrate diffuse, low-level internal echoes on ultrasonography.

In parts 1 and 2 of this 4-part series on adnexal pathology, we presented images detailing common benign adnexal cysts, including:

• simple and hemorrhagic cysts (Part 1:Telltale sonographic features of simple and hemorrhagic cysts)
• and mature cystic teratomas (dermoid cysts) and endometriomas (Part 2: Imaging the endometrioma and mature cystic teratoma).

In this part 3, we detail imaging for hydrosalpinx and pelvic inclusion cysts. In part 4 we will consider cystadenomas and ovarian neoplasias.

hydrosalpinx

These cysts are caused by fimbrial obstruction and result in tubal distention with serous fluid. A hydrosalpinx may occur following an episode of salpingitis or pelvic surgery.

Sonographic features diagnostic for hydrosalpinx include a tubular or S-shaped cystic mass separate from the ovary, with:

• “beads on a string” or “cogwheel” appearance (small round nodules less than 3 mm in size that represent endosalpingeal folds when viewed in cross section)
• “waist sign” (indentations on opposite sides)
• incomplete septations, which result from segments of distended tube folding over/adhering to other tubal segments

Levine and colleagues noted that 3-dimensional imaging may be helpful when the diagnosis is uncertain.¹

When a mass is noted that has features classic for hydrosalpinx, the Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommends¹:

• no further imaging is necessary to establish the diagnosis
• frequency of follow-up imaging should be based on the patient’s age and clinical symptoms

In FIGURES 1 through 6 below (slides of image collections), we present 5 cases, including one of a 45-year-old patient presenting with chronic pelvic pain who was found to have bilateral hydrosalginges and right-sided tubo-ovarian complex.

pelvic inclusion cysts

Pelvic/peritoneal inclusion cysts, or peritoneal pseudocysts, are typically associated with factors that increase the risk for pelvic adhesive disease (including endometriosis, pelvic inflammatory disease, or prior pelvic surgery).

Classic sonographic features of pelvic inclusion cysts are:

• cystic mass, usually with septations/loculations
• the mass follows the contour of adjacent organs
• ovary at edge of the mass or sometimes suspended within it
• with or without flow in septation on color Doppler

When a mass is noted that has features classic for a peritoneal inclusion cyst, the US Society of Radiologists in Ultrasound recommends that¹:

• no further imaging is necessary to establish the diagnosis (although further imaging may be needed if the diagnosis is uncertain)
• the frequency of follow-up imaging should be based on the patient’s age and clinical symptoms

In FIGURES 7 through 22 below (slides of image collections), we present several cases that demonstrate pelvic inclusion cysts on imaging. One case involves a 25-year-old patient presenting for 2- and 3-dimensional pelvic imaging due to infertility. She had a history of laparoscopic left ovarian cystectomy, right paratubal cystectomy, and lysis of adhesions. She was found to have a pelvic inclusion cyst and an endometrioma in the left ovary.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Figure 16

Figure 17

Figure 18

Figure 19

Figure 20

Figure 21

Figure 22

Ultrasonography is the preferred imaging method to evaluate most adnexal cysts. Most types of pelvic cyst pathology have characteristic findings that, when identified, can guide counseling and management decisions. For instance, simple cysts have thin walls, are uniformly hypoechoic, and show no blood flow on color Doppler. Endometriomas, on the other hand, demonstrate diffuse, low-level internal echoes on ultrasonography.

In parts 1 and 2 of this 4-part series on adnexal pathology, we presented images detailing common benign adnexal cysts, including:

• simple and hemorrhagic cysts (Part 1:Telltale sonographic features of simple and hemorrhagic cysts)
• and mature cystic teratomas (dermoid cysts) and endometriomas (Part 2: Imaging the endometrioma and mature cystic teratoma).

In this part 3, we detail imaging for hydrosalpinx and pelvic inclusion cysts. In part 4 we will consider cystadenomas and ovarian neoplasias.

hydrosalpinx

These cysts are caused by fimbrial obstruction and result in tubal distention with serous fluid. A hydrosalpinx may occur following an episode of salpingitis or pelvic surgery.

Sonographic features diagnostic for hydrosalpinx include a tubular or S-shaped cystic mass separate from the ovary, with:

• “beads on a string” or “cogwheel” appearance (small round nodules less than 3 mm in size that represent endosalpingeal folds when viewed in cross section)
• “waist sign” (indentations on opposite sides)
• incomplete septations, which result from segments of distended tube folding over/adhering to other tubal segments

Levine and colleagues noted that 3-dimensional imaging may be helpful when the diagnosis is uncertain.¹

When a mass is noted that has features classic for hydrosalpinx, the Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommends¹:

• no further imaging is necessary to establish the diagnosis
• frequency of follow-up imaging should be based on the patient’s age and clinical symptoms

In FIGURES 1 through 6 below (slides of image collections), we present 5 cases, including one of a 45-year-old patient presenting with chronic pelvic pain who was found to have bilateral hydrosalginges and right-sided tubo-ovarian complex.

pelvic inclusion cysts

Pelvic/peritoneal inclusion cysts, or peritoneal pseudocysts, are typically associated with factors that increase the risk for pelvic adhesive disease (including endometriosis, pelvic inflammatory disease, or prior pelvic surgery).

