Reslizumab: FDA panel recommends approval for adults, but not children

SILVER SPRING, MD. Members of the FDA Pulmonary-Allergy Drugs Advisory Committee voted 11-3 on Dec. 9 to recommend the approval of reslizumab, a humanized monoclonal antibody, for the treatment of asthma and elevated blood eosinophils in patients aged 18 years and older but did not recommend approval for children aged 12-17 years.

The advisers were tasked to consider a dosage of 3 mg/kg of reslizumab, administered intravenously once every 4 weeks for the management of severe asthma. The lack of a recommendation for the pediatric population is because of what panel members considered to be insufficient data culled from a small sample population (19 patients), along with results that did not provide enough evidence that the treatment was of significant benefit to adolescents.

There were “limited data” presented to support use of reslizumab in pediatrics, and “all the evidence was going in the wrong direction,” according to panel member Erica H. Brittain, Ph.D., of the National Institute of Allergy and Infectious Diseases, Bethesda, Md.

Panelist Dr. Thomas A.E. Platts-Mills, professor of medicine at the University of Virginia, Charlottesville, added that a larger study is needed in order to more accurately assess the drug’s efficacy, and should also include patients younger than the age of 12 years.

Both of the questions posited to the panel by the FDA regarding reslizumab approval for pediatric patients, “Do the efficacy data provide substantial evidence of a clinically meaningful benefit?” and “Do the available efficacy and safety data support approval of reslizumab?” received unanimous “No” votes from the 14-member voting panel.

The advisory panel members considered data from five separate trials evaluating the safety and efficacy of reslizumab to be marketed as Cinqair by Teva Pharmaceuticals. Those trials included two 16-week lung-function studies examining forced expiratory volume in 1 second (FEV₁₎, two year-long asthma exacerbation studies, and an open-label safety extension study.

Advisers generally agreed that reslizumab demonstrated substantial improvement in FEV₁ and asthma exacerbation in the adult population. Specifically, in the two exacerbation studies, clinical asthma exacerbations did not occur at all over the 12-month study period in 61% and 73% of subjects on reslizumab, vs. 44% and 52% of subjects in the control cohort, respectively, with FEV₁ dropping.

However, panelists voiced their concern about the risk of muscle toxicity and, especially, anaphylaxis. In a presentation regarding the treatment’s immunogenicity issues, João A. Pedras-Vasconcelos, Ph.D., of the FDA Office of Pharmaceutical Quality, cautioned that enough work was not done by the sponsors to “thoroughly investigate [the] root causes of anaphylaxis.”

Ultimately, the advisory committee largely agreed that the unmet need for reslizumab outweighed the potential risks associated with it.

In casting his “yes” vote regarding the adequacy of reslizumab’s safety profile, panel chair Dr. Dennis R. Ownby, professor of pediatrics at Georgia Regents University in Augusta, admitted that he was “reluctant” to endorse reslizumab, but said that he believes “this is a drug that clinicians will use very cautiously, [so] I’m placing faith on our practicing physicians” to prescribe the drug responsibly.

Advisers voted 11-3 to recommend approval of reslizumab as a safe and effective treatment of severe asthma and elevated blood eosinophils. Approval of reslizumab would make it the third monoclonal antibody to be FDA approved to treat asthma.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

dchitnis@frontlinemedcom.com

SILVER SPRING, MD. Members of the FDA Pulmonary-Allergy Drugs Advisory Committee voted 11-3 on Dec. 9 to recommend the approval of reslizumab, a humanized monoclonal antibody, for the treatment of asthma and elevated blood eosinophils in patients aged 18 years and older but did not recommend approval for children aged 12-17 years.

The advisers were tasked to consider a dosage of 3 mg/kg of reslizumab, administered intravenously once every 4 weeks for the management of severe asthma. The lack of a recommendation for the pediatric population is because of what panel members considered to be insufficient data culled from a small sample population (19 patients), along with results that did not provide enough evidence that the treatment was of significant benefit to adolescents.

There were “limited data” presented to support use of reslizumab in pediatrics, and “all the evidence was going in the wrong direction,” according to panel member Erica H. Brittain, Ph.D., of the National Institute of Allergy and Infectious Diseases, Bethesda, Md.

Panelist Dr. Thomas A.E. Platts-Mills, professor of medicine at the University of Virginia, Charlottesville, added that a larger study is needed in order to more accurately assess the drug’s efficacy, and should also include patients younger than the age of 12 years.

Both of the questions posited to the panel by the FDA regarding reslizumab approval for pediatric patients, “Do the efficacy data provide substantial evidence of a clinically meaningful benefit?” and “Do the available efficacy and safety data support approval of reslizumab?” received unanimous “No” votes from the 14-member voting panel.

