Date: 2012-04-27
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at the 64th Annual Meeting of the American Academy of Neurology (AAN)
Company: BiogenIdec (USA) Elan (Ireland)
Product: Tysabri® (natalizumab)
Action mechanism:
Disease: multiple sclerosis
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country:
Trial details:
Latest
news: Biogen Idec and Elan have announced findings from several studies of Tysabri® (natalizumab) evaluating its long-term safety and efficacy in the treatment of multiple sclerosis (MS) across the course of disease and impact on MS-related symptoms such as fatigue. These data, as well as data relating to the companies’ risk stratification algorithm as a way to help enable individual benefit risk assessment for patients with MS, were accepted for presentation at the 64th Annual Meeting of the American Academy of Neurology (AAN). Long-Term Observational Study of Tysabri®: Risk-Stratification Initiatives: A separate study, STRATIFY-2, an ongoing, longitudinal, observational U.S. study, is the largest data set to date to analyze anti-JCV antibody seroprevalence among MS patients. Baseline anti-JCV antibody testing results from more than 35,000 MS patients who were either receiving or considering treatment with Tysabri® showed that the overall prevalence of anti-JCV antibodies was 53.5 percent (95% confidence interval [CI]: 53.0%–54.0%), which is consistent with the prevalence of anti-JCV antibodies observed in MS patients in other clinical research. Interim results from STRATIFY-2 demonstrated prospectively that the PML incidence in Tysabri® -treated anti-JCV antibody negative patients was significantly lower than that in anti-JCV antibody positive patients (anti-JCV negative = 0, CI: 0–0.34; anti-JCV positive=1.02, CI: 0.53–1.78 [p=0.0004]). Final data from STRATIFY-2 will further characterize PML risk in anti-JCV antibody negative and positive patients. Tysabri® Impact on MS-related Fatigue: Data highlighted here is featured in the following poster and platform presentations at the AAN annual meeting:
Initial results from the Tysabri® Observational Program (TOP) indicate that post-baseline annualized relapse rates (ARR) after four years for patients receiving Tysabri® therapy decreased from 1.99 at baseline to 0.28 (p<0.0001); disability, as measured by the Expanded Disability Status Scale (EDSS), remained stable over time. TOP is an ongoing open-label, multicenter, observational study designed to assess long-term outcomes in patients with relapsing-remitting MS (RRMS) in Europe, Australia, and Canada. TOP is expected to enroll more than 4,500 patients who will be followed for 10 years. Neither reduction in ARR nor stabilization of a patient’s EDSS was affected by the type of treatment they were using before initiating Tysabri® therapy. However, ARR were lowest in immunosuppressant (IS) therapy-na?ve patients and highest in patients who had used IS therapy (p<0.0001).
The incidence and type of serious adverse events (SAEs) seen in these patients after long-term use was consistent with Tysabri® ’s known safety profile. There were no significant differences by baseline treatment history in the incidence of SAEs, infection-related SAEs, or progressive multifocal leukoencephalopathy (PML) during Tysabri® therapy, although there was a trend of higher incidence of PML in patients with prior IS use.
Biogen Idec and Elan developed a quantitative risk stratification algorithm to help physicians and people with MS have more confidence in their treatment decisions when considering Tysabri® . The algorithm provides guidance for physicians and patients about the varying degrees of PML risk associated with Tysabri® treatment. The variables impacting PML risk are: anti-JCV antibody status, prior IS use, and Tysabri® treatment duration.
PML risk was quantified by assessing more than 92,000 MS patients fromTysabri® post-marketing sources and clinical studies; through September 2011 there were 159 cases of PML among this patient population and data show PML risk was lowest in anti-JCV antibody negative patients (no PML cases occurred in anti-JCV antibody negative patients; with the inclusion of one hypothetical anti-JCV antibody negative case, the risk is ?0.10 cases per 1,000 patients treated). PML risk was highest in patients with all three risk factors: anti-JCV antibody positive status; prior immunosuppressant use; and 25-48 months of Tysabri® treatment (10.6 cases per 1,000 patients treated). The use of anti-JCV antibody status in this algorithm marks the first time a safety biomarker for risk stratification has been used to inform treatment decisions in MS and these data will be updated during the AAN presentation.
Initial findings from the TYNERGY study (Effects of Tysabri® Over 12 Months on MS Related Fatigue in Patients with RRMS) show that Tysabri® treatment was associated with improved MS-related fatigue. TYNERGY was a multicenter, 12-month clinical follow-up study conducted to evaluate the effect of Tysabri® on MS-related fatigue in patients with RRMS. Fatigue is considered the most common symptom of MS, impacting 75-95 percent of patients. Further, 50-60 percent of MS patients report fatigue as one of their most disabling symptoms, which can contribute to cognitive and physical difficulties. In the study, researchers measured MS-related fatigue at 0 and 12 months via the Fatigue Scale for Motor and Cognitive Functions (FSMC). Results indicate that treatment with Tysabri® impacted fatigue in patients with RRMS as evidenced by a median reduction of the FSMC score by 9.0 points (p<0.0001), which corresponds to an improvement from severe to moderate fatigue. Both the motor and the cognitive components of the FSMC showed similar improvement (p<0.0001). Researchers noted that these first results are promising but need further validation.
- Long-Term Safety and Efficacy and Association between Baseline Treatment History and Postbaseline Relapses in Multiple Sclerosis Patients Treated with Natalizumab in the Tysabri® Observational Program (TOP) (P04.134) was presented on Wednesday, April 25, 2012
- Updated Incidence of Progressive Multifocal Leukoencephalopathy in Natalizumab-Treated Multiple Sclerosis Patients Stratified by Established Risk Factors (S41.001) –presented by Dr. Gary Bloomgren on Thursday, April 26, 2012 from 1:00 to 1:15 p.m. CDT
- Anti-JCV Antibody Prevalence in Patients with Relapsing Multiple Sclerosis Receiving or Considering Treatment with Natalizumab: Baseline Results of STRATIFY-2 (S41.002) – presented by Dr. Sandra Richman on Thursday, April 26, 2012 from 1:15 to 1:30 p.m. CDT
- Natalizumab Reduces Fatigue as Measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC)—First Results from the TYNERGY trial (P07.081) – available for viewing on Thursday, April 26, 2012 from 2:00 to 6:30 p.m. CDT