Classic sonographic features of pelvic inclusion cysts are:

• cystic mass, usually with septations/loculations
• the mass follows the contour of adjacent organs
• ovary at edge of the mass or sometimes suspended within it
• with or without flow in septation on color Doppler

When a mass is noted that has features classic for a peritoneal inclusion cyst, the US Society of Radiologists in Ultrasound recommends that¹:

• no further imaging is necessary to establish the diagnosis (although further imaging may be needed if the diagnosis is uncertain)
• the frequency of follow-up imaging should be based on the patient’s age and clinical symptoms

In FIGURES 7 through 22 below (slides of image collections), we present several cases that demonstrate pelvic inclusion cysts on imaging. One case involves a 25-year-old patient presenting for 2- and 3-dimensional pelvic imaging due to infertility. She had a history of laparoscopic left ovarian cystectomy, right paratubal cystectomy, and lysis of adhesions. She was found to have a pelvic inclusion cyst and an endometrioma in the left ovary.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Figure 16

Figure 17

Figure 18

Figure 19

Figure 20

Figure 21

Figure 22

Endovascular stenting is a safe and effective way to treat iliofemoral obstructions in patients with postthrombotic syndrome, according to Dr. M. Yin of Shanghai (China) JiaoTong University, and associates.

The stenting process was achieved without major complications in 95% of cases. Cumulative primary, assisted primary, and secondary patency rates after 3 years were 69%, 79%, and 92%, respectively. Patients with severe postthrombotic syndrome (PTS) saw a significant drop in their Villalta score, compared with patients treated with elastic compression stockings (ECS) therapy, though scores were similar in patients with moderate PTS in both groups. The 24-month recurrence-free ulcer healing rate was significantly higher in the stenting group (87% vs. 71%).

“ECS therapy shows equal clinical effects with stent placement in patients with moderate PTS,” but the stented patients did not have to wear stockings after the procedure, the researchers wrote.

Find the full study in the European Journal of Vascular & Endovascular Surgery (doi: 10.1016/j.ejvs.2015.03.029).

Endovascular stenting is a safe and effective way to treat iliofemoral obstructions in patients with postthrombotic syndrome, according to Dr. M. Yin of Shanghai (China) JiaoTong University, and associates.

The stenting process was achieved without major complications in 95% of cases. Cumulative primary, assisted primary, and secondary patency rates after 3 years were 69%, 79%, and 92%, respectively. Patients with severe postthrombotic syndrome (PTS) saw a significant drop in their Villalta score, compared with patients treated with elastic compression stockings (ECS) therapy, though scores were similar in patients with moderate PTS in both groups. The 24-month recurrence-free ulcer healing rate was significantly higher in the stenting group (87% vs. 71%).

“ECS therapy shows equal clinical effects with stent placement in patients with moderate PTS,” but the stented patients did not have to wear stockings after the procedure, the researchers wrote.

Find the full study in the European Journal of Vascular & Endovascular Surgery (doi: 10.1016/j.ejvs.2015.03.029).

Endovascular stenting is a safe and effective way to treat iliofemoral obstructions in patients with postthrombotic syndrome, according to Dr. M. Yin of Shanghai (China) JiaoTong University, and associates.

The stenting process was achieved without major complications in 95% of cases. Cumulative primary, assisted primary, and secondary patency rates after 3 years were 69%, 79%, and 92%, respectively. Patients with severe postthrombotic syndrome (PTS) saw a significant drop in their Villalta score, compared with patients treated with elastic compression stockings (ECS) therapy, though scores were similar in patients with moderate PTS in both groups. The 24-month recurrence-free ulcer healing rate was significantly higher in the stenting group (87% vs. 71%).

“ECS therapy shows equal clinical effects with stent placement in patients with moderate PTS,” but the stented patients did not have to wear stockings after the procedure, the researchers wrote.

Find the full study in the European Journal of Vascular & Endovascular Surgery (doi: 10.1016/j.ejvs.2015.03.029).

The National Institute for Health and Care Excellence (NICE) has issued a new guideline on maintaining a healthy weight and preventing excess weight gain.

This guideline replaces section 1.1.1 of NICE’s guideline on obesity, CG43 (2006).

©wragg/iStockphoto.com

The guideline, for those who educate people on how to maintain a healthy weight or prevent excess weight gain, comprises the following recommendations:

• Encourage people to make changes in line with existing advice.

• Encourage physical activity habits to avoid low energy expenditure.

• Encourage dietary habits that reduce the risk of excess energy intake.

• Provide further advice for parents and carers of children and young people.

• Encourage adults to limit the amount of alcohol they drink.

• Encourage self-monitoring.

• Clearly communicate the benefits of maintaining a healthy weight.

• Clearly communicate the benefits of gradual improvements to physical activity and dietary habits.

• Tailor messages for specific groups.

• Ensure activities are integrated with the local strategic approach to obesity.

[email protected]

The National Institute for Health and Care Excellence (NICE) has issued a new guideline on maintaining a healthy weight and preventing excess weight gain.

This guideline replaces section 1.1.1 of NICE’s guideline on obesity, CG43 (2006).

