Companies: Genzyme/Sanofi, and Bayer HealthCare Pharmaceuticals
- Administered in one course yearly by intravenous infusion over three-to-five consecutive days
- Lemtrada is being studied in RRMSLemtrada is a humanized monoclonal antibody that targets a protein present on the surface of mature lymphocytes, and results in a rapid depletion/suppression of T and B cells. This agent has been approved for the treatment of B-cell leukemia, although as of 2012 it is being developed solely for MS.A Phase II study of 334 individuals with early, active RRMS compared Lemtrada to high-dose Rebif (44 mcg) in RRMS. In this three-year safety and efficacy trial, Lemtrada was more effective than Rebif at reducing the relapse rate and the risk for six-month sustained accumulation of disability in patients with RRMS. This trial is notable as Lemtrada-treated patients had the lowest relapse rate ever reported for an MS drug.
In a multi-year extension study of the 334 individuals who participated in the original Phase II study, Lemtrada yielded a 73-percent reduction in risk for sustained accumulation of disability, while 77 percent of Lemtrada-treated patients were relapse-free. A five-year assessment showed that 87 percent were free of sustained disability accumulation, 72 percent were relapse-free, and 65 percent were free of clinical-disease activity. These data indicate that Lemtrada’s treatment effect is durable; it halts clinical-disease activity in a significant proportion of RRMS patients through five years – even though many of those patients did not require subsequent re-treatment with the drug.
The CARE-MS I study20 compared the clinical and MRI results of treatment with Lemtrada, to treatment with subcutaneous Rebif (interferon beta-1a) in patients with RRMS who had not received prior treatment with any disease-modifying therapies. Rebif was given according to the regular dosing of three times per week, while Lemtrada was given intravenously for five days, and then a second time one year later for three days. CARE-MS I was a multicenter international trial. Data were collected for each patient during a two-year period from the time of the first infusion.
The ARR (annual relapse rate) was 0.18 (or slightly less than one relapse every five years) for Lemtrada-treated patients. This was as compared with 0.39 (or slightly less than one relapse every two-and-a-half years) for Rebif-treated patients. This means that Lemtrada reduced the ARR by 55 percent compared to Rebif. Supportive analyses of the risk of severe relapses found that the risk was lower with Lemtrada. Individuals taking Lemtrada had a 59-percent reduction in severe relapses requiring steroid treatment. These clinical data were supported by MRI outcomes. Through year two, fewer Lemtrada patients developed new gadolinium-enhancing lesions (areas of active inflammation and myelin damage in the brain) than Rebif-treated patients (15.2 percent versus 27.2 percent).
CARE-MS II21 is the third study to compare Lemtrada with Rebif. It was designed to evaluate the effect of Lemtrada on relapse and disability as compared to Rebif in people with RRMS who had relapsed on prior therapy – people for whom a first-line injectible medication was insufficient. The study design was otherwise the same as that in CARE-MS I. The co-primary efficacy endpoints were the ARR and time to six-month sustained accumulation of disability as measured by the Expanded Disability Status Scale (EDSS).
Relapse data showed that 65 percent of patients treated with Lemtrada were relapse-free at two years, as compared to 47 percent with Rebif. These data also showed a 49-percent reduction in relapse rate as compared to Rebif. The group treated with Lemtrada showed a decrease in the mean disability score, versus a slight worsening of disability in those treated with Rebif. Approximately 29 percent of patients treated with Lemtrada experienced a six-month sustained improvement in disability, as compared to 13 percent with Rebif.
Several safety concerns have been raised by the above studies, including infusion reactions to the medication, and an increased risk of infection and emergent autoimmune diseases in patients treated with Lemtrada. All three studies showed a modest increase in the incidence of infections, though no opportunistic infections occurred. No treatment-related fatalities were reported in the Phase III studies. In the CARE-MS I and II studies respectively, approximately 18 percent and 16 percent of Lemtrada patients developed an autoimmune thyroid disorder, and 0.8 percent and 1 percent developed a potentially severe bleeding disorder called immune thrombocytopenic purpura (ITP). A program to monitor for the development of thyroid issues and immune thrombocytopenia was successful in early detection of these known complications from Lemtrada.
With the side effects and adverse events in mind, the significant reduction in relapses with Lemtrada compared with high-dose, high-frequency Rebif suggest that there is potential for Lemtrada to be a meaningful addition to the presently available treatment options for RRMS. In June 2012, the parent company announced that Lemtrada had been submitted to both the FDA and the European Medicines Agency (EMA) for approval; a decision is expected in 2013.