HT Staff

acute myeloid leukemia

Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).

The generic drug is approved for the same indications as VIDAZA®.

This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.

It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.

“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.

“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”

acute myeloid leukemia

Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).

The generic drug is approved for the same indications as VIDAZA®.

This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.

It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.

“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.

“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”

acute myeloid leukemia

Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).

The generic drug is approved for the same indications as VIDAZA®.

This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.

It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.

“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.

“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”

Photo by Elise Amendola

ANAHEIM, CA—Results of a large study suggest a restrictive transfusion strategy is safe for moderate- to high-risk patients undergoing cardiac surgery.

Researchers found that patients had similar rates of various outcomes—death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis—whether they received red blood cell (RBC) transfusions according to a restrictive strategy or a liberal one.

C. David Mazer, MD, of St. Michael’s Hospital in Toronto, Ontario, Canada, presented these results at the American Heart Association’s Scientific Sessions 2017.

Results were simultaneously published in NEJM.

Dr Mazer and his colleagues studied 5243 adults undergoing cardiac surgery. They all had a European System for Cardiac Operative Risk Evaluation I score of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery).

Patients were randomized to receive RBC transfusions according to a restrictive strategy or a liberal one.

With the restrictive strategy, patients received transfusions if their hemoglobin level was below 7.5 g/dL, starting from induction of anesthesia.

With the liberal strategy, patients were transfused if their hemoglobin level was less than 9.5 g/dL in the operating room or intensive care unit (ICU) or was less than 8.5 g/dL in the non-ICU ward.

Results

There were 4860 patients in the per-protocol analysis—2430 in each transfusion group. Baseline characteristics were similar between the groups.

The rate of RBC transfusion was 52.3% in the restrictive group and 72.6% in the liberal group. The odds ratio (OR) was 0.41 (95% confidence interval [CI], 0.37 to 0.47).

Transfused patients received a median of 2 RBC units (interquartile range [IQR], 1 to 4) in the restrictive group and 3 units (IQR, 2 to 5) in the liberal group.

The study’s primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first.

This outcome occurred in 11.4% of patients in the restrictive group and 12.5% of those in the liberal group. The absolute risk difference was −1.11 percentage points (95% CI, −2.93 to 0.72), and the odds ratio was 0.90 (95% CI, 0.76 to 1.07; P<0.001 for noninferiority).

There were no significant differences between the groups when it came to the individual components of the composite outcome.

“We have shown that this [restrictive] approach to transfusion is safe in moderate- to high-risk patients undergoing cardiac surgery,” Dr Mazer said.

“Such practices can also reduce the number of patients transfused, the amount of blood transfused, the impact on blood supply, and costs to the healthcare system.”

Photo by Elise Amendola

ANAHEIM, CA—Results of a large study suggest a restrictive transfusion strategy is safe for moderate- to high-risk patients undergoing cardiac surgery.

Researchers found that patients had similar rates of various outcomes—death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis—whether they received red blood cell (RBC) transfusions according to a restrictive strategy or a liberal one.

C. David Mazer, MD, of St. Michael’s Hospital in Toronto, Ontario, Canada, presented these results at the American Heart Association’s Scientific Sessions 2017.

Results were simultaneously published in NEJM.

Dr Mazer and his colleagues studied 5243 adults undergoing cardiac surgery. They all had a European System for Cardiac Operative Risk Evaluation I score of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery).

Patients were randomized to receive RBC transfusions according to a restrictive strategy or a liberal one.

With the restrictive strategy, patients received transfusions if their hemoglobin level was below 7.5 g/dL, starting from induction of anesthesia.

With the liberal strategy, patients were transfused if their hemoglobin level was less than 9.5 g/dL in the operating room or intensive care unit (ICU) or was less than 8.5 g/dL in the non-ICU ward.

Results

There were 4860 patients in the per-protocol analysis—2430 in each transfusion group. Baseline characteristics were similar between the groups.

The rate of RBC transfusion was 52.3% in the restrictive group and 72.6% in the liberal group. The odds ratio (OR) was 0.41 (95% confidence interval [CI], 0.37 to 0.47).

Transfused patients received a median of 2 RBC units (interquartile range [IQR], 1 to 4) in the restrictive group and 3 units (IQR, 2 to 5) in the liberal group.