©wragg/iStockphoto.com

The guideline, for those who educate people on how to maintain a healthy weight or prevent excess weight gain, comprises the following recommendations:

• Encourage people to make changes in line with existing advice.

• Encourage physical activity habits to avoid low energy expenditure.

• Encourage dietary habits that reduce the risk of excess energy intake.

• Provide further advice for parents and carers of children and young people.

• Encourage adults to limit the amount of alcohol they drink.

• Encourage self-monitoring.

• Clearly communicate the benefits of maintaining a healthy weight.

• Clearly communicate the benefits of gradual improvements to physical activity and dietary habits.

• Tailor messages for specific groups.

• Ensure activities are integrated with the local strategic approach to obesity.

[email protected]

The National Institute for Health and Care Excellence (NICE) has issued a new guideline on maintaining a healthy weight and preventing excess weight gain.

This guideline replaces section 1.1.1 of NICE’s guideline on obesity, CG43 (2006).

©wragg/iStockphoto.com

The guideline, for those who educate people on how to maintain a healthy weight or prevent excess weight gain, comprises the following recommendations:

• Encourage people to make changes in line with existing advice.

• Encourage physical activity habits to avoid low energy expenditure.

• Encourage dietary habits that reduce the risk of excess energy intake.

• Provide further advice for parents and carers of children and young people.

• Encourage adults to limit the amount of alcohol they drink.

• Encourage self-monitoring.

• Clearly communicate the benefits of maintaining a healthy weight.

• Clearly communicate the benefits of gradual improvements to physical activity and dietary habits.

• Tailor messages for specific groups.

• Ensure activities are integrated with the local strategic approach to obesity.

[email protected]

Venous thromboembolism is common in patients undergoing oxaliplatin, capecitabine, and epirubicin chemotherapy for esophagogastric cancer, according to Dr. Anders Christian Larsen of Aalborg (Denmark) University Hospital and associates.

There were 21 cases of VTE among the 129 patients with esophagogastric cancer, a rate of 16%. Of the VTE cases, 14 were asymptomatic and 7 were symptomatic. Gastric cancer and late-stage cancer were significant VTE risk factors, with odds ratios of 6.4 and 5.2, respectively. The median survival time was 18 months in non-VTE patients and 14 months in VTE patients.

“The extent of treatment-related VTE in upper GI cancer patients (with active cancer) receiving both chemotherapy and curative intended surgery may be greater than previously estimated. … Our data demonstrate the need to address this clinical problem with randomized clinical trials on VTE prophylaxis, particularly in patients undergoing neoadjuvant chemotherapy for resectable cancer disease,” the investigators concluded.

The authors said that there were no conflicts; the study was funded by private foundations.

Find the full study in Thrombosis Research.

[email protected]

Venous thromboembolism is common in patients undergoing oxaliplatin, capecitabine, and epirubicin chemotherapy for esophagogastric cancer, according to Dr. Anders Christian Larsen of Aalborg (Denmark) University Hospital and associates.

There were 21 cases of VTE among the 129 patients with esophagogastric cancer, a rate of 16%. Of the VTE cases, 14 were asymptomatic and 7 were symptomatic. Gastric cancer and late-stage cancer were significant VTE risk factors, with odds ratios of 6.4 and 5.2, respectively. The median survival time was 18 months in non-VTE patients and 14 months in VTE patients.

“The extent of treatment-related VTE in upper GI cancer patients (with active cancer) receiving both chemotherapy and curative intended surgery may be greater than previously estimated. … Our data demonstrate the need to address this clinical problem with randomized clinical trials on VTE prophylaxis, particularly in patients undergoing neoadjuvant chemotherapy for resectable cancer disease,” the investigators concluded.

The authors said that there were no conflicts; the study was funded by private foundations.

Find the full study in Thrombosis Research.

[email protected]

Venous thromboembolism is common in patients undergoing oxaliplatin, capecitabine, and epirubicin chemotherapy for esophagogastric cancer, according to Dr. Anders Christian Larsen of Aalborg (Denmark) University Hospital and associates.

There were 21 cases of VTE among the 129 patients with esophagogastric cancer, a rate of 16%. Of the VTE cases, 14 were asymptomatic and 7 were symptomatic. Gastric cancer and late-stage cancer were significant VTE risk factors, with odds ratios of 6.4 and 5.2, respectively. The median survival time was 18 months in non-VTE patients and 14 months in VTE patients.

“The extent of treatment-related VTE in upper GI cancer patients (with active cancer) receiving both chemotherapy and curative intended surgery may be greater than previously estimated. … Our data demonstrate the need to address this clinical problem with randomized clinical trials on VTE prophylaxis, particularly in patients undergoing neoadjuvant chemotherapy for resectable cancer disease,” the investigators concluded.

The authors said that there were no conflicts; the study was funded by private foundations.

Find the full study in Thrombosis Research.

[email protected]

Rivaroxaban has been recommended by the U.K. National Institute for Health and Care Excellence (NICE) as a treatment option for prevention of blood clots in adults who have had acute coronary syndrome with elevated cardiac biomarkers, the agency announced in a statement.

