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Alemtuzumab, administered in two intravenous infusions over several days 1 year apart, has been approved by the Food and Drug Administration for patients with relapsing forms of multiple sclerosis, the manufacturer, Genzyme, announced on Nov. 14.
Alemtuzumab, a monoclonal antibody that targets CD52, a cell surface antigen present at high levels on T and B lymphocytes, will be marketed as Lemtrada. (Alemtuzumab was first approved in the United States in 2001 for treatment of B-cell chronic lymphocytic leukemia, and is marketed as Campath for that indication.)
“Because of its safety profile, the use of Lemtrada should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS,” according to the Genzyme statement. This wording is included in the approved indication in the prescribing information.
Exactly how alemtuzumab works in MS is unknown. After each treatment course, alemtuzumab “depletes circulating T and B lymphocytes,” which are “thought to be responsible for the damaging inflammatory process in MS,” according to Genzyme’s statement. “Lymphocyte counts then increase over time with a reconstitution of the lymphocyte population that varies for the different lymphocyte subtypes.”
Approval is based on two phase III, open-label studies comparing treatment with alemtuzumab to high-dose subcutaneous interferon beta-1a (Rebif) in patients with relapsing-remitting MS. The CARE-MS I trial enrolled patients who had not been treated previously, whereas the CARE-MS II trial involved patients who had relapsed while on treatment.
In the CARE-MS I study of about 550 patients, the annualized relapse rate (ARR) over 2 years was significantly lower among those on alemtuzumab, compared with those on interferon beta-1a (0.18 vs. 0.39, a relative risk reduction of 55%). There were no significant differences in the time to confirmed disability progression or on the primary MRI endpoint of change in T2 lesion volume. After 2 years, 78% of those on alemtuzumab were relapse free vs. 59% of those on interferon beta-1a, a significant difference, according to the prescribing information.
In the CARE-MS II study of about 600 patients treated previously, the ARR over 2 years was significantly lower among those on alemtuzumab (0.26 vs. 0.52, a relative risk reduction of 49%) and the time to onset of 6-month confirmed disability progression was also significantly delayed. At year 2, 13% of those on alemtuzumab has disability progression, compared with 21% of those on interferon, a 42% relative risk reduction. At year 2, 65% of those on alemtuzumab were relapse free vs. 47% of those on interferon, which was statistically significant. There was no significant difference in T2 lesion volume changes between the two treatment groups.
The most common adverse events, affecting at least 10% of those treated and that were more common than in those treated with interferon beta-1a, were rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infections, diarrhea, and fatigue.
Because of its serious risks, alemtuzumab will be available through a restricted distribution program, as part of its Risk Evaluation and Mitigation Strategy. The label includes a boxed warning about the risks, which include serious, “sometimes fatal autoimmune conditions,” such as immune thrombocytopenia and antiglomerular basement membrane disease, “serious and life-threatening infusion reactions,” and an increased risk of malignancies.
The approval process for alemtuzumab for MS has been long. In December 2013, Genzyme announced that the FDA had declined to approve alemtuzumab for the treatment of MS because of a lack of well-controlled data from clinical studies indicating that the benefits outweighed the risks. That announcement followed a November 2013 meeting of an FDA advisory committee, which voted 12-6 that the manufacturer had provided substantial evidence that the drug was effective as a treatment for patients with relapsing forms of multiple sclerosis.
Among the company’s postmarketing requirements for the drug is a U.S. pregnancy registry study that will compare the maternal, fetal, and infant outcomes in women with MS exposed to Lemtrada during pregnancy and in control groups of women with and without MS who did not take the drug, according to the FDA’s approval letter.
The drug was approved for MS in September 2013 in the European Union and is approved in more than 40 countries, according to Genzyme, a Sanofi company.
This story was updated 11/18/2014.
Alemtuzumab, administered in two intravenous infusions over several days 1 year apart, has been approved by the Food and Drug Administration for patients with relapsing forms of multiple sclerosis, the manufacturer, Genzyme, announced on Nov. 14.
Alemtuzumab, a monoclonal antibody that targets CD52, a cell surface antigen present at high levels on T and B lymphocytes, will be marketed as Lemtrada. (Alemtuzumab was first approved in the United States in 2001 for treatment of B-cell chronic lymphocytic leukemia, and is marketed as Campath for that indication.)
“Because of its safety profile, the use of Lemtrada should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS,” according to the Genzyme statement. This wording is included in the approved indication in the prescribing information.
Exactly how alemtuzumab works in MS is unknown. After each treatment course, alemtuzumab “depletes circulating T and B lymphocytes,” which are “thought to be responsible for the damaging inflammatory process in MS,” according to Genzyme’s statement. “Lymphocyte counts then increase over time with a reconstitution of the lymphocyte population that varies for the different lymphocyte subtypes.”
Approval is based on two phase III, open-label studies comparing treatment with alemtuzumab to high-dose subcutaneous interferon beta-1a (Rebif) in patients with relapsing-remitting MS. The CARE-MS I trial enrolled patients who had not been treated previously, whereas the CARE-MS II trial involved patients who had relapsed while on treatment.
In the CARE-MS I study of about 550 patients, the annualized relapse rate (ARR) over 2 years was significantly lower among those on alemtuzumab, compared with those on interferon beta-1a (0.18 vs. 0.39, a relative risk reduction of 55%). There were no significant differences in the time to confirmed disability progression or on the primary MRI endpoint of change in T2 lesion volume. After 2 years, 78% of those on alemtuzumab were relapse free vs. 59% of those on interferon beta-1a, a significant difference, according to the prescribing information.
