TYSABRI Rx

Crohn’s Disease

• The approval was based on 3 randomized, double-blind, placebo-controlled trials that evaluated Tysabri in 1414 adults with moderately to severe active Crohn’s disease (CDAI ≥220 and ≤450). Concomitant inhibitors of TNF-α were not permitted. Concomitant stable doses of aminosalicylates, corticosteroids, and/or immunosuppressants (e.g., 6-mercatopurine, azathioprine, or methotrexate) were permitted, and 89% of patients continued to receive at least one of these medications.

• In Study CD1, 896 patients were randomly assigned 4:1 to receive 3 monthly infusions of either Tysabri 300 mg or placebo. At week 10, results showed that 56% of the 717 patients receiving Tysabri were in response compared to 49% of the 179 patients receiving placebo (treatment effect: 7%; 95% CI, -1%, 16%; P =.067). In a post hoc analysis of the subset of 653 patients with elevated baseline C-reactive protein (CRP), indicative of active inflammation, 57% of Tysabri patients were in response compared to 45% of those receiving placebo (treatment effect: 12%; 95% CI: [3%, 22%]; nominal P =.01).

• In Study CD2, 509 patients were randomly assigned 1:1 to receive 3 monthly infusions of either Tysabri 300 mg or placebo. Induction with Tysabri achieved the following clinical response and remission at weeks 8 and 12 compared with placebo, respectively:

• Clinical Response at week 8: 56% vs 40% (treatment difference, 16%; 95% CI, 8-26)

• Clinical Response at week 12: 60% vs 44% (treatment difference, 16%; 95% CI, 7-25)

• Clinical Response at both weeks 8 & 12: 48% vs 32% (treatment difference, 16%; 95% CI, 7-24)

• Clinical Remission at week 8: 32% vs 21% (treatment difference, 11%; 95% CI, 3-19)

• Clinical Remission at week 12: 37% vs 25% (treatment difference, 12%; 95% CI, 4-21)

• Clinical Remission at both weeks 8 & 12: 26% vs 16% (treatment difference, 10%; 95% CI, 3-18)

• In Study CD3, maintenance therapy was evaluated in 331 patients who had a clinical response to Tysabri at both Weeks 10 and 12. Patients were re-randomly assigned 1:1 to continue receiving monthly infusions of either Tysabri 300 mg or placebo. Maintenance treatment with Tysabri achieved the following clinical response and remission at Months 9 and 15 compared with placebo, respectively:

• Clinical Response through Month 9: 61% vs 29% (treatment difference, 32%; 95% CI, 21-43)

• Clinical Response through Month 15: 54% vs 20% (treatment difference, 34%; 95% CI, 23-44)

• Clinical Remission through Month 9: 45% vs 26% (treatment difference, 19%; 95% CI, 6-31)

• Clinical Remission through Month 15: 40% vs 15% (treatment difference, 25%; 95% CI, 13-36)

Multiple Sclerosis

• The approval was based on 2 randomized, double-blind, placebo-controlled trials (Study MS1 and MS2) that evaluated Tysabri in patients with MS who experienced at least 1 clinical relapse during the prior year and had a Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 5.0. In both studies, neurological evaluations were performed every 12 weeks and at times of suspected relapse. MRI evaluations for T1-weighted Gd-enhancing lesions and T2-hyperintense lesions were performed annually.

• Study MS1 included patients who had not received any interferon-beta or glatiramer acetate for at least the previous 6 months. Patients were randomly assigned 2:1 to receive Tysabri 300mg IV infusion (n=627) or placebo (n=315) every 4 weeks for up to 28 months (30 infusions).

• Study MS2 included patients who had experienced one or more relapses while on treatment with Avonex (Interferon beta-1a) 30mcg intramuscularly (IM) once weekly during the year prior to study entry. Patients were randomly assigned to receive Tysabri 300mg (n=589) or placebo (n=582) every 4 weeks for up to 28 months (30 infusions). All patients received Avonex 30mcg IM once weekly.

• The primary endpoint at 2 years was time to onset of sustained increase in disability, defined as an increase of at least 1 point on the EDSS from baseline EDSS ≥ 1.0 that was sustained for 12 weeks, or at least a 1.5 point increase on the EDSS from baseline EDSS=0 that was sustained for 12 weeks.

• In Study MS1, treatment with Tysabri achieved the following results at 2 years compared with placebo, respectively:

• Percentage with sustained increase in disability: 17% vs 29% (relative risk reduction, 42%; 95% CI, 23-57)

• Annualized relapse rate: 0.22 vs 0.67 (relative reduction, 67%)

• Percentage of patients remaining relapse-free: 67% vs 41%

• New or newly enlarging T2-hyperintense lesions (median): 0.0 vs 5.0

• Gd-enhancing lesions (median): 0.0 vs 0.0

• In Study MS2, treatment with Tysabri achieved the following results at 2 years compared with placebo, respectively:

• Percentage with sustained increase in disability: 23% vs 29% (relative risk reduction, 24%; 95% CI, 4-39)

• Annualized relapse rate: 0.33 vs 0.75 (relative reduction, 56%)

• Percentage of patients remaining relapse-free: 54% vs 32%

• New or newly enlarging T2-hyperintense lesions (median): 0.0 vs 3.0

• Gd-enhancing lesions (median): 0.0 vs 0.0