NICE officials recommended rivaroxaban (Xarelto), in combination with aspirin plus clopidogrel or aspirin alone, as an option for preventing atherothrombotic events in patients who have had a heart attack. Assessment of clinical-effectiveness evidence was based on data from an international, multicenter, randomized controlled trial. An independent appraisal committee considered clinical and cost-effectiveness evidence before making the recommendation.

Rivaroxaban, manufactured by Bayer and marketed by Janssen Pharmaceuticals, is an orally active direct factor Xa inhibitor.

Clinicians should regularly reassess the benefits and risks of continuing treatment with rivaroxaban, the agency recommended, and a decision on continuation of treatment should be made no later than 12 months after starting treatment.

Read the full guideline statement here.

[email protected]

Rivaroxaban has been recommended by the U.K. National Institute for Health and Care Excellence (NICE) as a treatment option for prevention of blood clots in adults who have had acute coronary syndrome with elevated cardiac biomarkers, the agency announced in a statement.

NICE officials recommended rivaroxaban (Xarelto), in combination with aspirin plus clopidogrel or aspirin alone, as an option for preventing atherothrombotic events in patients who have had a heart attack. Assessment of clinical-effectiveness evidence was based on data from an international, multicenter, randomized controlled trial. An independent appraisal committee considered clinical and cost-effectiveness evidence before making the recommendation.

Rivaroxaban, manufactured by Bayer and marketed by Janssen Pharmaceuticals, is an orally active direct factor Xa inhibitor.

Clinicians should regularly reassess the benefits and risks of continuing treatment with rivaroxaban, the agency recommended, and a decision on continuation of treatment should be made no later than 12 months after starting treatment.

Read the full guideline statement here.

[email protected]

Rivaroxaban has been recommended by the U.K. National Institute for Health and Care Excellence (NICE) as a treatment option for prevention of blood clots in adults who have had acute coronary syndrome with elevated cardiac biomarkers, the agency announced in a statement.

NICE officials recommended rivaroxaban (Xarelto), in combination with aspirin plus clopidogrel or aspirin alone, as an option for preventing atherothrombotic events in patients who have had a heart attack. Assessment of clinical-effectiveness evidence was based on data from an international, multicenter, randomized controlled trial. An independent appraisal committee considered clinical and cost-effectiveness evidence before making the recommendation.

Rivaroxaban, manufactured by Bayer and marketed by Janssen Pharmaceuticals, is an orally active direct factor Xa inhibitor.

Clinicians should regularly reassess the benefits and risks of continuing treatment with rivaroxaban, the agency recommended, and a decision on continuation of treatment should be made no later than 12 months after starting treatment.

Read the full guideline statement here.

[email protected]

An untreated lesion pre-

treatment (top) and 16 weeks

after treatment began

Photo from Penn Medicine

Results of a phase 1 trial suggest a topical gel can prompt regression of both treated and untreated lesions in patients with

early stage cutaneous T-cell lymphoma (CTCL).

Of the 12 patients who received the treatment, resiquimod gel, 75% had a significant improvement in treated lesions.

And 92% of patients had a more than 50% improvement in body surface area involvement, which included untreated lesions. Two patients experienced complete disease clearance.

Adverse events associated with resiquimod were largely limited to the skin, although 2 patients had transient, low-grade fever. Five patients developed superficial skin erosions that healed when treatment was stopped and did not reappear after treatment began again.

Alain Rook, MD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these results in Blood.

“The results of the trial suggest that resiquimod is safely and effectively absorbed into the skin and, beyond diminishing treated lesions, also enhances the immune response, leading to healing of even untreated lesions,” Dr Rook said.

“To our knowledge, this is the first topical therapy that can clear untreated lesions and lead to complete remission in some patients.”

Treatment and response

Dr Rook and his colleagues tested resiquimod gel in 12 patients who had previously undergone an average of 6 treatments for early stage CTCL.

The patients applied specified doses of resiquimod (0.03% or 0.06%) to select skin lesions for 16 weeks. Some patients using the 0.06% dose had complete clearance of all malignant cells after 8 weeks.

By the final evaluation, treated lesions had significantly improved in 75% of patients, and 30% of patients had complete clearance of all treated lesions.

Resiquimod also improved untreated lesions, resulting in more than 50% improvement in body surface area involvement for 92% of patients.

Two participants, one of whom had been living with CTCL for more than 15 years without responding to treatment, experienced complete eradication of the disease.

Malignant cell analysis

The researchers used high-throughput sequencing to detect malignant cells in patient samples. The technique could identify a single malignant cell among 100,000 healthy cells.

The team analyzed DNA from biopsies of the same lesion before treatment and 8 weeks after treatment began.

They observed a significant reduction of malignant T cells in 9 of 10 patients tested, 3 of whom had complete eradication of the malignant population and 1 of whom had a 99.6% reduction.

Adverse events

Adverse events associated with resiquimod were all grade 1 and were primarily related to local skin irritation. There were no serious adverse events.

Five of 8 patients receiving resiquimod at the 0.06% dose developed superficial skin erosions at some sites of treatment. These erosions healed completely within a week of stopping treatment and did not recur with re-initiation of treatment.

Two patients receiving the 0.06% dose experienced 2 days of low-grade fever (less than 100.50 F) when treatment began.

