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Clinical Trials

Date: 2012-04-24

Type of information: Results

phase: 3

Announcement: results

Company: Genzyme (USA - MA), a Sanofi company (France)

Product: Lemtrada® (alemtuzumab)

Action mechanism:

This humanized monoclonal antibody targets the cell-surface glycoprotein CD52, which is often expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab depletes the T- and B-cells that may be responsible for the cellular damage in multiple sclerosis, while potentially sparing other cells of the immune system. Early alemtuzumab research has also suggested a distinctive pattern of lymphocyte reconstitution in patients following treatment.

Disease:

patients with relapsing-remitting multiple sclerosis (RRMS) who had relapsed while on prior therapy

Therapeutic area: Autoimmune diseases - Neurodegenerative diseases

Country:

Trial details:

CARE-MS II was a randomized Phase III clinical trial comparing the investigational drug alemtuzumab to Rebif® in patients with relapsing-remitting multiple sclerosis (RRMS) who had relapsed while on prior therapy. In the CARE-MS II trial, alemtuzumab 12 mg was given as an IV administration a total of eight times over the course of the two-year study. The first treatment course of alemtuzumab was administered on five consecutive days, and the second course was administered on three consecutive days 12 months later. Rebif ®44 mcg was administered by subcutaneous injection three times per week, each week, throughout the two years of study.

Latest news:

Genzyme has reported additional data from the Phase III CARE-MS II trial. Accumulation of disability was significantly slowed in patients with multiple sclerosis (MS) who were treated with alemtuzumab versus Rebif® (high dose subcutaneous interferon beta-1a), as measured by the Expanded Disability Status Scale (EDSS), a standard assessment of physical disability progression. In addition, significant improvement in disability scores was observed in some patients treated with alemtuzumab from baseline and compared to patients treated with Rebif®, suggesting a reversal of disability in these patients. In the trial, patients with pre-existing disability treated with alemtuzumab were more than twice as likely to experience a sustained reduction in disability than patients given Rebif®.

Key disability data from the CARE-MS II trial have been presented at the 64th Annual Meeting of the American Academy of Neurology. These date  include:
• The mean EDSS score for patients treated with alemtuzumab decreased over a two-year period, indicating an improvement in their physical disability, while the mean score for patients given Rebif® increased, indicating a worsening of disability (-0.17 vs. 0.24; p < 0.0001).
• At two years, 29 percent of patients treated with alemtuzumab had experienced a six-month sustained reduction in disability, meaning their level of disability improved, as compared to only 13 percent with Rebif® (p=0.0002).
• There was a 42 percent reduction in the risk of six-month sustained accumulation (worsening) of disability (SAD) as measured by EDSS in patients treated with alemtuzumab compared to Rebif® over two years of study (p=0.0084), as previously reported. This was a highly statistically significant result for this co-primary endpoint.
Key relapse data from the trial presented at AAN include:
• 65 percent of patients treated with alemtuzumab were relapse-free at two years, meaning they did not experience any relapses in the trial, compared to 47 percent with Rebif ®(47 percent risk reduction; p<0.0001).
• A 49 percent reduction in relapse rate was observed in patients treated with alemtuzumab 12 mg compared to Rebif® over two years of study (p<0.0001), a highly significant result for this co-primary endpoint, as previously reported.

Additional new data from the CARE-MS II study suggest that alemtuzumab provided significant improvement over Rebif® across a number of imaging endpoints, consistent with the effects observed in the clinical endpoints. In MS, imaging can be used to track the development of lesions, or patches of inflammation in the central nervous system (CNS). Statistically significant improvement was observed for alemtuzumab over Rebif ® in the percentage of patients with new or enlarging T2-hyperintense lesions (46 vs. 68; p<0.0001) and with gadolinium-enhancing lesions (19 vs. 34; p<0.0001). The change in T2-hyperintense lesion volume from baseline to year two, a secondary endpoint, was not significantly different (p=0.14). In the trial, patients treated with alemtuzumab experienced less change in brain parenchymal fraction (BPF), a measure of brain atrophy or loss of neurons and the connections between them, compared to Rebif (-0.62 vs. -0.81) median percent change from baseline (p=0.012), a significant result.

The most common adverse events associated with alemtuzumab in the CARE-MS Il study were infusion-associated reactions, which were generally mild to moderate. Infections were common in both groups, with a higher incidence in the alemtuzumab group. The most common infections included upper respiratory and urinary tract infections, cutaneous fungal infections and oral herpes. Serious infections occurred in 3.7 percent of the alemtuzumab group as compared to 1.5 percent of the Rebif group. Infections were predominantly mild to moderate in severity and none were fatal.
In the trial, 15.9 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event compared to 5.0 percent with Rebif, and 0.9 percent of alemtuzumab-treated patients developed immune thrombocytopenia (ITP) during the two-year study period. These cases were detected early through a monitoring program and managed using conventional therapies. Patient monitoring for ITP and thyroid or renal disorders is incorporated in all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS. All data reported above pertain to patients in the trial who received alemtuzumab 12 mg or Rebif ®44 mcg.

Genzyme is now  on track to file for U.S. and EU approval of alemtuzumab in relapsing MS in the second quarter of 2012.

Is general: Yes