Genzyme, a Sanofi company, has announced that new magnetic resonance imaging (MRI) data from the Lemtrada (alemtuzumab) clinical development programme will be presented at the 67th American Academy of Neurology (AAN) Annual Meeting.
In relapsing remitting multiple sclerosis (RRMS) patients treated with Lemtrada in the phase III pivotal studies, MRI effects observed in the two-year trials were maintained through two additional years in the extension study (years three and four). After the initial two courses of treatment in the pivotal studies, which were given at month zero and at month 12, approximately 70% of Lemtrada patients did not receive additional Lemtrada treatment during the following three years, through month 48.
The phase III trials of Lemtrada were randomised, two-year pivotal studies comparing treatment with Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had an inadequate response to another therapy (CARE-MS II).
Through year four, the adverse event profile of Lemtrada was consistent with that observed during the pivotal studies. The new data presented at AAN include:
- The rate of brain atrophy, as measured by brain parenchymal fraction (BPF), decreased progressively over four years among Lemtrada patients in CARE-MS I. Among CARE-MS II Lemtrada patients, the rate of brain atrophy decreased progressively over three years and remained low in year four. In both studies, the median yearly brain volume loss was less than -0.20% in years three and four, which was lower than what was observed during the two-year pivotal studies.
- In CARE-MS I and II, treatment with Lemtrada significantly reduced the risk of developing new lesions compared to interferon beta-1a. In the extension study, most of the Lemtrada-treated patients from CARE-MS I and II were free of new lesions and MRI activity in years three and four (approximately 70%).
Brain atrophy is a measure of the most destructive pathological processes that occur in MS. It is seen from the earliest stages of disease and may lead to irreversible neurological and cognitive impairment. Given its association with disability, control or prevention of brain atrophy is an important target for MS treatment. In addition, MRI measures including lesion activity are considered useful tools when evaluating the effect of MS therapies, and lesion activity is among several prognostic factors for unfavourable clinical outcomes.
“It is very promising that most Lemtrada patients experienced slowing of brain atrophy and remained free of new lesions despite receiving their last treatment course three years previously,” says Alasdair Coles, professor, Department of Clinical Neurosciences, University of Cambridge, UK. “These new MRI data are consistent with the clinical data from the extension study that provide additional evidence of the sustained efficacy of Lemtrada on both relapses and disability.”
Safety results from the second year of the extension study were previously reported. No new risks were identified. The most common side effects of Lemtrada are rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhoea, sinusitis, oropharyngeal pain, paraesthesia, dizziness, abdominal pain, flushing, and vomiting. Other serious side effects associated with Lemtrada include autoimmune thyroid disease, autoimmune cytopenias, infections and pneumonitis. A risk management programme incorporating education and monitoring helps support early detection and management of these identified risks.
“The four-year MRI data support the prolonged efficacy of Lemtrada,” says Genzyme president and chief executive officer, David Meeker. “These results are encouraging, as they provide further evidence of Lemtrada’s potential to change the treatment approach for people living with relapsing forms of MS.”
More than 90% of the patients who were treated with Lemtrada in the CARE-MS Phase III trials enrolled in the extension study. These patients were eligible to receive additional treatment with Lemtrada in the extension study if they experienced at least one relapse or at least two new or enlarging brain or spinal cord lesions. MRI scans were taken at CARE-MS baseline, and at 12, 24, 36 and 48 months.
In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualised relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualised relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.