“Overall, lesions responded far better to topical resiquimod than they have with other topical therapies, including some potent topical steroids and topical chemotherapy, and [resiquimod] was extremely well tolerated by patients,” Dr Rook said.

“Building upon previous research, our study suggests resiquimod might be useful in combination with other therapies in the treatment of more advanced CTCL. Further research with larger participant populations is needed to determine the best approach and application for these patients.”

An untreated lesion pre-

treatment (top) and 16 weeks

after treatment began

Photo from Penn Medicine

Results of a phase 1 trial suggest a topical gel can prompt regression of both treated and untreated lesions in patients with

early stage cutaneous T-cell lymphoma (CTCL).

Of the 12 patients who received the treatment, resiquimod gel, 75% had a significant improvement in treated lesions.

And 92% of patients had a more than 50% improvement in body surface area involvement, which included untreated lesions. Two patients experienced complete disease clearance.

Adverse events associated with resiquimod were largely limited to the skin, although 2 patients had transient, low-grade fever. Five patients developed superficial skin erosions that healed when treatment was stopped and did not reappear after treatment began again.

Alain Rook, MD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these results in Blood.

“The results of the trial suggest that resiquimod is safely and effectively absorbed into the skin and, beyond diminishing treated lesions, also enhances the immune response, leading to healing of even untreated lesions,” Dr Rook said.

“To our knowledge, this is the first topical therapy that can clear untreated lesions and lead to complete remission in some patients.”

Treatment and response

Dr Rook and his colleagues tested resiquimod gel in 12 patients who had previously undergone an average of 6 treatments for early stage CTCL.

The patients applied specified doses of resiquimod (0.03% or 0.06%) to select skin lesions for 16 weeks. Some patients using the 0.06% dose had complete clearance of all malignant cells after 8 weeks.

By the final evaluation, treated lesions had significantly improved in 75% of patients, and 30% of patients had complete clearance of all treated lesions.

Resiquimod also improved untreated lesions, resulting in more than 50% improvement in body surface area involvement for 92% of patients.

Two participants, one of whom had been living with CTCL for more than 15 years without responding to treatment, experienced complete eradication of the disease.

Malignant cell analysis

The researchers used high-throughput sequencing to detect malignant cells in patient samples. The technique could identify a single malignant cell among 100,000 healthy cells.

The team analyzed DNA from biopsies of the same lesion before treatment and 8 weeks after treatment began.

They observed a significant reduction of malignant T cells in 9 of 10 patients tested, 3 of whom had complete eradication of the malignant population and 1 of whom had a 99.6% reduction.

Adverse events

Adverse events associated with resiquimod were all grade 1 and were primarily related to local skin irritation. There were no serious adverse events.

Five of 8 patients receiving resiquimod at the 0.06% dose developed superficial skin erosions at some sites of treatment. These erosions healed completely within a week of stopping treatment and did not recur with re-initiation of treatment.

Two patients receiving the 0.06% dose experienced 2 days of low-grade fever (less than 100.50 F) when treatment began.

“Overall, lesions responded far better to topical resiquimod than they have with other topical therapies, including some potent topical steroids and topical chemotherapy, and [resiquimod] was extremely well tolerated by patients,” Dr Rook said.

“Building upon previous research, our study suggests resiquimod might be useful in combination with other therapies in the treatment of more advanced CTCL. Further research with larger participant populations is needed to determine the best approach and application for these patients.”

An untreated lesion pre-

treatment (top) and 16 weeks

after treatment began

Photo from Penn Medicine

Results of a phase 1 trial suggest a topical gel can prompt regression of both treated and untreated lesions in patients with

early stage cutaneous T-cell lymphoma (CTCL).

Of the 12 patients who received the treatment, resiquimod gel, 75% had a significant improvement in treated lesions.

And 92% of patients had a more than 50% improvement in body surface area involvement, which included untreated lesions. Two patients experienced complete disease clearance.

Adverse events associated with resiquimod were largely limited to the skin, although 2 patients had transient, low-grade fever. Five patients developed superficial skin erosions that healed when treatment was stopped and did not reappear after treatment began again.

Alain Rook, MD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these results in Blood.

“The results of the trial suggest that resiquimod is safely and effectively absorbed into the skin and, beyond diminishing treated lesions, also enhances the immune response, leading to healing of even untreated lesions,” Dr Rook said.

“To our knowledge, this is the first topical therapy that can clear untreated lesions and lead to complete remission in some patients.”

Treatment and response

Dr Rook and his colleagues tested resiquimod gel in 12 patients who had previously undergone an average of 6 treatments for early stage CTCL.

The patients applied specified doses of resiquimod (0.03% or 0.06%) to select skin lesions for 16 weeks. Some patients using the 0.06% dose had complete clearance of all malignant cells after 8 weeks.

By the final evaluation, treated lesions had significantly improved in 75% of patients, and 30% of patients had complete clearance of all treated lesions.

Resiquimod also improved untreated lesions, resulting in more than 50% improvement in body surface area involvement for 92% of patients.

Two participants, one of whom had been living with CTCL for more than 15 years without responding to treatment, experienced complete eradication of the disease.