The study’s primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first.

This outcome occurred in 11.4% of patients in the restrictive group and 12.5% of those in the liberal group. The absolute risk difference was −1.11 percentage points (95% CI, −2.93 to 0.72), and the odds ratio was 0.90 (95% CI, 0.76 to 1.07; P<0.001 for noninferiority).

There were no significant differences between the groups when it came to the individual components of the composite outcome.

“We have shown that this [restrictive] approach to transfusion is safe in moderate- to high-risk patients undergoing cardiac surgery,” Dr Mazer said.

“Such practices can also reduce the number of patients transfused, the amount of blood transfused, the impact on blood supply, and costs to the healthcare system.”

Photo by Elise Amendola

ANAHEIM, CA—Results of a large study suggest a restrictive transfusion strategy is safe for moderate- to high-risk patients undergoing cardiac surgery.

Researchers found that patients had similar rates of various outcomes—death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis—whether they received red blood cell (RBC) transfusions according to a restrictive strategy or a liberal one.

C. David Mazer, MD, of St. Michael’s Hospital in Toronto, Ontario, Canada, presented these results at the American Heart Association’s Scientific Sessions 2017.

Results were simultaneously published in NEJM.

Dr Mazer and his colleagues studied 5243 adults undergoing cardiac surgery. They all had a European System for Cardiac Operative Risk Evaluation I score of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery).

Patients were randomized to receive RBC transfusions according to a restrictive strategy or a liberal one.

With the restrictive strategy, patients received transfusions if their hemoglobin level was below 7.5 g/dL, starting from induction of anesthesia.

With the liberal strategy, patients were transfused if their hemoglobin level was less than 9.5 g/dL in the operating room or intensive care unit (ICU) or was less than 8.5 g/dL in the non-ICU ward.

Results

There were 4860 patients in the per-protocol analysis—2430 in each transfusion group. Baseline characteristics were similar between the groups.

The rate of RBC transfusion was 52.3% in the restrictive group and 72.6% in the liberal group. The odds ratio (OR) was 0.41 (95% confidence interval [CI], 0.37 to 0.47).

Transfused patients received a median of 2 RBC units (interquartile range [IQR], 1 to 4) in the restrictive group and 3 units (IQR, 2 to 5) in the liberal group.

The study’s primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first.

This outcome occurred in 11.4% of patients in the restrictive group and 12.5% of those in the liberal group. The absolute risk difference was −1.11 percentage points (95% CI, −2.93 to 0.72), and the odds ratio was 0.90 (95% CI, 0.76 to 1.07; P<0.001 for noninferiority).

There were no significant differences between the groups when it came to the individual components of the composite outcome.

“We have shown that this [restrictive] approach to transfusion is safe in moderate- to high-risk patients undergoing cardiac surgery,” Dr Mazer said.

“Such practices can also reduce the number of patients transfused, the amount of blood transfused, the impact on blood supply, and costs to the healthcare system.”

Photo by Aaron Logan

Preclinical research suggests PRO 140, a humanized anti-CCR5 monoclonal antibody, can prevent graft-versus-host disease (GVHD) in mice.

Mice that received 2 mg of PRO 140 twice weekly showed no signs of GVHD throughout the study period.

On the other hand, all control mice exhibited signs of GVHD, starting 25 days after engraftment, and had to be sacrificed early.

Researchers reported these results in Biology of Blood and Marrow Transplantation.

The study’s lead author, Denis R. Burger, PhD, is chief science officer of CytoDyn, the company developing PRO 140.

PRO 140 targets the CCR5 receptor, a molecule that modulates the immune cell trafficking crucial for the development of acute GVHD.

Previous clinical studies have shown that inhibiting CCR5 can reduce the clinical impact of acute GVHD without significantly affecting the engraftment of transplanted hematopoietic stem cells (HSCs).

This new study supports the idea that the CCR5 receptor on engrafted cells is critical for the development of acute GVHD and that preventing this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GVHD.

Dr Burger and his colleagues tested PRO 140 in NOD-scid IL-2Ry^null mice transplanted with human HSCs.

Mice received 2 different doses of PRO 140 or a control antibody—2 mg or 0.2 mg—twice weekly and were followed for a maximum of 75 days.

Engraftment at the higher dose

Mice that received the 2 mg dose of PRO 140 or the control antibody had received HSCs from a 56-year-old donor.

