Presentation of results from open-label extension study of Xenazine

Results achieved over 80 weeks of treatment consistent with statistically significant reduction in chorea demonstrated in pivotal study

Lundbeck Inc. today announced the presentation of results from an open-label extension study of Xenazine- (tetrabenazine) for the treatment of chorea associated with Huntington's disease (HD). Data from this study demonstrated that after an 80-week treatment period, subjects treated with Xenazine experienced a statistically significant reduction in chorea score (p< 0.0001) as measured using the Unified Huntington's Disease Rating Scale (UHDRS) compared with baseline. These results are consistent with the reduction in chorea score observed in a pivotal Phase 3 randomized, double-blind, placebo-controlled multi-center clinical study in which subjects were treated with Xenazine for 12 weeks. Data from the open-label study will be presented today at the 12th Annual American Society of Experimental NeuroTherapeutics (ASENT) meeting in Bethesda, Maryland (Poster No. 0029). Results of this study are published in BMC Neurology, an online open access journal at http://www.biomedcentral.com/bmcneurol. Xenazine carries a boxed warning for increased risk of depression and suicidality.

"The jerky, sporadic movements commonly seen with chorea associated with Huntington's disease may make it difficult for affected individuals to do tasks such as holding on to objects or even walking," said Dr. Samuel Frank, MD, assistant professor of neurology at the Boston University School of Medicine and lead investigator in this study. "Prolonged reduction of chorea associated with HD in some patients, as seen in this open-label study of Xenazine, is highly encouraging and suggests that Xenazine could be an important treatment option for those seeking to lessen chorea."

This open-label, multi-center extension study was designed to assess the long-term use of Xenazine as a treatment for chorea associated with Huntington's disease. The study enrolled 75 subjects, all of whom had previously completed 12 weeks of treatment with Xenazine in the pivotal Phase 3 trial, followed by a one week washout period. Xenazine was titrated over a maximum 12 weeks every three to seven days to the best individual dose, up to a maximum of 200 mg/day of Xenazine. Titration was permitted only during the first 11 weeks of the study. Patients who appear to require doses of greater than 50 mg/day should be genotyped for CYP2D6. Doses above 100 mg/day are not recommended for any patient in the Xenazine full prescribing information.

Of the 75 subjects enrolled in the study, 45 subjects completed the 80-week treatment period, of which 42 subjects continued on to complete a one-week washout period. Thirty subjects withdrew from the study, of which, three subjects withdrew due to adverse events associated with Xenazine, including depression, delusions associated with previous suicidal behavior and vocal tics, and 26 subjects withdrew for various other reasons. One subject died due to metastatic breast cancer.

The primary efficacy endpoint in this study was the Total Maximal Chorea (TMC) score from the UHDRS at week 80 compared with baseline TMC score. TMC score at week 80 was also compared to TMC score at week 81 following the washout period. The UHDRS is a validated rating system used to measure the severity of Huntington's disease. The rating system ranges from 0 units (absent chorea symptoms) to 28 units (marked/prolonged chorea).

Data from this study demonstrate a statistically significant reduction in chorea in patients compared to baseline who completed 80 weeks of Xenazine treatment, with a mean reduction in the TMC score of 4.6 UHDRS units. At week 81, following a one week washout period, the mean TMC score increased 5.3 UHDRS units compared to week 80 (p<0.001), suggesting that continued use of Xenazine at an individualized dose maintains reduction of chorea associated with HD for up to 80 weeks and confirming results from the pivotal study where discontinuation of Xenazine treatment was associated with the return of chorea, but without significant worsening compared to baseline.

When mild and unrelated adverse events (AEs) were excluded, the most common AEs in this study reported in >5% of subjects (three or more) were sedation/somnolence, depressed mood, anxiety, insomnia, akathisia, fatigue, agitation, fall, dysphagia and dystonia. Thirty-nine patients reported at least one AE during the titration phase compared to 20 patients during the maintenance period. Insomnia, somnolence and diarrhea emerged during titration and resolved during the maintenance period. Twelve serious AEs were reported including two falls, two cancer diagnoses, a single suicide attempt, pneumonia, elective hip replacement with post-op agitation, agitation, anxiety, akathisia, and one abnormal CA 27-29 titer in a patient who later died due to metastatic breast cancer.