Malignant cell analysis

The researchers used high-throughput sequencing to detect malignant cells in patient samples. The technique could identify a single malignant cell among 100,000 healthy cells.

The team analyzed DNA from biopsies of the same lesion before treatment and 8 weeks after treatment began.

They observed a significant reduction of malignant T cells in 9 of 10 patients tested, 3 of whom had complete eradication of the malignant population and 1 of whom had a 99.6% reduction.

Adverse events

Adverse events associated with resiquimod were all grade 1 and were primarily related to local skin irritation. There were no serious adverse events.

Five of 8 patients receiving resiquimod at the 0.06% dose developed superficial skin erosions at some sites of treatment. These erosions healed completely within a week of stopping treatment and did not recur with re-initiation of treatment.

Two patients receiving the 0.06% dose experienced 2 days of low-grade fever (less than 100.50 F) when treatment began.

“Overall, lesions responded far better to topical resiquimod than they have with other topical therapies, including some potent topical steroids and topical chemotherapy, and [resiquimod] was extremely well tolerated by patients,” Dr Rook said.

“Building upon previous research, our study suggests resiquimod might be useful in combination with other therapies in the treatment of more advanced CTCL. Further research with larger participant populations is needed to determine the best approach and application for these patients.”

Vials of drug

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved an intravenous human immune globulin (IVIG) product (Gammaplex) for pediatric patients age 2 years and older who have primary humoral immunodeficiencies.

This includes, but is not limited to, the humoral immune defect in common variable immunodeficiency, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott Aldrich syndrome, and severe combined immunodeficiencies.

The approval was based on data submitted to the FDA as part of a post-marketing commitment following approval of the product for replacement therapy in adults in 2009.

Data supporting the latest approval came from a study of 25 children and adolescents (ages 3 to 16) with primary immunodeficiencies who were treated with IVIG for 12 months.

The study’s primary efficacy endpoint was the incidence of serious, acute bacterial infections (SABIs) as defined by the FDA. Secondary endpoints were safety and tolerability.

Throughout the course of the study, there were 2 SABIs—both pneumonia—resulting in an annual SABI event rate of 0.09, well below the maximum SABI event rate of 0.5 per subject required for approval.

Fourteen subjects (56%) had an adverse event that was possibly related to IVIG. Two patients experienced events that were considered definitely related to the treatment—headache, fatigue, and myalgia.

The most common adverse events, occurring in ≥ 5% of subjects, were dyspnea (2/25, 8%), otitis media acute (2/25, 8%), and tonsillar disorder (2/25, 8%).

Two patients had a serious adverse event of lobar pneumonia. Neither of these was considered related to IVIG, and neither met FDA-defined SABI criteria. None of the subjects withdrew from the study due to adverse events.

IVIG is marketed as Gammaplex by Bio Products Laboratory Limited. For more details on the treatment, see the full prescribing information.

Vials of drug

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved an intravenous human immune globulin (IVIG) product (Gammaplex) for pediatric patients age 2 years and older who have primary humoral immunodeficiencies.

This includes, but is not limited to, the humoral immune defect in common variable immunodeficiency, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott Aldrich syndrome, and severe combined immunodeficiencies.

The approval was based on data submitted to the FDA as part of a post-marketing commitment following approval of the product for replacement therapy in adults in 2009.

Data supporting the latest approval came from a study of 25 children and adolescents (ages 3 to 16) with primary immunodeficiencies who were treated with IVIG for 12 months.

The study’s primary efficacy endpoint was the incidence of serious, acute bacterial infections (SABIs) as defined by the FDA. Secondary endpoints were safety and tolerability.

Throughout the course of the study, there were 2 SABIs—both pneumonia—resulting in an annual SABI event rate of 0.09, well below the maximum SABI event rate of 0.5 per subject required for approval.

Fourteen subjects (56%) had an adverse event that was possibly related to IVIG. Two patients experienced events that were considered definitely related to the treatment—headache, fatigue, and myalgia.

The most common adverse events, occurring in ≥ 5% of subjects, were dyspnea (2/25, 8%), otitis media acute (2/25, 8%), and tonsillar disorder (2/25, 8%).

Two patients had a serious adverse event of lobar pneumonia. Neither of these was considered related to IVIG, and neither met FDA-defined SABI criteria. None of the subjects withdrew from the study due to adverse events.

IVIG is marketed as Gammaplex by Bio Products Laboratory Limited. For more details on the treatment, see the full prescribing information.

Vials of drug

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved an intravenous human immune globulin (IVIG) product (Gammaplex) for pediatric patients age 2 years and older who have primary humoral immunodeficiencies.

This includes, but is not limited to, the humoral immune defect in common variable immunodeficiency, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott Aldrich syndrome, and severe combined immunodeficiencies.

The approval was based on data submitted to the FDA as part of a post-marketing commitment following approval of the product for replacement therapy in adults in 2009.

Data supporting the latest approval came from a study of 25 children and adolescents (ages 3 to 16) with primary immunodeficiencies who were treated with IVIG for 12 months.

The study’s primary efficacy endpoint was the incidence of serious, acute bacterial infections (SABIs) as defined by the FDA. Secondary endpoints were safety and tolerability.