In the CARE-MS II study of about 600 patients treated previously, the ARR over 2 years was significantly lower among those on alemtuzumab (0.26 vs. 0.52, a relative risk reduction of 49%) and the time to onset of 6-month confirmed disability progression was also significantly delayed. At year 2, 13% of those on alemtuzumab has disability progression, compared with 21% of those on interferon, a 42% relative risk reduction. At year 2, 65% of those on alemtuzumab were relapse free vs. 47% of those on interferon, which was statistically significant. There was no significant difference in T2 lesion volume changes between the two treatment groups.
The most common adverse events, affecting at least 10% of those treated and that were more common than in those treated with interferon beta-1a, were rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infections, diarrhea, and fatigue.
Because of its serious risks, alemtuzumab will be available through a restricted distribution program, as part of its Risk Evaluation and Mitigation Strategy. The label includes a boxed warning about the risks, which include serious, “sometimes fatal autoimmune conditions,” such as immune thrombocytopenia and antiglomerular basement membrane disease, “serious and life-threatening infusion reactions,” and an increased risk of malignancies.
The approval process for alemtuzumab for MS has been long. In December 2013, Genzyme announced that the FDA had declined to approve alemtuzumab for the treatment of MS because of a lack of well-controlled data from clinical studies indicating that the benefits outweighed the risks. That announcement followed a November 2013 meeting of an FDA advisory committee, which voted 12-6 that the manufacturer had provided substantial evidence that the drug was effective as a treatment for patients with relapsing forms of multiple sclerosis.
Among the company’s postmarketing requirements for the drug is a U.S. pregnancy registry study that will compare the maternal, fetal, and infant outcomes in women with MS exposed to Lemtrada during pregnancy and in control groups of women with and without MS who did not take the drug, according to the FDA’s approval letter.
The drug was approved for MS in September 2013 in the European Union and is approved in more than 40 countries, according to Genzyme, a Sanofi company.
This story was updated 11/18/2014.
Alemtuzumab, administered in two intravenous infusions over several days 1 year apart, has been approved by the Food and Drug Administration for patients with relapsing forms of multiple sclerosis, the manufacturer, Genzyme, announced on Nov. 14.
Alemtuzumab, a monoclonal antibody that targets CD52, a cell surface antigen present at high levels on T and B lymphocytes, will be marketed as Lemtrada. (Alemtuzumab was first approved in the United States in 2001 for treatment of B-cell chronic lymphocytic leukemia, and is marketed as Campath for that indication.)
“Because of its safety profile, the use of Lemtrada should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS,” according to the Genzyme statement. This wording is included in the approved indication in the prescribing information.
Exactly how alemtuzumab works in MS is unknown. After each treatment course, alemtuzumab “depletes circulating T and B lymphocytes,” which are “thought to be responsible for the damaging inflammatory process in MS,” according to Genzyme’s statement. “Lymphocyte counts then increase over time with a reconstitution of the lymphocyte population that varies for the different lymphocyte subtypes.”
Approval is based on two phase III, open-label studies comparing treatment with alemtuzumab to high-dose subcutaneous interferon beta-1a (Rebif) in patients with relapsing-remitting MS. The CARE-MS I trial enrolled patients who had not been treated previously, whereas the CARE-MS II trial involved patients who had relapsed while on treatment.
In the CARE-MS I study of about 550 patients, the annualized relapse rate (ARR) over 2 years was significantly lower among those on alemtuzumab, compared with those on interferon beta-1a (0.18 vs. 0.39, a relative risk reduction of 55%). There were no significant differences in the time to confirmed disability progression or on the primary MRI endpoint of change in T2 lesion volume. After 2 years, 78% of those on alemtuzumab were relapse free vs. 59% of those on interferon beta-1a, a significant difference, according to the prescribing information.
In the CARE-MS II study of about 600 patients treated previously, the ARR over 2 years was significantly lower among those on alemtuzumab (0.26 vs. 0.52, a relative risk reduction of 49%) and the time to onset of 6-month confirmed disability progression was also significantly delayed. At year 2, 13% of those on alemtuzumab has disability progression, compared with 21% of those on interferon, a 42% relative risk reduction. At year 2, 65% of those on alemtuzumab were relapse free vs. 47% of those on interferon, which was statistically significant. There was no significant difference in T2 lesion volume changes between the two treatment groups.
The most common adverse events, affecting at least 10% of those treated and that were more common than in those treated with interferon beta-1a, were rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infections, diarrhea, and fatigue.
Because of its serious risks, alemtuzumab will be available through a restricted distribution program, as part of its Risk Evaluation and Mitigation Strategy. The label includes a boxed warning about the risks, which include serious, “sometimes fatal autoimmune conditions,” such as immune thrombocytopenia and antiglomerular basement membrane disease, “serious and life-threatening infusion reactions,” and an increased risk of malignancies.
The approval process for alemtuzumab for MS has been long. In December 2013, Genzyme announced that the FDA had declined to approve alemtuzumab for the treatment of MS because of a lack of well-controlled data from clinical studies indicating that the benefits outweighed the risks. That announcement followed a November 2013 meeting of an FDA advisory committee, which voted 12-6 that the manufacturer had provided substantial evidence that the drug was effective as a treatment for patients with relapsing forms of multiple sclerosis.
Among the company’s postmarketing requirements for the drug is a U.S. pregnancy registry study that will compare the maternal, fetal, and infant outcomes in women with MS exposed to Lemtrada during pregnancy and in control groups of women with and without MS who did not take the drug, according to the FDA’s approval letter.
The drug was approved for MS in September 2013 in the European Union and is approved in more than 40 countries, according to Genzyme, a Sanofi company.
This story was updated 11/18/2014.