The advisory panel members considered data from five separate trials evaluating the safety and efficacy of reslizumab to be marketed as Cinqair by Teva Pharmaceuticals. Those trials included two 16-week lung-function studies examining forced expiratory volume in 1 second (FEV₁₎, two year-long asthma exacerbation studies, and an open-label safety extension study.

Advisers generally agreed that reslizumab demonstrated substantial improvement in FEV₁ and asthma exacerbation in the adult population. Specifically, in the two exacerbation studies, clinical asthma exacerbations did not occur at all over the 12-month study period in 61% and 73% of subjects on reslizumab, vs. 44% and 52% of subjects in the control cohort, respectively, with FEV₁ dropping.

However, panelists voiced their concern about the risk of muscle toxicity and, especially, anaphylaxis. In a presentation regarding the treatment’s immunogenicity issues, João A. Pedras-Vasconcelos, Ph.D., of the FDA Office of Pharmaceutical Quality, cautioned that enough work was not done by the sponsors to “thoroughly investigate [the] root causes of anaphylaxis.”

Ultimately, the advisory committee largely agreed that the unmet need for reslizumab outweighed the potential risks associated with it.

In casting his “yes” vote regarding the adequacy of reslizumab’s safety profile, panel chair Dr. Dennis R. Ownby, professor of pediatrics at Georgia Regents University in Augusta, admitted that he was “reluctant” to endorse reslizumab, but said that he believes “this is a drug that clinicians will use very cautiously, [so] I’m placing faith on our practicing physicians” to prescribe the drug responsibly.

Advisers voted 11-3 to recommend approval of reslizumab as a safe and effective treatment of severe asthma and elevated blood eosinophils. Approval of reslizumab would make it the third monoclonal antibody to be FDA approved to treat asthma.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

dchitnis@frontlinemedcom.com

SILVER SPRING, MD. Members of the FDA Pulmonary-Allergy Drugs Advisory Committee voted 11-3 on Dec. 9 to recommend the approval of reslizumab, a humanized monoclonal antibody, for the treatment of asthma and elevated blood eosinophils in patients aged 18 years and older but did not recommend approval for children aged 12-17 years.

The advisers were tasked to consider a dosage of 3 mg/kg of reslizumab, administered intravenously once every 4 weeks for the management of severe asthma. The lack of a recommendation for the pediatric population is because of what panel members considered to be insufficient data culled from a small sample population (19 patients), along with results that did not provide enough evidence that the treatment was of significant benefit to adolescents.

There were “limited data” presented to support use of reslizumab in pediatrics, and “all the evidence was going in the wrong direction,” according to panel member Erica H. Brittain, Ph.D., of the National Institute of Allergy and Infectious Diseases, Bethesda, Md.

Panelist Dr. Thomas A.E. Platts-Mills, professor of medicine at the University of Virginia, Charlottesville, added that a larger study is needed in order to more accurately assess the drug’s efficacy, and should also include patients younger than the age of 12 years.

Both of the questions posited to the panel by the FDA regarding reslizumab approval for pediatric patients, “Do the efficacy data provide substantial evidence of a clinically meaningful benefit?” and “Do the available efficacy and safety data support approval of reslizumab?” received unanimous “No” votes from the 14-member voting panel.

The advisory panel members considered data from five separate trials evaluating the safety and efficacy of reslizumab to be marketed as Cinqair by Teva Pharmaceuticals. Those trials included two 16-week lung-function studies examining forced expiratory volume in 1 second (FEV₁₎, two year-long asthma exacerbation studies, and an open-label safety extension study.

Advisers generally agreed that reslizumab demonstrated substantial improvement in FEV₁ and asthma exacerbation in the adult population. Specifically, in the two exacerbation studies, clinical asthma exacerbations did not occur at all over the 12-month study period in 61% and 73% of subjects on reslizumab, vs. 44% and 52% of subjects in the control cohort, respectively, with FEV₁ dropping.

However, panelists voiced their concern about the risk of muscle toxicity and, especially, anaphylaxis. In a presentation regarding the treatment’s immunogenicity issues, João A. Pedras-Vasconcelos, Ph.D., of the FDA Office of Pharmaceutical Quality, cautioned that enough work was not done by the sponsors to “thoroughly investigate [the] root causes of anaphylaxis.”

Ultimately, the advisory committee largely agreed that the unmet need for reslizumab outweighed the potential risks associated with it.

In casting his “yes” vote regarding the adequacy of reslizumab’s safety profile, panel chair Dr. Dennis R. Ownby, professor of pediatrics at Georgia Regents University in Augusta, admitted that he was “reluctant” to endorse reslizumab, but said that he believes “this is a drug that clinicians will use very cautiously, [so] I’m placing faith on our practicing physicians” to prescribe the drug responsibly.

Advisers voted 11-3 to recommend approval of reslizumab as a safe and effective treatment of severe asthma and elevated blood eosinophils. Approval of reslizumab would make it the third monoclonal antibody to be FDA approved to treat asthma.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

dchitnis@frontlinemedcom.com