Throughout the course of the study, there were 2 SABIs—both pneumonia—resulting in an annual SABI event rate of 0.09, well below the maximum SABI event rate of 0.5 per subject required for approval.

Fourteen subjects (56%) had an adverse event that was possibly related to IVIG. Two patients experienced events that were considered definitely related to the treatment—headache, fatigue, and myalgia.

The most common adverse events, occurring in ≥ 5% of subjects, were dyspnea (2/25, 8%), otitis media acute (2/25, 8%), and tonsillar disorder (2/25, 8%).

Two patients had a serious adverse event of lobar pneumonia. Neither of these was considered related to IVIG, and neither met FDA-defined SABI criteria. None of the subjects withdrew from the study due to adverse events.

IVIG is marketed as Gammaplex by Bio Products Laboratory Limited. For more details on the treatment, see the full prescribing information.

Thrombus

Image by Kevin MacKenzie

The US Food and Drug Administration (FDA) has granted fast track designation to OMS721 for the treatment of atypical hemolytic uremic syndrome (aHUS).

OMS721 is a monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a key regulator of the lectin pathway of the complement system.

The FDA previously granted OMS721 orphan designation for the prevention of thrombotic microangiopathies (TMAs).

Omeros Corporation, the company developing OMS721, has released results from a phase 1 trial of the drug in healthy subjects and an ongoing phase 2 trial in patients with TMAs, including aHUS.

Early positive responses in the phase 2 trial prompted the initiation of a compassionate use program for OMS721 to allow extended treatment of 2 patients who had completed 4 weeks of dosing.

Phase 1 results

In the phase 1 trial of healthy subjects, OMS721 was well tolerated and prompted a high degree of sustained lectin pathway inhibition, according to researchers.

Seven cohorts of subjects received OMS721 or placebo by either subcutaneous injection or intravenous infusion at increasing dose levels. The researchers observed no drug-related adverse events and no clinically significant abnormalities on laboratory tests or electrocardiograms.

At the highest dose evaluated, both routes of administration prompted inhibition of the lectin pathway and achieved the pharmacologic target of sustained inhibition for at least a week.

Phase 2 results and compassionate use

In the ongoing phase 2 study, all patients are receiving OMS721. The researchers said they have observed treatment-related, clinically meaningful improvements in disease markers among the patients treated thus far.

The first cohort in this trial consisted of 3 aHUS patients treated with the lowest dose of OMS721. All 3 patients had improvements in platelet counts after treatment. Serum haptoglobin improved in 2 patients, normalizing in 1.

Serum lactate dehydrogenase levels remained normal in 1 patient, substantially decreased to close to the normal range in another, and remained elevated in the third. Creatinine levels in the 1 patient with independent renal function improved.

One patient was taken off the trial because of a serious adverse event—a localized inflammatory response often related to certain types of infections, one of which the patient previously had for 3 years while on immunosuppressive therapy. All data to date indicate no active infection in this patient.

The patient relapsed after stopping OMS721 treatment. No other significant safety issues were observed in this trial or the phase 1 trial.

The other 2 aHUS patients in this cohort continue to receive OMS721 as part of a compassionate use program. Based on their improvements in disease markers, an investigator requested that Omeros continue to provide OMS721 to these patients.

Following European regulatory approval, Omeros released the shipment of OMS721 so these patients could continue treatment beyond the period that was initially planned for the phase 2 study.

About fast track and orphan designation

The FDA’s fast track program facilitates the development of drugs intended to treat serious or life-threatening conditions and that have the potential to address unmet medical needs. Fast track status affords the company developing a drug greater access to the FDA in order to expedite the drug’s development, review, and potential approval.

Many drugs that receive fast track designation also receive priority review, and their new drug applications may be accepted by the FDA as a rolling submission, in which portions of an application are reviewed before the complete application is submitted. Priority review and rolling submission can each provide further acceleration of the FDA’s approval process.

The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

Orphan designation provides a drug’s developer with opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, 7 years of US marketing exclusivity if the drug is approved, and other benefits.

Thrombus

Image by Kevin MacKenzie

The US Food and Drug Administration (FDA) has granted fast track designation to OMS721 for the treatment of atypical hemolytic uremic syndrome (aHUS).

OMS721 is a monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a key regulator of the lectin pathway of the complement system.

The FDA previously granted OMS721 orphan designation for the prevention of thrombotic microangiopathies (TMAs).

Omeros Corporation, the company developing OMS721, has released results from a phase 1 trial of the drug in healthy subjects and an ongoing phase 2 trial in patients with TMAs, including aHUS.

Early positive responses in the phase 2 trial prompted the initiation of a compassionate use program for OMS721 to allow extended treatment of 2 patients who had completed 4 weeks of dosing.

Phase 1 results

In the phase 1 trial of healthy subjects, OMS721 was well tolerated and prompted a high degree of sustained lectin pathway inhibition, according to researchers.

Seven cohorts of subjects received OMS721 or placebo by either subcutaneous injection or intravenous infusion at increasing dose levels. The researchers observed no drug-related adverse events and no clinically significant abnormalities on laboratory tests or electrocardiograms.