Engraftment was similar between control and PRO 140-treated mice for the first 30+ days. However, at day 50, there were significantly fewer human CD45+ cells in the PRO 140-treated mice (P=0.034).

At 54 days, control mice had greater engraftment of mature T cells than treated mice in the peripheral blood (63.2% vs 49.8%) and bone marrow (40.2% vs 26.4%).

GVHD at the higher dose

Throughout the study period, there were no physical signs of GVHD in the PRO 140-treated mice.

However, control mice exhibited signs of GVHD starting at day 25 after bone marrow engraftment. Signs included ruffled fur, lethargy, hunching, and weight loss.

There was a significant difference in survival between the 2 groups (P<0.01). All of the control mice had to be sacrificed early, by day 56, whereas all of the PRO 140-treated animals were alive until planned sacrifice at day 75.

Engraftment at the low dose

Mice that received the 0.2 mg dose of PRO 140 or the control antibody had received HSCs from a 26-year-old donor.

Mice in the treatment and control groups achieved the same percentage of CD45+ engraftment. However, PRO 140-treated mice achieved engraftment about 20 days later than control mice (P<0.01).

GVHD at the low dose

Both control and PRO 140-treated mice showed signs of GVHD. However, weight loss was significantly greater among control mice (P<0.05).

Survival was significantly worse among control mice as well (P<0.05). All control mice were dead by 31 days, and all PRO 140-treated mice were dead by 54 days.

The researchers said the difference in survival times between these mice and the mice treated with the higher dose of antibody suggest the younger HSC donor produced more aggressive GVHD.

“This research provided CytoDyn with strong rationale for exploring the use of PRO 140 in . . . the prevention of GVHD,” Dr Burger said.

“The potential of PRO 140 to prevent this life-threatening condition could help extend the use of [HSC] transplantation, an important and effective therapy, to more patients.”

CytoDyn is currently enrolling patients in a phase 2 trial of PRO 140 in leukemia patients undergoing transplant.

Photo by Aaron Logan

Preclinical research suggests PRO 140, a humanized anti-CCR5 monoclonal antibody, can prevent graft-versus-host disease (GVHD) in mice.

Mice that received 2 mg of PRO 140 twice weekly showed no signs of GVHD throughout the study period.

On the other hand, all control mice exhibited signs of GVHD, starting 25 days after engraftment, and had to be sacrificed early.

Researchers reported these results in Biology of Blood and Marrow Transplantation.

The study’s lead author, Denis R. Burger, PhD, is chief science officer of CytoDyn, the company developing PRO 140.

PRO 140 targets the CCR5 receptor, a molecule that modulates the immune cell trafficking crucial for the development of acute GVHD.

Previous clinical studies have shown that inhibiting CCR5 can reduce the clinical impact of acute GVHD without significantly affecting the engraftment of transplanted hematopoietic stem cells (HSCs).

This new study supports the idea that the CCR5 receptor on engrafted cells is critical for the development of acute GVHD and that preventing this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GVHD.

Dr Burger and his colleagues tested PRO 140 in NOD-scid IL-2Ry^null mice transplanted with human HSCs.

Mice received 2 different doses of PRO 140 or a control antibody—2 mg or 0.2 mg—twice weekly and were followed for a maximum of 75 days.

Engraftment at the higher dose

Mice that received the 2 mg dose of PRO 140 or the control antibody had received HSCs from a 56-year-old donor.

Engraftment was similar between control and PRO 140-treated mice for the first 30+ days. However, at day 50, there were significantly fewer human CD45+ cells in the PRO 140-treated mice (P=0.034).

At 54 days, control mice had greater engraftment of mature T cells than treated mice in the peripheral blood (63.2% vs 49.8%) and bone marrow (40.2% vs 26.4%).

GVHD at the higher dose

Throughout the study period, there were no physical signs of GVHD in the PRO 140-treated mice.

However, control mice exhibited signs of GVHD starting at day 25 after bone marrow engraftment. Signs included ruffled fur, lethargy, hunching, and weight loss.

There was a significant difference in survival between the 2 groups (P<0.01). All of the control mice had to be sacrificed early, by day 56, whereas all of the PRO 140-treated animals were alive until planned sacrifice at day 75.

