Sanofi and its subsidiary Genzyme have announced new magnetic resonance imaging (MRI) data from the Lemtrada (alemtuzumab) clinical development programme. In Lemtrada patients from the two Phase III clinical trials (both treatment-naïve patients and patients who had active disease on another therapy), MRI effects observed after two years were maintained during the first year of the extension study.
This data includes:
Consistent effects were seen across key measures of disease activity (gadolinium (gd)-enhancing, T2 hyperintense and T1 hypointense lesion activity) and effects seen after two years of treatment were sustained at year three;
During the third year of follow-up, more than 70% of patients were free of MRI activity indicative of acute inflammation, defined as gd-enhancing or new or enlarging T2 hyperintense lesions;
T2 lesion volumes, which reflect the combined burden of permanent brain injury and new lesion formation, increased from year two to three but remained below pre-treatment baseline;
The rate of atrophy, as measured by brain parenchymal fraction, already reduced after two years, continued to slow in the third year of follow-up;
Approximately 80% of patients treated with Lemtrada did not receive a third course of treatment in the first year of the extension.
"What's remarkable about this data is that the positive MRI effects of Lemtrada were sustained into the extension study, even though most patients did not receive additional Lemtrada treatment. This observation is unique amongst the current landscape of MS therapeutics," said Douglas Arnold, M.D., NeuroRx Research and Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University. "The new MRI results are an important addition to the clinical data from the extension study that demonstrated Lemtrada's effect on key measures of clinical disease activity including annualised relapse rates and sustained accumulation of disability."
The most common side effects of Lemtrada are infusion-associated reactions (headache, rash, pyrexia, nausea, fatigue, urticaria, insomnia, pruritus, diarrhea, chills, dizziness, and flushing), infections (upper respiratory tract and urinary tract), and lymphopenia. Autoimmune conditions (including immune thrombocytopenia, other cytopenias, glomerulonephritis and thyroid disease) and serious infections can occur in patients receiving Lemtrada. A comprehensive risk management programme incorporating education and monitoring will support early detection and management of these identified risks. Safety results from the first year of the extension study were previously reported for patients who received Lemtrada in the Phase III CARE-MS studies. No new risks were identified. As previously reported, there were two deaths in the extension study. One was from sepsis and the other was presumed accidental and deemed unrelated to study treatment.
The Phase III trials of Lemtrada were randomised, two-year 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 relapsed while on prior therapy (CARE-MS II). In these studies, patients on Lemtrada received two courses of treatment, the first administered via intravenous infusion on five consecutive days, and the second administered on three consecutive days, 12 months later.
Lemtrada-treated patients who continued uninterrupted follow-up in the extension study were eligible for re-treatment on evidence of disease activity. This analysis included 349 Lemtrada-treated patients from CARE-MS I and 393 Lemtrada-treated patients from CARE-MS II; 18% and 20%, respectively, received re-treatment. MRI scans were taken at CARE-MS baseline, and at 12, 24, and 36 months.
"Given the importance of MRI in measuring disease activity in MS, the Lemtrada data announced today are significant," said Genzyme President and CEO, David Meeker, M.D. "These results reinforce the potential that Lemtrada holds to transform the treatment of MS."
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.