At the highest dose evaluated, both routes of administration prompted inhibition of the lectin pathway and achieved the pharmacologic target of sustained inhibition for at least a week.

Phase 2 results and compassionate use

In the ongoing phase 2 study, all patients are receiving OMS721. The researchers said they have observed treatment-related, clinically meaningful improvements in disease markers among the patients treated thus far.

The first cohort in this trial consisted of 3 aHUS patients treated with the lowest dose of OMS721. All 3 patients had improvements in platelet counts after treatment. Serum haptoglobin improved in 2 patients, normalizing in 1.

Serum lactate dehydrogenase levels remained normal in 1 patient, substantially decreased to close to the normal range in another, and remained elevated in the third. Creatinine levels in the 1 patient with independent renal function improved.

One patient was taken off the trial because of a serious adverse event—a localized inflammatory response often related to certain types of infections, one of which the patient previously had for 3 years while on immunosuppressive therapy. All data to date indicate no active infection in this patient.

The patient relapsed after stopping OMS721 treatment. No other significant safety issues were observed in this trial or the phase 1 trial.

The other 2 aHUS patients in this cohort continue to receive OMS721 as part of a compassionate use program. Based on their improvements in disease markers, an investigator requested that Omeros continue to provide OMS721 to these patients.

Following European regulatory approval, Omeros released the shipment of OMS721 so these patients could continue treatment beyond the period that was initially planned for the phase 2 study.

About fast track and orphan designation

The FDA’s fast track program facilitates the development of drugs intended to treat serious or life-threatening conditions and that have the potential to address unmet medical needs. Fast track status affords the company developing a drug greater access to the FDA in order to expedite the drug’s development, review, and potential approval.

Many drugs that receive fast track designation also receive priority review, and their new drug applications may be accepted by the FDA as a rolling submission, in which portions of an application are reviewed before the complete application is submitted. Priority review and rolling submission can each provide further acceleration of the FDA’s approval process.

The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

Orphan designation provides a drug’s developer with opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, 7 years of US marketing exclusivity if the drug is approved, and other benefits.

Thrombus

Image by Kevin MacKenzie

The US Food and Drug Administration (FDA) has granted fast track designation to OMS721 for the treatment of atypical hemolytic uremic syndrome (aHUS).

OMS721 is a monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a key regulator of the lectin pathway of the complement system.

The FDA previously granted OMS721 orphan designation for the prevention of thrombotic microangiopathies (TMAs).

Omeros Corporation, the company developing OMS721, has released results from a phase 1 trial of the drug in healthy subjects and an ongoing phase 2 trial in patients with TMAs, including aHUS.

Early positive responses in the phase 2 trial prompted the initiation of a compassionate use program for OMS721 to allow extended treatment of 2 patients who had completed 4 weeks of dosing.

Phase 1 results

In the phase 1 trial of healthy subjects, OMS721 was well tolerated and prompted a high degree of sustained lectin pathway inhibition, according to researchers.

Seven cohorts of subjects received OMS721 or placebo by either subcutaneous injection or intravenous infusion at increasing dose levels. The researchers observed no drug-related adverse events and no clinically significant abnormalities on laboratory tests or electrocardiograms.

At the highest dose evaluated, both routes of administration prompted inhibition of the lectin pathway and achieved the pharmacologic target of sustained inhibition for at least a week.

Phase 2 results and compassionate use

In the ongoing phase 2 study, all patients are receiving OMS721. The researchers said they have observed treatment-related, clinically meaningful improvements in disease markers among the patients treated thus far.

The first cohort in this trial consisted of 3 aHUS patients treated with the lowest dose of OMS721. All 3 patients had improvements in platelet counts after treatment. Serum haptoglobin improved in 2 patients, normalizing in 1.

Serum lactate dehydrogenase levels remained normal in 1 patient, substantially decreased to close to the normal range in another, and remained elevated in the third. Creatinine levels in the 1 patient with independent renal function improved.

One patient was taken off the trial because of a serious adverse event—a localized inflammatory response often related to certain types of infections, one of which the patient previously had for 3 years while on immunosuppressive therapy. All data to date indicate no active infection in this patient.

The patient relapsed after stopping OMS721 treatment. No other significant safety issues were observed in this trial or the phase 1 trial.

The other 2 aHUS patients in this cohort continue to receive OMS721 as part of a compassionate use program. Based on their improvements in disease markers, an investigator requested that Omeros continue to provide OMS721 to these patients.

Following European regulatory approval, Omeros released the shipment of OMS721 so these patients could continue treatment beyond the period that was initially planned for the phase 2 study.

About fast track and orphan designation

The FDA’s fast track program facilitates the development of drugs intended to treat serious or life-threatening conditions and that have the potential to address unmet medical needs. Fast track status affords the company developing a drug greater access to the FDA in order to expedite the drug’s development, review, and potential approval.

Many drugs that receive fast track designation also receive priority review, and their new drug applications may be accepted by the FDA as a rolling submission, in which portions of an application are reviewed before the complete application is submitted. Priority review and rolling submission can each provide further acceleration of the FDA’s approval process.

The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

Orphan designation provides a drug’s developer with opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, 7 years of US marketing exclusivity if the drug is approved, and other benefits.