Engraftment at the low dose

Mice that received the 0.2 mg dose of PRO 140 or the control antibody had received HSCs from a 26-year-old donor.

Mice in the treatment and control groups achieved the same percentage of CD45+ engraftment. However, PRO 140-treated mice achieved engraftment about 20 days later than control mice (P<0.01).

GVHD at the low dose

Both control and PRO 140-treated mice showed signs of GVHD. However, weight loss was significantly greater among control mice (P<0.05).

Survival was significantly worse among control mice as well (P<0.05). All control mice were dead by 31 days, and all PRO 140-treated mice were dead by 54 days.

The researchers said the difference in survival times between these mice and the mice treated with the higher dose of antibody suggest the younger HSC donor produced more aggressive GVHD.

“This research provided CytoDyn with strong rationale for exploring the use of PRO 140 in . . . the prevention of GVHD,” Dr Burger said.

“The potential of PRO 140 to prevent this life-threatening condition could help extend the use of [HSC] transplantation, an important and effective therapy, to more patients.”

CytoDyn is currently enrolling patients in a phase 2 trial of PRO 140 in leukemia patients undergoing transplant.

Photo by Aaron Logan

Preclinical research suggests PRO 140, a humanized anti-CCR5 monoclonal antibody, can prevent graft-versus-host disease (GVHD) in mice.

Mice that received 2 mg of PRO 140 twice weekly showed no signs of GVHD throughout the study period.

On the other hand, all control mice exhibited signs of GVHD, starting 25 days after engraftment, and had to be sacrificed early.

Researchers reported these results in Biology of Blood and Marrow Transplantation.

The study’s lead author, Denis R. Burger, PhD, is chief science officer of CytoDyn, the company developing PRO 140.

PRO 140 targets the CCR5 receptor, a molecule that modulates the immune cell trafficking crucial for the development of acute GVHD.

Previous clinical studies have shown that inhibiting CCR5 can reduce the clinical impact of acute GVHD without significantly affecting the engraftment of transplanted hematopoietic stem cells (HSCs).

This new study supports the idea that the CCR5 receptor on engrafted cells is critical for the development of acute GVHD and that preventing this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GVHD.

Dr Burger and his colleagues tested PRO 140 in NOD-scid IL-2Ry^null mice transplanted with human HSCs.

Mice received 2 different doses of PRO 140 or a control antibody—2 mg or 0.2 mg—twice weekly and were followed for a maximum of 75 days.

Engraftment at the higher dose

Mice that received the 2 mg dose of PRO 140 or the control antibody had received HSCs from a 56-year-old donor.

Engraftment was similar between control and PRO 140-treated mice for the first 30+ days. However, at day 50, there were significantly fewer human CD45+ cells in the PRO 140-treated mice (P=0.034).

At 54 days, control mice had greater engraftment of mature T cells than treated mice in the peripheral blood (63.2% vs 49.8%) and bone marrow (40.2% vs 26.4%).

GVHD at the higher dose

Throughout the study period, there were no physical signs of GVHD in the PRO 140-treated mice.

However, control mice exhibited signs of GVHD starting at day 25 after bone marrow engraftment. Signs included ruffled fur, lethargy, hunching, and weight loss.

There was a significant difference in survival between the 2 groups (P<0.01). All of the control mice had to be sacrificed early, by day 56, whereas all of the PRO 140-treated animals were alive until planned sacrifice at day 75.

Engraftment at the low dose

Mice that received the 0.2 mg dose of PRO 140 or the control antibody had received HSCs from a 26-year-old donor.

Mice in the treatment and control groups achieved the same percentage of CD45+ engraftment. However, PRO 140-treated mice achieved engraftment about 20 days later than control mice (P<0.01).

GVHD at the low dose

Both control and PRO 140-treated mice showed signs of GVHD. However, weight loss was significantly greater among control mice (P<0.05).

Survival was significantly worse among control mice as well (P<0.05). All control mice were dead by 31 days, and all PRO 140-treated mice were dead by 54 days.

The researchers said the difference in survival times between these mice and the mice treated with the higher dose of antibody suggest the younger HSC donor produced more aggressive GVHD.

“This research provided CytoDyn with strong rationale for exploring the use of PRO 140 in . . . the prevention of GVHD,” Dr Burger said.

“The potential of PRO 140 to prevent this life-threatening condition could help extend the use of [HSC] transplantation, an important and effective therapy, to more patients.”

CytoDyn is currently enrolling patients in a phase 2 trial of PRO 140 in leukemia patients undergoing transplant.

Photo by Steven Harbour

US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.

A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.

Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.

However, patients who were already paying the most for their medications saw their monthly costs go up.

“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”

To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.

The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.

About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.

For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).

The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).

“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”

The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).

Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.

For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.

“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.

“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”

However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.

Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.

On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.

The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.

“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”

Photo by Steven Harbour

US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.

A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.

Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.

However, patients who were already paying the most for their medications saw their monthly costs go up.

“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”

To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.

The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.

About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.

For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).

The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).

“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”

The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).

Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.

For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.

“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.

“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”

However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.

Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.

On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.

The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.

“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”

Photo by Steven Harbour

US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.

A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.

Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.

However, patients who were already paying the most for their medications saw their monthly costs go up.

“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”

To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.

The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.

About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.

For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).

The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).

“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”

The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).

Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.

For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.

“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.

“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”

However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.

Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.

On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.

The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.

“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”

Medicine Media Relations

ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.

Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.

Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).

The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.

TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.

The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.

Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”

The researchers identified 691 VTEs during the 299,767 person-years of follow-up.

A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”

Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”

The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.

“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.

“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”

Medicine Media Relations

ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.

Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.

Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).

The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.

TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.

The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.

Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”

The researchers identified 691 VTEs during the 299,767 person-years of follow-up.

A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”

Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”

The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.

“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.

“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”

Medicine Media Relations

ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.

Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.

Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).

The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.

TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.

The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.

Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”

The researchers identified 691 VTEs during the 299,767 person-years of follow-up.

A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”

Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”

The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.

“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.

“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).

Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).

The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).

Phase 3 trials

Rurioctocog alfa pegol has been studied in 3 phase 3 trials.

One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.

Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.

A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).

Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).

The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).

Phase 3 trials

Rurioctocog alfa pegol has been studied in 3 phase 3 trials.

One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.

Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.

A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).

Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).

The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).

Phase 3 trials

Rurioctocog alfa pegol has been studied in 3 phase 3 trials.

One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.

Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.

A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).

The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The EC previously approved BV to treat:

• Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Adults with CD30+ HL at increased risk of relapse or progression following ASCT
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).

The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The EC previously approved BV to treat:

• Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Adults with CD30+ HL at increased risk of relapse or progression following ASCT
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).

The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The EC previously approved BV to treat:

• Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Adults with CD30+ HL at increased risk of relapse or progression following ASCT
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.

Phase 3 trial

The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.

The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.

Phase 3 trial

The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.

The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.

Phase 3 trial

The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.

The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Research Hospital

Dosing of hydroxyurea (HU) in young patients with sickle cell anemia (SCA) should target a fetal hemoglobin (HbF) level above 20%, according to researchers.

Their study, HUSTLE, showed that children and adolescents who received a maximum tolerated dose (MTD) of HU were able to achieve HbF levels above 20%.

And patients who achieved such HbF levels had a significantly lower risk of hospitalization for any reason, including vaso-occlusive crisis, acute chest syndrome, and fever.

Jeremie Estepp, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these results in the American Journal of Hematology.

“Our analysis showed that, using this approach, hospitalizations for the average patient fell to less than 1 every couple of years rather than 4 to 6 annually,” Dr Estepp said. “This frees children from the fevers, pain, and other symptoms of this disease and gives them and their families more chances to enjoy childhood and adolescence.”

The study enrolled 230 SCA patients. Most had the HbSS genotype (n=214; 93%), although 7% (n=16) had HbSb⁰ thalassemia. The patients’ median age at HU initiation was 7.4 years (range, 6 months to 17.9 years). The mean HbF level at enrollment was 9.7%, and the median was 7.9% (range, 1.0-32.9%).

The researchers used a dose-escalation approach to determine the MTD of HU for each of the patients in this study. The MTD was defined by an absolute neutrophil count of 2000-4000 x 10⁶/L or the presence of hematologic toxicity. The maximum absolute dose was 35 mg/kg/day or 2000 mg/day (whichever came first).

The mean daily dose of HU at the MTD was 26.7 mg/kg/day, and the median was 28.0 mg/kg/day (range, 13.0 to 35.0 mg/kg/day).

Three-quarters of patients (75.2%, 173/230) attained the MTD at the time of data censoring. Patients were followed for up to 4 years after study entry.

As far as treatment compliance, there were complete medication dispensation records available for 96% (220/230) of patients. And the patients were in possession of HU a mean of 93.6% of the time.

The researchers found that administering HU at the MTD resulted in a mean HbF of 26.7% and a median of 21.7% (interquartile range, 16.2% to 27.8%).

And the odds of being hospitalized were higher when a patient’s HbF level was less than 21%. The odds ratios for hospitalization were as follows:

• 4.1 for fever
• 2.6 for acute chest syndrome
• 2.2 for vaso-occlusive crisis
• 2.1 for any reason.

“These results support a hydroxyurea dosing strategy designed to produce fetal hemoglobin levels that exceed 20% in an effort to decrease hospitalization of children with sickle cell disease,” Dr Estepp said.

He and his colleagues are now conducting a multicenter trial to determine if toddlers with SCA would benefit from a similar dosing strategy or would respond better to a standard dose.

Research Hospital

Dosing of hydroxyurea (HU) in young patients with sickle cell anemia (SCA) should target a fetal hemoglobin (HbF) level above 20%, according to researchers.

Their study, HUSTLE, showed that children and adolescents who received a maximum tolerated dose (MTD) of HU were able to achieve HbF levels above 20%.

And patients who achieved such HbF levels had a significantly lower risk of hospitalization for any reason, including vaso-occlusive crisis, acute chest syndrome, and fever.

Jeremie Estepp, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these results in the American Journal of Hematology.

“Our analysis showed that, using this approach, hospitalizations for the average patient fell to less than 1 every couple of years rather than 4 to 6 annually,” Dr Estepp said. “This frees children from the fevers, pain, and other symptoms of this disease and gives them and their families more chances to enjoy childhood and adolescence.”

The study enrolled 230 SCA patients. Most had the HbSS genotype (n=214; 93%), although 7% (n=16) had HbSb⁰ thalassemia. The patients’ median age at HU initiation was 7.4 years (range, 6 months to 17.9 years). The mean HbF level at enrollment was 9.7%, and the median was 7.9% (range, 1.0-32.9%).

The researchers used a dose-escalation approach to determine the MTD of HU for each of the patients in this study. The MTD was defined by an absolute neutrophil count of 2000-4000 x 10⁶/L or the presence of hematologic toxicity. The maximum absolute dose was 35 mg/kg/day or 2000 mg/day (whichever came first).

The mean daily dose of HU at the MTD was 26.7 mg/kg/day, and the median was 28.0 mg/kg/day (range, 13.0 to 35.0 mg/kg/day).

Three-quarters of patients (75.2%, 173/230) attained the MTD at the time of data censoring. Patients were followed for up to 4 years after study entry.

As far as treatment compliance, there were complete medication dispensation records available for 96% (220/230) of patients. And the patients were in possession of HU a mean of 93.6% of the time.

The researchers found that administering HU at the MTD resulted in a mean HbF of 26.7% and a median of 21.7% (interquartile range, 16.2% to 27.8%).

And the odds of being hospitalized were higher when a patient’s HbF level was less than 21%. The odds ratios for hospitalization were as follows:

• 4.1 for fever
• 2.6 for acute chest syndrome
• 2.2 for vaso-occlusive crisis
• 2.1 for any reason.

“These results support a hydroxyurea dosing strategy designed to produce fetal hemoglobin levels that exceed 20% in an effort to decrease hospitalization of children with sickle cell disease,” Dr Estepp said.

He and his colleagues are now conducting a multicenter trial to determine if toddlers with SCA would benefit from a similar dosing strategy or would respond better to a standard dose.

Research Hospital

Dosing of hydroxyurea (HU) in young patients with sickle cell anemia (SCA) should target a fetal hemoglobin (HbF) level above 20%, according to researchers.

Their study, HUSTLE, showed that children and adolescents who received a maximum tolerated dose (MTD) of HU were able to achieve HbF levels above 20%.

And patients who achieved such HbF levels had a significantly lower risk of hospitalization for any reason, including vaso-occlusive crisis, acute chest syndrome, and fever.

Jeremie Estepp, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these results in the American Journal of Hematology.

“Our analysis showed that, using this approach, hospitalizations for the average patient fell to less than 1 every couple of years rather than 4 to 6 annually,” Dr Estepp said. “This frees children from the fevers, pain, and other symptoms of this disease and gives them and their families more chances to enjoy childhood and adolescence.”

The study enrolled 230 SCA patients. Most had the HbSS genotype (n=214; 93%), although 7% (n=16) had HbSb⁰ thalassemia. The patients’ median age at HU initiation was 7.4 years (range, 6 months to 17.9 years). The mean HbF level at enrollment was 9.7%, and the median was 7.9% (range, 1.0-32.9%).

The researchers used a dose-escalation approach to determine the MTD of HU for each of the patients in this study. The MTD was defined by an absolute neutrophil count of 2000-4000 x 10⁶/L or the presence of hematologic toxicity. The maximum absolute dose was 35 mg/kg/day or 2000 mg/day (whichever came first).

The mean daily dose of HU at the MTD was 26.7 mg/kg/day, and the median was 28.0 mg/kg/day (range, 13.0 to 35.0 mg/kg/day).

Three-quarters of patients (75.2%, 173/230) attained the MTD at the time of data censoring. Patients were followed for up to 4 years after study entry.

As far as treatment compliance, there were complete medication dispensation records available for 96% (220/230) of patients. And the patients were in possession of HU a mean of 93.6% of the time.

The researchers found that administering HU at the MTD resulted in a mean HbF of 26.7% and a median of 21.7% (interquartile range, 16.2% to 27.8%).

And the odds of being hospitalized were higher when a patient’s HbF level was less than 21%. The odds ratios for hospitalization were as follows:

• 4.1 for fever
• 2.6 for acute chest syndrome
• 2.2 for vaso-occlusive crisis
• 2.1 for any reason.

“These results support a hydroxyurea dosing strategy designed to produce fetal hemoglobin levels that exceed 20% in an effort to decrease hospitalization of children with sickle cell disease,” Dr Estepp said.

He and his colleagues are now conducting a multicenter trial to determine if toddlers with SCA would benefit from a similar dosing strategy or would respond better to a standard dose.

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for romiplostim (Nplate^®) to include children.

The CHMP is recommending authorization of romiplostim to treat patients age 1 and older who have chronic immune thrombocytopenia (ITP) that is refractory to other treatments.

The committee’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, a centralized marketing authorization will be granted that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The recommendation for romiplostim was based on 5 studies of the drug in children with ITP. This includes 4 completed studies—a phase 1/2, a phase 3, and 2 long-term safety and efficacy studies—and 1 ongoing long-term study.

Results from the phase 1/2 trial were published in Blood in 2011. Phase 3 results were published in The Lancet in April of last year.

And results from 2 of the long-term trials were presented at 22nd Congress of the European Hematology Association in June (abstract P367 and abstract P727).

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for romiplostim (Nplate^®) to include children.

The CHMP is recommending authorization of romiplostim to treat patients age 1 and older who have chronic immune thrombocytopenia (ITP) that is refractory to other treatments.

The committee’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, a centralized marketing authorization will be granted that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The recommendation for romiplostim was based on 5 studies of the drug in children with ITP. This includes 4 completed studies—a phase 1/2, a phase 3, and 2 long-term safety and efficacy studies—and 1 ongoing long-term study.

Results from the phase 1/2 trial were published in Blood in 2011. Phase 3 results were published in The Lancet in April of last year.

And results from 2 of the long-term trials were presented at 22nd Congress of the European Hematology Association in June (abstract P367 and abstract P727).

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for romiplostim (Nplate^®) to include children.

The CHMP is recommending authorization of romiplostim to treat patients age 1 and older who have chronic immune thrombocytopenia (ITP) that is refractory to other treatments.

The committee’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, a centralized marketing authorization will be granted that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The recommendation for romiplostim was based on 5 studies of the drug in children with ITP. This includes 4 completed studies—a phase 1/2, a phase 3, and 2 long-term safety and efficacy studies—and 1 ongoing long-term study.

Results from the phase 1/2 trial were published in Blood in 2011. Phase 3 results were published in The Lancet in April of last year.

And results from 2 of the long-term trials were presented at 22nd Congress of the European Hematology Association in June (abstract P367 and abstract P727).